Exploring Selenium Hydrogen Bonding through Gas Phase Spectroscopy Coupled with Quantum Chemical Calculations

Abstract

Non-covalent interactions play a significant role in the structure and function of biomolecules as well as materials. These weak intermolecular interactions are generally classified into different categories such as hydrogen bond, halogen bond, π-stacking, cation-π interaction, anion-π interaction, etc. Undoubtedly, the hydrogen bond is the most extensively studied non-covalent interaction among all others. The present thesis is dealt with molecular-level understanding of the nature and strength of selenium hydrogen bonding interaction through gas phase laser spectroscopy and quantum chemistry calculations. The concept of a hydrogen bond is about a century old. It was first reported in the literature by Latimer and Rodebush in 1920. Hydrogen-bond is one of the well-studied non-covalent interactions. However, there is still an ever-growing interest in the scientific community to understand this fascinating intermolecular interaction in further detail. Hydrogen-bonding interaction is highly directional, and it plays an important role in the molecular association. This non-bonding interaction controls and directs the structures of molecular assemblies in supramolecular chemistry. Pauling in his famous book ‘Nature of Chemical Bond’ mentioned that hydrogen bond is electrostatic in nature and the most electronegative atoms in the periodic table, e.g., O, N and F can only form hydrogen bond because of their high electronegativity. However, it has been found that hydrogen bond is not restricted to only conventional electronegative donor and acceptor atoms. It has also been confirmed later through Compton scattering and NMR experiments that hydrogen-bond contains the covalent character. IUPAC committee re-defined hydrogen bond in 2011. According to the recent definition of the hydrogen bond- “The hydrogen bond is an attractive interaction between a hydrogen atom from a molecule or a molecular fragment X–H in which X is more electronegative than H, and an atom or a

group of atoms in the same or a different mol¬ecule, in which there is evidence of bond formation.” Hydrogen bond is classified into conventional and unconventional based on the electronegativity of hydrogen bond donor and acceptor atoms. Conventional hydrogen bonds include conventional donors and acceptor atoms, i.e., atoms with higher electronegativity, e.g., O, N, and F. Conventional hydrogen bonds include N-H…N, O-H…O, N-H…O, etc. The typical bond energy for conventional hydrogen bond is 20-50 kcal/mol. On the other hand, non-conventional hydrogen bonds include hydrogen bonds having donor or acceptor atoms or both having less electronegativity. Non-conventional hydrogen bonding includes C-H…O, C-H…F, C-H…N, O-H…S, N-H…S, O-H…Se, N-H…Se, -hydrogen bonding, etc. The typical bond energy for conventional hydrogen bond is 1-20 kcal/mol. Selenium is considered as an essential trace element in animals and humans for growth and fertility. Selenocysteine is the 21st amino acid in ribosome-mediated protein synthesis. As oxygen and selenium atoms belong to the same group in the periodic table, they have the same physical properties. Replacement of oxygen with selenium does not change the physical properties of the nucleic acids. Rather selenium substitution facilitates the crystallization and solving the crystal structures of the nucleic acids because of higher electron density and larger size of Se. Biswal and co-workers carried out extensive protein data bank (PDB) analysis and reported that there are 24461 Mse (selenomethionine) residues present in 4472 protein structures which account for 4334 hydrogen bonds. They observed that out of these 4334 N-H...Se hydrogen bonds, 2342 are with the main chain and 1992 are with the side chain. Se is the third element in the chalcogen family after O and S. The electronegativity of Se is 2.55 which is comparable to S (2.58) but less than O (3.44). It has been reported that S forms hydrogen bond of similar strength as compared to O although it is less electronegative than O. S-hydrogen bond is studied quite extensively and it has been reported that dispersion interaction plays a major role in stabilization of sulfur-centered hydrogen-bonded complexes. However, spectroscopic investigation of Se-hydrogen bond is sparse in the literature except the one recently reported by Biswal and co-workers. The goal of the present thesis is the following: 1. It has already been reported in the literature that S forms hydrogen bond of similar strength as compared to O. Does selenium (Se) also forms hydrogen bond of similar strength as compared to S and O. What is the physical nature of hydrogen bond involving selenium? 2. What is the nature, strength and binding motifs of water-mediated selenium hydrogen bonding interactions which are present in proteins? 3. What will be the strength and nature of the hydrogen bond when both hydrogen bond donor and acceptor atoms are less electronegative? Chapter 1 starts with a brief introduction of the hydrogen bond followed by the introduction of selenium hydrogen bonding. We have discussed the physical nature of the hydrogen bond, in general. Various spectroscopic techniques to probe the hydrogen bond are also discussed in detail. We have discussed the importance of selenium hydrogen bonding interaction in biomolecules and materials. This chapter ends with the aim of the thesis. Chapter 2 gives detailed information of various spectroscopic techniques and computational details which have been used to study the complexes formed by hydrogen bond involving selenium. We have briefly discussed the principle of supersonic expansion, time of flight mass spectrometry, various spectroscopic techniques (1C-R2PI, 2C-R2PI, RIDIRS, UV-UV hole burn, and IR-UV hole burn) used to measure the electronic and IR spectra of the clusters. In Chapter 3, we have discussed the experimental evidence of direct selenium hydrogen bonding and the nature of selenium hydrogen bonding. We have synthesized the complexes of indole and phenol with dimethyl selenide (Me2Se) in supersonic jet and studied these complexes by various spectroscopic techniques. We observed that Se forms hydrogen bond of similar strength as compared to S and O. We have studied both N-H...Se and O-H...Se hydrogen bonds using gas phase spectroscopy and quantum chemistry calculations. We have explored various energy decomposition analyses to determine the origin of the IR red-shift in the X-H stretch frequency of the S/Se hydrogen bond as the electrostatic interaction in these complexes is smaller compared to that in conventional hydrogen-bonded complexes. It has been found that the charge transfer component of the interaction energy plays a significant role in the IR red shift in the X-H stretching frequency. Chapter 4 deals with the molecular level understanding of water-mediated selenium hydrogen bonding present in proteins. It has been reported from extensive PDB analysis that direct selenium hydrogen bonding between selenomethionine and other amino acid residues is abundant in proteins and this interaction plays an important role in the stability of the protein structures. However, water-mediated indirect selenium hydrogen bonding between two or more amino acid residues involving selenomethionine is not demonstrated in the literature. Generally, water molecules present in the core or interior of the proteins forming some cavities bind with two or more amino acid residues and contribute to the stability of the proteins. We have found from the PDB analysis that the number of water-mediated Se hydrogen bonding interaction is three times more than that of the direct Se hydrogen bonding interaction present in proteins. We have studied a model complex, consisting of indole (represents tryptophan), water and dimethyl selenide (represents selenomethionine), which mimics the structural motif of single water-mediated Se hydrogen bonding interaction present in proteins. In Chapter 5, we have discussed the nature and strength of the hydrogen bonds where both hydrogen bond donor and acceptor atoms are less electronegative, i.e., unconventional in nature. In the literature, there are reports of spectroscopic studies of unconventional hydrogen bonding involving either weak hydrogen bond donor (C-H) or weak hydrogen bond acceptor (S, Se or P), i.e., C-H..N, C-H…O or N-H…S, O-H…S, N-H…Se, N-H…P, etc. In this work, we have explored the nature and strength of the hydrogen bond interaction (S-H…S or S-H…Se) where both hydrogen bond donor and acceptor atoms are unconventional or less electronegative. Interestingly, it has been observed that S-H…S and S-H…Se interactions are of similar strength as O-H…S interaction. We have reported here that S forms a strong hydrogen bond when it is used as a hydrogen bond donor even though it is less electronegative than O. Chapter 6, the last chapter of the thesis, summarizes the whole thesis and discusses future perspectives.