Conformational Analysis, Molecular Structure and Solid State Simulation of the Antiviral Drug Acyclovir (Zovirax) Using Density Functional Theory Methods

Abstract

The five tautomers of the drug acyclovir (ACV) were determined and optimised at the MP2 and B3LYP quantum chemical levels of theory. The stability of the tautomers was correlated with different parameters. On the most stable tautomer N1 was carried out a comprehensive conformational analysis, and the whole conformational parameters (R, β, Φ, φ1, φ2, φ3, φ4, φ5) were studied as well as the NBO Natural atomic charges. The calculations were carried out with full relaxation of all geometrical parameters. The search located at least 78 stable structures within 8.5 kcal/mol electronic energy range of the global minimum, and classified in two groups according to the positive or negative value of the torsional angle φ1. In the nitrogen atoms and in the O2' and O5' oxygen atoms of the most stable conformer appear a higher reactivity than in the natural nucleoside deoxyguanosine. The solid state was simulated through a dimer and tetramer forms and the structural parameters were compared with the X-ray crystal data available. Several general conclusions were emphasized.

A structural analysis of 2,5‐diaryl‐4H‐2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐ones: NMR in the solid state, X‐ray crystallography, and GIPAW calculations

“…Conformational data are usually obtained in solution by nuclear magnetic resonance (NMR) [ 12,13 ] and quantum chemical calculations [ 14,15 ] and in the solid‐state by NMR, [ 16,17 ] crystallography, [ 18,19 ] and again by quantum calculations. [ 20,21 ]…”

“…Conformational data are usually obtained in solution by nuclear magnetic resonance (NMR) [12,13] and quantum chemical calculations [14,15] and in the solidstate by NMR, [16,17] crystallography, [18,19] and again by quantum calculations. [20,21] In our previous paper, [1] the NMR data of these compounds were determined in solution and reported in the experimental section without comments. We elected to pursue a more detailed discussion of compounds previously reported [1] with the following differences:…”

The evolution of nucleoside analogue antivirals: A review for chemists and non-chemists. Part 1: Early structural modifications to the nucleoside scaffold

“…In addition, the triphosphorylated Acyclovir is recognized and incorporated 100 fold more efficiently by the viral DNA polymerase as compared to the cellular polymerase (King, 1988; Reardon and Spector, 1989). It has also been shown that Acyclovir’s inherent flexibility allows for optimized interactions in target enzyme binding sites (Alvarez-Ros and Palafox, 2014; Tuttle and Krenitsky, 1984; Wesołowski et al, 1987).…”

Rational Nanotoolbox with Theranostic Potential for Medicated Pro‐Regenerative Corneal Implants

“…The Hyperquad Simulation and Speciation (HySS) was used to analyse zwitterion features of ACV to obtain the optimal conditions with the required flexibility for conjugation (Fig. 1b) 19,20 . Synthesized GNPs surface was capped with polybasic citrate (Fig.…”