Hydration of peptides and proteins has a strong impact on their structure and function. Infrared photodissociation spectra (IRPD) of size-selected clusters of the formanilide cation, FA(+)-(H2O)n (n = 1-5), are analyzed by density functional theory calculations at the ωB97X-D/aug-cc-pVTZ level to determine the sequential microhydration of this prototypical aromatic amide cation. IRPD spectra are recorded in the hydride stretch and fingerprint ranges to probe the preferred interaction motifs and the cluster growth. IRPD spectra of cold Ar-tagged clusters, FA(+)-(H2O)n-Ar, reveal the important effects of temperature and entropy on the observed hydration motifs. At low temperature, the energetically most stable isomers are prominent, while at higher temperature less stable but more flexible isomers become increasingly populated because of entropy. In the most stable structures, the H2O ligands form a hydrogen-bonded solvent network attached to the acidic NH proton of the amide, which is stabilized by large cooperative effects arising from the excess positive charge. In larger clusters, hydration bridges the gap between the NH and CO groups (n ≥ 4) solvating the amide group rather than the more positively charged phenyl ring. Comparison with neutral FA-(H2O)n clusters reveals the strong impact of ionization on the acidity of the NH proton, the strength and topology of the interaction potential, and the structure of the hydration shell.

Infrared photodissociation (IRPD) spectra of cationic formanilide (N-phenylformamide) clusters, FA(+)-Ln, with L = Ar (n = 1-8) and N2 (n = 1-6), are recorded in the hydride stretch (amide A, νNH, νCH) and fingerprint (amide I-III) ranges to probe the preferred interaction motifs and the cluster growth. Cold FA(+)-Ln clusters are generated by electron ionization in a supersonic expansion, which generates predominantly the most stable cluster isomers. Size- and isomer-specific νNH frequencies unravel the microsolvation process of FA(+) in a nonpolar (L = Ar) and a quadrupolar (L = N2) solvent. The H-bound FA(+)-L dimer with L binding to the NH proton of the amide group is the most stable isomer, and further ligands are attached to the aromatic ring (π-stacking). Ionization changes the preferred binding motif from π-stacking to H-bonding in FA((+))-L. Quantum chemical calculations at the ωB97X-D/aug-cc-pVTZ level confirm the experimentally derived sequential cluster growth and the vibrational and isomer assignments. The calculated FA(+)-L binding energies of D0(H) = 594/1054 cm(-1) for H-bound and D0(π) = 459/604 cm(-1) for π-bound Ar/N2 ligands are consistent with the observed photofragmentation branching ratios. Ionization of FA results from removal of a bonding π-electron delocalized over the phenyl and amide moieties and thus weakens the N-H bond and strengthens the C-O bond.

Most biochemical processes occur in aqueous solution. Here, we characterize the initial microhydration steps of the 5-hydroxyindole cation (5HI) in its A'' ground electronic state by infrared photodissociation (IRPD) spectroscopy of 5HI-W-L clusters (W = HO, L = Ar and N, n ≤ 4, m ≤ 2) in a molecular beam and dispersion-corrected density functional theory calculations (B3LYP-D3/aug-cc-pVTZ). Characteristic size- and isomer-dependent XH stretch frequencies (X = O, N) of 5HI-W reveal information about the preferred cluster growth and solvation energies. The IRPD spectrum of 5HI-W is a superposition of the spectra of two isomers, in which W is H-bonded to the acidic NH or OH group, whereby OHW hydrogen-bonds (H-bonds) are stronger than NHW H-bonds. Spectra of larger 5HI-W clusters (n ≥ 2) elucidate the competition between interior ion solvation and the formation of H-bonded water networks. The nature and strengths of the competing H-bonds are quantified by the noncovalent interaction approach. Comparison to results for neutral 5HI-W and 5HI-L clusters with nonpolar ligands reveals the effects of ionization and ligand type on the intermolecular interaction potential and cluster growth. Comparison to corresponding microhydrated clusters of the phenol, indole, and pyrrole cations illustrates the effects of substitution of functional groups and addition of aromatic rings on the hydration process.

Recognition properties of biologically relevant molecules depend on their conformation. Herein, the conformation of protonated glutamic acid (HGlu) isolated in quadruple ion traps is characterized by vibrational spectroscopy at room and cryogenic temperatures and dispersion-corrected density functional theory calculations at the B3LYP-D3/aug-cc-pVTZ level. The infrared multiple photon dissociation (IRMPD) spectrum recorded in the fingerprint range at room temperature using an IR free electron laser is attributed to the two most stable and nearly isoenergetic conformations (1-cc and 2-cc) with roughly equal population (ΔG = 0.0 kJ mol). Both have bridging C[double bond, length as m-dash]O(HNH)O[double bond, length as m-dash]C ionic H-bonds of rather different strengths but cannot be distinguished by their similar IRMPD spectra. In contrast, the higher-resolution single-photon IRPD spectrum of H-tagged HGlu recorded in the conformation-sensitive X-H stretch range in a trap held at 10 K distinguishes both conformers. At low temperature, 1-cc is roughly twice more abundant than 2-cc, in line with its slightly lower calculated energy (ΔE = 0.5 kJ mol). This example illustrates the importance of cryogenic cooling, single-photon absorption conditions, and the consideration of the X-H stretch range for the identification of biomolecular conformations involving hydrogen bonds.

The structure and activity of peptides and proteins strongly rely on their charge state and the interaction with their hydration environment. Here, infrared photodissociation (IRPD) spectra of size-selected microhydrated clusters of cationic acetanilide (AA, N-phenylacetamide), AA-(HO) with n ≤ 3, are analysed by dispersion-corrected density functional theory calculations at the ωB97X-D/aug-cc-pVTZ level to determine the stepwise microhydration process of this aromatic peptide model. The IRPD spectra are recorded in the informative X-H stretch (ν, ν, ν, amide A, 2800-3800 cm) and fingerprint (amide I-II, 1000-1900 cm) ranges to probe the preferred hydration motifs and the cluster growth. In the most stable AA-(HO) structures, the HO ligands solvate the acidic NH proton of the amide by forming a hydrogen-bonded solvent network, which strongly benefits from cooperative effects arising from the excess positive charge. Comparison with neutral AA-HO reveals the strong impact of ionization on the acidity of the NH proton and the topology of the interaction potential. Comparison with related hydrated formanilide clusters demonstrates the influence of methylation of the amide group (H → CH) on the shape of the intermolecular potential and the structure of the hydration shell.

We characterize stereospecific aspects of homochiral and heterochiral dimers of glutamic acid by infrared spectroscopy and first-principles molecular dynamics simulations.

Solvation plays an essential role in controlling the mechanism and dynamics of chemical reactions in solution. The present study reveals that changes in the local solute-solvent interaction have a great impact on the timescale of solvent rearrangement dynamics. Time-resolved IR spectroscopy has been applied to a hydration rearrangement reaction in the monohydrated 5-hydroxyindole-water cluster induced by photoionization of the solute molecule. The water molecule changes the stable hydration site from the indolic NH site to the substituent OH site, both of which provide a strongly attractive potential for hydration. The rearrangement time constant amounts to 8 ± 2 ns, and is further slowed down by a factor of more than five at lower excess energy. These rearrangement times are slower by about three orders of magnitude than those reported for related systems where the water molecule is repelled from a repulsive part of the interaction potential toward an attractive well. The excess energy dependence of the time constant is well reproduced by RRKM theory. Differences in the reaction mechanism are discussed on the basis of energy relaxation dynamics.

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