The main objective of this study is to encapsulate the serotonin hydrochloride (SER) molecule, as an important neurotransmitter, into the 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD) binding cavity. The results indicate the formation of the photo-stable 2-HP-β-CD:SER inclusion complex with the stoichiometry ratio of 1:1 (AL type) as an enthalpy-driven process. The complex was extensively characterized by using various spectroscopic techniques (FT-IR, 1H-NMR, XRD and ICD), scanning electron microscopy (FE-SEM), and thermal methods (TGA, DTG and DTA). Besides, molecular docking and molecular dynamics simulations were applied. In those simulations, explicit solvation models, emphasizing the role of the van der Waals forces and H-bonds in the complex formation were applied. Furthermore, the hydroxyl group of SER was found to be localized at the vicinity of the 2-HP-β-CD secondary rim. The study confirmed the possibility of utilizing this formulation as a CNS-active compound with improved solubility and stability to treat some behavioral dysfunctions and mental disorders.
