In silico study of therapeutic deep eutectic solvent for tetracaine liquid delivery.

[Display omitted] • Theoretical analyses confirm stable hydrogen bonding in dimer and tetramers with DFT and NCI. • CIT-TET bonds resist water showing comparable hydrogen bonding, with low water content. • MD aligns with experiments, revealing temperature-dependent behavior in pure THEDES. • Neat THEDES maintains stable CIT-TET interactions, confirmed by structural analyses. • Neat THEDES properties maintained upon water addition, underscoring structural and dynamic stability. The development of a drug delivery liquid formulation of ester – based tetracaine local anaesthetic is synthesised in silico via the formation of a therapeutic deep eutectic solvent in combination with citral, a natural monoterpenoid. The properties of the obtained liquid system, studied at the nanoscopic level, are derived from a combination of quantum chemistry and classical molecular dynamics simulations. The intermolecular forces (hydrogen bonding) were analysed and their relationship with liquid phase properties were established. Water effect on the liquid phase properties were also considered in terms of competing for hydrogen bonding sites in the components of the developed fluid. The systems proposed in this work were studied using CIT (HBA) 1:1 TET (HBD) molar ratio at temperatures ranging from 288 K to 318 K and 1 bar. The hydrogen bond network developed between the oxygen atom in citral molecules and the –NH group in tetracaine molecules under those conditions, confirmed via minimal cluster analysis, is maintained during the addition of water up to 1.3 wt% as the water molecules do not disrupt the intermolecular hydrogen bond but develop new interactions (hydrogen bonds) with citral and tetracaine monomers presented in the fluid. The reported results probed the suitability of the considered system as an alternative drug delivery method as well as the possibility of developing deep eutectic-based formulation of anaesthetics using natural compounds due to the formation of effective and strong intermolecular hydrogen bonds. [ABSTRACT FROM AUTHOR]