PHOTOPHYSICAL STUDIES OF LOCAL ANESTHETICS, TETRACAINE and PROCAINE: DRUG AGGREGATIONS
PHOTOPHYSICAL STUDIES OF LOCAL ANESTHETICS, TETRACAINE and PROCAINE: DRUG AGGREGATIONS
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局部麻醉剂、丁卡因和普鲁卡因的光物理研究：药物聚集
DOI：
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发表时间：
1990
影响因子：
3.3
通讯作者：
C. T. Lin
中科院分区：
文献类型：
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作者：
C. Mertz;A. Marques;L. Williamson;C. T. Lin
摘要采用低温（77 K）发射光谱研究了溶剂和浓度对叔胺类局部麻醉剂、丁卡因和普鲁卡因光物理性质的影响，并用HAM/3方法进行了理论验证。对于甲基环己烷中的丁卡因游离碱，当浓度大于1 × 10 - 3M时，在~ 375 nm处观察到宽荧光带。该条带在乙醇（即模型疏水环境）中消失，表明中性丁卡因更倾向于分子异缔合。在普鲁卡因- HCl水溶液中，即使在低至1 × 10−4M的浓度下，也可以检测到以~ 400 nm为中心的宽发射带，这归因于普鲁卡因- HCI的带电聚集体。本文对普鲁卡因、丁卡因和二布卡因进行了两个一般性观察：(1)乙醇溶液中的单位和游离碱局部麻醉剂具有相同的光物理性质，表明单位药物在乙醇中具有H+解离性。(2)计算出中性局部麻醉剂的最低单重态激发态具有从叔胺基团N上的非成键电子到芳香环π*轨道的电荷转移特征。本文讨论了局部麻醉药的去质子化、药物聚集和电荷转移激发在麻醉分子基础上可能产生的药理学意义。
Abstract— The effects of solvent and concentration on the photophysical properties of tertiary amine local anesthetics, tetracaine and procaine were studied experimentally using low temperature (77 K) emission spectroscopy and confirmed theoretically using a HAM/3 method. For tetracaine free base in methylcyclohexane, a broad fluorescence band observed at ˜375 nm for concentrations greater than 1 × 10−3M is assigned to the molecular self‐associated species. The disappearance of this band in ethanol (i.e. a model hydrophobic environment) indicates a greater tendency of neutral tetracaine towards molecular hetero‐association. In an aqueous solution of procainc‐HCl, a broad emission band centered at ˜400 nm is detected even at a concentration as low as 1 × 10−4M and is attributed to the charged aggregates of procaine‐HCI. Two general observations for procaine, tetracaine and dibucaine are noted: (1) the monocation and free base local anesthetics in ethanol solutions give identical photophysical properties, suggesting that the monocation drug species in ethanol is H+ dissociative. and (2) the lowest singlet excited state of neutral local anesthetics is calculated to have a charge‐transfer character originating from a non‐bonding electron in the N of tertiary amine group to the π* orbital of aromatic ring. The possible pharmacological implications of the deprotonation, the drug aggregations and the charge‐transfer excitations of local anesthetics on the molecular basis of anesthesia are discussed.