Experimental Determination of Conformational Isomerization Energy Thresholds in Serotonin

Abstract

Stimulated emission pumping-population transfer (SEP-PT) and hole-filling (SEP-HF) spectroscopies were used to determine the energy thresholds to isomerization between thirteen reactant-product conformer pairs in the biomolecule serotonin (SERO). Serotonin is a close structural analog of tryptamine (TRA), differing in having a hydroxyl group in the 5 position of the indole ring. A previous spectroscopic study (LeGreve; et al. J. Am. Chem. Soc. 2007, 129 (13), 4028) identified eight conformational isomers of SERO, whose interconversion involves motion of the 3-ethylamine side chain, the 5-OH group, or both. In the cases in which only an ethylamine side chain reorientation occurred, the barriers were found to be similar to, but systematically somewhat smaller than, those in TRA, which has been studied by similar methods (Dian; et al. Science 2004, 303 (5661), 1169; Clarkson; et al. J. Chem. Phys. 2005, 122 (21), Art. No. 214311). In most cases, the experimental thresholds are well reproduced by calculated transition states separating the conformational wells; however, tunneling effects may artificially reduce the thresholds observed for isomerization of SERO(A,Gpy(out)) and SERO(B,Gpy(up)) into SERO(C,Gph(out)). The A --> A' isomerization involving only the OH rotation from anti to syn was found to be 721-761 cm-1, in accordance with the calculated classical barrier. For isomerizations in which the ethylamine side chain reorients as does the OH group, the barriers to isomerization were consistent with sequential rather than concerted motion of both groups. Finally, some evidence for mode-specific effects in the product quantum yields near threshold is presented.

Structural and vibrational investigations of a neurotransmitter molecule: Serotonin (5-hydroxy tryptamine)

“…LeGreve et al [26] have proposed eight conformational isomers of serotonin while the same authors [34] have suggested that serotonin exist in 13 conformations. Cabezas et al [35] have found only three conformers from microwave spectroscopy.…”

Isolated Neutral Peptides

“…Yet, experimental techniques exist to measure conformational distribution [47], and even conformational energetics [149]. Even though conformational distributions have indeed been measured for a few peptides [47,71,72,125,126], conformational energetics have been measured only for slightly simpler systems [149,180,181]. Conclusions about conformational energetics from the majority of experiments have thus been limited so far to identifying major and minor conformations of the distribution.…”

“…The control of the excess energy deposited in the system, especially in UV/UV pump-dump experiments, together with the detection of the isomerisation (or population transfer) threshold, ultimately led to a convincing measurement of the relative energies of the conformers observed, together with the height of the barriers between them. This has been carried out for small biomolecules [149,181], but not yet for molecules of the size of a peptide.…”

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 purpose of current study is to explore the effect of pyridyl nitrogen in the ring on the conformational landscape of 7-azaserotonin. Moreover, three recent reports, one on the synthesis and photophysical study of 7-azaserotonin in condensed phase [18] and the other two on the conformational study of jet-cooled serotonin [3,5] encouraged us to investigate this molecule in gas phase by quantum chemical methods. We hope this study will compliment theoreticians to design appropriate force field method for 7-azaserotonin-receptor interaction and spectroscopists to assign the experimental spectra.…”