Tsutsumi Hiroyuki, Tanabe Haruka, Ishizu Takashi
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University.
Chem Pharm Bull (Tokyo). 2018;66(6):620-623. doi: 10.1248/cpb.c18-00027.
A mixture of pharmaceuticals having a xanthine skeleton, theophylline, proxyphylline, diprophylline and (-)-epigallocatechin-3-O-gallate (EGCg) in water created a sticky precipitates, which were thought to be 2 : 2 complexes of the pharmaceuticals and EGCg. The molecular capture ability of the pharmaceuticals having a xanthine skeleton by EGCg was estimated by the amount of the pharmaceuticals included in the precipitates of the complexes, and measured by the integrated value of proton signals in the quantitative H-NMR spectra. Based on changes in chemical shifts of proton signals of the pharmaceuticals with a xanthine skeleton in H-NMR spectra by adding standard amounts of EGCg, the xanthine skeleton of the pharmaceuticals was considered to exist in the hydrophobic space formed by the three aromatic A, B, B' rings of EGCg, and a part of the proxyphylline and diprophylline side chains existed out of the hydrophobic space. In the H-NMR spectra of the mixture of (R)- and (S)-proxyphylline, (R)- and (S)-diprophylline and an equimolecular amount of EGCg, the N-CH signal of (R)- and (S)-proxyphylline, and (R)- and (S)-diprophylline was clearly observed as two singlets. This suggested that EGCg recognized the chirality of proxyphylline and diprophylline in water.
在水中，含有黄嘌呤骨架的药物（茶碱、丙羟茶碱、二羟丙茶碱）与（-）-表没食子儿茶素-3-O-没食子酸酯（EGCg）的混合物产生了粘性沉淀物，这些沉淀物被认为是药物与EGCg的2∶2复合物。通过复合物沉淀物中所含药物的量来估算具有黄嘌呤骨架的药物被EGCg的分子捕获能力，并通过定量氢核磁共振谱中质子信号的积分值来测量。基于通过添加标准量的EGCg在氢核磁共振谱中具有黄嘌呤骨架的药物的质子信号化学位移的变化，认为药物的黄嘌呤骨架存在于由EGCg的三个芳香A、B、B'环形成的疏水空间中，并且丙羟茶碱和二羟丙茶碱侧链的一部分存在于疏水空间之外。在（R）-和（S）-丙羟茶碱、（R）-和（S）-二羟丙茶碱与等摩尔量EGCg的混合物的氢核磁共振谱中，（R）-和（S）-丙羟茶碱以及（R）-和（S）-二羟丙茶碱的N-CH信号清晰地观察为两个单峰。这表明EGCg在水中识别了丙羟茶碱和二羟丙茶碱的手性。
