Geometric consequences of electron delocalization for adenine tautomers in aqueous solution

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.

Figure

The total HOMED indices in water solution correlate well with those in the gas phase for the neutral and charged isomers of adenine

Chart 1

The canonical tautomer of adenine with all n- and π-electrons. The numbers refer to heavy atoms

Chart 2

Variations of the partial and total HOMED indices for the favored tautomers of neutral (a), positively (b), and negatively (c) ionized adenine when proceeding from the gas phase to aqueous solution

Fig. 1

Comparison of correlations between the total HOMED values and the relative energies (ΔE in kcal mol⁻¹) estimated for the neutral isomers of adenine in gas phase (a) and in water solution (b)

Fig. 2

Variations of the geometric (δHOMED10) and energetic (δE in kcal mol⁻¹) total effects of the exo NH₂ group for the neutral amine tautomers of adenine in the gas phase and in water solution. Numbers 1–9 correspond to the amine tautomers A1-A9, respectively

Fig. 3

Variations of the geometric (δHOMED11) and energetic (δE in kcal mol⁻¹) total effects of the exo = NH group for the neutral imine tautomers of adenine in the gas phase and in water solution. Numbers 1–14 correspond to the imine tautomers A10-A23, respectively