Solvent Effects on the Conformational Preferences of Serotonin: Serotonin−(H₂O)_n, n = 1,2

Abstract

Neutral serotonin-(H(2)O)(n) clusters with n = 1,2 have been studied under jet-cooled conditions using a combination of resonant two-photon ionization (R2PI), UV-UV hole-burning (UVHB), and resonant ion-dip infrared (RIDIR) spectroscopy. Serotonin (5-hydroxytryptamine, SERO) is a close analogue of tryptamine, differing by the addition of an OH substituent in the 5-position on the indole ring, but sharing the same ethylamine side chain in the 3-position. Three conformational isomers of SERO-(H(2)O)(1) were observed via UVHB, with S(0)-S(1) origins at 32 671 (A), 32 454 (B), and 32 188 cm(-1) (C). RIDIR spectroscopy provided infrared spectra in the hydride stretch region that reflected the hydrogen-bonding arrangement of each conformer. Two of the three SERO-(H(2)O)(1) conformers have RIDIR spectra nearly identical to that of the only observed conformer of tryptamine-(H(2)O)(1), differing only in the orientation of the 5-OH group (syn vs anti). In this structure, the H(2)O molecule acts as H-bond donor to the NH(2) group on the ethylamine side chain, which is configured in the Gpy(out) conformation that is the global minimum in the absence of water. Comparison of the OH stretch RIDIR spectrum of the third SERO-(H(2)O)(1) conformer with calculation leads to its assignment to a structure in which the water molecule forms a H-bonded bridge between the amino group and the 5-OH group of SERO, with the ethylamine side chain in the Gph(out) conformation that facilitates bridge formation, corresponding to the second most populated conformer in the isolated SERO monomer. The OH and CH stretch infrared absorptions for the single observed conformer of SERO-(H(2)O)(2) indicate that it is also a bridge structure linking the NH(2) and OH groups of SERO, retaining the same Gph(out) ethylamine conformation as in conformer C of SERO-(H(2)O)(1). The ultraviolet and infrared spectroscopy reflect the fact that the single-water bridge cannot optimally span the gap between the 5-OH and NH(2) groups, while the water dimer bridge forms a set of three strong H-bonds that lock in the Gph(out) ethylamine and anti 5-OH orientations in a near-optimal configuration.

Competing Insertion and External Binding Motifs in Hydrated Neurotransmitters: Infrared Spectra of Protonated Phenylethylamine Monohydrate

“…[18,19] In addition, it can play an important role in stabilizing specific conformations of af lexible solute molecule, as observedf or some neutral aromatic amines such as tryptamine and PEA. [20][21][22][23][24][25][26] Rotational spectroscopy,i onization-loss stimulated Raman,l aser-induced fluorescence, and multiphoton ionization experimentso ft he PEA monohydrate (PEA-H 2 O) have revealed the hydration-induced locking of the PEA conformation, [15,23,24,27,28] which is also observed for the related tryptamine-H 2 Oc omplex by UV spectroscopy at the level of rotational resolution. [21] The four PEA conformers that were detectedi nasupersonic beam and which differ by the orientation of the ethylamino side chain collapse into one single structure in which the H 2 Om olecule, the Ha tom of which is directedt oward the lone pair of the N atom of PEA, locks the side chain conformation into afavorable NH···p configuration.…”

It Is Important to Compute Intramolecular Hydrogen Bonding in Drug Design?

“…Useful information can be obtained from experimental gas-phase hydration/solvation studies augmented with theoretical calculations [108][109][110][111][112][113][114][115][116] or specific theoretical calculations for hydrated amino acid side chains, nucleotid base and sugar models [117][118][119][120][121].…”

Spectroscopic signatures and structural motifs in isolated and hydrated serotonin: a computational study

“…22 We have also performed the similar calculations for the Gpy(out)/anti conformation of serotonin forming complex with a water molecule for the bonding sites: indole NH donor, OH donor/acceptor, and amino group acceptor (see Fig. Our goal is to probe the preferred binding sites for the water molecules and to characterize the spectroscopic signatures and structural landscapes of the most stable hydrated complex of serotonin.…”