Studies on tautomeric stability and equilibrium of 5(4)-substituted-1,2,3 triazoles. I. Electronegativity and resonance effects of substituent

•Tautomeric equilibrium can be described by MPW1PW91/6-31+G* basis sets.•Charge on the substituent plays a large role in the tautomeric composition.•The NBO provides the appropriate keys to understanding the effect of substituents.•The predominant tautomeric form can vary considerably if we consider the solvent.

We have studied the 1,2,3-triazole system with a set of 25 substituents of different electronic features using several methods. Our aim is to find out a calculation method for the analysis of these molecules in biological systems. The combined AIM and NBO study permitted us to justify the observed tautomeric preferences. The absolute predominance of the 2H-tautomer forms is greatly changed when the substituent group possesses anionic character; therefore the pH of the medium is relevant. When the calculations were carried out in solution, noteworthy changes in the behavior of charged substituents were observed. These facts may be relevant when studying the interactions of these molecules with biological receptors.

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