Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco-UPV/EHU, Barrio Sarriena s/n, 48940 Leioa, Spain.
Phys Chem Chem Phys. 2014 Aug 28;16(32):16968-75. doi: 10.1039/c4cp01702a.
The interaction of the general anesthetic propofol with an individual residue of threonine in the membrane receptors has been modeled in the gas phase by examining the adduct of propofol with the isopropanol side-chain. We determined the structural preferences of the cluster using a combination of mass-resolved laser spectroscopy and quantum mechanical calculations. The first electronic transition of propofol-isopropanol was recorded with vibrational resolution using resonant two-photon ionization (R2PI) and ion dip IR spectroscopy. The spectra obtained were compared with density-functional calculations (DFT) using the M06-2X functional in order to obtain the cluster's structure. Three isomers have been detected. The results suggest that propofol acts as a Brønsted acid, donating a proton to the isopropanol molecule in a conformation that resembles that of propofol-water, but displaced towards the aromatic ring, due to the interaction with the aliphatic side of isopropanol. The higher affinity of propofol for isopropanol compared to water may correlate with the biological role of propofol at the protein binding site. On the other hand, propofol shows a similar affinity for isopropanol and phenol, which could explain the mobility that propofol experiences inside the GABAA cavity.
全麻药物异丙酚与膜受体中单个苏氨酸残基的相互作用已在气相中通过检查异丙酚与异丙醇侧链的加合物来模拟。我们使用质量分辨激光光谱和量子力学计算的组合来确定团簇的结构偏好。使用共振双光子电离 (R2PI) 和离子陷 IR 光谱，以振动分辨率记录了异丙酚-异丙醇的第一电子跃迁。获得的光谱与使用 M06-2X 函数的密度泛函计算 (DFT) 进行了比较，以获得团簇的结构。已经检测到三种异构体。结果表明，异丙酚作为布朗斯台德酸，在类似于异丙醇-水的构象中将质子捐赠给异丙醇分子，但由于与异丙醇的脂肪侧相互作用，向芳环位移。与水相比，异丙酚对异丙醇的亲和力更高，这可能与异丙酚在蛋白质结合部位的生物学作用有关。另一方面，异丙酚对异丙醇和苯酚表现出相似的亲和力，这可以解释异丙酚在 GABA 腔体内的迁移率。
