Purine tautomeric preferences and bond-length alternation in relation with protonation-deprotonation and alkali metal cationization

Abstract

Quantum chemical calculations were carried out for deprotonated (P−) and protonated purine (PH+) and for adducts with one alkali metal cation (P−M+ and PM+, where M+ is Li+ or Na+) in the gas phase {B3LYP/6-311+G(d,p)}, a model of perfectly apolar environment, and for selected structures in aqueous solution {PCM(water)//B3LYP/6-311+G(d,p)}, a reference polar medium for biological studies. All potential isomers of purine derivatives were considered, the favored structures indicated, and the preferred sites for protonation/deprotonation and cationization reactions determined. Proton and metal cation basicities of purine in the gas phase were discussed and compared with those of imidazole and pyrimidine. Bond-length alternations in the P, PH+, P−M+, and PM+ forms were quantitatively measured using the harmonic oscillator model of electron delocalization (HOMED) indices and compared with those for P. Variations of the HOMED values when proceeding from the purine structural building blocks, pyrimidine and imidazole, to the bicyclic purine system were also examined. Generally, the isolated NH isomers exhibit a strongly delocalized π-system (HOMED > 0.8). Deprotonation slightly increases the HOMED values, whereas protonation and cationization change the HOMED indices in different way. For bidentate M+-adducts, the HOMED values are larger than 0.9 like for the largely delocalized P−. The HOMED values correlate well in a comprehensive relationship with the relative Gibbs energies (ΔG) calculated for individual isomers whatever the purine form is, neutral, protonated, or cationized. When PCM-DFT model was utilized for P−, PH+, PM+, and P−M+ (M+ = Li+) both electron delocalization and relative stability are different from those for the molecules in vacuo. The solvation effects cause a slight increase in HOMEDs, whereas the ΔEs decrease, but in different ways. Hence, contribution of particular isomers in the isomeric mixtures of PH+, PM+, and P−M+ also varies.

On Prototropy and Bond Length Alternation in Neutral and Ionized Pyrimidine Bases and Their Model Azines in Vacuo

“…In the case of pyrimidine bases (U, T, C, and iC) containing one six-membered ring with two endo N atoms and two exo groups (NH 2 and/or OH), two labile protons can move between the conjugated sites according to the analogous scheme of proton-transfers as that given in Figure 1 [28]. For bicyclic purine bases (A and G) and their metabolites (HX, X, and UA) containing the six-membered pyrimidine fragment structurally fused with the five-membered imidazole ring, the imidazole part contains additional labile proton(s) and additional conjugated sites that can also participate in prototropy [29][30][31][32][33][34]. Consequently, the tautomeric equilibria for purine derivatives are more complex than those for pyrimidine bases.…”

Intramolecular Interactions in Derivatives of Uracil Tautomers

“…For this reason, RNA and DNA base pairs are built only from N9H tautomer of purine bases and N1H of pyrimidine bases [ 1 ]. However, relative stability of the tautomers can significantly change upon oxidation, reduction [ 17 ], substitution of the nucleobase [ 19 , 20 ], polarity of the environment [ 17 ] and even interaction with a metal cation [ 21 , 22 ]. Tautomerism of nucleobases is of interest in knowledge of biochemical processes.…”

On Analogies in Proton-Transfers for Pyrimidine Bases in the Gas Phase (Apolar Environment)—Cytosine Versus Isocytosine

“…The DFT level of theory has been chosen by Rodgers and his co-workers for an analysis of protonated forms of nucleic acid fragments [44], as well as by Koppel, Leito, Maksić, and their co-workers for estimation of acidity-basicity parameters for nitrogen bases in the gas phase [45,46]. It has also been selected by us for investigations of other tautomeric nucleobases, including adenine, xanthine, caffeine, and purine itself [47][48][49][50]. Because this level of theory has been employed previously for all tautomers-rotamers of neutral C and iC (Table 1) [6,7], and here for ionic forms, the complete acid-base equilibria could be analyzed.…”