Hydration of C-H groups in natural dithymidine nucleotide and its methylphosphonate analogues

In this paper we report our preliminary studies on the hydration pattern of selected C-H groups in natural thymidyl(3'-5)thymidine and its Rp and Sp-methylphosphonate analogues using Molecular Dynamic simulations in aqueous solutions. The methyl groups attached to the phosphorus center (P-Me) in methylphosphonate analogues are hydrated by water molecules as efficiently as the hydrophilic P=O group in the natural dithymidine nucleotide and better than the neutral P=O functions in these compounds, although the nature of the hydration is different. The C5-Me centers of the 3'-yl units seem to be better hydrated in the methylphosphonate analogues than in the natural dithymidine phosphate and than other centers of the thymine bases in methylphosphonate analogues. Due to chirality of the phosphorus center, the C5-Me group of the 5'-yl unit in the Sp diastereomer coordinates more water than that in the Rp diastereomer. The C6-H group in the 5'-yl unit of the Sp diastereomer exhibits a specific interaction with water.