Studies on the Molecular Mechanics Calculation of Drugs Including Simulation of Infrared and Raman Spectra

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Molecular mechanics calculation has drawn attention as a new approach to the study of structure-activity relationship of drugs. For complex polar molecules, however, the theromodynamical and structural data are hardly available in the isolated state. To overcome this difficulty, the present project has been planned to aim at utilizing the information on both the frequencies and the intensities of infrared and Raman spectra in the liquid or the crystalline state. The results so far obtained are as follows.1. The fluxes of effective atomic charges have been used as essential parameters for elucidating infrared absorption intensities. Introducing these fluxes also as the potential parameters, the equilibrium structures, the thermodynamic functions, the dipole moments and the infrared and Raman spectra of saturated hydrocarbons, ethers, ketones and aldehydes have been simulaneously fitted.2. Molecular mechanics calculation including the effect of intermolecular forces has been applied to the mixed crystals of benzoic acid and p-fluorobenzoic acid. The result is compatible with the fact that these two components form a solid solution.3. The potential model of hydrogen bonds previously used for the normal coordinates analysis of benzoic acid and aspirin has been slightly modified to fit the dissociation energy and the structure of fatty acid dimers. The changes of infrared spectra on dimerization have also been elucidated on the basis of this model.4. To simulate infrared and Raman spectra of large drug molecules in the crystalline state, an algorithm has been developed to include a given numer of low-frequency modes in the calculation of elastic constants. A specific effect of some normal modes on the elastic constants has been revealed by applying this method to -glycine crystal.