Dehydration-Driven Nanomechanical Responses of the Antiviral Drug EIDD-1931

Abstract

The hydrate dimorphs of the antiviral drug EIDD-1931 (EIDD) exist as tautomers possessing different conformations, synthon preferences, thermal decomposition profiles, and mechanical properties. This coexistence of manifold contrasting structural features is unusual and makes the hydrate dimorphs of EIDD-1931 exceptional. As analogs of uridine and cytidine, the tautomers corresponding to the crystal forms (Form I and Form II) of EIDD help effectively block viral RNA replication. With regard to the analogous nucleosides, the computed MESP of EIDD exhibits extensive alterations and disproportionate distribution of maxima and minima sites, contributing to its hydration characteristics. The water of crystallization and its efflorescence have a direct impact on the thermal decomposition profiles as well as the nanomechanical response of the crystal forms because of their distinct roles in the stabilization of the structure─as a two-donor, two-acceptor interaction center occupying isolated sites in Form I as opposed to a one-donor, one-acceptor moiety confined to a void-filling role in Form II. From a broader perspective, the nanomechanical responses correlated to the interaction characteristics, and dehydration events are remarkable in deriving a molecular basis of the properties in pharmaceutics wherein a major share of the pharmaceuticals exists as hydrates.