The ultraviolet and infrared spectroscopy of single conformations of neutral serotonin (5-hydroxytryptamine) have been studied in the gas phase using a combination of methods including laser-induced fluorescence, resonance-enhanced two-photon ionization, UV-UV hole-burning spectroscopy, and resonant ion-dip infrared spectroscopy. By comparison to its close analogue tryptamine, for which firm assignments to seven low-energy conformations have been made, UV and IR transitions due to eight conformations of serotonin are observed and assigned. The ultraviolet spectrum divides into two subsets of transitions separated from one another by approximately 230 cm-1 ascribable to syn and anti conformations of the 5-OH group. These two subsets are also distinguishable via their 5-OH stretch fundamentals, with the anti-OH subset shifted by approximately 4-5 cm-1 to lower frequency than those due to syn-OH conformers. The existing firm assignments for tryptamine play a decisive role in assignments in serotonin, where the alkyl CH stretch infrared spectrum is diagnostic of the conformation of the ethylamine side chain. Conformer A of serotonin (SERO(A)), with S1 <-- S0 origin transition at 32584 cm-1, is assigned to Gpy(out)/anti-OH, SERO(B) at 32548 cm-1 to Gpy(up)/anti, SERO(C) at 32545 cm-1 to Gph(out)/anti, SERO(D) at 32560 cm-1 to Anti(py)/anti, SERO(E) at 32537 cm-1 to Anti(up)/anti, SERO(F) at 32353 cm-1 to Gpy(out)/syn, SERO(G) at 32313 cm-1 to Gpy(up)/syn, and SERO(H) at 32282 cm-1 to Gph(out)/syn. The conformational preferences of serotonin differ from those of tryptamine most notably in the selective stabilization observed for the Gph(out)/anti-OH conformer SERO(C), which makes it the second-most intense transition in the ultraviolet spectrum, surpassed only by the Gpy(out)/anti-OH conformer SERO(A).

The two-step laser excitation scheme of stimulated emission pumping (SEP) induces shifts of a single water molecule between two remote hydrogen bonding sites on trans-formanilide. This reaction can be initiated by selective excitation of either isomer (CO-bound or NH-bound) with different SEP excitation wavelengths. Energy (E) thresholds for isomerization in both directions have been measured [796 wave numbers NH) CO)

Resonant two-photon ionization (R2PI), UV hole-burning (UVHB), and resonant ion-dip infrared (RIDIR) spectroscopies have been used to record single-conformation infrared and ultraviolet spectra of three model synthetic foldamers with heterogeneous backbones, alpha/beta-peptides Ac-beta(3)-hAla-L-Phe-NHMe (betaalphaL), Ac-beta(3)-hAla-D-Phe-NHMe (betaalphaD), and Ac-L-Phe-beta(3)-hAla-NHMe (alphabetaL), isolated and cooled in a supersonic expansion. BetaalphaL and betaalphaD are diastereomers, differing only in the configuration of the alpha-amino acid residue; betaalphaL and alphabetaL contain the same residues, but differ in residue order. In all three alpha/beta-peptides the beta(3)-residue has S absolute configuration. UVHB spectroscopy is used to determine that there are six conformers of each molecule and to locate and characterize their S(0)-S(1) transitions in the origin region. RIDIR spectra in the amide NH stretch region reflect the number and strength of intramolecular H-bonds present. Comparison of the RIDIR spectra with scaled, harmonic vibrational frequencies and infrared intensities leads to definite assignments for the conformational families involved. C8/C7(eq) double-ring structures are responsible for three conformers of betaalphaL and four of betaalphaD, including those with the most intense transitions in the R2PI spectra. This preference for C8/C7(eq) double rings appears to be dictated by the C7(eq) ring of the alpha-peptide subunit. Three of the conformers of betaalphaL and betaalphaD form diastereomeric pairs (A/A', C/C', and G/G') that have nearly identical S(0)-S(1) origin positions in the UV and belong to the same conformational family, indicating no significant change associated with the change in chirality of the alpha-peptide subunit. However, betaalphaL favors formation of a C6/C5 conformer over C11, while the reverse preference holds in betaalphaD. Calculations indicate that the selective stabilization of the lowest-energy C11(g(+)) structure in betaalphaD occurs because this structure minimizes steric effects between the beta(2) methylene group and C=O(1). In the alpha/beta-peptide alphabetaL, two conformers dominate the spectrum, one assigned to a C5/C8 bifurcated double-ring, and the other to a C5/C6 double-ring structure. This preference for C5 rings in the alpha/beta-peptide occurs because the C5 ring is further stabilized by an amide NH...pi interaction involving an NH group on the adjacent amide, as it is in the alpha-peptides. Comparison of the NH stretch spectra of C8/C7(eq) structures in betaalphaL with their C7(eq)/C8 counterparts in alphabetaL shows that the central amide NH stretch is shifted to lower frequency by some 50-70 cm(-1) due to cooperative effects associated with the central amide accepting and donating a H-bond to neighboring amide groups. This swaps the ordering of the C8 and C7 NH stretch fundamentals in the two molecules.