PLATINUM(II) BINDING TO N7 AND N1 OF GUANINE AND A MODEL FOR A PURINE-N1,PYRIMIDINE-N3 CROSS-LINK OF CISPLATIN IN THE INTERIOR OF A DNA DUPLEX

The preparation and X-ray structures of two dinuclear complexes 4 and 5, derived from [(dien)Pt(GH-N7)]2+(1), containing the 9-methylguanine anion G (4, 5) and deprotonated 1-methyluracil U (5) are reported. {[formula omitted(4) and cis-formula omitted](formula omitted (5) crystallize in the monoclinic (4) and triclinic (5) systems, space groups C2/c (4) and P1 (5). Cell dimensions are a = 32.494 (5) Å (4), 8.504 (3) Å (5), b = 17.052 (3) Å (4), 13.466 (3) Å (5), c = 11.507 (2) Å (4), 15.736 (3) Å (5), α = 104.34 (2)° (5), 0 = 104.65 (3)° (4), 108.66 (2)° (5), γ = 102.48 (2)° (5), V = 6168.5 A3 (4), 1566.1 Å3(5), and Z = 8 (4), 2 (5). In both cations, a (dien)PtIIentity is coordinated to the guanine via N7, whereas the N1 position is either occupied by a (dien)PtII(4) or a m-(NH3)2Pt(U) (5) residue. Coordination of the Pt at N1 takes place from 1 under virtually physiological pH conditions. Compound 5 represents the first example of a hypothetical DNA cross-link of cisplatin with N1 of a purine and N3 of a pyrimidine, two sites normally in the interior of a DNA double helix. Both nucleobases adopt a head-head orientation, thus making 5 a realistic model of a guanine, thymine cross-link. The large dihedral angle of 102° between the two bases and the long separation of 9.5 Å between the alkyl groups of both bases point toward a DNA distortion, which, if realized, should exceed that of the well-known G,G adduct at the DNA periphery by far. In slightly acidic medium, 1 interacts with Ag+without deprotonation at N1 but rather Ag+binding to N3. © 1990, American Chemical Society. All rights reserved.