Conformational Stability of Dimethyl Phosphate Anion in Water: Liquid-State Free Energy Simulations

The relative free energies of hydration of dimethyl phosphate anion in gauche—gauche, gauche—trans, and trans-trans conformations of phosphodiester torsion angles, computed with Monte Carlo method in the (T, V, N) ensemble at 25 °C, are reported. The free energy differences are determined by the probability ratio method using both umbrella sampling with harmonic weighting functions and adaptive umbrella sampling technique. The results indicate a stability trend of gg > gt > tt for the phosphodiester torsions in aqueous solutions. The magnitude of the conformational differences indicates the extended gt and tt conformations to be thermally accessible to some extent at ambient temperatures. Conclusions of the present study are in agreement with the IR and Raman inferences and ³¹P NMR investigations. Methodologically, the performance of the free energy simulations through probability ratio method along with the adaptive umbrella sampling technique is tested on a three-legged thermocycle and found to converge in a satisfactory manner.