Stasko A, Brezová V, Biskupic S, Ondrias K, Misík V
Department of Physical Chemistry, Faculty of Chemical Technology, Slovak Technical University, Bratislava.
Free Radic Biol Med. 1994 Dec;17(6):545-56. doi: 10.1016/0891-5849(94)90094-9.
Nifedipine, (1,4-dihydro-2,6,dimethyl-4-(2-nitrophenyl)-3, 5-pyridinedicarboxylic acid dimethyl ester) a calcium channel blocker widely used in treatment of hypertension, is strongly photolabile. This may represent a problem in patients taking nifedipine and in handling of nifedipine samples. Reactive radical intermediates were determined and characterized in the process of nifedipine illumination using EPR spectroscopy. On illumination of nifedipine by daylight or by a mercury lamp, a nitroxide radical, RIIL-NIFNO.X was observed (in the first step), in various solvents like benzene, cyclohexane, methanol, acetonitrile, dimethylsulphoxide, or aqueous suspensions of liposomes. RIIL-NIF represents the nifedipine skeleton centered with phenyl group, and X is an EPR silent substituent. The generation of RIIL-NIFNO.X is coupled with the formation of nitroso compound, RIIL-NIFNO, as characterized by UV-visible spectroscopy. In a further step, RIIL-NIFNO abstracts hydrogen from nifedipine skeleton under the formation of RIIL-NIFNO.H radical. In addition to this, in system containing RIIL-NIFNO and unsaturated lipids, nitroxide radicals RIIL-NIFNO.RLIPIDS are formed probably via a pseudo Diels-Alder mechanism (RLIPIDS represents lipidic skeleton). The unusually easy photochemical activation of nifedipine is probably stimulated by photosensitization of its nitro group interacting with suitably positioned hydrogen or carboxylic methyl ester group from the pyridinyl ring.
硝苯地平，（1,4 - 二氢 - 2,6 - 二甲基 - 4 -（2 - 硝基苯基）- 3,5 - 吡啶二甲酸二甲酯），一种广泛用于治疗高血压的钙通道阻滞剂，对光非常不稳定。这可能给服用硝苯地平的患者以及处理硝苯地平样品带来问题。利用电子顺磁共振波谱法（EPR）测定并表征了硝苯地平光照过程中的活性自由基中间体。当硝苯地平在日光或汞灯下照射时，在苯、环己烷、甲醇、乙腈、二甲基亚砜或脂质体水悬浮液等各种溶剂中观察到一种氮氧化物自由基RIIL - NIFNO·X（第一步）。RIIL - NIF代表以苯基为中心的硝苯地平骨架，X是一个EPR无信号取代基。RIIL - NIFNO·X的生成与亚硝基化合物RIIL - NIFNO的形成相关联，这通过紫外 - 可见光谱得以表征。在进一步的步骤中，RIIL - NIFNO从硝苯地平骨架上夺取氢，形成RIIL - NIFNO·H自由基。除此之外，在含有RIIL - NIFNO和不饱和脂质的体系中，氮氧化物自由基RIIL - NIFNO·RLIPIDS可能通过伪狄尔斯 - 阿尔德机制形成（RLIPIDS代表脂质骨架）。硝苯地平异常容易发生光化学活化，可能是由于其硝基与吡啶环上位置合适的氢或羧酸甲酯基团发生光敏化作用所激发。
