Carbon bonds (C‐bonds) are the highly directional noncovalent interactions between carbonyl‐oxygen acceptors and sp3‐hybridized‐carbon σ‐hole donors through n→σ* electron delocalization. We have shown the ubiquitous existence of C‐bonds in proteins with the help of careful protein structure analysis and quantum calculations, and have precisely determined C‐bond energies. The importance of conventional noncovalent interactions such as hydrogen bond (H‐bonds) and halogen bond (X‐bonds) in the structure and function of biological molecules are well established, while carbon bonds C‐bonds have still to be recognized. We have shown that C‐bonds are present in proteins, contribute enthalpically to the overall hydrophobic interaction and play a significant role in the photodissociation mechanism of myoglobin and the binding of nucleobases to 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.

Careful protein structure analysis unravels many unknown and unappreciated noncovalent interactions that control protein structure; one such unrecognized interaction in protein is selenium centered hydrogen bonds (SeCHBs). We report, for the first time, SeCHBs involving the amide proton and selenium of selenomethionine (Mse), i.e., amide-N-H···Se H-bonds discerned in proteins. Using mass selective and conformer specific high resolution vibrational spectroscopy, gold standard quantum chemical calculations at CCSD(T), and in-depth protein structure analysis, we establish that amide-N-H···Se and amide-N-H···Te H-bonds are as strong as conventional amide-NH···O and amide-NH···O═C H-bonds despite smaller electronegativity of selenium and tellurium than oxygen. It is in fact, electronegativity, atomic charge, and polarizability of the H-bond acceptor atoms are at play in deciding the strength of H-bonds. The amide-N-H···Se and amide-N-H···Te H-bonds presented here are not only new additions to the ever expanding world of noncovalent interactions, but also are of central importance to design new force-fields for better biomolecular structure simulations.

Thioamides are used as potential surrogates of amides to study the structure and dynamics of proteins and nucleic acids. However, incorporation of thioamides in biomolecules leads to changes in their structures and conformations mostly attributed to the strength of the amide-N-H···S═C hydrogen bond. In most cases, it is considered weak owing to the small electronegativity of sulfur, and in some cases, it is as strong as conventional H-bonds. Herein, adopting PDB structure analysis, NMR spectroscopy, and quantum chemistry calculations, we have shown that thioamides in a geometrical and structural constraint-free environment are capable of forming strong H-bonds like their amide counterparts. These studies also enabled us to determine the amide-N-H···S═C H-bond enthalpy (ΔH) very precisely. The estimated ΔH for the amide-N-H···S═C H-bond is ∼-30 kJ/mol, which suggests that the amide-N-H···S═C H-bond is a strong H-bond and merits its inclusion in computational force fields for biomolecular structure simulations to explore the role of amide-N-H···S═C H-bonds in nucleobase pairing and protein folding.

In addition to the classical N–H···O=C non-covalent interaction, less conventional types of hydrogen bonding, such as N–H···S, may play a key role in determining the molecular structure. In this work,...

Nature makes extensive and elaborate use of hydrogen bonding to assemble and stabilize biomolecular structures. The shapes of peptides and proteins rely significantly on N–H···O=C interactions, which are the linchpins...

A dual microwave and optical spectroscopic study of a capped cysteine aminoacid isolated in a supersonic expansion, combined with quantum chemistry modelling, enabled us to characterize the conformational preferences of...

Nowadays, piezoelectric materials have found various applications in fields like energy harvesting, precision mechanics and life sciences. In this regard organic molecules and their crystals are not explored in detail to be used as an alternative source for piezoelectric materials. Piezo‐coefficients of different H‐bond cluster were calculated. It was found that Sulfur Centered Hydrogen Bond (SCHB) complexes have the optimum hydrogen bond strength and dipole moment derivative for achieving maximum piezo‐response among the systems studied. Moreover, the computed piezo‐coefficient of Thiophenol‐nitrobenzene (SPH‐NBz) dimer was found to be 24.9 pm/V, greater than that of 2‐methyl‐4‐nitroaniline (14 pm/V), the organic crystal with the largest known piezoelectric response. A linear correlation between piezo‐coefficient and dipole moment/polarizability was established, suggesting that both dipole moment and polarizability of H‐bonded systems need to be considered carefully while designing high piezo materials. Keeping in mind the ubiquity of hydrogen bonds in chemistry, materials and biological systems, the present work emphasizes SCHB complexes to be considered and explored as efficient organic piezomaterials.