Pyrimidines electrochemical oxidation

Electrochemical oxidation of Chinoin-127 19 afforded 1,6-dimethyl-4-oxo-l,6,7,8-tetrahydro-4//-pyrido[l,2-a]pyrimidine-3-carboxamide 355 (87MI6). 

Pyrimidines. Reaction of Thy with photoexited menadione or its electrochemical oxidation yields mainly to the N(l)-C(5)-linked dimer (Hatta et al. 2001). This can be accounted for if the precursor radical cation deprotonates at N( 1) (see above). For this N(l)-centered radical a second mesomeric form with the spin at C(5) can be written. Head-to-tail recombination leads to the isopyrimi-dine-type dimer [reaction (12)]. Isopyrimdines are unstable (see below) and add rapidly water [reaction (13)]. This dimer is also formed in the reaction with S04 , albeit with a lower yield. 

The electrochemical behaviour and the adsorption of nucleic acid molecules and DNA constituents have been extensively studied over recent decades [1-6]. Electrochemical studies demonstrated that all DNA bases can be electrochemically oxidized on carbon electrodes [7-13], following a pH-dependent mechanism. The purines, guanine (G) and adenine (A), are oxidized at much lower positive potentials than the pyrimidines, cytosine (C) and thymine (T), the oxidation of which occurs only at very high positive potentials near the potential corresponding to oxygen evolution, and consequently are more difficult to detect. Also, for the same concentrations, the oxidation currents observed for pyrimidine bases are much smaller than those observed for the purine bases. Consequently, the electrochemical detection of oxidative changes occurring in DNA has been based on the detection of purine base oxidation peaks or of the major... 

G. Dryhurst and P.J. Elving, Electrochemical oxidation-reduction paths for pyrimidine, cytosine, purine and adenine. Correlation and application, Talanta, 16 (1969) 855-874. 

Faraggi M, Klapper MH (1993) Reduction potentials determination of some biochemically important free radicals. Pulse radiolysis and electrochemical methods. J Chim Phys 90 711-744 Faraggi M, Klapper MH (1994) One electron oxidation of guanine and 2 -deoxyguanosine by the azide radical in alkaline solutions. J Chim Phys 91 1062-1069 Faraggi M, Broitman F, Trent JB, Klapper MH (1996) One-electron oxidation reactions of some purine and pyrimidine bases in aqueous solutions. Electrochemical and pulse radiolysis studies. J Phys Chem 100 14751-14761... 

The proposed reaction pathway for the electrochemical reduction of 4-aminopyrimi-dine is rather complex and the reader is referred to the original publication Photochemical transformations were carried out to determine whether the 4-amino-pyrimidine wave I reduction product is susceptible to photochemical oxidation, as in the case of other pyrimidine derivatives The resulting data are summarized... 

Oscillographic current intensity vs. time curves of amino-substituted pyrimido[5,4-c/]pyrimidines have been measured.153 One- or two-electron oxidations with a platinum electrode have been observed, depending on the type of solvent.154 The electrochemical reduction of 2,6-dimor-... 

The SNAr reactions of heteroarenes can be realized in a similar manner, as in the series of arenes [71, 82]. These nucleophilic reactions are analogous to electrochemical Sn transformations of arenes [22, 24, 25]. Terrier and co-workers considered an opportunity for electrochemical methoxylation of 4,6-dinitrobenzofuroxan by action of the methoxide ion via the SnAt mechanism [21]. The intermediate o -complex formed was oxidized successfully into the corresponding substitution product. Analogously, the formation of heteroaromatic amines has been suggested to occur via intermediacy of the corresponding amino adducts, as exemplified by the oxidation of the o -complex derived fi om the reaction of pyrimidine with NH2 (Scheme 26) [3, 102-104]. 

Following these pioneering studies on electrochemical and optical chemical sensors based on functionalized poly thiophenes, many researchers decided to address the detection of small molecules of biomedical interest. For instance, in 1998, Bauerle and Emge described a method to detect the binding of purine or pyrimidine bases by covalently attaching a pyrimidine or triazine unit to polymers 6 or 7 (Scheme 22.1) [29]. Here, the addition of small concentrations of a complementary purine or pyrimidine resulted in an increase in the oxidation potential, and also a decrease in the electroactivity. 

At carbon electrodes, purine bases produce well-defined oxidation peaks within a wide pH range (0-12.5) [142,143]. Purine nucleosides and nucleotides are oxidized at potentials more positive than the parent bases [144]. Signals corresponding to the oxidation of purine bases, nucleotides, and nucleotides have also been obtained using chemically modified carbon electrodes [145,146] (for more details see Sect. 12.4.3). Recently, Cai and coworkers [147] proposed a method for trace A determination using an electrochemically/chemically modified (in alkahne sodium nitrate solution) carbon paste electrode (CPE). Pyrimidines are considered to be electroinactive on carbon electrodes however, Oliveira-Brett and Matysik recently reported [148] specific anodic peaks observed in solutions of T and C bases (but not their nucleosides). Sugar components of nucleotides can be oxidized at copper electrodes [149]. 

Van et al. [197] studied the electrochemical behavior of pyridazine using cyclic voltammetry in acetonitrile with different supporting electrolytes. Dark, greenish-blue polypyridazine formed on the anode when either lithium perchlorate or ammonium tetrafluoroborate was used as the supporting electrolyte. Also investigated were variations in the acidity of the solution during the course of electrolysis and the effects of the synthetic conditions on the electrochemical and other properties of the films. The pyridazine rings are believed to be para linked and the perchlorate or tetrafluoroborate counteranions are present in a 2 1 molar ratio. Two isomers of pyridazine—pyrazine and pyrimidine—could also be oxidized, but these isomers yielded only yellowish, powdery precipitates and no films. 

It was previously shown that two reduced forms of NAD, viz. NADH and the dimer (NAD)2, may revert photochemically to the parent, enz3fmati-cally active NAD. Similar photochemical ability has been found for electrochemically generated dimers of pyrimidine and purine derivatives . In the presence of oxygen this photochemical oxidation is accompanied by formation of H2O2, and the superoxide radical O2 is an intermediate in the reaction". ... 

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