Conspectus Hydrogen bonds (H-bonds) play important roles in imparting functionality to the basic molecules of life by stabilizing their structures and directing their interactions. Numerous studies have been devoted to understanding H-bonds involving highly electronegative atoms like nitrogen, oxygen, and halogens and consequences of those H-bonds in chemical reactions, catalysis, and structure and function of biomolecules; but the involvement of less electronegative atoms like sulfur and selenium in H-bond formation establishes the concept of noncanonical H-bonds. Initially belittled for the “weak” nature of their interactions, these perceptions have gradually evolved over time through dedicated efforts by several research groups. This has been facilitated by advancements in experimental methods for their detection through gas-phase laser spectroscopy and solution NMR spectroscopy, as well as through theoretical predictions from high level quantum chemical calculations. In this Account, we present insights into the versatility of the sulfur and selenium centered H-bonds (S/SeCHBs) by highlighting their multifarious applications in various fields from chemical reactions to optoelectronic properties to structural biology. Our group has highlighted the significance and strength of such H-bonds in natural and modified biomolecules. Here, we have reviewed several molecular assemblies, biomolecules, and functional materials, where the role of these H-bonds is pivotal in influencing biological functions. It is worth mentioning here that the precise experimental data obtained from gas-phase laser spectroscopy have contributed considerably to changing the existing perceptions toward S/SeCHBs. Thus, molecular beam experiments, though difficult to perform on smaller model thio- or seleno-substituted Molecules, etc. (amides, nucleobases, drug molecules), are inevitable to gather elementary knowledge and convincing concepts on S/SeCHBs that can be extended from a small four-atom sulfanyl dimer to a large 14 kDa iron–sulfur protein, ferredoxin. These H-bonds can also tailor a fascinating array of molecular frameworks and design supramolecular assemblies by inter- and intralinking of individual “molecular Lego-like” units. The discussion is indeed intriguing when it turns to the usage of S/SeCHBs in facile synthetic strategies like tuning regioselectivity in reactions, as well as invoking phenomena like dual phosphorescence and chemiluminescence. This is in addition to our investigations of the dispersive nature of the hydrogen bond between metal hydrides and sulfur or selenium as acceptor, which we anticipate would lead to progress in the areas of proton and hydride transfer, as well as force-field design. This Account demonstrates how ease of fabrication, enhanced efficiency, and alteration of physicochemical properties of several functional materials is facilitated owing to the presence of S/SeCHBs. Our efforts have been instrumental in the evaluation of various S/SeCHBs in flue gas capture, as well as design of organic ene...

Presently, there are no approved drugs or vaccines to treat COVID-19, which has spread to over 200 countries and at the time of writing was responsible for over 650,000 deaths worldwide. Recent studies have shown that two human proteases, TMPRSS2 and cathepsin L, play a key role in host cell entry of SARS-CoV-2. Importantly, inhibitors of these proteases were shown to block SARS-CoV-2 infection. Here, we perform virtual screening of 14,011 phytochemicals produced by Indian medicinal plants to identify natural product inhibitors of TMPRSS2 and cathepsin L. AutoDock Vina was used to perform molecular docking of phytochemicals against TMPRSS2 and cathepsin L. Potential phytochemical inhibitors were filtered by comparing their docked binding energies with those of known inhibitors of TMPRSS2 and cathepsin L. Further, the ligand binding site residues and non-covalent interactions between protein and ligand were used as an additional filter to identify phytochemical inhibitors that either bind to or form interactions with residues important for the specificity of the target proteases. This led to the identification of 96 inhibitors of TMPRSS2 and 9 inhibitors of cathepsin L among phytochemicals of Indian medicinal plants. Further, we have performed molecular dynamics (MD) simulations to analyze the stability of the protein-ligand complexes for the three top inhibitors of TMPRSS2 namely, qingdainone, edgeworoside C and adlumidine, and of cathepsin L namely, ararobinol, (+)-oxoturkiyenine and 3α,17α-cinchophylline. Interestingly, several herbal sources of identified phytochemical inhibitors have antiviral or anti-inflammatory use in traditional medicine. Further in vitro and in vivo testing is needed before clinical trials of the promising phytochemical inhibitors identified here.

The significance of dispersion contribution in the formation of strong hydrogen bonds (H-bonds) can no more be ignored. It was illustrated that less electronegative and electropositive H-bond acceptors such as S, Se, and Te are also capable of forming strong N–H···Y H-bonds, mostly due to the high polarizabilities of H-bond acceptor atoms. Herein, for the first time, we report the evidence of formation of nonconventional M-H···Y H-bonds between metal hydrides (M-H, M = Mn, Fe, Co) and chalcogen H-bond acceptors (Y = O, S, or Se). The nature and the strength of unusual M-H···Y H-bonds were revealed by several quantum chemical calculations and H-bond descriptors. The structural parameters, electron density topology, donor–acceptor natural bond orbital (NBO) interaction energies, and spectroscopic observables such as M-H stretching frequencies and 1H chemical shifts are well-correlated to manifest the existence and strength of M-H···Y H-bonding. The M-H···Y H-bonds are dispersive in nature, and the computed H-bond energies are found to be in the range from ∼5 to 30 kJ/mol, which can be compared to those of the conventional H-bonds such as O–H···O, N–H···O, and N–H···OC H-bonds, etc.