Okura Yuika, Santis Garrett D, Hirata Keisuke, Melissas Vasilios S, Ishiuchi Shun-Ichi, Fujii Masaaki, Xantheas Sotiris S
Department of Chemistry, School of Science, Tokyo Institute of Technology, 2-12-1 4259 Ookayama, Meguro-ku, Tokyo 152-8550, Japan.
Department of Chemistry, University of Washington, Seattle, Washington 98195, United States.
J Am Chem Soc. 2024 Feb 7;146(5):3023-3030. doi: 10.1021/jacs.3c08922. Epub 2024 Jan 23.
The switching of the protonation sites in hydrated nicotine, probed by experimental infrared (IR) spectroscopy and theoretical calculations, is facilitated via a Grotthuss instead of a bimolecular proton transfer (vehicle) mechanism at the experimental temperature ( = 130 K) as unambiguously confirmed by experiments with deuterated water. In contrast, the bimolecular vehicle mechanism is preferred at higher temperatures ( = 300 K) as determined by theory. The Grotthuss mechanism for the concerted proton transfer results in the production of nicotine's bioactive and addictive pyrrolidine-protonated (Pyrro-H) protomer with just 5 water molecules. Theoretical analysis suggests that the concerted proton transfer occurs via hydrogen-bonded bridges consisting of a 3 water molecule "core" that connects the pyridine protonated (Pyri-H) with the pyrrolidine-protonated (Pyrro-H) protomers. Additional water molecules attached as acceptors to the hydrogen-bonded "core" bridge result in lowering the reaction barrier of the concerted proton transfer down to less than 6 kcal/mol, which is consistent with the experimental observations.
通过实验红外（IR）光谱和理论计算探测到，水合尼古丁中质子化位点的切换，在实验温度（= 130 K）下是通过Grotthuss机制而非双分子质子转移（载体）机制实现的，这已被氘代水实验明确证实。相比之下，理论确定在较高温度（= 300 K）下双分子载体机制更占优势。协同质子转移的Grotthuss机制仅需5个水分子就能产生尼古丁具有生物活性和成瘾性的吡咯烷质子化（Pyrro-H）异构体。理论分析表明，协同质子转移通过由3个水分子“核心”组成的氢键桥发生，该“核心”连接吡啶质子化（Pyri-H）和吡咯烷质子化（Pyrro-H）异构体。作为受体附着在氢键“核心”桥上的额外水分子会使协同质子转移的反应势垒降低至小于6千卡/摩尔，这与实验观察结果一致。
