Structure of Gas Phase Monohydrated Nicotine: Implications for Nicotine’s Native Structure in the Acetylcholine Binding Protein

Santis, Garrett D.; Takeda, Naoya; Hirata, Keisuke; Tsuruta, Kazuya; Ishiuchi, Shun-ichi; Xantheas, Sotiris S.; Fujii, Masaaki

doi:10.1021/jacs.2c04064

Structure of Gas Phase Monohydrated Nicotine: Implications for Nicotine’s Native Structure in the Acetylcholine Binding Protein

Journal Article · Wed Aug 31 00:00:00 EDT 2022 · Journal of the American Chemical Society

DOI:https://doi.org/10.1021/jacs.2c04064· OSTI ID:1891995

Santis, Garrett D. ^[1]; Takeda, Naoya ^[2]; Hirata, Keisuke ^[2]; Tsuruta, Kazuya ^[2]; Ishiuchi, Shun-ichi ^[2]; ^[3]; ^[2]

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

In this work, we report a joint experimental–theoretical study of the never reported before structure and infrared spectra of gas phase monohydrated nicotine (NIC) and nornicotine (NOR) and use them to assign their protonation sites. NIC’s biological activity is strongly affected by its protonation site, namely, the pyrrolidine (Pyrro-NICH⁺, anticipated active form) and pyridine (Pyri-NICH⁺) forms; however, these have yet to be directly experimentally determined in either the nicotinic acetylcholine receptor (nAChR, no water present) or the acetylcholine-binding protein (AChBP, a single water molecule is present) but can only be inferred to be Pyrro-NICH⁺ from the intermolecular distance to the neighboring residues (i.e., tryptophan). Our temperature-controlled double ion trap infrared spectroscopic experiments assisted by the collisional stripping method and high-level theoretical calculations yield the protonation ratio of Pyri:Pyrro = 8:2 at 240 K for the gas phase NICH⁺···(H₂O) complex, which resembles the molecular cluster present in the AChBP. Therefore, a single water molecule in the gas phase enhances this ratio in NICH⁺ relative to the 3:2 for the nonhydrated gas phase NICH⁺ in a trend that contrasts with the almost exclusive presence of Pyrro-NICH⁺ in aqueous solution. In contrast, the Pyri-NORH⁺ protomer is exclusively observed, a fact that may correlate with its weaker biological activity.

View Accepted Manuscript (DOE)

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

Sponsoring Organization:: Japan Society for the Promotion of Science (JSPS); USDOE Office of Science (SC), Basic Energy Sciences (BES). Chemical Sciences, Geosciences & Biosciences Division

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1891995

Report Number(s):: PNNL-SA-172086

Journal Information:: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 37 Vol. 144; ISSN 0002-7863

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

References (38)

Alkali and Alkaline Earth Metal Ions Complexes with a Partial Peptide of the Selectivity Filter in K ⁺ Channels Studied by a Cold Ion Trap Infrared Spectroscopy Otsuka, Remina; Hirata, Keisuke; Sasaki, Yuta ChemPhysChem, Vol. 21, Issue 8 https://doi.org/10.1002/cphc.202000033	journal	March 2020
The Dipole Moment Surface and the Vibrational Transition Moments of H2O Jorgensen, U. G.; Jensen, P. Journal of Molecular Spectroscopy, Vol. 161, Issue 1 https://doi.org/10.1006/jmsp.1993.1228	journal	September 1993
Physicochemical properties of biological interest and structure of nicotine and its related compounds Fujita, Toshio; Nakajima, Minoru; Soeda, Yoshinori Pesticide Biochemistry and Physiology, Vol. 1, Issue 2 https://doi.org/10.1016/0048-3575(71)90190-8	journal	September 1971
Cellular mechanisms of nicotine addiction Dani, John A.; De Biasi, Mariella Pharmacology Biochemistry and Behavior, Vol. 70, Issue 4 https://doi.org/10.1016/S0091-3057(01)00652-9	journal	December 2001
Functional role of alpha7 nicotinic receptor in chronic neuropathic and inflammatory pain: Studies in transgenic mice AlSharari, Shakir D.; Freitas, Kelen; Damaj, M. Imad Biochemical Pharmacology, Vol. 86, Issue 8 https://doi.org/10.1016/j.bcp.2013.06.018	journal	October 2013
Effects of nicotine and minor tobacco alkaloids on intracranial-self-stimulation in rats Harris, Andrew C.; Tally, Laura; Muelken, Peter Drug and Alcohol Dependence, Vol. 153 https://doi.org/10.1016/j.drugalcdep.2015.06.005	journal	August 2015
High-cooling-efficiency cryogenic quadrupole ion trap and UV-UV hole burning spectroscopy of protonated tyrosine Ishiuchi, Shun-ichi; Wako, Hiromichi; Kato, Daichi Journal of Molecular Spectroscopy, Vol. 332 https://doi.org/10.1016/j.jms.2016.10.011	journal	February 2017
Exploring the Origins of Spectral Signatures of Strong Hydrogen Bonding in Protonated Water Clusters Huchmala, Rachel M.; McCoy, Anne B. The Journal of Physical Chemistry A, Vol. 126, Issue 8 https://doi.org/10.1021/acs.jpca.1c10036	journal	February 2022
Can the Partial Peptide SIVSF of the β₂-Adrenergic Receptor Recognize Chirality of the Epinephrine Neurotransmitter? Tamura, Masato; Sekiguchi, Tsubasa; Ishiuchi, Shun-ichi The Journal of Physical Chemistry Letters, Vol. 10, Issue 10 https://doi.org/10.1021/acs.jpclett.9b00184	journal	March 2019
Alkaloids of Tobacco. Jackson, Kirby E. Chemical Reviews, Vol. 29, Issue 1 https://doi.org/10.1021/cr60092a004	journal	August 1941
Site of Protonation of Nicotine and Nornicotine in the Gas Phase: Pyridine or Pyrrolidine Nitrogen? Graton, Jérôme; Berthelot, Michel; Gal, Jean-François Journal of the American Chemical Society, Vol. 124, Issue 35 https://doi.org/10.1021/ja017770a	journal	August 2002
Proton Transfer from the Inactive Gas-Phase Nicotine Structure to the Bioactive Aqueous-Phase Structure Gaigeot, Marie-Pierre; Cimas, Alvaro; Seydou, Mahamadou Journal of the American Chemical Society, Vol. 132, Issue 51 https://doi.org/10.1021/ja103759v	journal	December 2010
Isomers and Conformational Barriers of Gas-Phase Nicotine, Nornicotine, and Their Protonated Forms Yoshida, Tomoki; Farone, William A.; Xantheas, Sotiris S. The Journal of Physical Chemistry B, Vol. 118, Issue 28 https://doi.org/10.1021/jp501646p	journal	April 2014
Crystal structure of an ACh-binding protein reveals the ligand-binding domain of nicotinic receptors Brejc, KatjuS̆a; van Dijk, Willem J.; Klaassen, Remco V. Nature, Vol. 411, Issue 6835 https://doi.org/10.1038/35077011	journal	May 2001
X-ray structure of the human α4β2 nicotinic receptor Morales-Perez, Claudio L.; Noviello, Colleen M.; Hibbs, Ryan E. Nature, Vol. 538, Issue 7625 https://doi.org/10.1038/nature19785	journal	October 2016
Structural principles of distinct assemblies of the human α4β2 nicotinic receptor Walsh, Richard M.; Roh, Soung-Hun; Gharpure, Anant Nature, Vol. 557, Issue 7704 https://doi.org/10.1038/s41586-018-0081-7	journal	May 2018
Nicotinic acetylcholine receptors as targets for antidepressants Shytle, R. D.; Silver, A. A.; Lukas, R. J. Molecular Psychiatry, Vol. 7, Issue 6 https://doi.org/10.1038/sj.mp.4001035	journal	July 2002
Spectroscopic investigations into the acid–base properties of nicotine at different temperatures Clayton, Peter M.; Vas, Carl A.; Bui, Tam T. T. Anal. Methods, Vol. 5, Issue 1 https://doi.org/10.1039/C2AY25678A	journal	January 2013
Selecting and identifying gas-phase protonation isomers of nicotineH + using combined laser, ion mobility and mass spectrometry techniques Marlton, Samuel J. P.; McKinnon, Benjamin I.; Ucur, Boris Faraday Discussions, Vol. 217 https://doi.org/10.1039/C8FD00212F	journal	January 2019
Gas phase protonated nicotine is a mixture of pyridine- and pyrrolidine-protonated conformers: implications for its native structure in the nicotinic acetylcholine receptor Takeda, Naoya; Hirata, Keisuke; Tsuruta, Kazuya Physical Chemistry Chemical Physics, Vol. 24, Issue 10 https://doi.org/10.1039/D1CP05175J	journal	January 2022
Collision-assisted stripping for determination of microsolvation-dependent protonation sites in hydrated clusters by cryogenic ion trap infrared spectroscopy: the case of benzocaineH⁺(H₂O)_n Hirata, Keisuke; Haddad, Fuad; Dopfer, Otto Physical Chemistry Chemical Physics, Vol. 24, Issue 10 https://doi.org/10.1039/D1CP05762F	journal	January 2022
Long-range corrected hybrid density functionals with damped atom–atom dispersion corrections Chai, Jeng-Da; Head-Gordon, Martin Physical Chemistry Chemical Physics, Vol. 10, Issue 44 https://doi.org/10.1039/b810189b	journal	January 2008
Gaussian basis sets for use in correlated molecular calculations. I. The atoms boron through neon and hydrogen Dunning, Thom H. The Journal of Chemical Physics, Vol. 90, Issue 2 https://doi.org/10.1063/1.456153	journal	January 1989
A novel discrete variable representation for quantum mechanical reactive scattering via the S ‐matrix Kohn method Colbert, Daniel T.; Miller, William H. The Journal of Chemical Physics, Vol. 96, Issue 3 https://doi.org/10.1063/1.462100	journal	February 1992
An explicitly correlated coupled cluster calculation of the helium–helium interatomic potential Klopper, Wim; Noga, Jozef The Journal of Chemical Physics, Vol. 103, Issue 14 https://doi.org/10.1063/1.470440	journal	October 1995
On the importance of the fragment relaxation energy terms in the estimation of the basis set superposition error correction to the intermolecular interaction energy Xantheas, Sotiris S. The Journal of Chemical Physics, Vol. 104, Issue 21 https://doi.org/10.1063/1.471605	journal	June 1996
NWChem: Past, present, and future Aprà, E.; Bylaska, E. J.; de Jong, W. A. The Journal of Chemical Physics, Vol. 152, Issue 18 https://doi.org/10.1063/5.0004997	journal	May 2020
Coupling of torsion and OH-stretching in tert -butyl hydroperoxide. I. The cold and warm first OH-stretching overtone spectrum Hansen, Anne S.; Huchmala, Rachel M.; Vogt, Emil The Journal of Chemical Physics, Vol. 154, Issue 16 https://doi.org/10.1063/5.0048020	journal	April 2021
Coupling of torsion and OH-stretching in tert -butyl hydroperoxide. II. The OH-stretching fundamental and overtone spectra Vogt, Emil; Huchmala, Rachel M.; Jensen, Casper V. The Journal of Chemical Physics, Vol. 154, Issue 16 https://doi.org/10.1063/5.0048022	journal	April 2021
Potential Therapeutic Application for Nicotinic Receptor Drugs in Movement Disorders Quik, Maryka; Boyd, James T.; Bordia, Tanuja Nicotine & Tobacco Research, Vol. 21, Issue 3 https://doi.org/10.1093/ntr/nty063	journal	August 2018
Molecular dynamics studies of AChBP with nicotine and carbamylcholine: the role of water in the binding pocket Amiri, S.; Sansom, M. S. P.; Biggin, P. C. Protein Engineering Design and Selection, Vol. 20, Issue 7 https://doi.org/10.1093/protein/gzm029	journal	March 2007
The Nicotinic Acetylcholine Receptor as a Target for Antidepressant Drug Development Philip, Noah S.; Carpenter, Linda L.; Tyrka, Audrey R. The Scientific World Journal, Vol. 2012 https://doi.org/10.1100/2012/104105	journal	January 2012
The pharmacological activity of nicotine and nornicotine on nAChRs subtypes: relevance to nicotine dependence and drug discovery: Nornicotine activation of nAChR Papke, Roger L.; Dwoskin, Linda P.; Crooks, Peter A. Journal of Neurochemistry, Vol. 101, Issue 1 https://doi.org/10.1111/j.1471-4159.2006.04355.x	journal	February 2007
Pharmacology of Nicotine: Addiction, Smoking-Induced Disease, and Therapeutics Benowitz, Neal L. Annual Review of Pharmacology and Toxicology, Vol. 49, Issue 1 https://doi.org/10.1146/annurev.pharmtox.48.113006.094742	journal	February 2009
FACILITATION OF HUMAN TOBACCO SELF-ADMINISTRATION BY ETHANOL: A BEHAVIORAL ANALYSIS ¹ Griffiths, Roland R.; Bigelow, George E.; Liebson, Ira Journal of the Experimental Analysis of Behavior, Vol. 25, Issue 3 https://doi.org/10.1901/jeab.1976.25-279	journal	May 1976
α7 Nicotinic Receptor Agonists: Potential Therapeutic Drugs for Treatment of Cognitive Impairments in Schizophrenia and Alzheimer’s Disease Toyohara, Jun; Hashimoto, Kenji The Open Medicinal Chemistry Journal, Vol. 4 https://doi.org/10.2174/1874104501004010037	journal	May 2010
Nicotinic receptor modulation to treat alcohol and drug dependence Rahman, Shafiqur; Engleman, Eric A.; Bell, Richard L. Frontiers in Neuroscience, Vol. 8 https://doi.org/10.3389/fnins.2014.00426	journal	January 2015
Epibatidine: A Promising Natural Alkaloid in Health Salehi, Bahare; Sestito, Simona; Rapposelli, Simona Biomolecules, Vol. 9, Issue 1 https://doi.org/10.3390/biom9010006	journal	December 2018

Similar Records

Gas phase protonated nicotine is a mixture of pyridine- and pyrrolidine-protonated conformers: implications for its native structure in the nicotinic acetylcholine receptor

Journal Article · Thu Dec 09 19:00:00 EST 2021 · Physical Chemistry Chemical Physics. PCCP · OSTI ID:1915275

Switching of Protonation Sites in Hydrated Nicotine via a Grotthuss Mechanism

Journal Article · Mon Jan 22 19:00:00 EST 2024 · Journal of the American Chemical Society · OSTI ID:2406154

The Gas Phase Protonation Sites of Six Naturally Occurring Nicotinoids

Journal Article · Thu Jun 27 20:00:00 EDT 2024 · Journal of Physical Chemistry Letters · OSTI ID:2477172

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
electronic structure
hydration
infrared spectroscopy
nicotine
nornicotine

Structure of Gas Phase Monohydrated Nicotine: Implications for Nicotine’s Native Structure in the Acetylcholine Binding Protein

Citation Formats

References (38)

Similar Records

Related Subjects