Effects of Six-Membered-Ring Conformation on the Rotamer Distribution and Rate of Atropisomerization in Platinum(II)−Guanine Compounds: 2,4-Bis(methylamino)pentane Complexes

Abstract

NMR and CD spectroscopy and molecular mechanics and dynamics (MMD) calculations were used to characterize (Me2DAP)Pt(G)2 complexes (G = N9-substituted guanine derivative; Me2DAP = 2,4-bis(methylamino)pentane with N, C, C, and N stereochemistries of S,R,S,R, S,R,R,R, and R,R,R,R). NMR and MMD results indicated that the favored Me2DAP chelate ring conformations were chair. There are two possible head-to-tail rotamers (ΔHT and ΛHT) and, depending on the Me2DAP stereochemistry, one or two head-to-head (HH) rotamers. Rotation of the G bases around the Pt−N7 bond was found to be rapid on the NMR time scale for all compounds in D2O at room temperature; in contrast, slow rotation was reported for (Me2DAB)Pt(G)2 (Me2DAB = 2,3-bis(methylamino)butane by Xu et al.) Because of the additional flexibility of the six-membered chelate ring in the Me2DAP systems versus the five-membered ring in Me2DAB, the N-methyl groups of Me2DAP can occupy more pronounced axial positions, allowing a low-energy path to rotation as sugges...