ct0600316_si_002.pdf (977.53 kB)
0/0

Cation-π Interactions in Serotonin:  Conformational, Electronic Distribution, and Energy Decomposition Analysis

Download (977.53 kB)
journal contribution
posted on 09.05.2006 by Jaturong Pratuangdejkul, Pascale Jaudon, Claire Ducrocq, Wichit Nosoongnoen, Georges-Alexandre Guerin, Marc Conti, Sylvain Loric, Jean-Marie Launay, Philippe Manivet
An adiabatic conformational analysis of serotonin (5-hydroxytryptamine, 5-HT) using quantum chemistry led to six stable conformers that can be either +gauche (Gp), -gauche (Gm), and anti (At) depending upon the value taken by ethylamine side chain and 5-hydroxyl group dihedral angles φ1, φ2, and φ4, respectively. Further vibrational frequency analysis of the GmGp, GmGm, and GmAt conformers with the 5-hydroxyl group in the anti position revealed an additional red-shifted N−H stretch mode band in GmGp and GmGm that is absent in GmAt. This band corresponds to the 5-HT side-chain N−H bond involved in an intramolecular nonbonded interaction with the 5-hydroxy indole ring. The influence of this nonbonded interaction on the electronic distribution was assessed by analysis of the spin−spin coupling constants of GmGp and GmGm that show a marked increase for C2−C3 and C8−C9 bonds in GmGm and GmGp, respectively, with a decrease of their double bond character and an increase of their length. The Atoms in Molecules (AIM), Natural Bond Orbital (NBO), and fluorescence and CD spectra (TDDFT method) analyses confirmed the existence in GmGp and GmGm of a through-space charge-transfer between the HOMO and the HOMO-1 π-orbital of the indole ring and the LUMO σ* N−H antibonding orbital of the ammonium group. The strength of the cation-π interaction was determined by calculating binding energies of the NH4+/5-hydroxyindole complexes extracted from stable conformers. The energy decomposition analysis indicated that cationic-π interactions in the GmGp and GmGm conformers are governed by the electrostatic term with significant contributions from polarization and charge transfer. The lower stability of the GmGm over the GmGp comes from a higher exchange repulsion and a weaker polarization contributions. Our results provide insight into the nature of intramolecular forces that influence the conformational properties of 5-HT.

History

Exports