Theoretical study of hydrogenation of thiouracils and their base pairs with adenine

Abstract

ABSTRACT:The purpose of the present work is to employ theoretical chemical tools to explore the subtle features of the hydrogenation of uracil and its related thioderivatives. The reactions of hydrogenation are followed for the free uracil, 2-thiouracil, 4-thiouracil, and 2,4-dithiouracil as well as for adenine-thiouracil base pairs. It is shown for the first time that, in contrast to the hydrogenation pathways to the carbon atoms C 5 and C 6 of the studied molecules, characterized by the transition states, the hydrogenations at the sulphur atoms for thiouracils are barrierless and thus the latter are the kinetically most favorable pathways for hydrogenation. As also shown, these features are retained under the hydrogenation of the adenine-thiouracil base pairs. The present study clearly demonstrates that the base pairing destruction is the key radiation-induced lesion in the adenine-4-thiouracil and adenine-2,4-dithiouracil base pairs when the hydrogen radical H ⅐ , as one of the primary radiation products, resides at the sulphur atom S 4 .

Influence of Thioketo Substitution on the Properties of Uracil and Its Noncovalent Interactions with Alkali Metal Ions: Threshold Collision-Induced Dissociation and Theoretical Studies

“…The NH···S hydrogen bonds are 0.533 and 0.464 Å longer while the N···HN hydrogen bonds are 0.072 and 0.245 Å longer in the A::4SU and A::24SU base pairs, respectively, as compared to the corresponding hydrogen bonds in the unsubstituted A::U base pair. Similar trends, but less accurate energetics, for 2SU and 4SU were found in earlier theoretical studies. , …”

On protonation and methylation of benzene: A B3LYP DFT based study

“…Unlike diprotonation, dimethylation produces positive DH values (Table 3) and justifiably correspond to negative values of methyl cation affinities (Table 4). As, the applied functional is reported to be inadequate in producing an accurate picture of potential energy surface, [14][15][16] the results have been compared with single point MP2 calculations on UB3LYP optimized geometries. Plotting of MP2 energies of the reactant, transition state and products reproduce the energy ordering of DFT functional, but with an overall scaled down representation.…”

“…The self interaction error (SIE) influences the shape of the potential energy surface near the transition state by lowering the barrier height [15]. Being aware of this fact, our B3LYP results are further refined by carrying out single point calculations at MP2 level on the transition states [16].…”

Parametrization of 2-thiouracil and 4-thiouracil in CHARMM all-atom empirical force field

“…Chemically modified bases, including 2SU and 4SU were frequently studied for their numerous pharmacological, biochemical and biological capabilities. The 2SU and 4SU were also studied by theoretical chemists [18][19][20][21].…”