Encapsulation of serotonin in β-cyclodextrin nano-cavities: Fluorescence spectroscopic and molecular modeling studies

Serotonin is a physiologically important biogenic amine, deficiency of which leads to mental disorders such as Alzheimer's disease, schizophrenia, infantile autism, and depression. Both beta-cyclodextrin (beta-CD) and its chemically substituted synthetic varieties (often possessing enhanced aqueous solubility and improved drug complexing abilities) are finding wide applications as drug delivery vehicles. Here we have studied the encapsulation of serotonin in beta-CD and succinyl-2-hydroxypropyl p-cyclodextrin (SHP-beta-CD) by exploiting the intrinsic serotonin fluorescence. Enhanced fluorescence emission intensity (which increases by similar to 18% and 34% in beta-CD and SHP beta-CD respectively) and anisotropy (r) (r = 0.075 and 0.1 in beta-CD and SHP beta-CD respectively) are observed in presence of the cyclodextrins. From the fluorescence data host-guest interaction with 1:1 stoichiometry is evident, the association constants (K) being 126.06 M-1 and 461.62 M-1 for beta-CD and SHP beta-CD respectively. Additionally, molecular docking and semiempirical calculations have been carried out which provide, for the first time, detailed insights regarding the encapsulation process. In particular, it is evident that the indole ring is inserted within the beta-CD cavity with the aliphatic amine side chain protruding towards the primary rim of the beta-CD cavity. Docking calculations reveal that hydrogen bonding interactions are involved in the formation of the inclusion complex. Semiempirical calculations indicate that formation of the 1:1 inclusion complex is energetically favorable which is consistent with the fluorescence data. (C) 2010 Elsevier B.V. All rights reserved.