Microhydration of Phenyl Formate: Gas-Phase Laser Spectroscopy, Microwave Spectroscopy, and Quantum Chemistry Calculations.

Herein, we have investigated the structure of phenyl formate⋅⋅⋅water (PhOF⋅⋅⋅H2 O) dimer and various non-covalent interactions present there using gas-phase laser spectroscopy and microwave spectroscopy combined with quantum chemistry calculations. Two conformers of PhOF⋅⋅⋅H2 O (C1 and T1), built on the two cis/trans conformers of the bare molecule, have been observed in the experiment. In cis-PhOF, there is an nCO → π A r * ${{{\rm \pi }}_{{\rm A}{\rm r}}^{{\rm {^\ast}}}}$ interaction between the lone-pair orbital of the carbonyl oxygen atom and the π* orbital of the phenyl ring, which persists in the monohydrated C1 conformer of PhOF⋅⋅⋅H2 O according to the NBO and NCI analyses. On the other hand, this interaction is absent in the trans-PhOF conformer as the C=O group is away from the phenyl ring. The C1 conformer is primarily stabilized by an interplay between O-H⋅⋅⋅O=C hydrogen bond and O-H⋅⋅⋅π interactions, while the stability of the T1 conformer is primarily governed by the O-H⋅⋅⋅O=C hydrogen bond. The most important finding of the present work is that the conformational preference of the PhOF monomer is retained in its monohydrated complex.

Observation of an Unusually Large IR Red-Shift in an Unconventional S-H···S Hydrogen-Bond.

The S-H···S non-covalent interaction is generally known as an extremely unconventional weak hydrogen-bond in the literature. The present gas-phase spectroscopic investigation shows that the S-H···S hydrogen-bond can be as strong as any conventional hydrogen-bond in terms of the IR red-shift in the stretching frequency of the hydrogen-bond donor group. Herein, the strength of the S-H···S hydrogen-bond has been determined by measuring the red-shift (∼150 cm-1) of the S-H stretching frequency in a model complex of 2-chlorothiophenol and dimethyl sulfide using isolated gas-phase IR spectroscopy coupled with quantum chemistry calculations. The observation of an unusually large IR red-shift in the S-H···S hydrogen-bond is explained in terms of the presence of a significant amount of charge-transfer interactions in addition to the usual electrostatic interactions. The existence of ∼750 S-H···S interactions between the cysteine and methionine residues in 642 protein structures determined from an extensive Protein Data Bank analysis also indicates that this interaction is important for the structures of proteins.

Observation of a weak intra-residue C5 hydrogen-bond in a dipeptide containing Gly-Pro sequence.

Specific folded structures of peptides and proteins depend on the sequence of various amino acid residues as well as different types of noncovalent interactions induced by the backbone as well as side-chains of those residues. In general, secondary structures of peptides and proteins are stabilized by C6 (δ-turn), C7 (γ-turn), C10 (ß-turn), C13 (α-turn), and C15 (π-turn) hydrogen-bonded rings formed through inter-residue interactions. However, it has been reported recently that an intraresidue C5 hydrogen-bond, which is relatively weak in strength, can contribute significantly to the stability of peptides and proteins. The C5 hydrogen-bond is mostly present in the ß-sheet structures of peptides and proteins along with other inter-residue noncovalent interactions. In this work, we have studied structures and conformational preferences of a dipeptide Z-Gly-Pro-OH (Z = benzyloxycarbonyl) using mass-selected vibrationally resolved electronic spectroscopy and IR-UV double resonance spectroscopy coupled with quantum chemistry calculations. Two conformers of the peptide are observed in the experiment. One of the conformers has an extended ß-strand type structure stabilized by C5 hydrogen-bonding, while the other one is folded through O-H ⋯ π interaction. The noncovalent interactions present in the two observed structures of the peptide are validated by natural bond orbital and noncovalent interaction calculations.

Steric as well as n→π* Interaction Controls the Conformational Preferences of Phenyl Acetate: Gas-phase Spectroscopy and Quantum Chemical Calculations.

Herein, we report that the conformational preference of phenyl acetate is governed by steric effect and n→π* interaction. Conformation-specific electronic and IR spectroscopy combined with quantum chemistry calculations confirm the presence of only the cis conformer of phenyl acetate in the experiment. The cis conformer of phenyl acetate has n→π* interaction between the lone-pair electrons on the carbonyl oxygen atom and the π* orbitals of the phenyl group. The n→π* interaction is absent in the trans conformer which has additional steric repulsion between the methyl group and phenyl ring. The trans conformer is higher in energy than the cis conformer by ≈3 kcal mol-1 . We have found the effect of methyl substitution on the strength of the n→π* interaction, steric repulsion, and hyperconjugation in phenyl acetate. The red-shift observed in the cis conformer of phenyl acetate with respect to the trans conformer is affected due to the influence of the methyl substituent on the strength of the n→π* interaction as well as hyperconjugation. The present result demonstrates that the introduction of a bulkier substituent can induce steric as well as electronic control to reduce conformational heterogeneity of a molecular system. Understanding the effect of bulkier substituents to promote defined conformations having specific non-covalent interactions may have implication in better perception of the optimum structure and function of biomolecules as well as recognition of drugs by biomolecules.

Water-Mediated Selenium Hydrogen-Bonding in Proteins: PDB Analysis and Gas-Phase Spectroscopy of Model Complexes.

High-resolution X-ray crystallography and two-dimensional NMR studies demonstrate that water-mediated conventional hydrogen-bonding interactions (N-H···N, O-H···N, etc.) bridging two or more amino acid residues contribute to the stability of proteins and protein-ligand complexes. In this work, we have investigated single water-mediated selenium hydrogen-bonding interactions (unconventional hydrogen-bonding) between amino acid residues in proteins through extensive protein data bank (PDB) analysis coupled with gas-phase spectroscopy and quantum chemical calculation of a model complex consisting of indole, dimethyl selenide, and water. Here, indole and dimethyl selenide represent the amino acid residues tryptophan and selenomethionine, respectively. The current investigation demonstrates that the most stable structure of the model complex observed in the IR spectroscopy mimics single water-mediated selenium hydrogen-bonded structural motifs present in the crystal structures of proteins. The present work establishes that water-mediated Se hydrogen-bonding interactions are ubiquitous in proteins and the number of these interactions observed in the PDB is more than that of direct Se hydrogen-bonds present there.

A conformation-specific IR spectroscopic signature for weak C[double bond, length as m-dash]OC[double bond, length as m-dash]O n→π* interaction in capped 4R-hydroxyproline.

Collagen, the most abundant protein in animals, has a unique triple helical structure comprising three parallel left-handed polyproline II (PPII) strands while each of the strands consists of a repeating sequence of X-Y-Gly, where X = proline (Pro) and Y = 4-hydroxyproline (Hyp). Collagen forms a stable triple helix of very long polypeptide strands despite the absence of intra-strand hydrogen bonding in the individual polypeptide chains. It has been reported that non-covalent n→π* interaction plays a significant role in stabilizing the individual polypeptide strands in collagen. However, there is no direct spectroscopic evidence for the presence of this interaction in collagen or its building block. Herein, we have observed for the first time a conformation-specific IR spectroscopic signature for C[double bond, length as m-dash]OC[double bond, length as m-dash]O n→π*-amide interaction in a capped Hyp residue, the most important monomer building block of collagen, using isolated gas phase IR spectroscopy and quantum chemistry calculations. The proof of the existence of this interaction in a model monomer has implications for better understanding of its role not only in structures of collagen but also most of the other proteins and larger peptides.

Tripodal cyanurates as selective transmembrane Cl- transporters.

Tris-carboxyamide and tris-sulfonamide-based anion transporters with a cyanuric acid core are reported. Interestingly, Cl- ion binding and transmembrane transport properties of carboxyamides are better compared to those of their tris-sulfonamide analogs. The carboxyamide derivatives act as mobile carriers of Cl- and exchange anions via antiport mechanism.

The nature of selenium hydrogen bonding: gas phase spectroscopy and quantum chemistry calculations.

Subsequent to the recent re-definition of hydrogen bonding by the IUPAC committee, there has been a growing search for finding the presence of this ever interesting non-covalent interaction between a hydrogen atom in an X-H group and any other atom in the periodic table. In recent gas phase experiments, it has been observed that hydrogen bonding interactions involving S and Se are of similar strength to those with an O atom. However, there is no clear explanation for the unusual strength of this interaction in the case of hydrogen bond acceptors which are not conventional electronegative atoms. In this work, we have explored the nature of Se hydrogen bonding by studying indoledimethyl selenide (indmse) and phenoldimethyl selenide (phdmse) complexes using gas phase IR spectroscopy and quantum chemistry calculations. We have found through various energy decomposition analysis (EDA) methods and natural bond orbital (NBO) calculations that, along with electrostatics and polarization, charge transfer interactions are important to understand Se/S hydrogen bonding and there is a delicate balance between the various interactions that plays the crucial role rather than a single component of the interaction energy. An in-depth understanding of this type of non-covalent interaction has immense significance in biology as amino acids containing S and Se are widely present in proteins and hence hydrogen bonding interactions involving S and Se atoms contribute to the folding of proteins.

Direct Spectroscopic Evidence for an n→π* Interaction.

The n→π* interaction is an extremely weak but very important noncovalent interaction. Although this interaction is widely present in biomolecules and materials, its existence is counterintuitive and so has been debated extensively. Herein, we have reported direct spectroscopic evidence for an n→π* interaction for the first time by probing the carbonyl stretching frequency in phenyl formate using isolated gas-phase IR spectroscopy. This result also demonstrates that the conformational preference for the cis conformer of phenyl formate compared to the trans conformer arises due to the presence of the n→π* interaction in the former. The direct proof reported herein for this controversial but important noncovalent interaction should stimulate further experimental and theoretical investigation on this intriguing research topic.