FORCE-FIELD CALCULATIONS OF ANTITUMOR PLATINUM(II) COMPLEX-SYSTEMS

Strain-energy minimization calculations of adducts of platinum(II) com plexes containing 1,2-diaminocyclohexane (DACH) with the sequence d(pC pGpAp) d(pGpCpTp) of a synthetic B-DNA were carried out by using a mod ification of the MM2 program. (C, G, A, T, and p denote cytidine, guan osine, adenosine, thymidine, and phosphate, respectively). In result, the more antitumor-active trans-DACH complex adducts are about 37 kJ/m ol more stable than the cis complex in total energy. Platinum-complex adducts of 2-(aminomethyl)cyclohexylamine abbreviated as AMCHA were al so estimated. In calculations, the trans-AMCHA-complex adducts are abo ut 6 to 14 kJ/mol more stable than the cis ones. The differences are l ess than between the DACH complexes. In addition, this relaxation of s train occurred in the six-membered ring.