Interaction of serotonin and histamine with water and ethanol: Evidence from theoretical investigations

This manuscript focuses on studying the interactions between two crucial neurotransmitters, serotonin and histamine, and common solvents such as water and ethanol. By examining the stable conformers of serotonin and histamine, we investigate their interactions with water and ethanol at various reactive sites, calculating the corresponding binding energies. To understand the qualitative solvent interaction, we employ RDG analysis and estimate the specific contributions to different types of interactions through energy decomposition analysis. We confirm the nature of solvent interaction using approaches based on natural bond orbitals and atoms in molecules. The optimization processes are carried out using PBE0-D3/def2-TZVP, while the energy decomposition analysis utilizes the DLPNO-CCSD(T) level. Additionally, we explore the solvation dynamics in detail through ab initio molecular dynamics (AIMD). Our findings indicate that the interaction energy between serotonin and water (pore2) surpasses that of histamine and water (pore1). Notably, hydrogen bonding plays a significant role in these interactions, as revealed by QTAIM analysis. Furthermore, our results indicate that ethanol exhibits approximately 16 times greater interaction with these molecules compared to water. AIMD investigations further demonstrate that the serotonin-ethanol system exhibits higher dynamic stability compared to the histamine system.