Multiple Condensation Reactions Involving PtII/PdII−OH2, Pt−NH3, and Cytosine−NH2 Groups: New Twists in Cisplatin−Nucleobase Chemistry

The coordination chemistry of the antitumor agent cisplatin and related complexes with DNA and its constituents, that is, the nucleobases, appears to be dominated by 1:1 and 1:2 adducts of the types cis‐[Pta2(nucleobase)X] and cis‐[Pta2(nucleobase)2] (a=NH3 or amine; a2=diamine or diimine; X=Cl, OH or OH2). Here, we have studied the interactions of the putative 1:1 adducts cis‐[Pta2(1‐MeC‐N3)(OH2)]2+ (with a=NH3, a2=2,2′‐bpy (2,2′‐bipyridine), 1‐MeC=model nucleobase 1‐methylcytosine) with additional cis‐[Pt(NH3)2(OH2)2]2+ or its kinetically superior analogues [Pd(en)(OH2)2]2+ (en=ethylenediamine) and [Pd(2,2′‐bpy)(OH2)2]2+. Depending upon the conditions applied different compounds of different nuclearity are formed. Without exception they represent condensation products of the components, containing μ‐1‐MeC‐H, μ‐OH−, as well as μ‐NH2− bridges. In the presence of Ag+ ions, the isolated products in several cases display additionally Pt→Ag dative bonds. On the basis of the cytosine‐containing structures established by X‐ray crystallography, it is proposed that any of the feasible initial 1:1 nucleobase adducts of cisplatin could form dinuclear Pt complexes upon reaction with additional hydrolyzed cisplatin, thereby generating nucleobase adducts other than the presently established ones. Two findings appear to be of particular significance: First, hydrolyzed cisplatin can have a moderately accelerating effect on the formation of a secondary nucleobase product. Second, NH3 ligands of the cisplatin moiety can be converted into bridging amido ligands following condensation with the diaqua species of cisplatin. More than just coordinating: Alternative binding patterns of cisplatin through condensation reactions leading to μ‐OH, μ‐NH2, and μ‐nucleobase bridges (see scheme) have been investigated by using X‐ray crystallography, NMR spectroscopy and DFT calculations.