Experimental and theoretical studies of the vibrational spectrum of 5-hydroxytryptamine Sevgi Bayarı a, * , Semran Saglam b , Hasan F. Ustundag b a Hacettepe University, Faculty of Education, Department of Physics, Beytepe, Ankara, Turkey b Gazi University, Faculty of Science, Department of Physics, Besevler, Ankara, Turkey Received 12 November 2004; accepted 21 February 2005 Abstract 5-Hydroxytryptamine (serotonin, 5-HT) is a hormone and a neurotransmitter found in the central nervous system. The conformational flexibility of the alkyl side chains in 5-HT plays an important role in its binding to receptor sites. The FTIR spectra of 5-hydroxytryptamine in solution and as a solid form were obtained in the range of 4000–400 cm K1 . Geometry optimization based on molecular mechanics (using MMC force field), semi-empirical quantum mechanical calculations (using AM1, PM3 and MINDO) and HF and B3LYP levels using the 3- 21G and 6-31(d) basic sets were performed. The calculated geometric parameters were compared to the corresponding X-ray structure of 5- hydroxytryptamine. For the optimized structures by semi-empirical, ab initio and DFT calculations, vibrational spectra were also generated. The assignments of the observed bands corresponding to 5-HT were made on the basis of such calculation and the comparison with related molecules. q 2005 Elsevier B.V. All rights reserved. Keywords: 5-Hydroxytryptamine; Infrared spectra; Molecular calculations 1. Introduction 5-Hydroxytryptamine is a neurotransmitter, carrying neural messages from nerve cell to nerve cell. Imbalances in serotonin can result in migraines, depression, and exhaustion. It plays a significant role in the regulation of mood, eating, and sleep as well as other functions [1–3]. In our body, serotonin is synthesized from the amino acid tryptophan by various enzymes. The conformational flexibility of the ethylamine side chains in 5-HT plays an important role in its binding to receptor sites and knowledge of this interaction is important in drug design. Also because of their pharmaco- logical significance in particular, serotonin have been studied extensively by X-ray crystallographic and theo- retical methods, investigating the relationships between their pharmacological activities and conformational isomers [4–10]. It should be noted that the complete infrared data on serotonin are not plentiful in the literature. Mouric and Emson [9] performed theoretical study of the conformation- al landscape of serotonin and assigned frequencies for conformers only in the region 3000–2800 cm K1 . In the present work, we employ FT-IR spectroscopy to build on previous results in making a complete vibrational assignments of the infrared spectrum of 5-HT in the region 4000–400 cm K1 . An assignment of the observed bands of single conformation (optimized structure) is proposed by simulating IR spectra. The observed fundamental wave- numbers and the calculated results of 5-HT are compared with those of 5-methoxytryptamine (5-MT) [11]. Optimized geometries predicted by the MMC, AM1, PM3, MINDO, HF and B3LYP methods are compared with the X-ray data reported in Refs. [7,8]. For the pharmacological activity of drugs, it is of importance to have information about the conformation of drugs in solution. Intramolecular and intermolecular interaction play important role in the structural stabilization Journal of Molecular Structure: THEOCHEM 726 (2005) 225–232 www.elsevier.com/locate/theochem 0166-1280/$ - see front matter q 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.theochem.2005.02.078 * Corresponding author. Tel.: C90 312 297 8606; fax: C90 312 299 2083. E-mail address: bayari@hacettepe.edu.tr (S. Bayarı).