Aditi Bhattacherjee

The Intermolecular SH⋅⋅⋅Y (Y=S,O) Hydrogen Bond in the H2S Dimer and the H2S–MeOH Complex

The nature of the S−H⋅⋅⋅S hydrogen-bonding interaction in the H2 S dimer and its structure has been the focus of several theoretical studies. This is partly due to its structural similarity and close relationship with the well-studied water dimer and partly because it represents the simplest prototypical example of hydrogen bonding involving a sulfur atom. Although there is some IR data on the H2 S dimer and higher homomers from cold matrix experiments, there are no IR spectroscopic reports on S−H⋅⋅⋅S hydrogen bonding in the gas phase to-date. We present experimental evidence using VUV ionization-detected IR-predissociation spectroscopy (VUV-ID-IRPDS) for this weak hydrogen-bonding interaction in the H2 S dimer. The proton-donating S−H bond is found to be red-shifted by 31 cm(-1) . We were also able to observe and assign the symmetric (ν1 ) stretch of the acceptor and an unresolved feature owing to the free S−H of the donor and the antisymmetric (ν3 ) SH stretch of the acceptor. In addition we show that the heteromolecular H2 S-MeOH complex, for which both S−H⋅⋅⋅O and O−H⋅⋅⋅S interactions are possible, is S-H⋅⋅⋅O bound.

O-H···S hydrogen bonds conform to the acid-base formalism.

Hydrogen bonding interaction between the ROH hydrogen bond donor and sulfur atom as an acceptor has not been as well characterized as the O-H···O interaction. The strength of O-H···O interactions for a given donor has been well documented to scale linearly with the proton affinity (PA) of the H-bond acceptor. In this regard, O-H···O interactions conform to the acid-base formalism. The importance of such correlation is to be able to estimate molecular property of the complex from the known thermodynamic data of its constituents. In this work, we investigate the properties of O-H···S interaction in the complexes of the H-bond donor and sulfur containing acceptors of varying proton affinity. The hydrogen bonded complexes of p-Fluorophenol (FP) with four different sulfur containing acceptors and their oxygen analogues, namely H2O/H2S, MeOH/MeSH, Me2O/Me2S and tetrahydrofuran (THF)/tetrahydrothiophene (THT) were characterized in regard to its S1-S0 excitation spectra and the IR spectra. Two-color resonantly enhanced multiphoton ionization (2c-R2PI), resonant ion-dip infrared (RIDIR) spectroscopy, and IR-UV hole burning spectroscopic techniques were used to probe the hydrogen bonds in the aforementioned complexes. The spectroscopic data along with the ab initio calculations were used to deduce the strength of the O-H···S hydrogen bonding interactions in these system relative to that in the O-H···O interactions. It was found that, despite being dominated by the dispersion interaction, the O-H···S interactions conform to the acid-base formalism as in the case of more conventional O-H···O interactions. The dissociation energies and the red shifts in the O-H stretching frequencies correlated very well with the proton affinity of the acceptors. However, the O-H···S interaction did not follow the same correlation as that in the O-H···O H-bond. The energy decomposition analysis showed that the dissociation energies and the red shifts in the O-H stretching frequencies follow a unified correlation if these two parameters were correlated with the sum of the charge transfer and the exchange component of the total binding energy.

Critical Assessment of the Strength of Hydrogen Bonds between the Sulfur Atom of Methionine/Cysteine and Backbone Amides in Proteins

Gas-phase vibrational spectroscopy, coupled cluster (CCSD(T)), and dispersion corrected density functional (B97-D3) methods are employed to characterize surprisingly strong sulfur center H-bonded (SCHB) complexes between cis and trans amide NH and S atom of methionine and cysteine side chain. The amide N-H···S H-bonds are compared with the representative classical σ- and π-type H-bonded complexes such as N-H···O, N-H···O═C and N-H···π H-bonds. With the spectroscopic, theoretical, and structural evidence, amide N-H···S H-bonds are found to be as strong as the classical σ-type H-bonds, despite the smaller electronegativity of sulfur in comparison to oxygen. The strength of backbone-amide N-H···S H-bonds in cysteine and methionine containing peptides and proteins are also investigated and found to be of similar magnitudes as those observed in the intermolecular model complexes studied in this work. All such SCHBs also confirm that the electronegativities of the acceptors are not the sole criteria to predict the H-bond strength.

Nature and strength of sulfur-centred hydrogen bonds: laser spectroscopic investigations in the gas phase and quantum-chemical calculations

The importance of Sulfur centred hydrogen bonds (SCHBs) cannot be underestimated given the current day knowledge of its non-covalent interactions prevalent in many biopolymers as well as in organic systems. Based on the distance/angle constraints available from the structural database, these interactions have been interchangeably termed as van der Waals/hydrogen bonded complexes. There is a lack of sufficient spectroscopic evidence that can unequivocally term these interactions as hydrogen bonding interactions. In this review we present laser spectroscopic investigations of isolated binary complexes of H-bond donor-acceptor molecules containing Sulfur atom. The complexes were formed using supersonic jet expansion method and the IR/UV spectroscopic investigations were carried out on mass selected binary complexes. The pertinent questions regarding SCHBs addressed herein are (1) Is electronegativity the controlling factor to be a potent H-bond donor/acceptor? (2) How do SCHBs compare with their oxygen counterpart? (3) What is the nature of SCHBs, i.e. what are the dominating forces in stabilising these hydrogen bonds? (4) Do SCHBs follow classical H-bond acid–base formalism? (5) Are SCHBs found in peptides and proteins? If so, what are their strengths? Do they control the structure of the peptides? The experimental investigations were also supported by high level of ab initio computations.

Water bridges anchored by a C–H⋯O hydrogen bond: the role of weak interactions in molecular solvation

The imidazole group, characterized by an activated C(2)-H bond sandwiched between two N atoms, occurs in several biomolecules including alkaloids, amino acids, and nucleobases. The speculated role of this potential hydrogen bond donor in shaping the solvation shell around the neutral imidazole moiety, however, remains unidentified. In contrast, hydrogen bonding and electrostatic interactions are commonly observed in the imidazolium cation where the acidity of the C(2)-H bond is markedly enhanced. Here, we show direct evidence of the weakly activated C(2)-H bond in shaping the solvation shell of neutral imidazole, via spectroscopic characterization of the water clusters (Wn, n = 2-4) of two model compounds, benzimidazole (BIM) and N-methylbenzimidazole (MBIM). Infrared spectra in the OH, NH, and CH stretching regions allow unambiguous detection of a N-WW-C(2)H binding motif in the doubly hydrated cluster of both molecules. Remarkably, H-bonded water bridges between the N atom and N-H bond in BIM-W3,4 clusters are switched to the C(2)-H bond in MBIM-W3,4 with comparable binding strength, indicating that the weakly activated C(2)-H bond in the neutral imidazole moiety can serve as a potent H-bond donor.

N–H···S Interaction Continues To Be an Enigma: Experimental and Computational Investigations of Hydrogen-Bonded Complexes of Benzimidazole with Thioethers

The N-H···S hydrogen bond, even though classified as an unconventional hydrogen bond, is found to bear important structural implications on protein structure and folding. In this article, we report a gas-phase study of the N-H···S hydrogen bond between the model compounds of histidine (benzimidazole, denoted BIM) and methionine (dimethyl sulfide, diethyl sulfide, and tetrahydrothiophene, denoted Me2S, Et2S, and THT, respectively). A combination of laser spectroscopic methods such as laser-induced fluorescence (LIF), two-color resonant two-photon ionization (2cR2PI), and fluorescence depletion by infrared spectroscopy (FDIR) is used in conjunction with DFT and ab initio calculations to characterize the nature of this prevalent H-bonding interaction in simple bimolecular complexes. A single conformer was found to exist for the BIM-Me2S complex, whereas the BIM-Et2S and BIM-THT complexes showed the presence of three and two conformers, respectively. These conformers were characterized on the basis of IR spectroscopic results and electronic structure calculations. Quantum theory of atoms in molecules (QTAIM), natural bond orbital (NBO), and energy decomposition (NEDA) analyses were performed to investigate the nature of the N-H···S H-bond. Comparison of the results with the N-H···O type of interactions in BIM and indole revealed that the strength of the N-H···S H-bond is similar to N-H···O in these binary gas-phase complexes.

Conformational Heterogeneity and the Role of the C(2)–H Donor in Mono- and Dihydrated Clusters of Benzoxazole

The significance of the heteroatom in influencing the acidity and binding affinity of the C(2)-H donor in five-membered heterocyclic rings is explored. The water clusters of benzoxazole (BOX) are studied in a supersonic jet by IR-UV double resonance spectroscopy and compared with those of benzimidazole (BIM) and its N-methyl derivative (MBIM). Two conformers are identified for the monohydrated cluster, both of which are O-H···N bound and differ in their orientation with respect to the intermolecular hydrogen bond. IR spectroscopy of the doubly hydrated cluster shows the presence of an intensity enhanced C(2)-H (carbon atom between the heteroatoms in the five-membered ring) stretching mode in addition to two red-shifted bound OH stretches, indicating that the water molecules form a hydrogen-bonded bridge encompassing the N acceptor and the weakly activated C(2)-H bond in oxazole. Comparison of the topological parameters of electron density, natural bond orbital analyses, and computed binding energies of the analogous hydrated structures of BOX, BIM, and MBIM indicates that the C(2)-H bond in the former is a more potent H-bond donor.

Nature and Hierarchy of Non-Covalent Interactions in Gas-Phase Binary Complexes of Indole and Benzimidazole with Ethers

Hierarchy among the weak noncovalent interactions such as van der Waals, electrostatic, hydrogen bonding, etc. dictates the secondary and tertiary structures of proteins as well as their interactions with various ligands. In this work, we investigate the competition between conventional (N-H···O) hydrogen bonds, unconventional (C-H···O) hydrogen bonds, and the van der Waals interaction in the model compounds of the chromophores of the amino acids, tryptophan, and histidine. These include indole (IND), benzimidazole (BIM), and its N-methylated analog (N-methylbenzimidazole, MBIM), which present multiple docking sites. The binary complexes of these molecules with ethers (dimethyl ether, diethyl ether, and tetrahydrofuran), which possess high proton affinity but lack acidic protons (thereby only act as hydrogen bond acceptors), are investigated. The complexes are formed in a supersonic jet and jointly studied by electronic and vibrational spectroscopy as well as quantum chemical calculations. Only the N-H···O bound structures are observed for the complexes of IND and BIM with ethers, although computations predict reasonably competent C-H···O type of structures. Remarkably, IND and BIM produce three (N-H···O) conformers with Me2O but single conformers with Et2O and THF. In the case of MBIM, which lacks a conventional hydrogen bond donor, no evidence for C(2)-H···O hydrogen bonds is seen; instead, the complexes are found to be bound purely by van der Waals interactions. The results indicate that strong N-H···O and even weak van der Waals interactions are thermodynamically favored over C(2)-H···O bound structures in these binary gas-phase complexes.