Intra and Intermolecular Modulation of n→π* Non-covalent Interaction: Gas-phase Laser Spectroscopy and Quantum Chemistry Calculations

Abstract

The importance of non-covalent interactions (NCIs) can be envisaged by the existence of water in the liquid state through hydrogen bonding. One of the NCIs named n→π* interaction is analogous to the hydrogen bonding in terms of delocalization of lone pair electron density of the nitrogen, oxygen, and sulfur atom into the π* orbital of the C=O group or aromatic ring. The n→π* interaction was first discovered in 1953 in protopine by E. H. Mottus, 40 years after the discovery of the hydrogen bond. The n→π* interaction has emerged as a promising candidate for NCIs due to its diverse applicability in isomerization, transition state stabilization, dynamic covalent chemistry, stabilizing molecular clusters, and folding of flexible side chains. Thus, it is imperative to have a detailed understanding of the n→π* interaction by various spectroscopic techniques and computational studies. In the gas phase, one can study isolated molecules or molecular clusters free from any perturbation caused by the same and/or solvent molecule otherwise present in the solution-phase. Additionally, microsolvation in the gas-phase allows exploring the n→π* interaction in a solvated environment, mimicking its behavior in a solution-phase. This thesis involves tuning the strength of n→π* interaction and detecting it via the change observed in the redshift of C=O stretching frequency using isolated gas-phase electronic and vibrational spectroscopy parallel with quantum chemistry calculations. In line with this, the strength of C=O∙∙∙aromatic n→π* interaction was increased intramolecularly in phenyl acetate, which is the ester analog of the phenyl formate, by substituting the methyl group at the n→π* donor site. It was shown that the steric and n→π* interaction governs the conformational preference of phenyl acetate. Microsolvated phenyl formate∙∙∙water complex was synthesized in the gas-phase to give the overview of the behavior of C=O∙∙∙aromatic n→π* interaction in the presence of a strong hydrogen bond. For the very first time, gas-phase IR spectroscopic evidence of N∙∙∙C=O n→π* interaction was provided in ethyl-2-(2-(dimethylamino) phenyl) acetate along with studying the chemical shift of the carbonyl carbon atom (n→π* acceptor) by variable temperature 13C NMR spectroscopy. Furthermore, the role of N∙∙∙C=O n→π* interaction in the folding of flexible propanal side-chain in 3 [2-(dimethylamino) phenyl] propanal and in stabilizing molecular clusters of para-substituted pyridines with aldehydes has been shown using gas- and solution-phase ab-initio calculations. In a nutshell, the strength of n→π* interaction was tuned and studied using experimental and theoretical approaches in various molecular systems. Some of the preliminary applications of n→π* interaction have been studied in this work. The understanding and detection of n→π* interaction using spectroscopic tools will have implications in drug designing with conformational specificity and molecular recognition based on the specific non-covalent interactions.