An ab initio molecular orbital analysis of phosphorothioate mono-anion.

Ab initio calculations at the STO-3G level show that the energy of the highest occupied molecular orbital (HOMO) of the di-protonated phosphorothioate mono-anion is 0.0421 a.u. higher than that of the HOMO of the corresponding phosphate mono-anion. The electron density in the phosphorothioate HOMO is highly focused on the sulfur atom. The results of this ab initio molecular orbital analysis are consistent with the model of the phosphorothioate sulfur as a soft nucleophile. The ab initio molecular orbital analysis presented in this paper will be useful for predicting and rationalizing the probability of reaction of phosphorothioate anions with electrophiles and helps to provide a basis for the rational design of phosphorothioate-based oligonucleotide drugs.