A Hybrid statistical mechanics—quantum chemical model for proton transfer in 5‐azauracil and 6‐azauracil in water solution

Abstract

A hybrid statistical physics—quantum‐chemical methodology was implemented to study the water‐assisted intramolecular proton‐transfer processes in 5‐ and 6‐azauracils in aqueous solutions. The solvent effects were included in the model by explicit inclusion of two pairs of water molecules, which model the relevant part of the first hydration shell around the solute. The position of these water molecules was initially estimated by carrying out a classical Metropolis of dilute water solutions of the title compounds and subsequently analyzing solute–solvent intermolecular interactions in the Monte Carlo‐generated configurations. Sequentially to the statistical physics simulation, ab initio quantum mechanical (QM) level of theory was implemented. The effects of the water as solvent (at ab initio QM level) were introduced at two different levels—using solute–solvent clusters (four‐water molecules) and using the same clusters embedded in an external continuum. Full geometry optimizations of these complexes were carried out at MP2/6–31 + G(d, p) and conductor‐polarizable continuum model (C‐PCM)/MP2/6–31 + G(d, p). Single point calculations were performed at CCSD(T)/6–31 + G(d, p)//MP2/6–31 + G(d, p) computational level to obtain more accurate energies. According to our calculations hydrated azauracils should exist in three forms: mainly dioxo form and two hydroxy forms. The calculated proton transfer activation energies for tautomeric reactions of 5‐azauracil and 6‐azauracil show different pictures for these two compounds. According to C‐PCM/MP2/6–31 +G(d, p) data, water‐assisted proton transfer in 5‐azauracil realizes through two parallel reactions: 1,3,5‐triazine‐2,4(1H,3H)‐dione → 6‐hydroxy‐1,3,5‐triazin‐2(1H)‐one and 1,3,5‐triazine‐2,4(1H,3H)‐dione → 4‐hydroxy‐1,3,5‐triazin‐2(1H)‐one. Tautomeric equilibrium in 6‐azauracil in water could occur by two contiguous reactions: 1,2,4‐triazine‐3,5(2H,4H)‐dione → 5‐hydroxy‐1,2,4‐triazin‐3(2H)‐one and 5‐hydroxy‐1,2,4‐triazin‐3(2H)‐one → 3‐hydroxy‐1,2,4‐triazin‐5(2H)‐one. The proton transfer investigated reactions in 5‐ and 6‐azauracils involve concerted atomic movement. © 2015 Wiley Periodicals, Inc.

Tautomerism of Inosine in Water: Is It Possible?

“…Therefore, the experimental IR and Raman spectra of inosine in water have no evidence of the enol tautomer presence but according to our theoretical predictions with regard to kinetics of tautomeric conversion in water of inosine, the enol form B should be presented in solution. We have shown ,− that the calculated barriers in the range of 12–17 kcal mol –1 for the water-assisted proton transfer reactions indicate that the tautomeric conversions are kinetically feasible processes. The detection of the rare tautomeric forms by spectroscopic methods is not possible and a probable exception might be fluorescence spectroscopy …”

Single-Molecule Detection of a Fluorescent Nucleobase Analogue via Multiphoton Excitation

“…Assuming all of the Rh110 molecules are detected, this implies that ∼1/180 of the DMA th aU molecules that go through the focus are emissive, which agrees with the finding from bulk measurements that ∼96% of the molecules are in a dark state. On the basis of the discussion above, and previous reports of tautomerism of FBAs, − we assign this dark state to a long-lived tautomer of DMA th aU …”

“…Ground-state density functional theory (DFT) calculations, in the gas phase and within a solvent continuum, show that the molecule exists preferentially as rotamer A (Chart ), with rapid (nanoseconds) interconversion between rotamers . In contrast, the three tautomers of the core 6-aza-uracil heterocycle have been shown to interconvert on much longer time scales (microseconds to milliseconds) . Although the ensemble-average quantum yield of DMA th aU in buffer is much less than that in dioxane, two of its emitting species have longer lifetimes, and hence higher individual quantum yields, than found in dioxane.…”

Computational Study of Proton Transfer in Tautomers of 3‐ and 5‐Hydroxypyrazole Assisted by Water

“…The energy profile presented in Figure 6 shows that the most important difference between the prototropic tautomerism of monohydrated species and the isolated compound is associated with the activation barriers, which become almost half or even less than half of those obtained for the isolated compound; this is a well‐known phenomenon 61–68. Considering the G3B3 gas‐phase data, the inclusion of a molecule of water lowers the barrier between 1 a and 2 from 214.1 to 75.1 kJ mol −1 .…”