Tautomeric Equilibrium of Uracil and Thymine in Model Protein−Nucleic Acid Contacts. Spectroscopic and Quantum Chemical Approach

Abstract

This work deals with tautomeric transformations of uracil (Ura) and thymine (Thy) in their model complexes with the deprotonated carboxylic group. Essential changes in the UV spectra of the bases upon their interaction with NaAc, vanishing signals of both imino protons in (1)H NMR spectra, and a perceptible decrease in intensity of both IR bands, related to the stretching vibrations nu(C=O) of the carbonyl groups, imply involvement of enolic tautomers. Results of quantum chemical calculations of the double complexes of the Ura(Thy) tautomers with CH(3)COO(-) at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory proved to be incompatible with the spectral features: despite the fact that the complexes of the enolic tautomers are much closer in energy to the diketo ones as compared to isolated tautomers, the energy gap between them is such that in tautomeric equilibrium dominate diketo forms. Calculations of triple complexes of the type CH(3)COO(-):Ura(Thy) tautomer:Na(+), taking into account the effect of the Na(+) coordination with tautomers, show that three triple complexes formed by enolic tautomers appeared more stable than those formed by diketo ones. This makes the UV and (1)H NMR data understandable, but the high residual intensity of the nu(C=O) bands in the IR spectra remains unclear. At that ion, Na(+) itself was not able to disturb the tautomeric equilibrium in the coordination complexes of the type Ura(Thy) tautomer:Na(+). To evaluate the DMSO effect, the CPCM solvation model was applied to triple complexes of the Ura tautomers. It appeared that in the solution there is coexistence between the diketo and enolic tautomers in a ratio of 53%:47%. This makes possible reconciliation of our experimental data. The biological significance of high-energy tautomers of nucleotide bases is discussed.

Structural significance of modified nucleoside 5-taurinomethyl-2-thiouridine, τm5s2U, found at ‘wobble’ position in anticodon loop of human mitochondrial tRNALys

“…DFT method has been used extensively to search conformational landscape of canonical nucleosides [49][50][51]. However, hybrid method B3LYP evidently affords improved results [52][53][54].…”

Elementary Molecular Mechanisms of the Spontaneous Point Mutations in DNA: A Novel Quantum-Chemical Insight into the Classical Understanding

“…It is generally believed that Thy exists in the canonical diketo form in the gas phase as well as in the aqueous solution (Kwiatkowski & Pullman, 1975), but there is experimental evidence of small amounts of its rare tautomeric forms in the gas phase (Fujii et al, 1986;Tsuchiya et al, 1988) and in the solution (Hauswirth & Daniels, 1971;Katritzky & Waring, 1962;Morsy et al, 1999;Samijlenko et al, 2010;Suwaiyan et al, 1995). Also laser ablation in combination with MB-FTMW spectroscopy spectroscopy has been used to establish unambiguously the presence of the diketo form of thymine in the gas phase and to obtain its structure (López et al, 2007).…”

“…Of particular interest were their interactions with amino acids (Fan et al, 2010;Samijlenko et al, 2001Samijlenko et al, , 2004Stepanyugin et al, 2002aStepanyugin et al, , 2002b and protons or alkali metal cations (Lippert et al, 1986;Lippert & Gupta, 2009;Samijlenko et al, 2010;Šponer et al, 2001), as the extra positive charge could stabilize the structure of rare tautomers through an intramolecular salt bridge. Moreover, the coordination of metal ions to nucleobases is known to lead frequently to the stabilization of rare tautomeric forms (Burda et al, 2000;Lippert et al, 1986;Lippert & Gupta, 2009;Samijlenko et al, 2010), with numerous examples reported for various nucleobases (Lippert & Gupta, 2009;Lippert et al, 1986;Schoellhorn et al, 1989;Renn et al, 1991;Zamora et al, 1997). In these metal-stabilized rare tautomers, the metal is located at a position that is usually occupied by a proton, forcing the proton to move to another position and thereby generating the rare tautomer.…”

X-ray structure and conformational study of tris(2-(dimethylamino)phenyl)methanol salt derivatives: Roles of anions and hydrogen bond

“…Further calculation shows that the interaction between E&E' and Na 2 SO 3 could significantly decrease the conformational energy of the models F&F'. Considering the low compatibility of Na 2 SO 3 and E&E', this result should indicate the existence of the saltesalt interaction between them [37,38]. That said, except the cationeanion interaction and the solvation, the saltesalt interaction should also play a role in stabilizing the [LH] þ cation salt in solution.…”