MODEL OF THE 2ND MOST ABUNDANT CISPLATIN-DNA CROSS-LINK - X-RAY CRYSTAL-STRUCTURE AND CONFORMATIONAL-ANALYSIS OF CIS-[(NH3)(2)PT(9-MEA-N7)](9-ETGH-N7)(NO3)CENTER-DOT-2H(2)O (9-MEA=9-METHYLADENINE, 9-ETGH=9-ETHYLGUANINE)

A model compound of the second most abundant DNA adduct of the antitum or agent cisplatin has been synthesized and structurally and spectrosc opically characterized and its conformational behavior examined: cis-[ (NH3)(2)Pt- (9-MeA-N7)(9-EtGH-N7)](NO3)(2) . 2H(2)O (9-MeA = 9-methyla denine; 9-EtGH = 9-ethylguanine) crystallizes in the monoclinic system , space group P2(1)/n (No. 14) with a = 7.931(2), b = 11.035(3), c = 2 6.757(6) Angstrom, beta = 94.94(2)degrees, and Z = 4. The two purine b ases adopt a head-to-head orientation, with NH2 of 9-MeA and CO of 9-E tGH being at the same side of the Pt coordination plane. A theoretical conformational analysis of the complex cis-[(NH3)(2)Pt(Ade)(Gua)](2+) (Ade = adenine; Gua = guanine) based on molecular mechanics calculati ons of the nonbonded energy has revealed four minimum-energy zones sim ilar to those derived previously for cis-[(NH3)(2)-Pt(Gua)(2)](2+) (Ko zelka; et al. Ear. J. Biochem. 1992, 205, 895). This conformational an alysis has allowed, together with the calculation of chemical shifts d ue to ring effects, the attribution of the two conformers observed for cis-[(NH3)(2)Pt{d(ApG)}](+) by Dijt et al. (fur. J. Biochem. 1989, 17 9, 344) to the two head-to-head conformational zones. The orientation of the two nucleobases in the crystal structure of cis-[(NH3)(2)Pt(9-M eA)(9-EtGH)](2+) corresponds, according to our analysis, roughly to th at preferentially assumed by the minor rotamer of cis-[(NH3)(2)-Pt{d(A pG)}](+).