Cisplatin complexes

Figure 14.26. Three-dimensional structure of the decanucleotide-cisplatin complex. The cisplatin is shown in CPK format and the turned-out cytidines are shown in black. The coordinates were supplied by B. P. Hoskins. (From ref. 7. Copyright 1995 by the American Association for the Advancement of Science. Excerpted with permission.)...

Competitive effects for the interactions of cisplatin with various active sites in the cellular environment are discussed in papers of Deubel.55,56 In the earlier paper, energetic and structural data of complexes with the different substituted ligands were explored. The more recent work deals with kinetic factors in the relation to the transition state (TS) for water replacement of the semihydrated cisplatin complex (cis-[Pt(NH3)2(H20)Cl]+ ) with either an N- or S-containing ligand (thiopheneimidazol, dimethyl sulphide, or methanethiolate which serve as amino acid models). Deubel concluded the kinetic preference of N-sites over S-nucleophiles where the important role is played by the electrostatic terms. In addition, the aliphatic/aromatic character of the substituent as well as the influence of different dielectric constants of the environment are very important. A more realistic model for the aqua-ligand replacement with adenine and guanine was studied in works of Chval et al.53,57 and Eriksson and coworkers.58 They performed independently the estimation of the thermodynamic and kinetic parameters of this process. 

In the other cases, there is not only qualitative but also quantitative agreement for all of the considered reactions. Regarding the markedly different biochemical roles of Pt- and Pd-based compounds, the very high degree of similarity between the calculated hydration surfaces of the Pd and Pt compounds does not correspond with the QSAR principle. The differences are considerably smaller compared to those we have recently noticed between Zn2+ and Mg2+ cations.100,109 This clearly demonstrates that an understanding of the anticancer activity of the cisplatin complex is related not only to the thermodynamical description, but also some additional factors have to be included. This will be discussed in the next section. 

Cisplatin complexes with ATP. In a continuation of previous studies, Jiang and Mao reported the results of a study of the complexation of the anticancer drug cisplatin with ATP. The authors made use of long-range HMBC data in the study, and although... 

Zilberberg et al. reported the influence of chelated cisplatin complex with guanine(06d 7) on Watson-Crick base pairing (Zilberberg et al. 1997). In such chelate structures, more distinct perturbation of base pairing was revealed. However, such chelate binding pattern is imUkely to be relevant to real ds-DNA conditions. 

The groups of Morel and Gautier reported a series of [(NHC)AgCl] complexes that demonstrated exceptional activity against a variety of cancer cell lines, compared with cisplatin. Complexes 14, 22, and 23 (also examined as antimicrobial agents by Roland et. al, see Figure 15.3) along with complexes of... 

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