X-ray crystallographic, energy minimization and quantum mechanical calculations been employed on compounds of biological interest to give insights into and explanation of their modes of behavior. Various compounds showing promise against the AIDS virus are being systematically investigated to obtain structural and electronic properties which may help elucidate the mechanism of their action and thus lead to improved analogs. The x-ray structures of 2',3'-dideoxyadenosine (DDA) and 2',3'- dideoxycytidine (DDC) have been determined. Strain energies and quantum calculations have been carried out on these compounds. Calculations have been completed on the eight possible epimers of 3'-azido-2',3'-dideoxy-thymidine (AZT), as well as the corresponding bases: cytidine, adenosine, inosine, 2'-deoxycytidine and 3'-amino-3'-deoxyadenosine for comparison. Strain energies and quantum calculations on isocolchicine, which binds to tubulin, and isocolchicine, which does not, have been completed. Isocolchicine is more strained by about 8 kcals./mol. The factor which differentiates the binding ability of the two isomers seems to be different inter-oxygen distances which affect hydrogen bonding ability in isocolchicine.
