Exploring weak n→π* non-covalent Interaction: Gas Phase Spectroscopy and Quantum Chemical Calculations

Abstract

n→π* non-covalent interaction is widely present in biomolecules (proteins, nucleic acids, neurotransmitters etc.) as well as materials. In spite of its immense significance in the structures of various molecular systems, this non-covalent interaction has been recognized only recently (during last two decades) by the scientific community due to its counterintuitive and weak (strength) nature. The n→π* interaction is quite analogous to the well-known hydrogen bonding interaction in terms of electron delocalization. The n→π* interaction involves delocalization of lone pair (n) electrons on any electronegative atom into the π* orbital of a nearby carbonyl group or an aromatic ring. This non-bonding interaction follows the Burgi-Dunitz trajectory of approach of a nucleophile towards an electrophile during nucleophilic addition reaction. Several Protein Data Bank (PDB) and Cambridge Structural Database (CSD) analyses show that the n→π* interaction has a high propensity to occur in bio-molecules as well as materials. It has been found that the n→π* interaction is most prominent in the protein collagen which is interestingly the most abundant protein in animals. Collagen has a repititive sequence of amino acid residues –Pro-Hyp-Gly- and its triple helical structure lacks intrastrand hydrogen bonding interaction. It has been found that n→π* interactions between successive carbonyl groups play a significant role in the stability of individual strand of collagen protein. Further evidence and understanding of n→π* interaction come from the low-temperature NMR spectroscopy studies performed on proline derivatives. These studies reveal that n→π* interaction plays an important role in governing the conformational preferences of these molecules. Herein, we have explored this n→π* interaction in various molecular systems including phenyl formate, salicin, hydroxyproline derivatives etc. in isolated gas phase using UV and IR laser based different spectroscopic techniques combined with quantum chemistry calculations. For the first time, we have obtained gas phase IR spectroscopic evidence for the n→π* interaction by probing the C=O stretching frequency in a variety of molecular systems. Both the conformers, cis and trans, of these molecular systems are observed in the experiment. The presence of the n→π* interaction in the cis conformer against the absence of this interaction in the trans conformer has been proved by the observation of the red-shift in the C=O stretching frequency in the former one with respect to that in the latter one. Our studies also show that n→π* interaction can govern the conformational preferences of the molecular systems even in the presence of strong non-covalent interactions like hydrogen bonding. The current research has great implication in quantitative understanding of this weak n→π* interaction and further modulating the strength of this interaction.