Application of Quantum Chemistry to Drugs and Their Interactions

Abstract

Whether or not quantum mechanics is the supreme intellectual accomplishment of man-an allegation that appears less of a conceit as one reads its history (1-3)­ it has certainly fostered philosophical speculation ( I , 4-7) and a great deal of very practical achievements. It is reassuring to learn that quantum mechanics does not exclude life (8) and at the same time that it can account for laboratory observations that otherwise elude explanation. Molecular orbital (MO) methods, which have been more widely applied than the other m ethod of quantum m echanics (the va­ lence-bond or resonance method), have explained many of the physical and chemical properties of molecules of interest to the chemist (9-15). Evidence is accumulating that MO methods can also explain the physical and chemical properties of large biomolecules and, by inference, their biological activities (16-18). The relative ioni­ zation potentials and dipole moments of a series of purines (18, 19) were consistent with those predicted ten years earlier in the Pullmans' laboratory by MO theory. MO calculations on biomolecules have yielded information in agreement with that obtained by nuclear magnetic resonance spectroscopy (20--23), infrared spectros­ copy (20), X-ray diffraction analysis (21, 24, 25) and, reasonably, with circular dichroic spectra (26). In most of this work, the results of the calculations have clear biological implications even to enzymatic m echanisms (16, 17, 27-32). Many of the inferences from MO calculations have been supported by subsequent experiment, a surprising number in consideration of the simple methods available when this work began and the inherent shortcomings of even modern MO techniques. Despite these successes in accounting for the biological properties of molecules, there has been m uch less effort to use quantum-mechanical m ethods to account for the biological effects of molecules. This relative lack is strange, because the first application of quantum mechanics in biology was to analyze carcinogenic hydrocar-