Conformational landscape, internal dynamics, and non-covalent interactions of flexible molecular systems by rotational spectroscopy and quantum chemistry calculations

Abstract

Non-covalent interactions govern the three-dimensional structures of molecules and are thus central to their function, reactivity, and spectroscopic fingerprints, but despite this pivotal role, remain undercharacterized. Rotational spectroscopy is an ideal tool to study the structure, conformational flexibility and internal dynamics of molecules and molecular clusters under collision free and isolated conditions. In this thesis, rotational spectroscopy (6–24 GHz) and quantum chemistry calculations were used to study the effects ruling the geometric preferences of selected molecular systems (monomers and water complexes) with a wide range of applicability from biological to astrophysical interest. The studied monomers are 3 mercaptopropionic acid (HO(C=O)CH2CH2SH, MPA), methyl 3 mercaptopropionate (CH3O(C=O)CH2CH2SH, MP) and N allylmethylamine (CH2CHCH2NHCH3, AMA) which are models for elucidating intramolecular interactions involving thiols and amines. Regarding the molecular aggregates, water complexes of AMA and non-aromatic, trimethylene sulfide (c-C3H6S) and oxide (c-C3H6O), and aromatic (C4H4S, thiophene) heterocycles, which are prototypes of the intermolecular interactions occurring in the first steps of water solvation, were investigated. In particular, the focus of this research is to provide accurate and detailed experimental data on the nature of non-covalent interactions involving oxygen, nitrogen, and sulfur and to characterize their influence on the stabilization of the studied molecules. The experimental measurements for these systems validated the computational methods employed in terms of both relative energies and molecular structures. To understand the underlying complex effects that drive their unusual conformational preferences, quantum theory of atoms in molecules, non-covalent interaction, natural bond orbital and an energy decomposition analysis scheme were employed. Collectively, general observations could be made including drastic changes in the conformational equilibria in moving from interactions involving O and N to those with S and that the inclusion of water disrupts the conformational distribution further. Although weaker than classical hydrogen bonds (HBs), non-classical sulfur HBs and secondary contacts (e.g. involving C–H groups) which are longer-range and more dispersive in nature were proven to play a crucial role in the stabilization of both monomers and molecular aggregates. The results presented in this thesis lay groundwork for the improvement of chemical modelling tools and deepen our understanding of non-covalent interactions that are ubiquitous in many fields of science including molecular recognition, self-assembly and supramolecular chemistry.