Binding Site Switch by Dispersion Interactions: Rotational Signatures of Fenchone–Phenol and Fenchone–Benzene Complexes

Abstract

Non‐covalent interactions between molecules determine molecular recognition and the outcome of chemical and biological processes. Characterising how non‐covalent interactions influence binding preferences is of crucial importance in advancing our understanding of these events. Here, we analyse the interactions involved in smell and specifically the effect of changing the balance between hydrogen‐bonding and dispersion interactions by examining the complexes of the common odorant fenchone with phenol and benzene, mimics of tyrosine and phenylalanine residues, respectively. Using rotational spectroscopy and quantum chemistry, two isomers of each complex have been identified. Our results show that the increased weight of dispersion interactions in these complexes changes the preferred binding site in fenchone and sets the basis for a better understanding of the effect of different residues in molecular recognition and binding events.

Pinacolone-Alcohol Gas-Phase Solvation Balances as Experimental Dispersion Benchmarks

“…This has led to the concept of ketone solvation balances, which were introduced for acetophenone and its derivatives in combination with alcohols as hydrogen bond donors [10,11] and tested for other ketones [12,13]. The idea is to have two very comparable lone electron pairs available at the acetophenone oxygen, to which alcohols can either dock from the phenyl or from the alkyl side, with little difference in ZPVE.…”

Structural Changes Induced by Quinones: High‐Resolution Microwave Study of 1,4‐Naphthoquinone

“…[22] Rotational spectroscopy is a high-resolution spectroscopic technique sensitive to minute structural changes and therefore ideally suited to structural studies, with applications in biomolecular characterisation, astrochemistry and atmospheric chemistry. [23][24][25][26][27][28][29][30] Nowadays rotational spectroscopy is combined with supersonic jets, which provide a collisionless environment where molecules are virtually isolated and free from any of the interactions with the solvent or lattice constraints that occur in condensed phases. Rotational spectroscopy data can then be compared directly with that from in vacuo theoretical calculations and used to benchmark the accuracy of different theoretical methods.…”

“…Here we present the structural study of 1,4‐NQ using chirped‐pulse Fourier transform microwave spectroscopy (CP‐FTMW) [22] . Rotational spectroscopy is a high‐resolution spectroscopic technique sensitive to minute structural changes and therefore ideally suited to structural studies, with applications in biomolecular characterisation, astrochemistry and atmospheric chemistry [23–30] . Nowadays rotational spectroscopy is combined with supersonic jets, which provide a collisionless environment where molecules are virtually isolated and free from any of the interactions with the solvent or lattice constraints that occur in condensed phases.…”

Pinacolone-Alcohol Gas-Phase Solvation Balances as Experimental Dispersion Benchmarks

“…This has led to the concept of ketone solvation balances, which were introduced for acetophenone and its derivatives in combination with alcohols as hydrogen bond donors [10,11] and tested for other ketones. [12,13] The idea is to have two very comparable lone electron pairs available at the acetophenone oxygen, to which alcohols can either dock from the phenyl or from the alkyl side, with little difference in ZPVE. Besides the intrinsic preference of a docking alcohol for the methyl side due to the more favourable local hydrogen bond geometry [11], the alkyl group of the alcohol will interact dispersively (and by Pauli repulsion) with the two ketone substituents and thus contribute to the preference for one of the docking sides.…”