Abstract
Synthetic methods are described leading to polysubstituted spin labeled polysaccharides (dextran 70, 110, 200, and arabinogalactan), which are potential contrast agents in magnetic resonance imaging. The nitroxyl moieties bound to a polysaccharide yield relaxivity enhanced by a factor of 1.6 (at 0.47 T and 37°C) compared to that of the small hydrophilic radicals. An EPR study at variable temperature and viscosity (by adding sucrose) reveals the presence of two mobile bound spin labels. The less mobile ones are characterized by an order parameterS≅0.6 and a macromolecular rotational correlation time of ∼1.6 ns at 20°C for the substituted dextrans. Substitution rate effects are observed and might be related to conformational changes.
Similar content being viewed by others
References
Colacicchi S, Ferrari M, Sotgiu A (1992)In vivo electron paramagnetic resonance spectroscopy/imaging: first experiences, problems, and perspectives.Int J Biochem 24 205–214.
Lurie DJ, Bussell DM, Bell LH, Mallard JR (1988) Proton-electron double magnetic resonance imaging of free radical solutions.J Magn Reson 76: 366–370.
Grucker D (1990)In vivo detection of injected free radicals by Overhauser effect imaging.Magn Reson Med 14: 140–147.
Swartz HM (1987) Use of nitroxides to measure redox metabolism in cells and tissues.J Chem Soc Faraday Trans 83: 191–202.
Swartz HM (1989) Metabollically responsive contrast agents. InAdvances in Magnetic Resonance Imaging, (Feig E, ed) Norwood, NJ: Ablex Publishing Company.
Swartz HM, Glockner JF (1989) Measurements of the concentration of oxygen in biological systems using EPR techniques. InAdvanced EPR in Biology and Biochemistry (Hoff AT, ed) pp. 753–782. Amsterdam: Elsevier Science Publishers.
Swartz HM, Glockner JF (1991) Measurement of oxygen by EPRI and EPRS. InEPR Imaging and In Vivo EPR (Eaton GR, Eaton SS, Ohno K, eds), pp. 261–290. Boca Raton, FL: CRC Press.
Brasch RC (1983) Work in progress: methods of contrast enhancement for NMR imaging and potential applications.Radiology 147: 781–788.
Gallez B, Demeure R, Debuyst R, Leonard D, Dejehet R, Dumont P (1992) Evaluation of nonionic nitroxyl lipids as potential organ-specific contrast agents.Magn Reson Imaging 10: 445–455.
Gallez B, Debuyst R, Demeure R, Dejehet F, Grandin C, Van Beers B, Taper H, Pringot J, Dumont P (1993) Evaluation of a nitroxyl fatty acid as liver contrast agent.Magn Reson Med 30: 592–599.
Reynolds JEF (ed) (1989) Blood products and substitutes.Martindale, 29th ed, pp. 814–816. London: The Pharmaceutical Press.
Beuth J, Ko HL, Oette K, Pulverer G, Roszkowski K, Uhlenbruck G (1987) Inhibition of liver metastasis in mice by blocking hepatocyte lectins with arabinogalactan infusions andd-galactose.J Cancer Res Clin Oncol 113: 51–55.
Vansteenkiste S, Schacht E, Duncan R, Seymour L, Pawluczyk I, Baldwin R (1991) Fate of glycosylated dextrans afterin vivo administration.J Controlled Release 16: 91–100.
Weissleder R, Reimer PE, Lee AS, Wittenberg J, Brady TJ (1990) MR receptor imaging: ultrasmall iron oxide particles targeted to asialoglycoprotein receptors.Am J Roentgenol 155: 1161–1167.
Slane JMK, Lai C-S, Hyde JS (1986) A proton relaxation enhancement investigation of the binding of fatty acid spin labels to human serum albumin.Magn Reson Med 3: 699–706.
Bennett HF, Brown RD, Keana JFW, Koenig SH, Swartz HM (1990) Interactions of nitroxides with plasma and blood: effect on 1/T1 of water protons.Magn Reson Med 14: 40–55.
Vallet P (1992) Relaxivité des radicaux libres stables de type nitroxyde. Evaluation par la méthode du champ cyclé et optimisation. Ph.D. Thesis, Université de Mons-Hainaut, Belgium.
Corey EJ, Chaykovsky M (1965) Methylsulfinyl carbanion. Formation and applications to organic synthesis.J Amer Chem Soc 87: 1345–1355.
Mawhinney TP, Florine KL, Feather MS, Cowan DL (1983) Spin-labeling of polysaccharides by esterification using chloroformyl-2,2,5,5-tetramethylpyrroline-l-oxide. Carbohydr Reson116 C1-C4.
Dubois M, Gilles KA, Hamilton JK, Rebers PA, Smith F (1956) Colorimetric method for determination of sugars and related substances.Anal Chem 28: 350–356.
Kivelson D (1960) Theory of ESR linewidths of free radicals. JChem Phys 33: 1094–1106.
Tormala P (1979) Spin label and probe studies of polymeric solids and melts. J Macrol Sci-Rev Macrol ChemC17 297–357.
Poggi G, Johnson CS (1970) Factors involved in the determination of rotational correlation times for spin labels.J Magn Reson 3: 436–445.
Timofeev VP, Dudich IV, Volkenstein MV (1980) Comparative study of dynamic structure of pig and chicken aspartate aminotransferases by measuring the rotational correlation time.Biophys Struct Mech 7: 41–49.
Timofeev VP, Tsetlin VI (1983) Analysis of mobility protein side chains by spin label technique.Biophys Struct Mech 10: 93–108.
Timofeev VP (1986) Segmental mobility of Poly(U) and the spin label method.Molek Biol (USSR) 20: 697–711.
Gallez B, Lacour V, Demeure R, Debuyst R, Dejehet F, De Keyser J-L, Dumont P (1994) Spin labelled arabinogalactan as MRI contrast agent.Magn Reson Imaging 12: 61–69.
Florine KI, Cowan DL, Mawhinney TP (1984) Molecular motion of spin-labelled dextrans in dilute aqueous solution.Macromolecules 17: 2417–2420.
Fischman ML, Damert WC, Philips JG, Barford RA (1987) Evaluation of root-mean-square radius of gyration as a parameter for universal calibration of polysaccharides.Carbohydr Res 160: 215–225.
Basedow AM, Ebert KH, Feigenbutz W (1980) Polymer-solvent interactions: dextran in water and DMSO.Makromol Chem 181: 1071–1080.
Gantchev TG, Shopova MB (1990) Characterization of spin-labeled fatty acids and hematoporphyrin binding sites interactions in serum albumin.Biochim Biophys Acta 1037 422–34.
Author information
Authors and Affiliations
Additional information
Address for correspondence: Laboratory of Medicinal Chemistry, CMFA/UCL 7340, Avenue E. Mounier, B-1200 Brussels, Belgium. Additional reprints of this chapter may be obtained from the Reprints Department, Chapman & Hall, One Penn Plaza, New York, NY 10119.
Rights and permissions
About this article
Cite this article
Gallez, B., Debuyst, R., Dejehet, F. et al. Relaxivity and molecular dynamics of spin labeled polysaccharides. MAGMA 2, 61–68 (1994). https://doi.org/10.1007/BF01709801
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01709801