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Notes: Abstract A new method is proposed for calculating correlation effects in atomic and molecular systems. The basis of the method is the formulation of a set of partial configuration expansions which yield directly variational orbital correlation corrections which are appropriately summed in order to obtain an estimate of the total correlation energy. This method is applied to the ground state of boron hydride and its cation at the equilibrium distance of BH. The results of the method are compared in detail with independent electron pair results and second order CI results. It is further shown that multiple substitutions are approximately accounted for in this method and the extent to which they are included is compared with other approximations. Finally, three methods of increasing accuracy, aimed at reducing the necessary computational effort, are given for determining the vertical ionization potential. The most economical method yields an IP of 9.70 eV or 0.03 eV less than the experimental IP. Completion of the basis is estimated to improve this value to 9.77 eV.

Notes: Abstract A new method is proposed for calculating correlation effects in atomic and molecular systems. The basis of the method is the formulation of a set of partial configuration expansions which yield directly variational orbital correlation corrections which are appropriately summed in order to obtain an estimate of the total correlation energy. This method is applied to the ground state of boron hydride and its cation at the equilibrium distance of BH. The results of the method are compared in detail with independent electron pair results and second order CI results. It is further shown that multiple substitutions are approximately accounted for in this method and the extent to which they are included is compared with other approximations. Finally, three methods of increasing accuracy, aimed at reducing the necessary computational effort, are given for determining the vertical ionization potential. The most economical method yields an IP of 9.70 eV or 0.03 eV less than the experimental IP. Completion of the basis is estimated to improve this value to 9.77 eV.

Notes: Abstract Ab Initio, molecular orbital methods are being used to analyze and interpret structure-activity relationships in anti-inflammatory phenols, benzoates and salicylates. The results show a correlation between the potency of the active compounds as inhibitors of prostaglandin production in cell cultures and the orbital energy of the highest occupied molecular orbital with a correlation coefficient ofr ∼ 0.8. The mode(s) of action and structural requirements of anti-inflammatory, non-narcotic analgesics continues to defy rationalization. Even the most plausible proposed molecular mechanism of their anti-inflammatory action, i.e., inhibition of prostaglandin biosynthesis [1], is still subject to controversy [2, 3]. Therefore other approaches may be fruitful for relating the NSAID's biological activity to molecular structure and properties. One such approach is to relate the biological activity to structural indices obtained from molecular orbital theory. From the results of such quantum chemical calculations it is hoped that deeper insight can be obtained into the NSAID's mode(s) of action by evaluating their dependance on the electronic structure of the biologically active species. A complicating factor in the present studies is that the existence of a specific receptor has not yet been firmly established. For the present work biological activity is defined as the potency of the given compound to inhibit the 12-O-tetradecanoylphorbol-13-acetate (TPA) induced PGE2 release from macrophages isolated from the peritoneum of young male NMRI mice. For methodological details see Ref. [4]. From about 80 compounds which have been assayed a sample of 30 molecules was selected for quantum chemical study. The sample comprises phenol, benzoic acid, and salicylic acid and their hydroxy, fluoro- and chloro congenrs. All calculations were carried out usingab initio molecular orbital methods with programs developed in this laboratory. The σ and π orbital energies of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were analyzed for correlation with the potency of 18 (or 17) active molecules. As the correlation coefficients in Table 1 show, the π-HOMO orbital energies exhibit a significant correlation with the pIC50's, whereas the σ-HOMO and the LUMO orbital energies do not. The observed correlation shows that potency increases with increasing π-HOMO orbital energy, i.e., weaker binding of the π-HOMO electrons, which enhances the potential for interaction with specific or non-specific interaction sites. Examination of the correlations reported in Table 1 suggests that the first and second row substituents correlate similarly with the π-HOMO orbital energy, but that the second row group is displaced from the first row group. Separate analysis of the two groups is also given in Table 1. These latter correlation coefficients are about 10% higher than for the whole sample. It is noteworthy that for the other orbital energies the single group correlation coefficients can also be quite high, but that the combined correlation is small to completely random. Three models have been proposed for the cyclooxygenase receptor where the NSAID's carry out their purported inhibitory function [5–7]. Although these models differ considerably in their details, all three include a π-electron interaction (acceptor) region. The present results support the need for such a region and suggest that enhanced ability to donate π-electrons helps increase potency in inhibiting the release of PGE2 in macrophages. A detailed report of this work will be given elsewhere.

Notes: A theorem is proved which demonstrates the relationship between a product of group functions describing the correlated motion of a particular group of electrons in an N-electron system and a wave function obtained from the exact wave function which describes the correlation of the same group of electrons. By considering such products of group functions as elements in a variational wave function, an expansion for correlated wave functions is suggested, which emphasizes the correlated motion of groups of electrons in the whole system.

Notes: A simple method is presented for the construction of contracted Gaussian basis sets with little or no energy-optimization. The contraction coefficients are fitted by a least-squares procedure to the orbital expansion coefficients of the completely decontracted basis. The method is applied to the construction of minimum basis sets of first-row atoms from (6s, 3p) uncontracted atomic basis sets, and of [6s, 4p] contracted bases from (12s, 8p) uncontracted bases of second-row atoms. The results are better than using the expansion coefficients directly and are usually comparable to fully energy-optimized bases.The method can also be used to generate balanced atomic contraction coefficients from molecular calculations. This is shown with a (7s, 3p) and a (6s, 3p) basis, both contracted to a minimum basis. The contracted basis sets are employed in several small molecules, and the results are compared with calculations done with the decontracted bases and with contracted bases where the contraction coefficients were energy optimized in the molecules.