DFT study on foscarnet as an antiviral drug: Conformer analysis, gas phase acidity, metal ion affinity and influence of metal complexation on gas phase acidity

• The gas phase acidity of foscarnet and its complexes with some cations were calculated.
• The ligand affinity of foscarnet towards Li+, Na+, K+, Mg2+, Ca2+ ions are investigated.
• The relationship between binding ΔG and charge transfer values illustrated using NBO theory.
• The nature of interactions during complexation process described using QTAIM theory.

This work presents a density functional theory study of Foscarnet (FOS), an anti-viral drug. In this study conformational analysis, gas phase acidity and metal ion affinity (MIA) of foscarnet with selected cations from alkalis (Li+, Na+, and K+) and alkaline earths (Ca2+ and Mg2+) were calculated. All of the structure optimizations and frequency calculations were performed at the B3LYP level of theory with 6-311++G(d,p) basis set. The calculations showed the MIA order to be K+ < Na+ < Li+ < Ca2+ < Mg2+, in agreement with increasing gas phase acidity of the foscarnet molecule during complexation. Natural bond orbital theory (NBO) and quantum theory of atoms in molecules (QTAIM) were used to investigate the charge transfer process and the nature of interactions in the formed complexes. The results of the NBO analysis revealed that Mn+ acts as charge acceptor and the amount of charge transfer is in agreement with MIA. The QTAIM analysis shows that (MO) coordinations are electrostatic in nature, and their strengths are in agreement with electron densities at their bond critical points (BCP).