Gas phase protonated nicotine is a mixture of pyridine- and pyrrolidine-protonated conformers: implications for its native structure in the nicotinic acetylcholine receptor
Gas phase protonated nicotine is a mixture of pyridine- and pyrrolidine-protonated conformers: implications for its native structure in the nicotinic acetylcholine receptor
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气相质子化尼古丁是吡啶和吡咯烷质子化构象异构体的混合物：对其烟碱乙酰胆碱受体中天然结构的影响
DOI：
10.1039/d1cp05175j
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发表时间：
2022
影响因子：
3.3
通讯作者：
Fujii Masaaki
中科院分区：
文献类型：
--
作者：
Takeda Naoya;Hirata Keisuke;Tsuruta Kazuya;Santis Garrett D.;Xantheas Sotiris S.;Ishiuchi Shun-ichi;Fujii Masaaki
气相质子化尼古丁的红外（IR）光谱在从未探测过的N-H“指纹区域”（3200-3500 cm−1）中进行了测量。由电喷雾源产生的质子化分子在第一离子阱中用水蒸气和He气体在预定温度下热化，然后在第二离子阱中在4K下通过IR光谱进行探测。红外光谱显示出两个N-H伸缩带，借助于高级电子结构计算，将其归属于吡啶和吡咯烷的原异构体。这一发现是在鲜明的对比，以前的光谱研究，提出了一个单一的人口的吡啶原异构体。两种原聚体的相对数量随热化阱温度在180 - 300 K之间的变化而变化。在240 K和300 K的相对构象的人口很好地再现的理论计算，明确地确定，气相尼古丁是一个3：2的混合物，在室温下的吡啶和吡咯烷原异构体。 加热无水蒸汽不会导致任何人口变化。它更确切地表明了水在实现两种原聚体之间的平衡中的催化作用。红外光谱和电子结构计算的结合建立了尼古丁中吡啶和吡咯烷原异构体之间的小能量差。其中一种气相尼古丁吡咯烷原异构体与烟碱乙酰胆碱受体（nAChR）中尼古丁的X射线结构在所有低能异构体中具有最接近的构象相似性。
The infrared (IR) spectra of gas phase protonated nicotine has been measured in the never-before probed N–H “fingerprint region” (3200–3500 cm−1). The protonated molecules generated by an electrospray source are thermalized in the first ion trap with water vapor and He gas at a pre-determined temperature prior to being probed by IR spectroscopy in the second ion trap at 4 K. The IR spectra exhibit two N–H stretching bands which are assigned to the pyridine and pyrrolidine protomers with the aid of high-level electronic structure calculations. This finding is in sharp contrast to previous spectroscopic studies that suggested a single population of the pyridine protomer. The relative populations of the two protomers vary by changing the temperature of the thermalizing trap from 180−300 K. The relative conformer populations at 240 K and 300 K are well reproduced by the theoretical calculations, unequivocally determining that gas phase nicotine is a 3 : 2 mixture of both pyridine and pyrrolidine protomers at room temperature. The thermalizing anhydrous vapor does not result in any population change. It rather demonstrates the catalytic role of water in achieving equilibrium between the two protomers. The combination of IR spectroscopy and electronic structure calculations establish the small energy difference between the pyridine and pyrrolidine protomers in nicotine. One of the gas phase nicotine pyrrolidine protomers has the closest conformational resemblance among all low-lying energy isomers with the X-ray structure of nicotine in the nicotinic acetylcholine receptor (nAChR).