The conformational space of the neurotransmitter serotonin: how the rotation of a hydroxyl group changes all

Abstract

The 5-hydroxytryptamine receptors (5HTn) are optimized for 5-hydrotryptamine molecules, resulting in a significantly enhanced psychoactive response compared with the 4-, 6-, 7-isomers. This is despite their relatively similar energetic stabilities, excited state lifetimes and emission characteristics. In this work we investigate the conformational space of serotonin (5-hydroxytryptamine) using a combination of rotationally resolved electronic spectroscopy and ab initio calculations. The geometries of the four most abundant conformers are assigned from their molecular parameters in the electronic ground and excited state. We find a conformer-dependent competition between two polar groups trying to establish a hydrogen bond with the same H-atom in the most stable conformer of serotonin. The result explains some remarkable deviations with respect to the conformational space of the closely related neurotransmitter tryptamine. Based on the comparison to other 5-substituted indoles we propose to generalize this finding to explain the conformational preferences of indole-based neurotransmitters.

<i>Ab-initio</i> study of pyrrole ring deformation in the indole group of 5-HT interacting with water molecules

“…Some experimental and theoretical attempts have been made to clarify 5-HT conformations [12,20–25]. Of these studies, LeGreve’s work [23] has reached the results close to ours.…”

“…The validity of this selection was confirmed on the basis of previous work by Wilke et al [12], in which our selected conformation was called anti -serotonin, and the other conformation was called syn -serotonin. They concluded that the anti -conformers are always more stable in the ground state [12]. In the present study, we prepared 12 molecular structures as the initial condition in gas phase.…”

“…Conformation (A) is called anti -serotonin, and conformation (B) is called syn -serotonin. Conformation (A) has lower total energy than conformation (B) [12].…”

Improved Design of the Lurgi Reactor for Methanol Synthesis Industry

“…), which could preserve the catalyst from deactivation. The results confirmed that the catalyst was highly influenced by the temperature inside the reactor . Besides, the best design parameters of the tubular methanol synthesis reactor were obtained from a sensitivity analysis of operating parameters conducted above in this study.…”

Excited‐State Dipole Moments and Transition Dipole Orientations of Rotamers of 1,2‐, 1,3‐, and 1,4‐Dimethoxybenzene

“…However, inductive (+I or −I) effects and even through‐space effects also influence the electron distribution between the ligand and the chromophore. For the hydroxy and methoxy substituents, it has been found that the adjacent C‐atom to which the lone pairs of the O‐atom points, has the lower electron density . Thus, it is interesting to investigate the dipole moments of different rotamers of disubstituted benzenes, which either can talk to each other electronically ( ortho and para ), or communicate only via inductive effects ( meta ).…”