Platinum nucleobase-metal binding

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... 

Another question related to the dynamics of platinum—nucleobase chemistry is the rotational freedom or otherwise of the metal—purine bonds. This point is relevant to the formation of, for instance, an intrastrand link upon binding of the platinum to the first base. Studies on the cis-[Pt(NH3)2(Guo)2] cation indicated little restriction around the Pt—purine bond [65, 66] but with bulkier ligands (A, A-Me2-en, N,N,N N -Mq - vl) restricted rotation is observed [65,67]. 

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. 

Especially the various studies that made use of NMR techniques have contributed a lot to a better understanding of the manner in which DNA fragments react with metal ions. High-field NMR spectroscopy is a very useful tool to determine the platinum binding sites in nucleic add fragments, since crystal structure determinations have been reported only for a limited number of cases. The NMR evidence for platinum binding to nucleobases can be summarized as follows ... 

The determination of crystal structures for many platinum metal—nucleobase complexes has elucidated many of the binding features, although the foregoing discussion is evidence of the complexity of these mixtures in solution. The bases studied range from unsubstituted purines and pyrimidines to the nucleosides and nucleotides. One feature of this area is the general difficulty of obtaining suitable crystalline samples of the sugar... 

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