Geometric consequences of electron delocalization for adenine tautomers in aqueous solution.

Ewa D Raczyńska,Mariusz Makowski

doi:10.1007/s00894-014-2234-4

Abstract

Geometric consequences of electron delocalization were studied for all possible adenine tautomers in aqueous solution by means of ab initio methods {PCM(water)//DFT(B3LYP)/6-311+G(d,p)} and compared to those in the gas phase {DFT(B3LYP)/6-311+G(d,p)}. To measure the consequences of any type of resonance conjugation (π-π, n-π, and σ-π), the geometry-based harmonic oscillator model of electron delocalization (HOMED) index, recently extended to the isolated (DFT) and hydrated (PCM//DFT) molecules, was applied to the molecular fragments (imidazole, pyrimidine, 4-aminopyrimidine, and purine) and also to the whole tautomeric system. For individual tautomers, the resonance conjugations and consequently the bond lengths strongly depend on the position of the labile protons. The HOMED indices are larger for tautomers (or their fragments) possessing the labile proton(s) at the N rather than C atom. Solvent interactions with adenine tautomers slightly increase the resonance conjugations. Consequently, they slightly shorten the single bonds and lengthen the double bonds. When going from the gas phase to water solution, the HOMED indices increase (by less than 0.15 units). There is a good relation between the HOMED indices estimated in water solution and those in the gas phase for the neutral and ionized forms of adenine. Subtle effects, being a consequence of intramolecular interactions between the neighboring groups, are so strongly reduced by solvent that the relation between the HOMED indices and the relative energies for the neutral adenine tautomers seems to be better in water solution than in the gas phase. FigureThe total HOMED indices in water solution correlate well with those in the gas phase for the neutral and charged isomers of adenine Electronic supplementary materialThe online version of this article (doi:10.1007/s00894-014-2234-4) contains supplementary material, which is available to authorized users.

Highlights

Various natural products, including pyrimidine and purine bases of nucleic acids, display prototropic tautomerism, the phenomenon which strongly influences their structure and biochemical transformations [1,2,3,4]
We investigated the geometric consequences of electron delocalization for the hydrated adenine tautomers and compared them to those reported previously for isolated ones [12]
The number of the prototropic tautomers for adenine is a consequence of the number of the labile protons and conjugated tautomeric sites

Summary

Introduction

Various natural products, including pyrimidine and purine bases of nucleic acids, display prototropic tautomerism, the phenomenon which strongly influences their structure and biochemical transformations [1,2,3,4]. Very often experimental techniques, applied to tautomeric compounds, cannot give the complete information on the structure of all possible tautomers. Many internal and external factors such as polarity, aromaticity, stability of functionalities, acid–base properties of conjugated tautomeric sites, substituent and solvent effects, intra- and/or intermolecular interactions, oxidizing and reducing agents, ions, electrons, UV, γ-, and X-ray, etc. Depending on the tautomeric system, one or the other factor dictates the tautomeric preferences. In the case of simple tautomeric systems, a relation between prototropy and electron delocalization ( called resonance or mesomerism) has been signaled more than 50 years ago by Pauling [5].

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Conclusion