The Gas Phase Protonation Sites of Six Naturally Occurring Nicotinoids

Okura, Yuika; Santis, Garrett D.; Hirata, Keisuke; Xantheas, Sotiris S.; Fujii, Masaaki; Ishiuchi, Shun-Ichi

doi:10.1021/acs.jpclett.4c01206

The Gas Phase Protonation Sites of Six Naturally Occurring Nicotinoids

Journal Article · Fri Jun 28 00:00:00 EDT 2024 · Journal of Physical Chemistry Letters

DOI:https://doi.org/10.1021/acs.jpclett.4c01206· OSTI ID:2477172

Okura, Yuika ^[1]; Santis, Garrett D. ^[2]; Hirata, Keisuke ^[1]; ^[3]; ^[4]; Ishiuchi, Shun-Ichi ^[1]

Tokyo Institute of Technology (Japan)
Univ. of Washington, Seattle, WA (United States)
Univ. of Washington, Seattle, WA (United States); Tokyo Institute of Technology (Japan); Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Tokyo Institute of Technology (Japan); Chuo University, Kasuga (Japan)

We have determined the gas phase protonation sites of six naturally occurring nicotinoids, namely nicotine (NIC), nornicotine (NOR), anabasine (ANB), anatabine (ANT), cotinine (COT) and myosmine (MYO) from experimental cryogenic ion trap infrared spectroscopy and first principles electronic structure calculations. The structural motif of these compounds consists of a common Pyridine and a differing non-Pyridine rings. The protonation site on either of these two rings correlates with the nicotinoid’s biological activity (addiction). At room temperature NIC is a mixture of Pyridine and Pyrrolidine (non-Pyridene) protomers, NOR, ANB, ANT and COT are pure Pyridine protomers and finally MYO is mostly a Pyroline (non-Pyridine) protomer. Their biological activity (addiction) correlates with the protonation preference in the nonPyridine protomer, with the exception of MYO, which, although is protonated in the Pyroline (non-Pyridine) protomer, it is not addictive because of a conjugated p system that induces a flat structure that is not optimally interacting with the environment in the in the binding pocket of the human brain.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division (CSGB)

Grant/Contract Number:: AC05-76RL01830; AC02-05CH11231

OSTI ID:: 2477172

Report Number(s):: PNNL-SA--197953

Journal Information:: Journal of Physical Chemistry Letters, Journal Name: Journal of Physical Chemistry Letters Journal Issue: 27 Vol. 15; ISSN 1948-7185

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: English

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