Journal of Molecular Graphics and Modelling 80 (2018) 224–237 Contents lists available at ScienceDirect Journal of Molecular Graphics and Modelling j ourna l h om epa ge: www.elsevier.com/locate/JMGM Conformational and NBO studies of serotonin as a radical scavenger. Changes induced by the OH group Rosana M. Lobayan ∗ , María Celia Pérez Schmit Departamento de Física, Facultad de Ciencias Exactas y Naturales y Agrimensura, Universidad Nacional del Nordeste, Avda. Libertad 5300, 3400 Corrientes, Argentina a r t i c l e i n f o Article history: Received 3 December 2017 Received in revised form 9 January 2018 Accepted 10 January 2018 Keywords: Serotonin Atoms in molecules theory Density functional theory Ionization potentials Bond dissociation enthalpies Molecular electrostatic potential Natural bond orbital analysis Conformational search a b s t r a c t Serotonin (5-hydroxytryptamine, SER) is a neurotransmitter that affects many different processes within the human body. We studied the conformational space of SER, and explored in depth the significant stereoelectronic features for the structure stabilization and antioxidant activity. Forty-eight equilibrium structures were described at the B3LYP/6-311++G(d,p) level, characterizing four non-previously reported conformers. Electron distributions were analyzed by topological QTAIM (Quantum Theory of atoms in molecules) and natural bond orbital (NBO) studies. The study was supplemented by an exploration of molecular electrostatic potential (MEP). Intramolecular hydrogen interactions were also investigated; N10· · ·H C4 or N10· · ·H C2 hydrogen bondings were depicted in 5 conformers. The conformer stabilization and the corresponding energy arrangement were explained by hypercon- jugation interactions obtained by NBO analysis. The present study is based on the effect of the 5-OH group on geometric and electronic behavior that we have previously reported on the similar structure tryptamine (TRA). Our interest also lies in SER’s free radical scavenging capacity as a member of the indole family. The H-atom abstraction and single-electron transfer mechanisms were taken into account. Our results showed that donor-acceptor interactions play a major role in explaining the changes induced by the OH group, and free-radical scavenging capability of the indole compounds. © 2018 Elsevier Inc. All rights reserved. 1. Introduction Serotonin (5-hydroxytryptamine, SER) is a neurotransmitter that affects many different processes within the human body [1–5]. Its biological activity is achieved by interacting with more than fif- teen different receptors to carry out various functions [1,5]. The flexibility of the ethylamine side chain and 5-OH group was asso- ciated with the ability of SER to combine to numerous different receptor sites, thus changing its configuration to fit each recep- tor; a free radical scavenging activity of SER using electron spin resonance was also demonstrated [6]. Several theoretical conformational studies on SER and other tryptamine derivatives have been previously reported in the lit- erature. Early analysis employed only semiempirical methods. The first ab initio calculations accounted for a more expanded conformational search for SER and bufotenin (5-hydroxy-N,N- dimethyltryptamine) using the SCF method with the STO-3G basis set [7]. ∗ Corresponding author. E-mail address: rlobayan@unne.edu.ar (R.M. Lobayan). At the B3LYP/6-31+G(d) level of theory, twenty-three structures were theoretically characterized [8], linking the findings to previ- ous theoretical and experimental studies on tryptamine (TRA) and 3-indolepropionic acid. Two available configurations for OH group were reported (anti and syn on the indole N H group). Experimentally, eight neutral SER conformers were observed by comparison with the very close structural analog TRA. Ultraviolet and Infrared transitions were assigned, and OH-syn and OH-anti structures were also distinguished [9]. The knowledge of SER conformers continues to attract the attention of the international scientific community. Recently, the microwave spectrum of SER was observed for the first time [10], a new theoretical study of SER and its hydrated complexes was reported [11], and rotationally resolved electronic spectra together with ab initio structural study of SER were also shown [12]. The aim of this work was to carry out a detailed study based on the donor-acceptor interactions of the SER conformational land- scape. The structural behavior of conformers was described by characterizing and quantifying the geometric and electron changes induced by the 5-OH group of the indole moiety, taking as reference our previous report on electron distribution of TRA [13]. https://doi.org/10.1016/j.jmgm.2018.01.006 1093-3263/© 2018 Elsevier Inc. All rights reserved.