A theoretical study of the conformational landscape of serotoninElectronic supplementary information (ESI) available: computed harmonic hydride stretch frequencies and intensities of the serotonin (OH-anti) and (OH-syn) conformers. See http://www.rsc.org/suppdata/cp/b2/b207565b/

Abstract

The conformational landscape of neutral serotonin has been investigated by several theoretical methods. The potential energy surface was scanned by systematically varying the three dihedral angles that determine the conformation of the alkyl side chain. In addition, the two possible conformations of the phenol hydroxyl group (anti and syn with respect to the indole NH) were considered. The OH-anti stationary points located with SCF/ 6-31G* have been re-optimised with B3LYP/6-31+G*, which resulted in twelve true minima. Eleven of these have a corresponding OH-syn conformer that is 1-4 kJ mol À1 higher in energy. IR vibrational spectra of all twenty-three serotonin conformers, computed at the B3LYP/6-31+G* level of theory, are presented. The initial scan of the serotonin potential energy surface has been repeated with several computationally cheaper methods, to assess their reliability for locating the correct serotonin conformers. It is found that the semi-empirical methods AM1 and PM3 do not yield sufficiently accurate results, due to their inability to account for subtle intramolecular interactions within the serotonin molecule. On the other hand, SCF in combination with the 3-21G* basis set is ascertained to be a good alternative to SCF/6-31G* for performing the initial scan of the potential energy surface of flexible molecules.y Electronic supplementary information (ESI) available: computed harmonic hydride stretch frequencies and intensities of the serotonin (OH-anti) and (OH-syn) conformers. See

IR, Raman, SERS and DFT study of pindolol and verapamil

“…However, excepting the cases where intra-molecular interactions play a significant role, such conformers are usually very close in energy (within 10 kcal/mol) and also, the corresponding calculated vibrational spectra do not differ substantially, particularly in band positions [23].…”

Effect of pyridyl nitrogen on the conformational landscape of 7-azaserotonin: A computational study

“…There have been a lot of experimental and theoretical studies on multiconformer biomolecular systems in gas phase [1][2][3][4][5]. Among all the neurotransmitters serotonin has been studied extensively whose flexible ethylamine chain has attracted the most for the quantum chemical investigations.…”

“…The stability of different conformers of serotonin is determined by the interaction of ethylamine chain with aromatic p-electron density [4,5]. The interest in the conformational studies on these large flexible biomolecules has been enhanced by the growing accuracy of quantum mechanical calculations.…”

“…The interest in the conformational studies on these large flexible biomolecules has been enhanced by the growing accuracy of quantum mechanical calculations. A great number of theoretical papers treating the conformational landscapes of serotonin and tryptamine have been published [4,5,[7][8][9][10][11] both of which have an ethylamine side chain attached to an indole moiety.…”

“…1) and in the same way as described by Mourik and Emson for serotonin [4]. The initial search was performed at lower moderate level of theory (AM1, PM3, SCF/3-21G Ã and SCF/6-31G Ã ).…”