X-ray crystallographic, energy minimization and quantum mechnical 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 and published. The x- ray structures of 2' ,3'-dideoxyinosine (DDI) and 2' ,3'- dideoxyguanosine are being determined. Strain energies and quantum calculations have been carried out on these compounds. Calculations have been completed on the eight possible empimers of 3'-azido-2' ,3'-dideoxythymidine (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 colchicine, 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 hvdrogen bonding ability in isocolchicine.
