Pyrimidines protonation, basicity

Platination of the N3 position in 1-substituted uracil and thymine derivatives requires proton abstraction and usually occurs only at high pH, but the Pt-N3 bond, once formed, is thermodynamically stable (log K 9.6) [7]. Platinum binding to N3 increases the basicity of 04, which becomes an additional binding site leading to di- and trinuclear complexes. A list of X-ray structurally characterized species is given by Lippert [7]. Pt complexes of uracil and thymine can form intensely colored adducts (e.g. platinum pyrimidine blues), which show anticar-cinogenic activity analogously to the monomeric species [7]. 

The reaction was found to fail with l-methyl-5-nitrouracil and 5-nitrouracil. This is because both uracils, containing dissociable protons, exist in the basic solution in the anionic forms, which inhibit the addition of the nucleophiles at the C-6 position. Attempts to bring about these pyrimidine-to-pyrimidine ring transformations with cyanoacetamide, ace-toacetamide, and phenylacetamide were not successful. A substituent at C-6 of 5-nitrouracil suppressed the reaction l,3,6-Trimethyl-5-nitrouracil was recovered almost quantitatively. 

The basic ionization constants of a large number of 2,4-diaminopyrimidines and condensed pyrimidine derivatives have recently been measured and earlier values verified (Roth and Strelitz, 1969). The first protonation occurs at the N-1 ring atom (pAT = 7 40) and the effect of 5-substituents is correlated quite well with -constants for the -t-M substituents (p = 4 85). The —M substituents (—NO2, —CN) show an enhanced base-weakening effect, which may be accounted for in terms of the direct conjugation shown in [65]. This provides additional evidence for protonation at N-1. 

Purine [93] is analogously protonated on N-1 (Cobum et al., 1965). With a pT a Value of 2 30, it has an enhanced basicity compared with that of pyrimidine (pA a " T23). In the nmr spectrum in trifluoroacetic acid, the resonance of the captured proton is not observable owing to exchange, but it can be observed in... 

Pyrimidines and purines, which contain the -NH2 group, are weakly basic. The cationic protonated conjugate acid forms of cytidine, adenosine, and guanosine have pKa values of 4.2,3.5, and 2.7, respectively. Similar values are observed for the 5 -nucleotides. In these compounds it is not the -NH2 group that binds the proton but an adjacent nitrogen atom in the ring (Eq. 5-3). 

The weakly basic portion of thiamin or of its coenzyme forms is protonated at low pH, largely on N-l of the pyrimidine ring. 86 88 The pKa value is 4.9. In basic solution, thiamin reacts in two steps with an opening of the thiazole ring (Eq. 14-15) to give the anion of a thiol form which may be crystallized as the sodium salt.79 84 This reaction, like the competing reaction described in Eq. 7-19, and which leads to a yellow... 

Interestingly, the second electronegative heteroatom reduces the capacity of the diazines to tolerate the positive charge resulting from protonation. Pyridazine 10.1 (pKa= 2.24), pyrimidine 10.2 (pAfa = 1.23), and pyrazine 10.3 (pA a = 0.51) are all far less basic than pyridine (pKa - 5.23). 

Again we allow for competition between the proton and metal ion for the basic N(l) sites on purine and N(3) sites on pyrimidine 5 -nucleoside monophosphates to find for neutral solutions at pH 7.4 the sequence... 

In the course of pulse radiolysis studies of purine and pyrimidine bases, Fielden et al. (1970) and Greenstock et al. (1973b) have been able to follow the kinetics of deprotonation of these compounds by OH- produced in the irradiated aqueous solution. The observation is made possible by the difference in ultraviolet absorption between the neutral and basic forms. The rate constants for deprotonation were found to be (1-2) x 101 0 M s-1 and those for the protonation of the anion by H+, 4 x 1010 M I s-1. 

Azoloazines having NH functions are weakly acidic and are also basic. TV-Alkylated derivatives act only as bases. Carbon-13 NMR studies on l-isopropyl-4-amino-pyrazolo[3,4-r/]pyrimidine and isomeric 2-isopropyl derivative indicate that N-5 and N-7 are the respective protonation sites <77JA7257>. Allopurinol as well as its derivatives have been shown by UV and NMR to form mono-and diprotonated species in sulfuric acid solutions <75KGS838>. 

There are two important articles by Steenken on electron-induced acidity/basicity of purines and pyrimidines bases [5, 6], These papers discuss the changes in the oxidation state of the DNA bases induced by electron loss or electron capture, and the influence these changes may have on the base-pair via proton transfer. These results are considered here in terms of the radicals observed in the solid-state. 

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