Platinum-nucleobase model complexes

Ruiz J, Lorenzo J, Sanglas L, Cutillas N, Vicente C, Villa MD, Aviles FX, Lopez G, Moreno V, Perez J, Bautista D (2006) Palladium(II) and platinum(II) organometallic complexes with the model nucleobase anions of thymine, uracil, and cytosine antitumor activity and interactions with DNA of the platinum compounds. Inorg Chem 45 6347-6360... 

The availability of different metal ion binding sites in 9-substituted purine and pyrimidine nucleobases and their model compounds has been recently reviewed by Lippert [7]. The distribution of metal ions between various donor atoms depends on the basicity of the donor atom, steric factors, interligand interactions, and on the nature of the metal. Under appropriate reaction conditions most of the heteroatoms in purine and pyrimidine moieties are capable of binding Pt(II) or Pt(IV) [7]. In addition, platinum binding also to the carbon atoms (e.g. to C5 in 1,3-dimethyluracil) has been established [22]. However, the strong preference of platinum coordination to the N7 and N1 sites in purine bases and to the N3 site in pyrimidine bases cannot completely be explained by the negative molecular electrostatic potential associated with these sites [23], Other factors, such as kinetics of various binding modes and steric factors, appear to play an important role in the complexation reactions of platinum compounds. 

Coordination compounds have become very usable in medicine [361-364]. In this respect, use of metal complexes (mostly those of lanthanides) as diagnostic [365-367] and anticancer [368-370] media should be specially emphasized. Among the last complexes, the aminoplatinum-containing compounds play an important role, so the structural study of platinum complexes as a model of nucleobases [371] is a topic of renewed interest. The new issue of Comprehensive Coordination Chemistry II [372] contains a wide description of nanoparticles (vols. 6 and 7), biocoordination chemistry (vol. 8), and other aspects of application of coordination compounds. 

Attempts to model the intrastrand d(GpG) crosslink with nucleobases have met with only moderate success. Usually the 06 atoms of the two guanosine rings are on opposite sides of the platinum coordination plane ( head-to-tail isomer). Only for cw-[Pt(NH3)2(9-EtG)2] was the correct isomer obtained. Nucleobase complexes of the ds-diammineplatinum(II) moiety have been valuable for testing the controversial proposal of N7,06 chelate formation, which to date has not been observed. Several interesting discoveries of metal-nucleobase chemistry are that metal binding can stabilize rare tautomers, for example, the... 

Abstract This review summarizes computational studies devoted to interactions of metal cations with nucleobases, nucleotides, and short oligonucleotides considered as DNA/RNA models. Since this topic is complex, basically only the results obtained using ab initio and DFT methods are discussed. Part 1 focuses mainly on the interactions of the isolated bases with metal cations in bare, hydrated, and ligated forms. First, interactions of bare cations with nucleobases in gas phase approach are mentioned. Later, solvation effects using polarizable continuum models are analyzed and a comparison with explicitly hydrated ions is presented. In Part II, adducts of alkali metal, metal of alkaline earth, and zinc group metal cations with canonical base pairs are discussed. A separate section is devoted to platinum complexes related to anticancer treatment. Stacked bases and larger systems are discussed in last section. Here, semiempirical methods and molecular modeling are also discussed due to extensive size of studied complexes. 

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