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  • ddc:004
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  • 1
    Publication Date: 2020-12-11
    Description: Im Mai 2009 wurde Wolfram|Alpha gestartet, ein Service, der seinen Namen von seinem Entwickler, dem britischen Mathematiker Stephen Wolfram, ableitet. Dem Benutzer soll nicht nur eine Liste von Webseiten als Ergebnis auf Anfragen geliefert werden, sondern Antworten auf konkrete Fragen geben. In diesem Report soll gezeigt werden, warum sichWolframjAlpha von Suchmaschinen abgrenzt und was die Berechnung von Antworten auf natürlichsprachliche Fragen möglich machen kann.
    Description: Wolfram|Alpha was started in May 2009 and it's a service whose name derives from the british mathematician Stephen wolfram. As a result for a request the user is not just supported with a list of websites but with answers for concrete questions. In this report it will be shown why Wolfram|Alpha seperates from search engines and moreover what makes the computation of answers for natural language queries possible.
    Keywords: ddc:004
    Language: German
    Type: reportzib , doc-type:preprint
    Format: application/pdf
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  • 2
    Publication Date: 2016-06-30
    Description: Executing applications in the Grid often requires access to multiple geographically distributed resources. In a Grid environment, these resources belong to different administrative domains, each employing its own scheduling policy. That is, at which time an activity (e.g., compute job, data transfer) is started, is decided by the resource's local management system. In such an environment, the coordinated execution of distributed applications requires guarantees on the quality of service (QoS) of the needed resources. Reserving resources in advance is an accepted means to obtain QoS guarantees from a single provider. The challenge, however, is to coordinate advance reservations of multiple resources. This work presents a system architecture and mechanisms to coordinate multiple advance reservations -- called co-reservations -- for delivering QoS guarantees to complex applications. We formally define the co-reservation problem as an optimization problem. The presented model supports three dimensions of freedom: the start time, the duration and the service level of a reservation. Requests and resources are described in a simple language. After matching the static properties and requirements of either side in a mapping, the reservation mechanism probes information about the future status of the resources. The versatile design of the probing step allows the efficient processing of requests, but also lets the resources express their preferences among the myriads of reservation candidates. Next, the best mapping is found through an implementation of the formal co-reservation model. Then, the mapping has to be secured, i.e., resources need to be allocated to a co-reservation candidate with all-or-nothing semantics. We study several goal-driven sequential and concurrent allocation mechanisms and define schemes for handling allocation failures. Finally, we introduce the concept of virtual resources for seamlessly embedding co-reservations into Grid resource management.
    Description: Die Ausführung von Anwendungen erfordert oft mehrere, geographisch verteilte Ressourcen. In Grid-Umgebungen gehören diese Ressourcen zu verschiedenen administrativen Organisationen, wobei jede ihre eigene Schedulingregeln verwendet. Das bedeutet, zu welcher Zeit eine Aktivität gestartet wird (z.B. ein Rechenjob), wird vom lokalen Ressourcenmanagementsystem entschieden. Die koordinierte Ausführung von verteilten Anwendungen erfordert Dienstgütegarantien für die benötigten Ressourcen. Das Reservieren von Ressourcen im Voraus ist ein Mittel, um Dienstgütegarantien von einem einzelnen Ressourcenanbieter zu erhalten. Die Herausforderung in dieser Arbeit ist, Vorausreservierungen von mehreren Ressourcen zu koordinieren. Es wird ein System für die Koordinierung mehrerer Vorausreservierungen -- Co-Reservierungen genannt -- für die Bereitstellung von Dienstgütegarantien vorgestellt. Wir definieren das Co-Reservierungsproblem als Optimierungsproblem. Das vorgestellte Modell unterstützt drei Freiheitsgrade: die Startzeit, die Dauer und die Dienstgüte einer Reservierung. Anfragen und Ressourcen werden in einer einfachen Sprache beschrieben. Nachdem statische Eigenschaften und Anforderungen beider Seiten überprüft wurden, ermittelt der Reservierungsmechanismus Informationen über den zukünftigen Zustand der Ressourcen. Dieser Schritt ist so allgemein gehalten, daß er sowohl ein effizientes Bearbeiten der Anfragen erlaubt als auch den Ressourcen ermöglicht ihre Präferenzen auszudrücken. Im Anschluss wird die optimale Zuweisung von Anfragen zu Ressourcen ermittelt. Im letzten Schritt muss diese Zuweisung umgesetzt werden, d.h., entweder alle oder keine Ressource wird allokiert. Es werden mehrere sequentielle und parallele Allokationsverfahren vorgestellt sowie deren Auswirkung auf verschiedene Metriken untersucht. Die Einbettung von Co-Reservierungen in das Grid-Ressourcenmanagement wird anhand des Konzeptes der virtuellen Ressource dargestellt.
    Keywords: ddc:004
    Language: English
    Type: doctoralthesis , doc-type:doctoralThesis
    Format: application/pdf
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  • 3
    Publication Date: 2016-06-30
    Description: Aktuelle Entwicklungen zeigen, dass Peer-to-Peer (P2P) Anwendungen wie Skype oder Bittorrent im Internet immer mehr an Bedeutung gewinnen. In den letzten Jahren hat es einen explosionsartigen Anstieg an Nutzern und Daten in solchen Netzen gegeben. Dabei stellt der eigentliche Dateitransfer zwischen zwei Rechnern kein großes Problem mehr dar und auch der Speicherbedarf für die große Menge an Daten kann durch die Weiterentwicklung der Hardware gut gedeckt werden. Das eigentliche Problem liegt vielmehr darin, den Rechner zu finden, der die gewünschten Daten hat. Client-Server Architekturen, wie zum Beispiel Napster, haben sich als ungünstig herausgestellt. Wenige Server, die eine große Anzahl an Clients bedienen müssen, sind einerseits sehr anfällig gegenüber Angriffen und Ausfällen (Single Point of Failure)und kommen auch nicht mit der ständig wachsenden Anzahl an Nutzern zurecht. Verteilte Hashtabellen (DHT) bieten hier einen guten Lösungsansatz, der mit einer großen Anzahl an Nutzern skaliert und ausfallsicher ist. Andere dezentrale Lösungen, wie zum Beispiel das P2P Netzwerk Gnutella haben zwar das Problem des Single Point of Failure gelöst, jedoch haben sie starke Nachteile bei der Suche nach Keys. Bei einer Suche wird ein Broadcast verwendet (jeder schickt die Anfrage an jeden weiter) und damit ein enormer Netzwerkverkehr erzeugt. In "Why Gnutella Can't Scale. No, Really" wird erklärt, dass eine Suchanfrage bei Standardeinstellungen in der Clientsoftware einen Netzwerkverkehr von 17MB erzeugt. Deswegen wird zusätzlich eine Lösung benötigt, die Keys und Values geordnet verteilt, damit sie gezielt gesucht werden können. Aus diesem Grund beschäftigt sich die folgende Arbeit mit einer völlig dezentralen Architektur, die außerdem eine sinnvolle Platzierung der Keys vornimmt. Die dezentrale Architektur hat den Vorteil, dass die Endgeräte den Hauptteil des Dienstes selbst erbringen und damit jeder zusätzliche Teilnehmer seine eigenen Ressourcen beisteuert. Diese Arbeit präsentiert Chord#, eine dezentrale, skalierbare und selbstorganisierende verteilte Hashtabelle. Chord# wurde ausgewählt, da in dieser Arbeit auch Wert auf Bereichsabfragen gelegt wurde. Diese sind zum Beispiel bei dem Chord Algorithmus nicht möglich, da dieser eine Hashfunktion für die Keys verwendet und somit die Daten zwar gleichmäßig aber unsortiert auf die Teilnehmer verteilt. Es wird in dieser Arbeit gezeigt, dass mit Hilfe von Chord# auch ohne die Hashfunktion gute Ergebnisse erzielt werden. Außerdem können durch den Verzicht auf die Hashfunktion Bereichsabfragen ermöglicht werden. Dafür wird der Chord# Algorithmus in Java implementiert (ca. 1500 Zeilen Code) und in dem Forschungsnetz PlanetLab ausführlich auf Laufzeiten, Instandhaltungskosten und Skalierung getestet.
    Description: Recent developments show that peer-to-peer (p2p) applications, such as Skype or Bittorrent have become increasingly important in the internet. Over the last years there has been a rapid growth of both users and data in such networks. However, the actual file transfer between two peers is not really an issue anymore. The same holds true for data storage, since the new hardware grants users enough space to store their data. The real problem is finding the peers that possess the desired data. Client-server architectures like Napster have proven to be ineffective addressing that problem. One or few servers being responsible for many peers are vulnerable to attacks or failures (single point of failure). Additionally, they are unable to cope with the rapidly growing number of peers. Distributed hashtables (DHT) are a good approach to solve these problems, since they scale nicely with large numbers of peers and provide a high tolerance for errors. Other decentralized solutions like the p2p network Gnutella solved the problem of Single Point of Failure but show considerable disadvantages when searching for keys. The peers in Gnutella use a broadcast (sending the message to all peers they know)resulting in massive traffic. According to "Why Gnutella Can't Scale. No, Really.", each search using standard client settings yields 17MB traffc. This calls for a different solution, distributing keys and values to peers quickly and efficiently so they can be found fast. For that reason this thesis focuses on a fully distributed architecture using organized key placement. One major advantage of distributed architecture is the fact, that the peers do most of the work themselves. This way, new peers joining the network add resources to it. This thesis presents Chord#, a scalable, self-organizing and completely decentralized DHT. It has been chosen due to its capability to allow range queries. The regular Chord algorithm does not support range queries, because of the hashfunction it uses to evenly distribute the keys among the peers. This results in similar or logical coherent keys most likely not being close together in the network. This thesis shows Chord# achieving same results as Chord - regarding performance costs - without the hashfunction. In dropping the hashfunction this algorithm allows the use of range queries. The Chord# algorithm is implemented in Java (about 1500 lines of code) and thoroughly tested in the research network PlanetLab. The results are evaluated regarding performance, maintenance and scalability.
    Keywords: ddc:004
    Language: German
    Type: masterthesis , doc-type:masterThesis
    Format: application/pdf
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  • 4
    Publication Date: 2017-11-02
    Description: One of the biggest impacts on the performance of a Distributed Hash Table (DHT), once established, is its ability to balance load among its nodes. DHTs supporting range queries for example suffer from a potentially huge skew in the distribution of their items since techniques such as consistent hashing can not be applied. Thus explicit load balancing schemes need to be deployed. Several such schemes have been developed and are part of recent research, most of them using only information locally available in order to scale to arbitrary systems. Gossiping techniques however allow the retrieval of fairly good estimates of global information with low overhead. Such information can then be added to existing load balancing algorithms that can use the additional knowledge to improve their performance. Within this thesis several schemes are developed that use global information like the average load and the standard deviation of the load among the nodes to primarily reduce the number of items an algorithm moves to achieve a certain balance. Two novel load balancing algorithms have then been equipped with implementations of those schemes and have been simulated on several scenarios. Most of these variants show better balance results and move far less items than the algorithms they are based on. The best of the developed algorithms achieves a 15-30% better balance and moves only about 50-70% of the number of items its underlying algorithm moves. This variation is also very robust to erroneous estimates and scales linearly with the system size and system load. Further experiments with self-tuning algorithms that set an algorithm’s parameter according to the system’s state show that even more improvements can be gained if additionally applied. Such a variant based on the algorithm described by Karger and Ruhl shows the same balance improvements of 15-30% as the variant above but reduces the number of item movements further to 40-65%.
    Keywords: ddc:004
    Language: English
    Type: masterthesis , doc-type:masterThesis
    Format: application/pdf
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  • 5
    Publication Date: 2020-12-15
    Description: Entwurf und Entwicklung eines eingebetteten Hauptspeicher-Datenbanksystems mit Snapshot-Reads.
    Description: Design and implementation of an embedded main memory database with snapshot reads.
    Keywords: ddc:004
    Language: German
    Type: masterthesis , doc-type:masterThesis
    Format: application/pdf
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  • 6
    Publication Date: 2016-06-30
    Description: Das Ziel dieser Arbeit ist die Schaffung einer Zugriffs-Komponente für das Grid-Datenmanagement-System ZIB-DMS, das dessen transparente Einbindung in den Verzeichnisbaum eines Linux-Systems erlaubt. Dazu wird unter Verwendung des FUSE-Rahmenwerkes ein Userspace-Dateisystem mit Anbindung an das ZIB-DMS konzipiert und implementiert. Im Fokus stehen dabei die Abbildung der erweiterten Verwaltungsmechanismen des Systems auf die limitierte Schnittstelle hierarchischer Dateisysteme und die dazu notwendigen Änderungen am ZIB-DMS.
    Description: The goal of this work is to create an access component for the Grid data management system ZIB-DMS, that allows a transparent integration into the directory tree of a Linux system. For this purpose the FUSE framework is used to design and implement a userspace file system with connections to the ZIB-DMS. The focus is on the mapping of the extended management mechanisms of the system to the limited interface of hierarchical file systems and the therefore necessary changes to ZIB-DMS.
    Keywords: ddc:004
    Language: German
    Type: masterthesis , doc-type:masterThesis
    Format: application/pdf
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  • 7
    Publication Date: 2021-01-22
    Description: We present a framework for transactional data access on data stored in a DHT. It allows to atomically read and write items and to run distributed transactions consisting of a sequence of read and write operations on the items. Items are symmetrically replicated in order to achieve durability of data stored in the SON. To provide availability of items despite the unavailability of some replicas, operations on items are quorum-based. They make progress as long as a majority of replicas can be accessed. Our framework processes transactions optimistically with an atomic commit protocol that is based on Paxos atomic commit. We present algorithms for the whole framework with an event based notation. Additionally we discuss the problem of lookup inconsistencies and its implications on the one-copy serializability property of the transaction processing in our framework.
    Keywords: ddc:004
    Language: English
    Type: reportzib , doc-type:preprint
    Format: application/pdf
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  • 8
    Publication Date: 2020-12-11
    Description: When planning teams for projects with specific goals, employees of a company have to group together so well, that all necessary knowledge for conquering the project’s challenges are met within the member’s skills. A tool that facilitates semantic web technologies can support the team recruiter, who is responsible for chosing the members of the team, in terms of finding the most efficient combinations of the company’s employees based on their expertises.
    Keywords: ddc:004
    Language: English
    Type: reportzib , doc-type:preprint
    Format: application/pdf
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  • 9
    Publication Date: 2021-01-22
    Description: Key/value stores which are built on structured overlay networks often lack support for atomic transactions and strong data consistency among replicas. This is unfortunate, because consistency guarantees and transactions would allow a wide range of additional application domains to benefit from the inherent scalability and fault-tolerance of DHTs. The Scalaris key/value store supports strong data consistency and atomic transactions. It uses an enhanced Paxos Commit protocol with only four communication steps rather than six. This improvement was possible by exploiting information from the replica distribution in the DHT. Scalaris enables implementation of more reliable and scalable infrastructure for collaborative Web services that require strong consistency and atomic changes across multiple items.
    Keywords: ddc:004
    Language: English
    Type: reportzib , doc-type:preprint
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  • 10
    Publication Date: 2022-07-19
    Description: Basierend auf einem vorhandenen Ansatz zur Einführung von anisotropen Tetraedern im Randbereich eines reinen Tetraedergitters wird ein Gittergenerator für hybride Gitter implementiert. Das hybride Gitter besteht in Randnähe primär aus anisotropen Prismen und im Inneren der Geometrie aus isotropen Tetraedern. Eine erhöhte Auflösung im Randbereich soll zu besseren Ergebnissen von numerischen Strömungssimulationen führen, für welche eine problemangepasste Diskretisierung des zu untersuchenden Gebietes benötigt wird. In dem zuvor genannten Ansatz wird eine Reihe von Übergangselementen vorgeschlagen, die an scharfen Kanten der Oberfläche platziert werden sollen. Im Rahmen dieser Diplomarbeit wird die Idee der Übergangselemente aufgegriffen und bei hybriden Gittern eingesetzt, um auch komplexe Eingabegeometrien vergittern zu können. Der ursprüngliche Gittergenerierungprozess wird überarbeitet und erweitert. Eine neue Menge an Übergangselementen wird eingeführt, es werden gekrümmte Extrusionsvektoren verwendet und es wird die Auswertung der medialen Oberfläche vorgenommen, um Überschneidungen im hybriden Gitter zu vermeiden. Der Gittergenerator wird als Modul in das Visualisierungs- und Analyseprogramm Amira implementiert und die erstellten hybriden Gitter werden auf ihre Elementqualität und die Güte der Strömungssimulationsergebnisse hin überprüft.
    Description: Based on an existing approach for the introduction of anisotropic tetrahedra near the surface boundary of a tetrahedral grid a grid generator for hybrid grids is implemented. The hybrid grid consists near the surface boundary primarily of anisotropic prisms and inside the geometry of isotropic tetrahedra. An increased resolution near the boundary should lead to better results of numerical flow simulations, which needs a problem specific discretization of the analyzed domain. In the aforementioned approach a set of transition elements is suggested, which should be placed at sharp surface corners. As a part of this diploma thesis the concept of using transition elements is applied for creating hybrid grids even for very complex input geometries. The initial grid generation process is revised and enhanced. A new set of transition elements is introduced, curved extrusion vectors are used and the medial surface is evaluated to avoid intersections in the hybrid grid. The grid generator is implemented as a module for the visualization and analysis tool Amira and the element quality of the generated hybrid grids and the quality of flow simulations performed on the grids are tested.
    Keywords: ddc:004
    Language: German
    Type: masterthesis , doc-type:masterThesis
    Format: application/pdf
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  • 11
    Publication Date: 2016-06-30
    Description: We study performance and scaling of the Berlin Quantum Chromodynamics Program (BQCD) on the SGI Altix 4700 at Leibniz Supercomputing Centre (LRZ). We employ different communication methods (MPI, MPI with two OpenMP threads per process, as well as the shmem library) and run the MPI version on the two types of nodes of that machine. For comparison with other machines we made performance measurements on an IBM p690 cluster and a Cray XT4.
    Keywords: ddc:004
    Language: English
    Type: reportzib , doc-type:preprint
    Format: application/pdf
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  • 12
    Publication Date: 2022-07-19
    Description: In dieser Arbeit wird eine Serie von Remeshing-Verfahren um die Berücksichtigung von nicht-mannigfaltigen Dreiecksvernetzungen und Merkmalskantenzügen erweitert. Die betrachteten Verfahren arbeiten im Wesentlichen lokal. Daher können die im Rahmen dieser Arbeit entwickelten Erweiterungen, die nicht-mannigfaltige Kantenzüge und Merkmalskantenzüge betreffen, separat beschrieben werden. Dabei wird ein Ansatz verfolgt, beide Arten von besonderen Kantenzügen aufgrund ihrer Gemeinsamkeiten einheitlich zu behandeln. Dieser besteht zum einen darin, eine Korrespondenz zwischen Kantenzügen auf der Eingabe- und der Ausgabefläche zu erhalten, indem die Remeshing-Operationen auf den Kantenzügen in entsprechend eingeschränkter Weise verwendet werden. Zum anderen wird beschrieben, wie die Abtastdichte der Kantenzüge dynamisch an die Abtastdichte der Umgebung angepasst werden kann, um für weitgehende Isotropie in der Nähe von Merkmalskantenzügen zu sorgen.
    Description: A unified approach for consistent remeshing of arbitrary non-manifold triangle meshes with additional user-defined feature lines is presented. The method is based on local operations only and produces meshes of high regularity and triangle quality while preserving the geometry as well as topology of the feature lines as well as the input mesh.
    Keywords: ddc:004
    Language: German
    Type: masterthesis , doc-type:masterThesis
    Format: application/pdf
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  • 13
    Publication Date: 2022-07-19
    Description: This work introduces a novel streamline seeding technique based on dual streamlines that are orthogonal to the vector field, instead of tangential. The greedy algorithm presented here produces a net of orthogonal streamlines that is iteratively refined resulting in good domain coverage and a high degree of continuity and uniformity. The algorithm is easy to implement and efficient, and it naturally extends to curved surfaces.
    Description: In dieser Arbeit wird eine neue Strategie zur Platzierung von Stromlinien vorgestellt. Hierzu werden zusätzliche duale Stromlinien verwendet, die --im Gegensatz zur üblichen Definition-- orthogonal zum Vektorfeld verlaufen. Der vorgestellte Greedy-Algorithmus berechnet ein Netz aus orthogonalen Stromlinien, welches iterativ verfeinert wird, was zu einer guten Abdeckung der Domäne und einer gleichmäßigen Verteilung der Stromlinien führt. Es handelt sich um einen einfach zu implementierenden und effizienten Algorithmus, der direkt auf gekrümmten Oberflächen anwendbar ist.
    Keywords: ddc:004
    Language: English
    Type: reportzib , doc-type:preprint
    Format: application/pdf
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  • 14
    Publication Date: 2020-12-11
    Description: In dieser Diplomarbeit wird untersucht, wie auf der Basis von Literaturreferenzen ein Zitationsgraph durch ein automatisches Verfahren aufgebaut werden kann. Zur Lösung des Problems werden Probabilistische Relationale Modelle herangezogen. Eine problemspezifische Erweiterung des Modells ermöglicht es, dass bestehende Unsicherheiten im Zitationsgraphen mit Hilfe eines Inferenzverfahrens aufgelöst werden können. Zur Evaluierung des Verfahren werden Experimente auf dem Cora-Datensatz durchgeführt.
    Keywords: ddc:004
    Language: German
    Type: masterthesis , doc-type:masterThesis
    Format: application/pdf
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  • 15
    Publication Date: 2016-06-30
    Description: Die Diplomarbeit präsentiert ein Transaktionsverfahren für strukturierte Overlay-Netzwerke, das an die Erfordernisse verteilter Informationssysteme mit relationalem Datenmodell angepasst ist. Insbesondere wird der Einsatz von Transaktionen für verteilte Wikis betrachtet, die moderne Funktionalitäten, wie Metadaten und zusätzliche Indexe für die Navigation, unterstützen. Konsistenz und Dauerhaftigkeit der gespeicherten Daten erfordert die Behandlung von Knotenausfällen. Die Arbeit schlägt dafür das Zellenmodell vor: Das Overlay wird aus replizierten Zustandsmaschinen gebildet, um Verfügbarkeit zu gewährleisten. Das Transaktionsverfahren baut darauf auf und verwendet Two-Phase-Commit mit Fehlererkennung und Widerherstellung von ausgefallenen Transaktionsmanagern. Anwendungen wird eine Auswahl an pessimistischen und hybrid-optimistischen Nebenläufigkeitskontrollverfahren geboten, die die Minimierung von Latenzeffekten und die schnelle Ausführung von Nur-Lese-Transaktionen ermöglichen. Für die Beispielanwendung Wiki wird der erforderliche Pseudocode angegeben und die verschiedenen Nebenläufigkeitskontrollverfahren hinsichtlich ihrer Nachrichtenkomplexität verglichen.
    Description: The diploma thesis presents a transaction processing scheme for structured overlay networks and uses it to develop a distributed Wiki application based on a relational data model. The Wiki supports rich metadata and additional indexes for navigation purposes. Ensuring consistency and durability requires handling of node failures. Such failures are masked by providing high availability of nodes. This in turn is achieved by constructing the overlay from replicated state machines (cell model). Atomicity is realized using two phase commit with additional support for failure detection and restoration of the transaction manager. The developed transaction processing scheme provides the application with a mixture of pessimistic, hybrid optimistic and multiversioning concurrency control techniques to minimize the impact of replication on latency and optimize for read operations. The pseudocode of the relevant Wiki functions is presented and the different concurrency control techniques are evaluated in terms of message complexity.
    Keywords: ddc:004
    Language: German
    Type: masterthesis , doc-type:masterThesis
    Format: application/pdf
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  • 16
    Publication Date: 2016-06-30
    Description: Die Arbeit präsentiert ein Transaktionsverfahren für strukturierte Overlay-Netzwerke, das an die Erfordernisse verteilter Informationssysteme mit relationalem Datenmodell angepasst ist. Insbesondere wird der Einsatz von Transaktionen für verteilte Wikis betrachtet, die moderne Funktionalitäten, wie Metadaten und zusätzliche Indexe für die Navigation, unterstützen. Konsistenz und Dauerhaftigkeit der gespeicherten Daten erfordert die Behandlung von Knotenausfällen. Die Arbeit schlägt dafür das Zellenmodell vor: Das Overlay wird aus replizierten Zustandsmaschinen gebildet, um Verfügbarkeit zu gewährleisten. Das Transaktionsverfahren baut darauf auf und verwendet Two-Phase-Commit mit Fehlererkennung und Widerherstellung von ausgefallenen Transaktionsmanagern. Anwendungen wird eine Auswahl an pessimistischen und hybrid-optimistischen Nebenläufigkeitskontrollverfahren geboten, die die Minimierung von Latenzeffekten und die schnelle Ausführung von Nur-Lese-Transaktionen ermöglichen. Für die Beispielanwendung Wiki wird der erforderliche Pseudocode angegeben und die verschiedenen Nebenläufigkeitskontrollverfahren hinsichtlich ihrer Nachrichtenkomplexität verglichen.
    Description: The report presents a transaction processing scheme for structured overlay networks and uses it to develop a distributed Wiki application based on a relational data model. The Wiki supports rich metadata and additional indexes for navigation purposes. Ensuring consistency and durability requires handling of node failures. Such failures are masked by providing high availability of nodes. This in turn is achieved by constructing the overlay from replicated state machines (cell model). Atomicity is realized using two phase commit with additional support for failure detection and restoration of the transaction manager. The developed transaction processing scheme provides the application with a mixture of pessimistic, hybrid optimistic and multiversioning concurrency control techniques to minimize the impact of replication on latency and optimize for read operations. The pseudocode of the relevant Wiki functions is presented and the different concurrency control techniques are evaluated in terms of message complexit
    Keywords: ddc:004
    Language: German
    Type: reportzib , doc-type:preprint
    Format: application/pdf
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  • 17
    Publication Date: 2016-06-30
    Description: Berlin als Stadtstaat ist Kommune und Land der Bundesrepublik zugleich und Standort vieler renommier-ter Wissenschafts- und Kultureinrichtungen. In enger Zusammenarbeit der Wissenschaftseinrichtungen mit dem IT-Dienstleistungszentrum Berlin (ITDZ, ehemals Landesbetrieb für Informationstechnik), der für die Behörden Berlins zuständigen Einrichtung, wurde seit 1993 ein landeseigenes Glasfasernetz mit einer derzeitigen Länge von 856 km Glasfaserkabel (je Kabel bis zu 144 Einzelfasern) zur gemeinsamen Nutzung von Wissenschaft und Verwaltung errichtet und weiter ausgebaut. 1994 erfolgte der offizielle Start des Berliner Wissenschaftsnetzes BRAIN (Berlin Research Area Information Network), als durch einen Beschluss des Senats von Berlin die Nutzung des landeseigenen Glasfasernetzes durch die Wissen-schaftseinrichtungen festgeschrieben wurde. Bereits 1995 wurden durch die Wissenschaftseinrichtungen auf diesem Glasfasernetz die ersten sieben Anschlüsse in ATM-Technik (Classical BRAIN-ATM) in Betrieb genommen, 1999 wurden anschließend auch erste Strecken in Ethernet-Technik (Classical BRAIN-GE) betrieben. Diese heterogenen Netze mit unterschiedlichen Netzgeräten wurden dezentral von den Netzadministratoren der beteiligten Einrichtungen nach globalen Absprachen betreut. Die dezentrale Administration erschwerte das Management und die Erweiterungen der Gesamtnetze. Basierend auf den vorliegenden Erfahrungen vereinbarten die Berliner Wissenschaftseinrichtungen, ein technisch neues Verbundnetz in Gigabit-Ethernet-Technik mit einheitlichen Geräten und einem zentralen Netzwerkmana-gement aufzubauen und zu betreiben. Seit November 2003 betreibt BRAIN auf dem landeseignen Glasfasernetz ein auf MPLS-Technik basie-rendes Gigabit-Ethernet-Netz, das „BRAIN-Verbundnetz“, mit den Diensten LAN-to-LAN-Kopplung der Einrichtungen, regionaler IP-Verkehr, Übergang zum Verwaltungsnetz und WiN-Backup. Das BRAIN-Verbundnetz löste die dezentral betreuten Vorläufernetze komplett ab. Von den derzeit 27 BRAIN-Teilnehmern nutzen 24 Einrichtungen an 53 in der Stadt verteilten Standorten die Dienste des BRAIN-Verbundnetzes, 18 Standorte sind mit 1000 Mbit/s und 35 Standorte mit 100 Mbit/s angeschlossen. Für verteilte Standorte einer Einrichtung besteht zudem die Möglichkeit, diese über dedizierte Fasern oder Bandbreiten miteinander zu vernetzen. Seit dem 2. Quartal 2007 wird im Rahmen eines Pilotprojekts der Nutzen eines zentral gemanagten Fibre Channel-Netzwerks "BRAIN-SAN" ermittelt, um Möglichkeiten einer verteilten Datenhaltung der Berliner Hochschulen und wissenschaftlichen Einrichtungen zu schaf-fen. Zusätzlich zu den vorgenannten Diensten nutzt der DFN-Verein die BRAIN-Struktur für die Verbindun-gen der X-WiN-Kernnetzknoten in Berlin und Potsdam untereinander und für Zugangsleitungen zu den Anwendern. Mit Stand 2007 nutzt das Berliner Wissenschaftsnetz BRAIN vom landeigenen Glasfasernetz 2100 km Einzelfasern und verbindet insgesamt 43 Einrichtungen (BRAIN-Teilnehmer und DFN-Anwender) aus Wissenschaft, Bildung und Kultur mit 129 Standorten. Der Betrieb von BRAIN wird im wesentlichen durch seine Nutzer finanziert. Das Land Berlin trägt aller-dings pauschal die überwiegenden Kosten für die Wartung des Glasfasernetzes, soweit es vom ITDZ be-reit gestellt wird. Zentrales Planungs- und Steuerungsorgan für BRAIN ist die von der Senatsverwaltung für Bildung, Wis-senschaft und Forschung eingerichtete BRAIN-Planungsgruppe. Sie besteht aus Mitarbeitern der Rechen-zentren der drei Berliner Universitäten und des ZIB. Nach außen wird BRAIN in rechtlicher und wirtschaftlicher Hinsicht treuhänderisch vom ZIB vertreten, die BRAIN-Geschäftsstelle befindet sich ebenfalls im ZIB.
    Description: Berlin as a city state is both local authority and federal state of the Federal Republic, as well as a location of many renowned institutions of research and culture. In close cooperation of the institutions of research with the IT service centre Berlin (ITDZ, the former Landesbetrieb für Informationstechnik) - which is the appropriate facility for the authorities of Berlin - a glass fibre network of a total extension of 856 kilome-tres of fibre optics (144 fibres each cable optic) for the common use of research and administration has been established and advanced since 1993. In 1994, when a resolution of the Senate of Berlin laid down the use of the appropriate fibre networks by the research facilities, this was the official beginning of the Berlin Research Area Information Network (BRAIN). The first seven interfaces in this fibre network in ATM technology (Classical BRAIN-ATM) were already established by the research facilities in 1995. In 1999, first systems run in Ethernet technology (Classical BRAIN-GE). These heterogeneous networks with different interfaces have been supported locally by the network administrators of the research facili-ties following global agreements. Management and advancement of the overall networks were encum-bered by these local administrations. Based on the existing experience, Berlin's research facilities agreed on the building and advancement of a technically new integrated network in gigabit Ethernet technology with standardised facilities and a centrally managed network. Since November 2003 the Berlin Research Area Information Network established a Gigabit Ethernet - called “BRAIN Integrated Network” - based on MPLS technology, including LAN to LAN linking of the facilities, local IP traffic, interface to the administration's network and WIN back-up. This BRAIN Inte-grated Network has completely replaced the locally administered predecessor networks. 24 of 27 BRAIN participants use the services of the BRAIN Integrated Network on 53 locations spread all over the city. 18 locations are connected with 1000 Mbit/s and 35 locations with 100 Mbit/s. Moreover, spread locations of a single facility have the possibililty to communicate by dedicated fibres or bandwidths. From the 2nd quarter 2007 within the scope of a pilot scheme, the advantage of a centrally administered fibre channel network "BRAIN-SAN" will be determined in order to accomplish possibilities of a spread data manage-ment of Berlin's universities and research facilities. In addition to the aforementioned services the DFN association makes use of BRAIN's structure for the connection of the X-WiN-core network nodes in Berlin and Potsdam und for access pathways to the us-ers. As from 2007, Berlin's research network BRAIN uses 2100 kilometres of single fibres from the country's fibre glass network and connects a total of 43 facilities (BRAIN participants and DFN users) from re-search, education and culture with 129 locations. The operations of BRAIN are funded basically by its users. However, the country of Berlin bears most of the costs for the maintenance of the glass fibre network, as far as it is provided by ITDZ. Central planning and steering body for BRAIN is the BRAIN planning group, which has been arranged by the administration of the Senatsverwaltung für Bildung, Wissenschaft und Forschung. It consists of staff from the computing centres of Berlin's three universities and of ZIB. BRAIN is represented legally and economically on a trust basis by the ZIB, where the BRAIN office is located also.
    Keywords: ddc:004
    Language: German
    Type: reportzib , doc-type:preprint
    Format: application/pdf
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  • 18
    Publication Date: 2022-07-19
    Description: For medical diagnosis, visualization, and model-based therapy planning three-dimensional geometric reconstructions of individual anatomical structures are often indispensable. Computer-assisted, model-based planning procedures typically cover specific modifications of “virtual anatomy” as well as numeric simulations of associated phenomena, like e.g. mechanical loads, fluid dynamics, or diffusion processes, in order to evaluate a potential therapeutic outcome. Since internal anatomical structures cannot be measured optically or mechanically in vivo, three-dimensional reconstruction of tomographic image data remains the method of choice. In this work the process chain of individual anatomy reconstruction is described which consists of segmentation of medical image data, geometrical reconstruction of all relevant tissue interfaces, up to the generation of geometric approximations (boundary surfaces and volumetric meshes) of three-dimensional anatomy being suited for finite element analysis. All results presented herein are generated with amira ® – a highly interactive software system for 3D data analysis, visualization and geometry reconstruction.
    Keywords: ddc:004
    Language: English
    Type: reportzib , doc-type:preprint
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  • 19
    Publication Date: 2022-07-19
    Description: This work introduces novel internal and external memory algorithms for computing voxel skeletons of massive voxel objects with complex network-like architecture and for converting these voxel skeletons to piecewise linear geometry, that is triangle meshes and piecewise straight lines. The presented techniques help to tackle the challenge of visualizing and analyzing 3d images of increasing size and complexity, which are becoming more and more important in, for example, biological and medical research. Section 2.3.1 contributes to the theoretical foundations of thinning algorithms with a discussion of homotopic thinning in the grid cell model. The grid cell model explicitly represents a cell complex built of faces, edges, and vertices shared between voxels. A characterization of pairs of cells to be deleted is much simpler than characterizations of simple voxels were before. The grid cell model resolves topologically unclear voxel configurations at junctions and locked voxel configurations causing, for example, interior voxels in sets of non-simple voxels. A general conclusion is that the grid cell model is superior to indecomposable voxels for algorithms that need detailed control of topology. Section 2.3.2 introduces a noise-insensitive measure based on the geodesic distance along the boundary to compute two-dimensional skeletons. The measure is able to retain thin object structures if they are geometrically important while ignoring noise on the object's boundary. This combination of properties is not known of other measures. The measure is also used to guide erosion in a thinning process from the boundary towards lines centered within plate-like structures. Geodesic distance based quantities seem to be well suited to robustly identify one- and two-dimensional skeletons. Chapter 6 applies the method to visualization of bone micro-architecture. Chapter 3 describes a novel geometry generation scheme for representing voxel skeletons, which retracts voxel skeletons to piecewise linear geometry per dual cube. The generated triangle meshes and graphs provide a link to geometry processing and efficient rendering of voxel skeletons. The scheme creates non-closed surfaces with boundaries, which contain fewer triangles than a representation of voxel skeletons using closed surfaces like small cubes or iso-surfaces. A conclusion is that thinking specifically about voxel skeleton configurations instead of generic voxel configurations helps to deal with the topological implications. The geometry generation is one foundation of the applications presented in Chapter 6. Chapter 5 presents a novel external memory algorithm for distance ordered homotopic thinning. The presented method extends known algorithms for computing chamfer distance transformations and thinning to execute I/O-efficiently when input is larger than the available main memory. The applied block-wise decomposition schemes are quite simple. Yet it was necessary to carefully analyze effects of block boundaries to devise globally correct external memory variants of known algorithms. In general, doing so is superior to naive block-wise processing ignoring boundary effects. Chapter 6 applies the algorithms in a novel method based on confocal microscopy for quantitative study of micro-vascular networks in the field of microcirculation.
    Description: Die vorliegende Arbeit führt I/O-effiziente Algorithmen und Standard-Algorithmen zur Berechnung von Voxel-Skeletten aus großen Voxel-Objekten mit komplexer, netzwerkartiger Struktur und zur Umwandlung solcher Voxel-Skelette in stückweise-lineare Geometrie ein. Die vorgestellten Techniken werden zur Visualisierung und Analyse komplexer drei-dimensionaler Bilddaten, beispielsweise aus Biologie und Medizin, eingesetzt. Abschnitt 2.3.1 leistet mit der Diskussion von topologischem Thinning im Grid-Cell-Modell einen Beitrag zu den theoretischen Grundlagen von Thinning-Algorithmen. Im Grid-Cell-Modell wird ein Voxel-Objekt als Zellkomplex dargestellt, der aus den Ecken, Kanten, Flächen und den eingeschlossenen Volumina der Voxel gebildet wird. Topologisch unklare Situationen an Verzweigungen und blockierte Voxel-Kombinationen werden aufgelöst. Die Charakterisierung von Zellpaaren, die im Thinning-Prozess entfernt werden dürfen, ist einfacher als bekannte Charakterisierungen von so genannten "Simple Voxels". Eine wesentliche Schlussfolgerung ist, dass das Grid-Cell-Modell atomaren Voxeln überlegen ist, wenn Algorithmen detaillierte Kontrolle über Topologie benötigen. Abschnitt 2.3.2 präsentiert ein rauschunempfindliches Maß, das den geodätischen Abstand entlang der Oberfläche verwendet, um zweidimensionale Skelette zu berechnen, welche dünne, aber geometrisch bedeutsame, Strukturen des Objekts rauschunempfindlich abbilden. Das Maß wird im weiteren mit Thinning kombiniert, um die Erosion von Voxeln auf Linien zuzusteuern, die zentriert in plattenförmigen Strukturen liegen. Maße, die auf dem geodätischen Abstand aufbauen, scheinen sehr geeignet zu sein, um ein- und zwei-dimensionale Skelette bei vorhandenem Rauschen zu identifizieren. Eine theoretische Begründung für diese Beobachtung steht noch aus. In Abschnitt 6 werden die diskutierten Methoden zur Visualisierung von Knochenfeinstruktur eingesetzt. Abschnitt 3 beschreibt eine Methode, um Voxel-Skelette durch kontrollierte Retraktion in eine stückweise-lineare geometrische Darstellung umzuwandeln, die als Eingabe für Geometrieverarbeitung und effizientes Rendering von Voxel-Skeletten dient. Es zeigt sich, dass eine detaillierte Betrachtung der topologischen Eigenschaften eines Voxel-Skeletts einer Betrachtung von allgemeinen Voxel-Konfigurationen für die Umwandlung zu einer geometrischen Darstellung überlegen ist. Die diskutierte Methode bildet die Grundlage für die Anwendungen, die in Abschnitt 6 diskutiert werden. Abschnitt 5 führt einen I/O-effizienten Algorithmus für Thinning ein. Die vorgestellte Methode erweitert bekannte Algorithmen zur Berechung von Chamfer-Distanztransformationen und Thinning so, dass diese effizient ausführbar sind, wenn die Eingabedaten den verfügbaren Hauptspeicher übersteigen. Der Einfluss der Blockgrenzen auf die Algorithmen wurde analysiert, um global korrekte Ergebnisse sicherzustellen. Eine detaillierte Analyse ist einer naiven Zerlegung, die die Einflüsse von Blockgrenzen vernachlässigt, überlegen. In Abschnitt 6 wird, aufbauend auf den I/O-effizienten Algorithmen, ein Verfahren zur quantitativen Analyse von Mikrogefäßnetzwerken diskutiert.
    Keywords: ddc:004
    Language: English
    Type: doctoralthesis , doc-type:doctoralThesis
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  • 20
    Publication Date: 2022-07-19
    Description: One crucial step in virtual drug design is the identification of new lead structures with respect to a pharmacological target molecule. The search for new lead structures is often done with the help of a pharmacophore, which carries the essential structural as well as physico-chemical properties that a molecule needs to have in order to bind to the target molecule. In the absence of the target molecule, such a pharmacophore can be established by comparison of a set of active compounds. In order to identify their common features,a multiple alignment of all or most of the active compounds is necessary. Moreover, since the “outer shape” of the molecules plays a major role in the interaction between drug and target, an alignment algorithm aiming at the identification of common binding properties needs to consider the molecule’s “outer shape”, which can be approximated by the solvent excluded surface. In this thesis, we present a new approach to molecular surface alignment based on a discrete representation of shape as well as physico-chemical properties by points distributed on the solvent excluded surface. We propose a new method to distribute points regularly on a surface w.r.t. a smoothly varying point density given on that surface. Since the point distribution algorithm is not restricted to molecular surfaces, it might also be of interest for other applications. For the computation of pairwise surface alignments, we extend an existing point matching scheme to surface points, and we develop an efficient data structure speeding up the computation by a factor of three. Moreover, we present an approach to compute multiple alignments from pairwise alignments, which is able to handle a large number of surface points. All algorithms are evaluated on two sets of molecules: eight thermolysin inhibitors and seven HIV-1 protease inhibitors. Finally, we compare the results obtained from surface alignment with the results obtained by applying an atom alignment approach.
    Description: Die Identifizierung neuer Leitstrukturen (lead structures) zur Entwicklung optimierter Wirkstoffe ist ein äußerst wichtiger Schritt in der virtuellen Wirkstoffentwicklung (virtual drug design). Die Suche nach neuen Leitstrukturen wird oft mit Hilfe eines Pharmakophor-Modells durchgeführt, welches die wichtigsten strukturellen wie auch physiko-chemischen Eigenschaften eines bindenden Moleküls in sich vereint. Ist das Zielmolekül (target) nicht bekannt, kann das Pharmakophor-Modell mit Hilfe des Vergleiches aktiver Moleküle erstellt werden. Hier ist insbesondere die gleichzeitige Überlagerung (multiple alignment) aller oder nahezu aller Moleküle notwendig. Da bei der Interaktion zweier Moleküle die "äußere Form" der Moleküle eine besondere Rolle spielt, sollte diese von jedem Überlagerungsalgorithmus, der sich mit der Identifizierung von Bindungseigenschaften befasst, berücksichtigt werden. Dabei kann die "äußere Form" durch eine bestimmte Art von molekularer Oberfläche approximiert werden, die man als solvent excluded surface bezeichnet. In dieser Arbeit stellen wir einen neuen Ansatz zur Überlagerung molekularer Oberflächen dar, der auf einer diskreten Repräsentation sowohl der Form als auch der molekularen Eigenschaften mittels Punkten beruht. Um die Punkte auf der molekularen Oberfläche möglichst regulär entsprechend einer gegebenen Punktdichte zu verteilen, entwickeln wir eine neue Methode. Diese Methode ist nicht auf Moleküloberflächen beschränkt und könnte daher auch für andere Anwendungen von Interesse sein. Basierend auf einem bekannten Point-Matching Verfahren entwickeln wir einen Point-Matching Algorithmus für Oberflächenpunkte. Dazu erarbeiten wir u.a. eine effiziente Datenstruktur, die den Algorithmus um einen Faktor von drei beschleunigt. Darüberhinaus stellen wir einen Ansatz vor, der Mehrfachüberlagerungen (multiple alignments) aus paarweisen Überlagerungen berechnet. Die Herausforderung besteht hierbei vor allem in der großen Anzahl von Punkten, die berücksichtigt werden muss. Die vorgestellten Algorithmen werden an zwei Gruppen von Molekülen evaluiert, wobei die erste Gruppe aus acht Thermolysin Inhibitoren besteht, die zweite aus sieben HIV-1 Protease Inhibitoren. Darüberhinaus vergleichen wir die Ergebnisse der Oberflächenüberlagerung mit denen einer Atommittelpunktüberlagerung.
    Keywords: ddc:004
    Language: English
    Type: doctoralthesis , doc-type:doctoralThesis
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  • 21
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 26-34 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: A set of 4-monosubstituted cyclopentenes, , were synthesized and their relative rates (kX/kH) for bromination and chlorination were determined in methanol, ethanol and acetic acid at 25 °C by competitive method. log(kX/kH) for most of the substituents can be correlated by means of Taft's equation, log(kX/kH) = ρI σI + C. In methanol ρI, Br2 = -2·91, ρI, Cl2 = -0·49, in ethanol ρI, Br2 = -3·07, ρI, Cl2 = -0·70 and in acetic acid ρI, Br2 = -1·64, ρI, Cl2 = -0·65. The presence of C(〈0) is due to a constant steric effect. The deviation of X = H is ascribed to the absence of the steric effect and that of X = CO2Me and CO2Et is accounted for in terms of anchimeric assistance. For chlorination no anchimeric assistance was observed.
    Additional Material: 1 Ill.
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  • 22
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 57-88 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The cation radical vinylcyclobutane (VCB) rearrangement is found to be a reaction of substantial scope, synthetic utility, and exceptional kinetic facility. In conjuction with cation radical cyclobutanation, it constitutes an effective method for net (indirect) Diels-Alder addition to electron rich dienophiles. Reactions can be carried out with either aminium salt or photosensitized electron transfer (PET) initiation and are powerfully facilitated by ionizable substituents such as p-anisyl, phenylthio, and phenoxy at the 2-position of the vinylcyclobutane. The intramolecularity of the reaction is clearly established and in four discrete systems preferred sr (suprafacial/retention) stereochemistry is observed. A theoretical basis for sr stereochemistry in the cation radical VCB rearrangement is advanced. The transition state for the reaction is considered to be similar to that for the direct cation radical Diels-Alder cycloaddition, another cation radical pericyclic reaction which converges on the same product. This model of the VCB rearrangement transition state is used to rationalize the strong rate-retarding effect of a Z-methyl substituent attached to the vinyl group and of a methyl substituent at the 4-position of the vinylcyclobutane ring cis to the vinyl substituent.
    Type of Medium: Electronic Resource
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  • 23
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 1-14 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The mechanism of aromatic nucleophilic substitutions by amines in protic solvents is well established; on the contrary the mechanism/s of the reactions in aprotic solvents is/are still subject of controversy. The present paper describes several systems for which fourth-order kinetics (third-order in amine) were observed. A mechanism is proposed to account for this as well as other observation such as: overall negative energies of activation, quadratic dependence of kA with non-nucleophilic tertiary bases, spectacular effects of hydrogen-bond donor (HBD) and hydrogen-bond acceptor (HBA) catalysts, etc. Other alternative mechanisms are also discussed.
    Additional Material: 5 Ill.
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  • 24
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The kinetics and mechanisms of the reactions between 1-phenylethyl benzenesulfonates (1-PEB) with N,N-dimethylanilines are investigated in methanol at 35·0°C. Reactivity and selectivity trends were found to be similar to those for the reactions of 1-PEB with anilines, but the magnitudes of cross interaction constants, ρXZ, between substituents X in the nucleophile and Z in the leaving group were substantially smaller indicating no hydrogen-bond bypass bridge formation in the transition state. However, the magnitude of ρXZ suggested a direct electrostatic interaction between the reaction centers in the nucleophile and leaving group in the frontside nucleophilic attack with a loose transition state structure.
    Additional Material: 6 Tab.
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  • 25
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 183-186 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The harmonic vibrational frequencies were calculated analytically at the 6-31** level for azetidine using the GAUSSIAN 82 program. The results strongly indicate the presence of several errors in a recent assignment of the fundamentals of azetidine based on a normal coordinate analysis and a revised assignment is suggested. It is concluded that reliable vibrational data for azetidine in the gas phase are needed in order to resolve the remaining ambiguities in the interpretation of the spectra.
    Additional Material: 1 Tab.
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  • 26
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989) 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 27
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 110-116 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The transamination reaction of α-amino acids with glyoxylic acid as catalyzed by copper(II) ions was investigated kinetically in an aqueous medium at pH 5·0 and 30·0°C. L-Phenylalanine transferred its amino group to glyoxylic acid most readily among seven different amino acids used here in the single-walled bilayer vesicle formed with N,N-dihexadecyl-Nα-[6-(trimethylammonio)hexanoyl]-L-histidinamide bromide (N+C5His2C16). Such rate enhancement was found to originate from the cooperative trifunctional catalysis: a coordination effect exercised by copper(II) ions, a general acid-base catalysis by the imidazolyl group of the lipid, and a hydrophobic field effect provided by the bilayer vesicle. Lack of any of the three functions failed to give out significant rate enhancement. As regards correlation between the reactivity and the nature of α-amino acids, the copper(II)-catalyzed transamination was progressively enhanced as hydrophobicity of the α-amino acid was increased in the N+C5His2C16 vesicle.
    Additional Material: 4 Ill.
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  • 28
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 43-50 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The cyclic vinyl ether dihydro-1,4-dioxin is converted to its cyclic hemiacetal hydration product, 2-hydroxy-1,4-dioxane, in aqueous solution by an acid-catalyzed reaction for which kH+ = 1·80 × 10-5 M-1 S-1 at 25°C. This reactivity and the solvent isotope effect kH+/kD+ = 2·2 show that the reaction occurs by rate-determining proton transfer from catalyst to substrate and not by a pre-equilibrium mechanism as recently proposed.2
    Additional Material: 1 Ill.
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  • 29
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 161-176 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Cyclobutanediyl (2) has been studied in both its singlet and triplet states by ab initio electronic structure theory. The triplet, which is the ground state of the molecule, exists in both C2h and C2v forms which interconvert via a Cs transition state. For the singlet, only a C2h form is found. It passes, via a Cs transition state, onto the C2v surface on which bicyclobutane (3) is the only minimum. The ring-flipping (inversion) process in 3 includes the singlet biradical as an intermediate, and involves a novel, non-least motion path similar to one previously proposed by Gassman. Semiclassical periodic orbit theory indicates that the various minima on both the singlet and triplet surfaces can interconvert via quantum mechanical tunneling.
    Additional Material: 5 Ill.
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  • 30
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 89-92 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Spectral characteristics of several simple substituted B,B-bis(mesityl)pyrroloboranes are reported which support a theoretical treatment by Bonacic-Koutecky and Michl (J. Am. Chem. Soc. 107, 1765 (1985)) describing the excited states of simple aminoboranes as an example of twisted internal charge transfer. In the aminoboranes the pyrrolo moiety functions as the electron donor group and the empty p-orbital of the boron atom as the acceptor.
    Additional Material: 1 Ill.
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  • 31
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 103-109 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: A preliminary theoretical study of the mechanisms for the reactions of the perchlorofluoroethanes CF2ClCCl3 (1), CF2ClCCl2F (2) and CF3CCl3 (3), with nucleophiles has been carried out by the MNDO method, following the experimentally suggested process shown in Scheme 1. The unlikely chlorophilic attack in the first step of Scheme 1 has been shown to be feasible for 1, 2 and 3 by analysis of the MO interactions. The second step has been found to be affected by the anionic hyperconjugation which stabilizes the anions CF2ClCCl2- (4), CF2ClCClF- (5) and CF3CCl2- (6) and would make reactions (2) (the second step) unfeasible in gas phase, but in solution reaction (2) may still easily occur for 4 and 5.
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  • 32
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    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 146-160 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The alkaline hydrolysis of several alkylphosphonates and alkylphosphonyl chlorides has been investigated by molecular mechanics calculations (MM2, 1985 version). The difference of the steric energies (ΔE) between tetracoordinate substrate and pentacoordinate transition state of phosphorus compounds represents the activation energy (ΔE≠) in hydrolysis. The change of ΔE for various alkyl groups relative to methyl group (ΔΔER) is suggested as a measure of the steric effect of substituents. Thus the correlation analysis involving log k and ΔΔER of the branched alkyl group gives good results and it is reasonable to anticipate that analogous treatment using ΔΔER for the straight chain alkyl group is not satisfactory owing to the minor contribution of steric effect of the latter. However, the multiple regression analysis of log k with ΔΔER and Taft's σ* provides very good results. As shown by us, for the hydrolytic reactions studied, the proposed ΔΔER is much better than Taft's Es and Charton's ν, the commonly used well-known steric parameters in the chemistry of carbon compounds.
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  • 33
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    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 205-213 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Mechanism of the Grignard reactions of aromatic ketones in THF was studied by spectroscopic and kinetic methods. The stable radical intermediates generated in the initial electron transfer from Grignard reagent to ketones are in a state of aggregated dimer of corresponding ion-radical pairs; in which two ketone anion radicals are bridged by a dimer di-cation of Grignard reagent. Subsequent alkyl radical transfer from dimeric Grignard reagent cation moiety to ketone anion radical aggregated each other are promoted by a participation of another neutral Grignard reagent. Proposed mechanism by present authors is able to explain well addition products/reduction products ratios in the Grignard reactions.
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  • 34
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    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 232-242 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Characteristic vector analysis of a set of six physical and empirical parameters of 103 commonly used organic solvents (bp, ∊r, μ, nD, ETN, and δ) gives four vectors describing 95% of the total data variability. Non-hierarchical cluster analysis, applied to our results, leads to ten separate classes of organic solvents.
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  • 35
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    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989) 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
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  • 36
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    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 15-25 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Solvolysis of 2-X-2-phenylpropane (1-X) in 25 vol% acetonitrile in water at 25°C produces 2-hydroxy-2-phenylpropane (1-OH) and 2-phenylpropene (3). The carbocationic intermediate discriminates between different nucleophiles; azide anion, acetate anion, and methanol are more efficient nucleophiles than water, kN3/kH2O = 42 kOAc/kH2O = 3, and kMeOH/kH2O = 2·9 (ratio of second-order rate constants). The fraction of the elimination product 3 increases with increasing basicity of the leaving group X as well as by addition of general bases. The Brønsted parameter for this catalysis is small, β = 0·13, with substituted acetate anions. The kinetic deuterium isotope effect for the dehydronation of the intermediate has been measured (assuming the reaction from intermediate to alcohol is insensitive to isotopic substitution) employing the hexadeuterated substrate d6-1-X as k3H/k3d6 = 3·5 ± 0·2 for the chloride 1-Cl with acetate anion, and, without added base, 3·1 ± 0·2 for the acetate 1-OAc, and 3·1 ± 0·2 for the p-nitrobnzoate 1-PNB, respectively, and ∼5 for the protonated methyl ether 1-OMeH+. The variation in isotope effect with change in leaving group is discussed in terms of elimination from contact ion pairs and ‘free’ carbocation. The overall kinetic isotope effect for the solvolysis was found to be kobsH/kobsd6 = 1·31 (1-OMeH+), 1·38 (1-OAc), 1·40 (1-PNB), and 5·7 (1-OH2+). These isotope effects consist of the isotope effect k12H/k12d6 for the formation of the substitution product 1-OH and k13H/k13d6 for production of the olefin 3. It is concluded that the latter isotope effect is enlarged owing to a branched mechanism in which the deprotonation of the carbocationic intermediate competes with formation of the substitution product. As large an isotope effect as k13H/k13d6 ∼6·5 has been measured for 1-OMeH+.
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  • 37
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    Chirality 1 (1989), S. 99-120 
    ISSN: 0899-0042
    Keywords: asymmetry ; enantiomers ; geometric isomers ; (+)- (-)-isomers ; D- and L-isomers ; R- and S-isomers ; Z- and E-isomers ; drug metabolism ; stereoselectivity and stereospecificity in drug action ; stereoselectivity and stereospecificity in drug metabolism ; psychotropic drugs ; stimulants ; antidepressants ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Many drugs contain a chiral centre, or such a centre is introduced during metabolism of the drug in man and in animals. If a single chiral centre is present, the drug will normally exist as a mixture of two enantiomers, of which one may have quite different pharmacologic and/or toxic effects than the other. Chiral drugs that are used in psychiatry, and some other pharmacologically related drugs are identified, and the implications of the presence of one or two chiral centres in these drugs are discussed. Differences in pharmacologic properties of drug and metabolite enantiomers are identified and discussed. Also reviewed are the properties of some drugs used in psychiatry that both are chiral and display geometric isomerism.
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  • 38
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    Chirality 1 (1989), S. 10-13 
    ISSN: 0899-0042
    Keywords: (S)-, (R,S)-propranolol ; pharmacokinetic ; human study ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The pharmacokinetics of (S)-propranolol were compared after the oral administration of a 40 mg dose of the pure enantiomer and an 80 mg dose of a racemic mixture of (R,S)-propranolol. The results of this study indicate that the bioavailability of (S)-propranolol, as expressed by the mean area uner the concentration-time curve (AUC) and maximum serum concentration, is lower after 40mg of the optically pure drug than after the racemic drug.
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  • 39
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    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 1 (1989) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 40
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    Chirality 1 (1989), S. 192-196 
    ISSN: 0899-0042
    Keywords: propranolol enantiomers ; enantiomers ; propranolol ; β-receptor-blocking drugs ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Only limited information is available on the stereochemistry of the in vivo distribution of β-receptor-blocking drugs. In this study we determined the levels of the propranolol enantiomers in plasma, cerebrospinal fluid (CSF) and central nervous system (CNS), and peripheral tissues in the dog following an intravenous dose of a deuterium-labeled pseudoracemate. The appearance of the propranolol enantiomers in the CSF was rapid and nonstereoselective, with maximum concentrations reached at 15 min after dosing. The levels of the enantiomers in both CSF and plasma then declined in a parallel biphasic fashion, with a terminal t1/2 of about 125 min. Except for an early high CSF/plasma concentration ratio of 0.35, the CSF propranolol levels corresponded to the unbound concentration in plasma, CSF/plasma 0.20. All areas of the brain showed a similar uptake of propranolol, with a tissue concentration exceeding that in plasma about 10-fold during the terminal phase of elimination. The uptake of propranolol by peripheral tissues varied widely, ranging from a 50-fold accumulation by the lungs compared to plasma to no accumulation by adipose tissue. However, as for the CSF, there was no evidence of stereoselective uptake of propranolol by any CNS or peripheral tissue except for the liver. A significantly higher level of (+)- vs. (-)-propranolol in liver tissue presumably was a reflection of stereoselective hepatic metabolism of (-)-propranolol by this tissue. The slight stereoselectivity in plasma binding of propranolol known to exist in the dog had no significant influence on tissue or CSF distribution.
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  • 41
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    Chirality 1 (1989), S. 209-215 
    ISSN: 0899-0042
    Keywords: enantiomeric separation ; bioanalysis ; α1-acid glycoprotein column ; disposition (R)- and (S)-atenolol ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A method for the determination of (R)- and (S)-atenolol in human plasma and urine is described. The enantiomers of atenolol are extracted into dichloromethane containing 3% heptafluorobutanol followed by acetylation with acetic anhydride at 60°C for 2 h. The acetylated enantiomers were separated on a chiral α1-AGP column. Quantitation was performed using fluorescence detection. A phosphate buffer pH 7.1 (0.01 M phosphate) containing 0.25% (v/v) acetonitrile was used as mobile phase. The described procedure allows the detection of less than 6 ng of each enantiomer in 1 ml plasma. The relative standard deviation is 4.4% at 30 ng/ml of each enantiomer in plasma. The plasma concentration of (R)- and (S)- atenolol did not differ significantly in two subjects who received a single tablet of racemic atenolol. The R/S ratio of atenolol in urine was ∼ 1.
    Additional Material: 7 Ill.
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  • 42
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    Chirality 1 (1989), S. 246-248 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 43
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    Chirality 1 (1989), S. 243-245 
    ISSN: 0899-0042
    Keywords: stereochemistry ; enantiomers ; direct separation ; alfuzosin ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Described is a direct enantioselective separation of the enantiomers of alfuzosin hydrochloride on the second generation α1-AGP column which offers improved efficiency, shorter analysis, and improved stability with respect to the first generation columns. The method has been applied to the analysis of drug substance in rat plasma. This highly efficient extraction method and the use of fluorimetric detection result in selective and sensitive determination of the enantiomers. The analytical validation parameters demonstrate the applicability of this method to pharmacokinetic and metabolic studies.
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  • 44
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    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 1 (1989), S. 251-264 
    ISSN: 0899-0042
    Keywords: optical activity ; optical rotation ; chiroptical detection ; enantiomeric purity ; chiral separation ; enantioselective reactions ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Chiroptical detection for HPLC is particularly useful as a selective detection method for chiral molecules, and in enantiomeric purity determination with partial chiral separation or without chiral separation. The recent development of laser-based polarimeters with microdegree sensitivity has increased the applicability of optical rotation detection in HPLC. The detection limit of these instruments is submicrogram on-column for many chiral compounds in analytical HPLC. A variety of applications of the selective detection of optically active molecules are reviewed. The use of polarimetric detection with partial chiral separation is considered, both as an aid to method development and for enantiomeric purity determination. Finally applications to enantiomeric purity determination without chiral separation are reviewed, with the dual use of nonchirally selective and chiroptical detectors to determine the total amount and optical purity of the analyte. Determinations of chiral purity for samples of high enantiomeric excess are described, which with laser-based instrumentation may give accuracies of better than ± 1% with sample loadings of 50 μg on an achiral column. Applications to the study of enantioselective reactions are also considered, with determination of enantiomeric excess in near-racemates to better than ± 0.1%.
    Additional Material: 9 Ill.
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  • 45
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    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 1 (1989), S. 271-275 
    ISSN: 0899-0042
    Keywords: HSA-affinity chromatography ; interconverting conformers ; conformational selectivity ; conformational diastereomers ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: 2,3-Benzodiazepines containing a centre of asymmetry at C-5 possess both central and helical chiralities, and the solution of their racemates contains four molecular species. The binding of these compounds to human serum albumin (HSA) was studied by affinity chromatography. The binding strength depended both on the steric orientation of the 5-ethyl substituent and on the conformation of the diazepine ring. Conformation P (defined by the positive sign of C-1-N-2-N-3-C-4 torsion angle) is favoured, while the quasiaxial orientation -of the 5-ethyl substituent is not favoured by the albumin molecule.
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  • 46
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    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 1 (1989), S. 293-300 
    ISSN: 0899-0042
    Keywords: optical isomers ; chirality and odour ; chiral flavour compound resolution ; enantiomer separation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantioseparation of the sherry aroma components 5-oxo-4-hydroxyhexanoic acid γ-lactone (solerone) and 4,5-dihydroxyhexanoic acid γ-lactone (solerole) is achieved, using Chiraspher (Merck) as the chiral HPLC phase and the optical purity ascertained directly by HRGC with heptakis(3-O-acetyl-2,6-di-O-pentyl)-β-cyclodextrin (Lipodex D) as the chiral stationary phase. The absolute configurations of 4,5-dihydroxyhexanoic acid γ-lactones are assigned by 1H-NMR spectral data of diastereomeric α-methoxy-α-trifluoromethylphenylacetic acid (MTPA) esters, according to Mosher's model. Sensory qualities of the isomers are given.
    Additional Material: 4 Ill.
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  • 47
    ISSN: 0899-0042
    Keywords: ifosfamide enantiomers, GC chiral stationary phase, pharmacokinetic studies, clinical validation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: An enantioselective gas chromatographic method has been developed and validated for the determination of the plasma concentration of the enantiomers of the anticancer drug ifosfamide (IFF). In this approach, the IFF enantiomers are separated from the plasma matrix by solid phase extraction, chromatographically resolved by gas chromatography on a chiral stationary phase, and detected by mass selective detection using selective ion monitoring. The assay has been validated for routine clinical and pharmacokinetic use and has a limit of detection in plasma of 250 ng/ml of each isomer.
    Additional Material: 3 Ill.
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  • 48
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    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 1 (1989), S. 137-141 
    ISSN: 0899-0042
    Keywords: resolution by crystallization ; racemic mixture ; dansyl-D-leucine ; dansyl-L-leucine ; dansyl-D-norleucine ; dansyl-L-norleucine ; dansyl-D-phenylalanine ; dansyl-L-phenylalanine ; β-cyclodextrin ; γ-cyclodextrin ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Optical enrichment from racemic dansyl-leucine, dansyl-norleucine, and dansyl-phenylalanine with both β- and γ-cyclodextrins in water is reported. Initial crystallization yielded the dansyl-L-leucine isomer complexed in excess with β-cyclodextrin with an optical purity of 62-78% depending on experimental conditions. The optical purities obtained for L-norleucine and L-phenylalanine were 71 and 64%, respectively. The optical purity can be increased with continued recrystallization. The dansyl-D-leucine isomer was obtained in the mother liquor with an optical purity of 54-93% depending on experimental conditions. The optical purities obtained for D-norleucine and D-phenylalanine were 72 and 58%. The optical purity of the isomer depended on the molar ratio of host:guest and the pH value of the solution. Optimum enrichment of both enantiomers was achieved with host:guest ratios of 2 : 1 and 3 : 1. Although maximum crystalline yield of the dansyl-leucine/CD inclusion complex was obtained at a pH of 3.5, optical purity of both enantiomers was less than that obtained at other pHs. The influence of the molar ratio of host:guest and the pH value of the solution are discussed. This method is suitable for large-scale enantiomeric separations.
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  • 49
    ISSN: 0899-0042
    Keywords: enantiomeric separations ; chiral stationary phase ; Pirkle-type phases ; HPLC ; anthelmintics ; benzimidazole sulfoxides ; albendazole ; fenbendazole ; oxfendazole ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The direct enantiomeric resolution of albendazole sulfoxide (SOABZ), an anthelmintic drug belonging to the benzimidazole class, is reported on a chiral stationary phase (CSP) synthesized by covalent binding of (S)-N-(3,5-dinitrobenzoyl)tyrosine-O-(2-propen-1-yl) methyl ester on a γ-mercaptopropylsilanized silica gel. A comparison with the resolution achieved on commercially available Pirkle-type CSPs obtained from N-(3,5-dinitrobenzoyl) derivatives of (R)-phenyglycine or (S)-phenylalanine is described. Some structurally related chiral sulfoxides including oxfendazole (SOFBZ) are also studied. Optimization of the mobile phase nature and composition is investigated showing that a hexane-dioxane-ethanol ternary mixture affords an almost baseline resolution (Rs = 1.25); however, in this case, albendazole sulfone (SO2ABZ) is eluted between the two sulfoxide enantiomers; accordingly, a hexane-ethanol mobile phase would be preferred for biological samples containing both metabolites. The influence of temperature on the resolution is depicted with a hexane-ethanol mobile phase. Finally, application to the enantiomeric assays of SOABZ in plasmatic extracts of rat, sheep, bovin, and man after oral administration of albendazole (sulfoxidized to SOABZ and SO2ABZ) is reported. Some distortions in the enantiomeric ratios are evidenced depending on the species.
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  • 50
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    Chirality 1 (1989), S. 1-1 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 51
    ISSN: 0899-0042
    Keywords: terutaline ; enantiomers ; determination ; liquid ; chromatography ; coupled columns ; cyclodextrin ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The purpose of this work was to develop and validate a method for the separation and determination of the enantiomers of terbutaline in plasma and intestinal juice. Terbutaline was extracted from plasma and intestinal juice by liquid-solid extraction on small C18 cartridges. The extract was then analyzed by coupled column liquid chromatography with amperometric detecton. For ciral separation a β-cyclodextrin phase was used.The within-day variation (Cv) on spiked plasma samples was in the rane 0.8-6.4% at 3.8-33.8 nmol/liter for the (-)-enantiomer, and 2.6-23.0% at 1.3-11.3 nmol/liter for the (+)-enantiomer. The between-day variation on spiked plasma samples was 5.5% at 10.7 nmol/liter and 13.6% at 4.3 nmol/liter for the (-)- and (+)-enantiomers, respectively. The within-day variation for inestinal juice was i the range 0.7-1.5% at 5.6-30.0 μmol/liter for the (+)-enantiomer.
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  • 52
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    Chirality 1 (1989), S. 69-79 
    ISSN: 0899-0042
    Keywords: chiral recognition ; three-point model ; distance matrix ; molecular graph ; molecular complexes ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A general criterion is formulated for molecular recognition. The criterion for recognition is the ineqality of the distance matrices of complexes of different compounds with a resolving agent under ambient experimental conditions. It is shown how this criterion provides for an objective, cell-defined, and simple explanation for recognition of chiral compounds. This approach may be used to explain models (e.g., three-point of attachment1) and relationships for chiral recognition. It is also shown how one-, two-, or three-point mechanisms are equivalent in this formalism and could result in chiral recognition. Examples are used to illustrate how the so called one- or two-point mechanisms may be operative in many experimental findings. Symmetry rreqirements of resolving agents may also be derived from considerations of distance matrices. Finally, the reciprocal relationship of chiral resolving agents is easily derived from the present method of analysis.
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  • 53
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    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 1 (1989) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 54
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    Chirality 1 (1989), S. 97-97 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 55
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    Chirality 1 (1989), S. 57-62 
    ISSN: 0899-0042
    Keywords: chiral stationary phase ; α-amino phosphonate ; chromatographic separation of enantiomers ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A chiral statonary phase (CSP) derived from an N-(3,5-dinitrobenzoyl)-α-aminobenzylphosphonate has been prepared and evaluated for its utility in the direct separation of enantiomers. This CSP, 2, is structurally related to earlier N-(3,5-dinitrobenzoyl)-α-acids acid-derived phases (e.g., CSP 1), but the mode of attachment to the support is different. In scope; CSP 2 is qualitaively similar to CSP 1. However, it differs quantitatively from CSP 1, showing either greater or lesser selectivity for different pairs of enantiomers.
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  • 56
    ISSN: 0899-0042
    Keywords: enantiomeric separations ; chiral stationary phases ; tyrosine chiral selector ; γ-mercaptopropyl silica gel ; HPLC ; SubFC ; preparative LC ; chiral recognition mechanisms ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Chromatographic applications of three novel chiral stationary phases (CSPs) deriving from (S)-(N)-(3,5-dinitrobenzoyl)tyrosine are reported, under liquid chromatographic (LC) and subscritical fluid chromatographic (SubFC) conditions. Two grafting modes of the chiral moiety have been experimented starting either from γ-mercaptopropyl-silanized (type 1) or γ-aminopropyl-silanized (type 2) silica gels. For type 2 CSPs an evaluation of the stability of the amide linkage was achieved by means of SubFC; the relative contriution of ionic and covalent bindings to the ciral recognitio aility was then outlined. The chromatographic properties of these CSPs were compared with those of the corresponding CSPs deriving from phenylglycine, p-hydroxyphenylglycine, and phenylalanine for the resolution of some tertiary phosphine oxide, naphthoyl amide, and α-methylene γ-lactam enantiomers. Some simple requirements regarding the solute and CSP structures for chiral recognition ability can be inferred from these results. In addition, the resolutio of π-acid α-N-(3,5-dinitrobenzoyl)amino esters was investigated on these π-acid CSPs. An example of preparative scale chromatography is also presented.
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  • 57
    ISSN: 0899-0042
    Keywords: crystal structure ; inclusion ; chiral host ; complexation ; glucopyranose ; cellulose triacetate ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: X-ray analysis of the crystalline product obtained by reaction of 2,3,4,6-Tetra-O-acetyl-D-glycopyranose with phenylethylamine revealed the formation of a real one-to-one inclusion complex. This complexaion is highly stereoselective, because only the (+)-R-enantiomeric form of the amine is included. Analogies to the mode of complexation of cellulose triaceate with chiral molecules in „inclusion chromatography“ are discussed.
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  • 58
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    Chirality 1 (1989), S. 89-91 
    ISSN: 0899-0042
    Keywords: asmmetric induction ; bacterial cell wall ; D-Ala-D-Ala ; dipeptide ; peptidoglycan ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Absolute stereochemical control is employed in the synthesis of isosteres for dipeptide subunits 1; see Fig. (1) in which the amide linkage has been replaced by a trans carbon-caron double bond. The synthesis affords access to the four stereoisomers of 1 in which R and R' = CH3, including the isostere of D-alanine-d-alanine (D-ala-D-Ala), 2.
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  • 59
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    Chirality 1 (1989), S. 92-93 
    ISSN: 0899-0042
    Keywords: ciral resolution ; high-performance liquid chromatography ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Epinephrine enantiomers were derived into diastereoisomers with the chiral reagent 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosylisothiocyanate. The resolutions was carried out on a C18 column. The RS between (-)-R- and (+)-S-isomers was 2.3. The retention time could be changed by adding a proper amount of acetonirile into the mobile phase. The results showed that (+)-S-isomer in the epinephrine hydrochloride injections increased during the period of storage.
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  • 60
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    Chirality 1 (1989), S. 183-191 
    ISSN: 0899-0042
    Keywords: enantiomorphism ; dissymmetry ; chirality ; enantioselectivity ; diastereoselectivity ; steric complementarity ; asymmetric induction ; three-point contact ; circularly polarized radiation ; circular dichroism ; parity nonconservation ; electroweak interaction ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Pasteur's conjecture (1860) that biomolecular homochirality arose from a chiral natural force as yet inaccessible in the laboratory was supplanted by Fischer's (1894) “key and lock” hypothesis of stereoselection in enantiomer to diastereomer conversions, whether in the laboratory or in living organisms. Elaborations of the “key and lock” hypothesis by Haldane (1930) and Pauling (1948) have been illustrated and supported with modification by X-ray diffraction crystal structures of enzyme-substrate complexes over the past quarter century.Two types of mechanism for the product diastereoselectivity in the reactions of an enantiomer with an achiral reagent, early proposed, have recent support: one proposes a quasidiastereomeric structure for the enantiomer attacked in the ground state, the other for the corresponding transition state of the reaction. Approaches to the differential biological activity of two enantiomers postulate either the complete binding of each isomer to a chiral receptor site, resulting in diastereomeric complexes with inequivalent bioactivities, or the differential binding of the two isomers to a set of three sites, with which only one isomer is sterically congruent.Biochemical homochirality, based on the chiral stereoselectivity of both biosynthetic and metabolic reactions, derives from the evolutionary pressure for a progressive enhancement of the kinetic efficiency and economy of those reactions. Recently Pasteur has been vindicated in part, and the problem of the original prebiotic enantiomeric excess left outstanding by Fischer has been solved. The unification of the electromagnetic with the weak interaction provided a universal chiral natural force, the electroweak interaction, which favours the chiral series selected during the course of biochemical evolution, both the D-sugars and the L-amino acids.
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  • 61
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    Chirality 1 (1989) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 62
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    Chirality 1 (1989), S. 249-250 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 63
    ISSN: 0899-0042
    Keywords: benzo[a]pyrene diol-epoxides ; benzo[a]pyrene tetrols ; high-performance liquid chromatography ; chiral stationary phase ; optical isomers ; resolution of enantiomers ; absolute configuration ; circular dichroism spectra ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Enantiomers of diastereomeric benzo[a]pyrene (BP) diol-epoxides, r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydro-BP (BP 7,8-diol-anti-9,10-epoxide), r----7,t-8-dihydroxy-c-9,10-epoxy-7,8,9,10-tetrahydro-BP (BP 7,8-diol-syn-9,10-epoxide), r-9,t-10-dihydroxy-t-7,8-epoxy-7,8,9,10-tetrahydro-BP (BP 9,10-diol-antiy7,8-epoxide), and several 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrenes (BP tetrols) were resolved by high-performance liquid chromatography (HPLC) using columns packed with either (R)-N-(3,5-dinitrobenzoyl)phenylglycine[(R)-DNBPG] or (S)-N-(3,5-dinitrobenzoyl)leucine [(S)-DNBL], which is either ionically or covalently bonded to γ-aminopropylsilanized silica. Resolution of enantiomers was confirmed by ultraviolet-visible absorption and circular dichroism spectral analyses. Resolved enantiomers of BP diol-epoxides were each hydrolyzed in acidic solution to a pair of diastereomeric tetrols which were separated by reversed-phase HPLC. Absolute stereochemistries of enantiomeric diol-epoxides were deduced by the absolute configuration of their hydrolysis products.
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  • 64
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    Chirality 1 (1989), S. 284-292 
    ISSN: 0899-0042
    Keywords: absolute configuration ; crystal structure ; resolution ; solid-state circular dichroism ; torsional isomerism ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The crystal structure and absolute configuration of the (-)589-dibenzoylmonohydrogentartrate salt of the cation [Co(pyridine)4Cl2]+ have been determined from a three-dimensional X-ray analysis. Single crystals were grown from dimethylsulfoxide: space group P212121, Z = 4, and cell dimensions a = 21.463(4), b = 23.112(3), and c = 7.490(1) Å. Full-matrix least-squares refinement on F converged at R = 0.075, 196 variables and 2029 observations. The cation has pseudotetragonal coordinate geometry, with axial Cl and equatorial N atoms. The dihedral angles between the pyridine ligands and the equatorial plane are 47(1), 39(1), 50(1), and 45(1)° and torsional isomerism is responsible for the solid-state chiroptical properties of the cation. The preferential crystallization of the P atropisomer of the cation is attributed to a general electrostatic attraction between cation and anion.
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  • 65
    ISSN: 0899-0042
    Keywords: enantiomers ; diastereoisomeric ureas ; high-performance liquid chromatography (HPLC) ; fluorophores ; inversion of optical rotation ; antiarrhythmics ; propranolol ; plasma ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The synthesis and analytical testing of two new fluorescent chiral derivatizing agents (-)-(S)-flunoxaprofen and (-)-(S)-naproxen isocyanate, is described. In a few simple steps the free carboxylic acids [(S)-flunoxaprofen and (S)-naproxen] are activated with ethyl chloroformate/sodium azide and transformed to the corresponding isocyanates. The crystalline reaction products display high enantiomeric and chemical purity and stability. The direction of the optical rotation of both substances is inverse to that of the corresponding carboxylic acids. At ambient temperature the reagents swiftly react with primary and secondary amines, yielding highly fluorescent ureas. The applicability of the two reagents for the resolution of racemic amines was tested with a number of pharmaceuticals (antiarrhythmics, β-adrenergic antagonists, calcium channel blockers, centrally acting antidepressants). The diastereoisomeric derivatives were efficiently resolved and separated from side-products by means of normal and reversed-phase high-performance liquid chromatography (HPLC). The use and sufficient sensitivity of the two reagents for pharmacokinetic studies were demonstrated with a determination of plasma levels of propranolol enantiomers after oral administration of the racemic drug [80 mg (R,S)-propranolol-HCl] to two volunteers.
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  • 66
    ISSN: 0899-0042
    Keywords: optical resolution ; HPLC ; chromatography ; antiinflammatory drug ; ibuprofen ; ketoprofen ; flurbiprofen ; tiaprofenic acid ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Direct optical resolution of antiinflammatory drugs such as ibuprofen, ketoprofen, flurbiprofen, and tiaprofenic acid were attempted by high-performance liquid chromatography using tris(3,5-dimethylphenylcarbamate)s of cellulose and amylose as chiral stationary phases. Although ibuprofen was not sufficiently resolved, the other three 2-arylpropionic acids were completely resolved by amylose tris(3,5-dimethylphenylcarbamate). Ibuprofen was resolved as anilide derivative.
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  • 67
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The stereoselectivity of carvedilol, a novel β-adrenoceptor antagonist and vasodilator with one asymmetric carbon atom, was examined at α1- and β1-adrenoceptors in vitro and in vivo. (-)-(S)-Carvedilol is a potent, competitive antagonist of the β1-adrenoceptor-mediated positive chronotropic response to isoproterenol in guinea pig atrium, with a dissociation constant (KB) of 0.4 nM. (+)-(R)-Carvedilol was more than 100-fold less potent than the (-)-S-enantiomer as an antagonist of β;1-andrenoceptors, having a KB of approximately 45 nM. Consistent with these findings (-)-(S)-carvedilol (0.1 mg/kg, i.v.) produced a 25-fold rightward shift in the β1-adrenoceptor-mediated positive chronotropic response to isoproterenol in pithed rats, whereas the (+)-R-enantiomer had no β1-adrenoceptor blocking activity in vivo at this dose. In contrast to the marked degree of stereoselectivity observed at βl1-adrenoceptors, both (-)-(S)- and (+)-(R)-carvedilol produced equal antagonism of the α1----adrenoceptor-mediated vasoconstrictor response to norepinephrine in rabbit aorta, with KB values of 14 and 16 nM, respectively. Furthermore, in the pithed rat, the α1-adrenoceptor-mediated pressor dose-response curve to cirazoline was shifted approximately 6-fold to the right by both the (+)-R- and (-)-S-enantiomers of carvedilol at a dose of 1 mg/kg, i.v. In anesthetized spontaneously hypertensive rats, (-)-(S)-carvedilol was 6-fold more potent as an antihypertensive than (+)-(R)-carvedilol. The vasodilator and acute antihypertensive activity of carvedilol results from α1-andrenoceptor blockade produced by both enantiomers, and the concomitant β1-adrenoceptor blockade produced by the (-)-S-enantiomer, which prevents reflex tachycardia that can offset the antihypertensive response, leading to greater overall antihypertensive potency of (-)-(S)-carvedilol relative to the (+)-R-enantiomer. These data also suggest that distinct regions of the carvedilol molecule are responsible for blocking α1- and β1-adrenoceptors, with β1-adrenoceptor blockade resulting from an area of the molecule containing the asymmetric carbon atom, specifically the carbazolyloxy propanolamine moiety, and α1-adrenoceptor blockade resulting from a part of the molecule that does not contain the asymmetric carbon atom, most likely the phenoxyethylamine moiety.
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  • 68
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    Chirality 1 (1989), S. 309-312 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 69
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    Chirality 1 (1989), S. 7-9 
    ISSN: 0899-0042
    Keywords: substrate enantioselectivity ; product enantioselectivity ; Michaelis-Menten analysis ; intrinsic activity ; potency ; receptor affinity ; efficacy ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 70
    ISSN: 0899-0042
    Keywords: affinity ; efficacy ; dissociation ; constants ; steroselectivity ; entropy ; enthalpy ; receptor ; interaction ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: After alkylation of a fraction of the total α-adrenoreceptors by phenoxybenzamine in rat vas deferens, the dissociation constants of (-)- and (+)-epinephrine in functional studies were 7 × 10-7 M and 2 × 10-5 M, respectively. In the adrenoreceptor-containing tissue fraction, when 3H-labeled WB4101 was used as the interacting ligand, for each enantiomer who affinity sites were found. Only the low-affinity dissociation consant for each isomer correlates with the constant obtained from the functional studies. If the change in Gibb's free energy. ΔG°, is calculated from the low-affinity binding constants, the values -8.1 and -6.2 kcal/mol for (-)- and (+)-isomer, respectively, are obained. The small difference in the value between isomers forms a hydrogen bond with the receptor. The interaction of epinephrine with this receptor appears to be driven largely by the entropy of the drug-receptor interaction with only a small nonsteroselective contribution from the enthalpy of ineraction.
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  • 71
    ISSN: 0899-0042
    Keywords: column liquid chromatography ; chiral separations ; chymotrypsin on silica ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The stereochemical separation of free and derivatized amino acids on active α-chymotrypsin bonded to silica is governed by two mechanisms based on the structure of the solutes or on the enzymatic activity of the enzyme. Te deactivation of the hydrolytically active site of the enzyme demonstrated that a significant portion of the retention on this support is due to hydrophobic interactions at other sites. These sites appear to be stereoselective for the ester derivatives of amino acids but not for the other studied solutes.
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  • 72
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    Chirality 1 (1989), S. 63-68 
    ISSN: 0899-0042
    Keywords: optical resolution ; chromatography ; amino acid derivatives ; molecular recognition ; preparative ciral separation ; macroporous polymers ; mass transfer limitaions ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A moleclar imprinting technique based on electrostatic and hydrogen bonding interactions was used to prepare polymers of high selectvity for the original print molecule (D or L form of an amino acid derivative). In the chromatographic mode ig enantioselectivity was observed, in particular for amino acid amides and basic amino acid esters. As indicated y he broad peaks obtained, the mass transfer, including the kinetics of the binding and dissociation process, was slow and appeared to be slower in systems where a higher number of interactions between the solute and the stationary phase could be expected. In such systems enhanced selectivity was observed. For polymers prepared at a lower temperature the mass transfer was more rapid and a higher selectivity was observed, wich allowed the separations to be performed at room temperature. A more rapid mass transfer and a higher selectivity could also be achieved by increasing the column temperature. Furthermore the polymers showed a high sample load capacity and a high stability, and the can easily be prepared.
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  • 73
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    Chirality 1 (1989), S. 86-88 
    ISSN: 0899-0042
    Keywords: stereochemistry ; stereoselective snthesis ; (S)-2-hydroxypropanoic acid ; chiral synthon ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The (+)- and (-)-enantiomers of benproperinium dihydrogen phosphate, an antitussive drug, have been assigned the R- and S-configurations, respectively, by syntheses of both enantiomers using (S)-2-hydroxypropanoic acid (L-lactic acid) as chiral synthon. The key intermediate, (S)-2-metyl-2-[-2-(phenylmethyl)phenoxy]ethyl p-toluenesulfonate, was subjected to an SN2-type reaction with piperidine furnishing (+)-(R)-benproperinium dihydrogen phosphate. (-)-(S)-Benproperinium dihydrogen phosphate was obtained by submitting the same tosylate to two consecutive SN2-type reactions with Br- and piperidine, respectively, acting as nucleophiles.
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  • 74
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    Chirality 1 (1989), S. 94-95 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 75
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    Chirality 1 (1989), S. 170-173 
    ISSN: 0899-0042
    Keywords: phenglutarimide enantiomers ; enantioselectivity ; antiparkinsonian drugs ; M1-selective antagonists ; rabbit vas deferens ; pirenzepine ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The affinity of the enantiomers of phenglutarimide at three muscarinic receptor subtypes was examined in vitro using field-stimulated rabbit vas deferens (M1 receptors) and guinea pig atria (M2α receptors) and ileum (M2β receptors). Extremely high stereoselectivity was observed and higher affinities (up to 6000-fold) were found for the (+)-S-enantiomer. The stereoselectivity ratios were different at the three subtypes, and the stereochemical demands made by the muscarinic receptors were most stringent at M1 receptors. (+)-(S)-Phenglutarimide was found to be a potent M1-selective antagonist (pA2 at M1 = 8.53). Its receptor selectivity profile is qualitatively similar to that of pirenzepine. (-)-(R)-Phenglutarimide showed no comparable discriminatory properties.
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  • 76
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    Chirality 1 (1989) 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 77
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    Chirality 1 (1989), S. 2-6 
    ISSN: 0899-0042
    Keywords: optical isomers ; stereochemistry ; enantiomers ; Food and Drug Administration ; drug development ; drug regulation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The current regulatory position of the Food and Drug Administration is discussed with regard to the approval of racemates and pure stereoisomers. Circumstances in which stereochemically sensitive analytical methods are necessay to ensure the safety and efficacy of a drug are described. Regulatory guidelines are interpreted for applications for the approval of a pure enantiomer in which the racemate is marketed, for the approval of eitehr a racemate or a pure enantiomer in which neither is marketed, and for clinical investigations to compare the safety and efficacy of a racemate and its enantiomers. Examples of te basis for such regulation are drawn from historical situations (thalidomide, benoxaprofen) as well as currently marketed drugs (arylproionic acids, disopyramide, indacrinone).
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  • 78
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    Chirality 1 (1989), S. 27-37 
    ISSN: 0899-0042
    Keywords: mutarotation ; sugars ; carbohydrates ; isomeric ; separation ; temperature effects ; selectvity ; optimization ; hemiacetal ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A brief review of sugar stereochemistry is given. The separation of 84 different pairs of anomers was accomplished on both α- and β-cyclodextrin columns. Five different mobile phases were evaluated. The separation of anomers temperature, flow rate, and so on. The separation of anomers that mutarotate is somewhat more difficult than those that do not. Prior knowledge as to the rate of mutaroation is useful so that the chromatographic conditions can be arranged to minimize any deleterious effects on the separation.
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  • 79
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    Chirality 1 (1989), S. 121-126 
    ISSN: 0899-0042
    Keywords: stereoselective metabolism ; sulfate conjugation ; in vitro sulfation ; sympathomimetic amines ; chiral separation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Little is known about the stereochemistry of sulfation of chiral phenolic drugs. In this study we examined several in vitro approaches to this question, using (+)-, (-)-, or (±)-terbutaline as the substrate and the rat liver cytosol as the phenolsulfotransferase enzyme source. The cosubstrate PAPS was either generated by the cytosol from inorganic sulfate and ATP or added to the cytosol. The intact sulfate conjugates formed were determined by HPLC. Using the PAPS generating system, which is best suited for the production of relatively large quantities of sulfate conjugates, with the individual enantiomers as substrates, (+)-terbutaline was conjugated to a much greater extent than (-)-terbutaline; the (+)/(-)-enantiomer ratio was 7.3 ± 0.3 (mean ± SE). When (±)-terbutaline was the substrate and chiral derivatization was employed to separate the sulfate enantiomers formed, a similar (+)/(-)-enantiomer ratio of 7.9 ± 0.2 was obtained. With PAP35S added to the cytosol, an approach best suited for kinetic studies, the substrate concentration dependence of sulfation could be determined. The Km app for this reaction was identical for (+)- and (-)-terbutaline. However, the Vmax app was 8.1 ± 0.4 times greater for (+)-terbutaline. This study for the first time shows enantioselectivity in sulfation of a chiral phenolic drug. The experimental approaches used should be valuable for human studies of stereoselectiven sulfation of terbutaline and other chiral drugs.
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  • 80
    ISSN: 0899-0042
    Keywords: chromatography ; chirality ; chiral recognition ; β-aminoalcohols ; stereochemistry ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Three chiral stationary phases, obtained by derivatizing γ-mercaptopropylsilanized silica gel with quinine, quinidine, and cinchonidine, have been employed in the resolution of N-acyl derivatives of β-hydroxyphenethylamines. The use of circular dichroism for detection and NMR analysis of analyte-selector mixtures provides an experimental basis for preliminary assignment of a recognition mechanism.
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  • 81
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    Chirality 1 (1989), S. 154-160 
    ISSN: 0899-0042
    Keywords: enantiomers ; chiral discrimination ; drugs ; hydrophobic interaction ; biopolymers ; elution order ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Optical resolution on the analytical scale of a number of racemic pharmaceuticals and some other biologically active compounds has been studied using immobilized bovine serum albumin (BSA) as the stationary phase. For some of the compounds the elution order was determined by the use of optically enriched fractions obtained from a preceding passage of a sample through a preparative column containing microcrystalline triacetylcellulose (MCTA). The reversal in the sign of optical rotation shown in the polarimetric elution profile from the latter, combined with the integrated peak area ratio obtained on resolution on the analytical column, gave directly the order of elution. For one of the benzothiadiazines studied (bendroflumethiazide), increasing the pH of the mobile phase produced opposite effects on the retention of the two enantiomers, leading to a large effect on the separation factor. For many of the compounds studied, high separation factors (α 〉 2) could be achieved.
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  • 82
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    Chirality 1 (1989), S. 178-179 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 83
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    Chirality 1 (1989), S. 174-177 
    ISSN: 0899-0042
    Keywords: pharmacokinetics ; terbutaline ; enantiomers ; human ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Terbutaline is a β2-agonist and administered as the racemic mixture. The pharmacokinetics of the separate enantiomers differ with respect to degree of absorption and clearance. In the present study, repeated doses of racemic terbutaline were given to six healthy volunteers. Plasma was analyzed for the concentrations of the two enantiomers. The observed plasma concentrations at steady state differed from those predicted from the values observed after single dose administration of the separate enantiomers. The difference between the observed and predicted values can be tentatively explained by a combined influence of (-)-terbutaline on the absorption of (+)-terbutaline and the influence of (+)-terbutaline on the elimination of (-)-terbutaline. The results have implications for the interpretation of effect/concentration studies with terbutaline, but do not affect the doses used in clinical practice.
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  • 84
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    Chirality 1 (1989), S. 98-98 
    ISSN: 0899-0042
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
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  • 85
    ISSN: 0899-0042
    Keywords: enantioselective epoxidation ; cytochrome P-450-dependent monooxygenases ; species dependence of microsomal epoxidation ; product enantioselectivity ; substrate enantioselectivity ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The enantioselectivity of the in vitro conversion of simple prochiral and chiral aliphatic alkenes into oxiranes by liver microsomes of untreated or induced (phenobarbital) rats, of untreated or induced (phenobarbital, benzo[α] pyrene) mice, and of humans was determined by complexation gas chromatography. The enantiomeric excess (ee) of the epoxides extends from 0 (trimethyloxirane) to 50% (ethyloxirane). The configuration (R or S) of the enantiomers formed in excess is consistent for homologous oxiranes but is species dependent and in some cases influenced by enzyme induction. Enantioselectivity differences of aliphatic alkene epoxidation by human liver microsomes of four individuals are negligible.
    Additional Material: 2 Ill.
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  • 86
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 1 (1989), S. 167-169 
    ISSN: 0899-0042
    Keywords: enantioselectivity ; three-point model ; chiral receptors ; chiral separations ; didactic model ; elusion of the three-point model ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Hands can be used to demonstrate the three-point model of chiral recognition. The points of attachment are thumb, forefinger, and middle finger. This vivid model has the advantages of simplicity, perspicuity, and availability at any time, although two persons are necessary. It can be shown that two interactions are not sufficient for chiral recognition but that three attractive or two attractive and one repulsive attraction are needed. It can also be used to explain some possibilities of weakening or elusion of the three-point model.
    Additional Material: 6 Ill.
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  • 87
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 1 (1989), S. 178-179 
    ISSN: 0899-0042
    Keywords: CD spectra ; optical rotation ; phthalideisoquinoline base and salts ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The appearance of positive charge on the nitrogen moiety of phthalideisoquinoline alkaloids brings about a strong change in the intensities of CD Cotton effects. Hence the optical rotations of enantiomeric salts and their parent base of identical configuration are often of opposite sign. Thus, the name (+)-bicuculline-methiodide for the methiodide salt of (+)-bicuculline is false.
    Additional Material: 1 Ill.
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  • 88
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 1 (1989), S. 202-208 
    ISSN: 0899-0042
    Keywords: opioid ligand ; 4-arylpiperidines ; conformation, NMR ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The synthesis and stereochemistry (configuration and preferred solute conformation) of some 4-alkyl (methyl, n-propyl, isobutyl)-4-(3-hydrxyphenyl)-1-methylpiperidines and corresponding 3-methyl diastereoisomeric pairs are reported, together with their in vivo and in vitro activities as opioid ligands. All potent agonists exhibit a preference for axial 4-aryl chair conformations when protonated, and stereochemical analogies with rigid opioids of the benzomorphan class are discussed. Antagonist properties are found in compounds with preference for equatorial 4-aryl chairs, notably the cis 3,4-dimethyl derivative.
    Additional Material: 3 Tab.
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  • 89
    ISSN: 0899-0042
    Keywords: fenofibrate ; chiral reduction ; species differences ; prochiral to chiral transformation ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: The prochiral carbonyl group of fenofibrate (isopropyl 2-[4-(4-chlorobenzoyl)phenoxy]-2-methyl propionate) is reduced during its metabolism giving rise to a chiral secondary alcohol, “reduced fenofibric acid.” Chiral and diastereomeric HPLC methods have been developed for the determination of its enantiomeric composition and these have been applied to the measurement of the “reduced fenofibric acid” enantiomers in urine of rats, guinea pigs, dogs, and human volunteers given [14C]fenofibrate. In the three animal species, the reduction is markedly enantioselective for the (-)-isomer, the enantiomeric ratios (-/ +) being 95:5. This was not due to differences in the excretion of the enantiomers, since when racemic “reduced fenofibric acid” was given to rats it was recovered in the urine with the same enantiomeric composition as the dose form. In humans the ratio was 52:48 showing the lack of stereoselectivity of reduction in this species.
    Additional Material: 2 Ill.
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  • 90
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    Chirality 1 (1989), S. 216-222 
    ISSN: 0899-0042
    Keywords: 4-acetoxy-2-azetidinone ; antibiotics ; carbapenem ; chiral stationary phases ; cellulose tris(phenylcarbamate) ; amylose tris(3,5-dimethylphenylcarbamate) ; CD spectra ; absolute configuration ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Separation and optical resolution of 6 diastereomers and 25 racemates of β-lactams were examined by HPLC on chiral stationary phases composed of six cellulose and one amylose tris(phenylcarbamate) derivatives. Most β-lactams were optically resolved at least by one of the derivatives. The absolute configuration of β-lactams was estimated by CD spectroscopy.
    Additional Material: 2 Ill.
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  • 91
    ISSN: 0899-0042
    Keywords: β-adrenergic blocker ; chiral resolution ; Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Penbutolol is a β-adrenoceptor blocking agent, and it contains the clinically relevant (-)-S-enantiomer. It was reported that the (+)-R-enantiomer of penbutolol is pharmacologically 50 times less active than the (-)-S-isomer in β-sympatholysis and without intrinsic sympathomimetic activity and refractory period in the heart muscle. Furthermore, the (+)-R-enantiomer does possess mutagenic activity.A high-performance liquid chromatographic (HPLC) method is described for direct identification, stereochemical separation, and quantitation of (+)-R-enantiomer in the clinically used (-)-S-isomer. The method involves the use of cellulose tris-3,5-dimethylphenyl carbamate chiral stationary phase coated on silica gel (OD-Chiralcel column). The capacity factors (k′) for the first eluted enantiomer and stereochemical separation factor (α) obtained were 1.32 and 1.98, respectively. The maximum stereochemical resolution factor (R) was 5.05. The method could be applied for optical purity determination of (-)-(S)-penbutolol in pharmaceutical formulation to detect for the presence of the undesirable (+)-R-enantiomer.
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  • 92
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The principal components factors F1 and F2 in the equation \documentclass{article}\pagestyle{empty}\begin{document}$$ \log K = {\rm BDP}_0 + S_1 F_1 + S_2 F_2 $$\end{document} have been used to obtain S1 and S2 values for sets of hydrogen-bond bases against 32 reference acid/solvent systems. The constants S1 and S2 define an angle θ = tan-1 S2/S1 that is a measure of the electrostatic:covalent bonding ratio in the hydrogen-bond complex. It is shown that θ can vary from 53 (4-fluorophenol in CH2Cl2)to 86 degrees (Ph2NH in CCl4) depending on the reference acid and solvent. This variation in θ can lead to family dependent behaviour in plots of log K for bases against a given reference acid system vs log K for bases against another reference acid system, and precludes the construction of any general scale of hydrogen-bond basicity using log K values. Amongst a quite wide range of reference acid/solvent systems θ varies only from 64 to 73 degrees, and for bases against these reference systems a ‘reasonably general’ scale could be set up. Such a scale could be extended to bases against reference acid/solvent systems outside the 64-73 degree range provided that certain classes of base (e.g. pyridines, alkylamines) were excluded from the additional reference acid/solvent systems.
    Additional Material: 6 Tab.
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  • 93
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 300-322 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Various modifications of the Marcus equation have been applied to the problem of photochemical proton transfer, using available data on general acid-catalyzed photohydration reactions. These include incorporation of asymmetry and tightness parameters, as well as distance variation as a function of exoor endothermicity. The intersecting state model of Formosinho has also been successfully applied to these reactions. The overall conclusion from all of these approaches is that the reactions are characterized by somewhat asymmetric and ‘loose’ transition states, with a small but significant degree of charge development on the in-flight proton at the transition state. Estimates of the intrinsic barriers and work terms place these in the 5-7 kcal and 2-3 kcal ranges respectively. A simple valence bond configuration mixing model leads to similar qualitative conclusions about the nature of the transition states in these reactions.
    Additional Material: 10 Ill.
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  • 94
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The difference in reactivity of small [n]cyclophanes towards CF3CO2H is discussed in terms of charge densities, strain energies and proton affinities. These data are calculated with MNDO and MINDO/3 for para-, meta- and ortho-cyclophanes and for their ipso-protonation products; an attempt is made to transform gas phase ΔHf0 values into liquid phase ΔH0f values. Experimental evidence is presented that the acid catalyzed rearrangement of [5]paracyclophane to its ortho-isomer proceeds via two consecutive 1,2-carbon shifts without deprotonation; intermediate adducts were identified by NMR-spectroscopy. Thus, a gradual shift in reaction pattern in the series [4]-, [5]- and [6]paracyclophane is observed experimentally, in line with the calculational results.
    Additional Material: 2 Tab.
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  • 95
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989) 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 96
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 367-376 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The relative rates of hydrogen atom abstraction from a series of twelve saturated cyclic ethers and sulfides were determined at 70°C. The abstracting radical could be generated from bromotrichloromethane both photolytically or by the thermal decomposition of AIBN. The reaction rates did not show a dependence upon method of radical generation. Reaction occurred only at the position adjacent to the heteroatom. The reactivity of the cyclic ethers was in the order C4H8O 〉 C6H12O 〉 C3H6O 〉 C5H10O. This trend would indicate appreciable influence by ring strain, however, the slightly greater reactivity of tetrahydrofuran relative to oxepane suggests a contribution by stereoelectronic factors as well. The reactivity of the cyclic sulfides, which reacted faster than the corresponding ethers, was in the order C4H8S 〉 C5H10S 〉 C6H12S. This would imply little influence of ring strain. The major structural effect would be that of variable electron donating ability of the sulfur atom. The rate of reaction of thietane was also determined. It was found to preferentially undergo SH2 attack at the sulfur atom followed by ring opening rather than hydrogen abstraction. The reactivities of both series of compounds were decreased by the inductive effect of a second heteroatom beta to the reaciton site.
    Additional Material: 1 Ill.
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  • 97
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 410-416 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Barriers for group transfers between nucleophiles have been postulated to be lowered when the transferring group can carry a considerable negative charge. Furthermore, anions readily subject to one electron oxidation appear to lead to lower barriers than do those of high oxidation potential. These suggestions are pursued here on the identity reaction ArSe- + ArSeSeAr → ArSeSeAr + ArSe-. Indeed the reaction is very fast, as shown by the appearance of only a single peak in the 77Se-NMR in an acetonitrile solution containing both ArSeNa and ArSeSeAr. The rate constant can be only very roughly estimated at low temperatures and dilute solutions, and is likely diffusion controlled for Ar = phenyl and p-methoxyphenyl. A stable intermediate (ArSe)3-, analogous to Br3-, is indicated, but quantitative stability could not be determined, from either the NMR or the UV spectra. Some properties of 77Se-NMR are discussed.
    Additional Material: 2 Tab.
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  • 98
    Electronic Resource
    Electronic Resource
    Chichester : Wiley-Blackwell
    Journal of Physical Organic Chemistry 2 (1989), S. 425-427 
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: Distribution between pentane and trifluoromethanesulfonic acid (TFMSA) and carbon-13 NMR measurements showed that benzene and toluene are not protonated to any significant extent in TFMSA. This finding contradicts previous reports, and validates the ranking of superacids based on the extent of benzene protonation.
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  • 99
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: A two-hydron transfer mechanism involving hydron transfers from carbon to nitrogen and from nitrogen to carbon was studied. The rearrangement of 1,3,3-triphenylpropene (1) into 1,1,3-triphenylpropene (2) catalyzed by 2,10-diazabicyclo[4.4.0]dec-1-ene (3) in benzene at 25·00°C was studied by 2H-labeling experiments and kinetic 2H-isotope effects. The synthesis and purification of [6,10-2H2]-2,10-diazabicyclo[4.4.0]dec-1-ene ([6,10-2H2]-3), [3-2H]-1,3,3-triphenylpropene ([3-2H]-1), [3-2H]-1,1,3-triphenylpropene ([3-2H]-2) and [3,3-2H2]-1,1,3-triphenylpropene ([3,3-2H2]-2) together with their precursors are reported. Partial reaction of [3-2H]-1 with [6,10-1H2]-3 gave 42% conversion into product 2, which was shown by 1H NMR to be composed of 88% [3-1H]-2 and 12% [3-2H]-2. Partial reaction of [3-1H]-1 with [6,10-2H2]-3 gave 43% of 2, composed of 73% [3-1H]-2 and 27% [3-2H]-2.These results clearly show that a substantial fraction of the reaction takes place in a bifunctional manner but isotope exchange and/or monofunctionally catalyzed reactions interfere. The following kinetic deuterium isotope effects on the rearrangement 1 → 2 were measured: kHH/kDH = 6·56; kHH/kHD = 1·19; kHH/kDD = 7·08; kHD/kDD = 5·94; and kDH/kDD = 1·08.On the basis of these results, a concerted two-hydron transfer mechanism is excluded. Instead, a stepwise mechanism is favored, in which at first the 3-hydron of 1 is abstracted by 3 yielding an ion pair(s), the carbanion of which in a separate step is then hydronated to yield the product 2.The abstraction of the 3-hydron from 1 might be hydrogen bond assisted. The two hydron transfer transition states are together rate limiting, although they limit the rate to different extents. A detailed mechanistic analysis is presented together with the results of an investigation of the nature of the catalyst. The dimerization constant for 3 was determined by 1H NMR to be 1·67 l mol-1 at 25·0°C. Isotopomer composition was measured by 1H NMR and GLC was used for the separation of the substrate and products. Computer-assisted capillary GLC was used for the kinetics.
    Additional Material: 6 Ill.
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  • 100
    ISSN: 0894-3230
    Keywords: Organic Chemistry ; Physical Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology , Physics
    Notes: The Kinetics of reactions of phenacyl benzenesulphonates with benzylamines were investigated in methanol at 45·0 °C and the cross-interaction constants λXY, λYZ and βXZ were determined in order to elucidate the transition-state structure. The unusually small magnitude of λXY can only be accounted for by the resonance ‘shunt’ effect of the α-CO group of the phenacyl system. Large |λYZ| values indicate a small degree of bond breaking whereas relatively large |βXZ| values compared with those for the dissociative SN2 reaction indicate a relatively tight transition state for the reactions. Further, the similar magnitudes of βXZ values compared with those of the corresponding aniline nucleophile series suggest a similar transition-state structure for the two armatic amine nucleophile series.
    Additional Material: 1 Ill.
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