On Some Origins of Tautomeric Preferences in Neutral Creatinine in Vacuo: Search for Analogies and Differences in Cyclic Azoles and Azines

Abstract

In order to look for the origins of tautomeric preferences in neutral creatinine in vacuo, we examined prototropic conversions for model azoles, namely mono-hydroxy and mono-amino imidazoles, and also for their selected 1-methyl derivatives. All possible isomeric forms of creatinine and model compounds, resulting from intramolecular proton transfer (prototropy), conformational isomerism about –OH, and configurational isomerism about =NH, were studied in the gas phase (model of non-polar environment) by means of quantum-chemical methods. Because the bond-length alternation is a consequence of the resonance phenomenon, it was measured for all DFT-optimized structures by means of the harmonic oscillator model of electron delocalization (HOMED) index. Important HOMED analogies were discussed for investigated azoles and compared with those for previously studied cyclic azines, including pyrimidine nucleic acid bases. The internal effects were taken into account, and the stabilities of the investigated tautomers-rotamers were analyzed. Significant conclusions on the favored factors that can dictate the tautomeric preferences in creatinine were derived.

Strong Bases and beyond: The Prominent Contribution of Neutral Push–Pull Organic Molecules towards Superbases in the Gas Phase

“…To our knowledge, the stability of the quinonimine form of 4-aminobenzamidine and the exo imino forms of azoles have never been experimentally proven. In the case of azoles, the exo imino forms of 2- and 4(5)-aminoimidazoles have been only theoretically investigated [ 83 ]. These protomers (<0.001%) possess considerably weaker electron delocalization and higher Gibbs energies than those of the dominating exo-amino forms.…”

“…These conjugated systems continue to arouse interest as a canonical structure for strong bases design. In this regard, a few significant papers published after 2016 can be cited [ 70 , 72 , 73 , 74 , 75 , 82 , 83 , 116 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 ]. Note that theoretical investigations have no such difficulties as those connected with experiments.…”