五种质子泵抑制剂S异构体的电子结构及理论ECD谱

Theoretical studies on the structures and ECD spectra of S isomer of PPIs

奥美拉唑钠、兰索拉唑钠、泮托拉唑钠、雷贝拉唑钠和艾普拉唑钠五个质子泵抑制剂分子中含有手性亚砜结构,具有一对对映异构体.为了解以上五个质子泵抑制剂分子电子结构特征和ECD谱性质,采用量子化学密度泛函理论和极化连续介质模型在B3LYP/6-311++G**水平上对上述化合物的S异构体在水溶液中的电子结构特征进行了理论研究.在此基础上,采用含时密度泛函理论在相同基组水平对其理论ECD谱进行了研究.结果表明:(1)S-奥美拉唑钠、S-兰索拉唑钠、S-泮托拉唑钠、S-雷贝拉唑钠、S-艾普拉唑钠五种质子泵抑制剂中,Na(21)与N(11)、O(2)之间均存在键鞍点,同时成键.(2)S-奥美拉唑钠、S-艾普拉唑钠的ECD谱近似,在300nm附近均存在负性CD吸收带,主要来源于π→π*电荷跃迁;S-艾普拉唑钠在242nm附近还存在正性CD吸收带,该吸收带主要来源于苯并咪唑环到Na(21)的π→d的电荷跃迁.S-兰索拉唑钠、S-泮托拉唑钠和S-雷贝拉唑钠的ECD谱相似,在230、300nm附近存在两个负性CD吸收带,均来源于π→π*的电荷跃迁.

Sodium salts of Omeprazole, Lansoprazole, Pantoprazole, Rabeprazole and Ilaprazole are pro- ton pump inhibitors （PPIs） containing the chiral sulfoxide, so each has a pair of enantiomers. In order to understand the electronic structures of above five PPIs, the density functional theory （DFT） and the polarizable continuum model （PCM） were performed on the S isomers in water at B3LYP/6-311＋ ＋G＊＊ level. On this basis, the ECD spectra of these molecules were studied using the time-dependent density functional theory （TD-DFT） at the same level. The calculation results demonstrate two conclusions： （1） In the S isomers of above five PPIs, the bond critical points indicating the formation of the bonds ex-ists between Na（21） and N（ll）, the similar phenomenon exists between Na （21） and 0（2） ; （2） S-ome- prazole sodium and S-Ilaprazole sodium have the similar ECD spectrum, both having negative cotton effect near 300 nm mainly derived from π→π charge transition, besides S-Ilaprazole sodium having a positive cotton effect mainly derived from π→π charge transition of benzimidazole ring to Na （21）;S- Lansoprazole sodium, S-Pantoprazole sodium and S-Rabeprazole sodium have the similar ECD spectrum, having two negative cotton effects at 230 and 300 nm both mainly derived from the π→π charge transition.