Exploring the Universality of Unusual Conformations of the 17-Membered Pt(d(G~*pG~*))Macrochelate Ring.Dependence of Conformer Formation on a Change in Bidentate Carrier Ligand from an sp~3 to an sp~2 Nitrogen Donor

摘要

Early studies on cis-PtA_2(d(G~*pG~*))(A_2=diamine or two amines,G~*=N7-platinated G)and cis-Pt(NH3)2(d(G~*pG~*))models for the key cisplatin-DNA cross-link suggested that they exist exclusively or mainly as the HH1 conformer(HH1=head-to-head G~* bases,with 1 denoting the normal direction of backbone propagation).These dynamic models are difficult to characterize.Employing carrier A_2 ligands designed to slow dynamic interchange of conformers,we found two new conformers,AHT(head-to-tail G~* bases with a A chirality)and HH2(with 2 denoting the backbone propagation direction opposite to normal).However,establishing that the non-HH1 conformations exist as an intrinsic feature of the 17-membered Pt(d(G~*pG~*))ring requires exploring a range of different carrier ligands.Here we employ the planar aromatic sp~2 N-donor 5,5'-Me_2bipy(5,5'-dimethyl-2,2'-bipyridine)ligand,having a shape very different from those of previously used nonplanar sp~3 N-donor bidentate carrier ligands,which often bear NH groups.The 5,5'-Me_2bipy H6 and H6'protons project toward the d(G~*pG~*)moiety and hinder the dynamic motion of 5,5'-Me_2bipyPt(d(G~*pG~*)).We again found HH1,HH2,and AHT conformers with typical properties,supporting the conclusions that the new AHT and HH2 conformers exist universally in dynamic cis-PtA_2(d(G~*pG~*))adducts,including cis-Pt(NH_3)_2(d(G~*pG~*)),and that the carrier ligand typically has little influence on the overall structure of the Pt(d(G~*pG~*))macrocyclic ring of a given conformer.The sizes of the G~* H8 to H6/H6'NOE cross-peaks indicate little base canting in all 5,5'-Me_2bipyPt(d(G~*pG~*))conformers,suggesting that carrier-ligand NH groups favor the canting of one G~* base in the HH1 and HH2 conformers of typical cis-PtA_2(d(G~*pG~*))adducts.