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Title:Conformational Isomers Of Nicotine, Nornicotine And Their Hydrated Clusters
Author(s):Santis, Garrett D
Contributor(s):Xantheas, Sotiris; Fujii, Masaaki; Tsuruta, Kazuya; Ishiuchi, Shun-ichi; Takeda, Naoya
Subject(s):Comparing theory and experiment
Abstract:Tobacco addiction plagues society and stems from the neuroactivity of nicotine, a natural compound that is abundant in tobacco leaves. Recent studies have determined that the protonation sites for nicotine are different in its gas (at the pyridine ring) and aqueous (at the pyrrolidine ring) states. These two different protonation sites are expected to trigger different biological activity in the native, anhydrous environment of the binding pocket of the human brain. Infrared (IR) spectroscopy is a powerful tool, which records the molecular vibrations associated with a specific bond and its environment. With the aid of first principles (ab-initio) electronic structure calculations, the IR spectra can be decoded and associated to underlying molecular structures. In this context, protonation in different sites is associated with spectral bands of different frequencies. We have relied on different hierarchical approximations of electronic structure methods, such as Density Functional Theory (DFT), Second Order M\o{}ller-Plesset Perturbation Theory (MP2) and Coupled Cluster Theory [CCSD(T)] to compute the IR spectra of nicotine, nornicotine, and their hydrated clusters to investigate the transition of the protonation site from the pyridine to the pyrrolidine rings with an increasing number of water molecules in the cluster. The experimentally observed stabilization of the pyrrolidine protonation site is facilitated by the formation of strong hydrogen bonds to both nitrogen centers, which requires multiple waters. The result is a strong red-shift in the acidic N-H vibrational bands. Notably, nicotine favors the pyrrolidine protonation site more than nornicotine at each hydration level. This increased stability of the pyrrolidine protonation in nicotine is suggested to support stronger binding of nicotine to tryptophan in the nicotinic acetylcholine receptor. The quantification of the incremental hydration for nicotine and nornicotine manifests the multiple energetically relevant hydrated states, which is currently considered in biological applications, such as binding strength to neuroreceptors.
Issue Date:2021-06-22
Publisher:International Symposium on Molecular Spectroscopy
Genre:Conference Paper / Presentation
Date Available in IDEALS:2021-09-24

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