Platination selectivity

Alguero, B. Lopez de la Osa, J. Gonzalez, C. Pedroso, E. Marchan, V. Grandas, A. Selective platination of modified oligonucleotides and duplex cross-links. Angew. Chem. Int. Ed. 2006, 45, 8194-8197. 

Electrochemical biosensors based on detection of hydrogen peroxide at platinized electrodes were found to be more versatile allowing a decrease in detection limit down to 1 i,mol L 1 [109]. However, all biological liquids contain a variety of electrochemically easily oxidizable reductants, e.g. ascorbate, urate, bilirubin, catecholamines, etc., which are oxidized at similar potentials and dramatically affect biosensor selectivity producing parasitic anodic current [110]. 

Shen et al. have reported studies on procaine-selective electrodes embodying PVC membranes [57]. Various ion-pair complexes (procaine derivatives with tetraphenylborate, dipicrylamine, tetraiodomecurate, and reineckate) were incorporated into platinized PVC membranes, and with dinonyl phthalate as the solvent mediator, formed procaine selective electrodes. The efficiency and performance of these were compared, and it was found that procaine picrylamine and procaine tetraphenylborate were the best electroactive materials. The procaine picrylamine electrode exhibited a Nemstian response over the range 10 pM to 0.1 M, and was used as the indicator electrode for the potentiometric determination of procaine. The method recovery was found to be 99.8%, with a standard deviation of 0.9%. 

A few studies did address chemical selectivity in these oxidations. Pattenden and coworkers, for example, showed that primary alcohols could be selectively oxidized to the corresponding aldehydes, without appreciable overoxidation, when the platinized TiO2 photocatalyst was suspended in benzene, Eq. (11). Poor yields were obtained... 

The photoelectrochemical synthesis of amino acids from simple molecules has also been reported. Low efficiencies were observed in the conversion of mixtures of methane, ammonia and water to several amino acids on platinized TiOz Amino acids and peptides were reported when glucose replaced methane as the carbon source in a parallel experiment Higher quantum efficiencies (20-40%) were observed in the conversion of alpha-keto acids or alpha-hydroxy acids to the corresponding alpha-amino acids Moderate levels of enantiomeric selectivity (optical yields of about 50%) were reported when chiral starting materials were employed. Photoinduced Michael-like reactions were observed when alpha, beta unsaturated acids were used as substrates for the amino acid synthesis... 

The minor perturbation of the DNA structure caused by cis-platin may well not be detected in a cell which has a deficiency in the repair mechanism, whereas a normal cell might have a more selective repair mechanism. Whether this is the mechanism of action of the platinum anticancer drugs still has to be established, but it is the first model which satisfactorily accounts for all the known chemical and structural restraints. In addition, it suggests further modeling experiments with the more effective second generation drugs. 

Legendre, F. and Chottard, J.-C. (1999) Kinetics and Selectivity of DNA-Platination in Cisplatin Chemistry and Biochemistry of a Leading Anticancer Drug, pp. 223-245 (Lippert, B., Ed.) Verlag Helvitica Chimica Acta, Zurich. 

Many reviews covering several aspects of these topics have appeared in the recent years [1-7]. The purpose of this contribution is to focus on the major common features of the DNA-binding reactions of a now wide variety of complexes. The aim is to identify the specific parameters of each step of the overall platination reactions in order to design sequence-selective drugs. 

We can now identify the major factors which play a role in the DNA-platination and chelation steps i) The nature and charge of the actual platinum species, ii) the bases to be platinated and their neighboring sequences, and iii) the nature of the nonleaving platinum ligands and their eventual interaction with the nucleic acid. To get a deeper insight into these parameters, in order to achieve selective DNA-platination, the study of oligonucleotide models is an appropriate approach. 

More work is needed to clearly establish the role of outer-sphere association in DNA-platination. We can infer its influence on the rate of platination according to the relation kp = kK0 [N]/(l + K0 [N]) (with N = nucleotide-binding sites of Pt, i.e., N G, [N] [Pt]) (Scheme 3). It could also influence the selectivity of platination via selective association between the cationic species and the sites of higher negative electrostatic potential. To test this hypothesis one will have to analyze the influence of various sequences, of different types of platinum ligands, and of the ionic status of the DNA medium. 

Oligonucleotide Studies to Understand Platination and Chelation Selectivities... 

Fig. 6. Scheme for selective platination of polyamines such as spermidine... 

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