First-principles DFT study of cyclic and acyclic nucleoside phosphonates

In this paper, we have studied the properties and successfully explained the effectiveness of nucleoside phosphonates as antiviral agents. Working within the framework of first-principles density functional theory (DFT) using the B3LYP functional and the 6-311+G(d,p) basis set, the structural, energetics, and electronic properties of cyclic and acyclic nucleoside phosphonates were determined. Conceptual DFT was used to determine chemical parameters. By comparing the reactivities with those of the competing natural nucleotide during diphosphorylation, we show that, as is, commonly believed, the drugs act by terminating the viral DNA chain. A good correlation has been obtained between the experimental biological activity and the computed DFT-based global chemical reactivity descriptors.