哌嗪衍生物SIPI5357与环糊精分子非共价复合物的制备与分析

Preparation and Analysis of Non-covalent Complexes of Cyclodextrins with Piperazine Derivative Compound SIPI5357

报道了用电喷雾电离质谱(ESI-MS)和紫外光谱(UV)等方法研究一种具有抗抑郁活性的芳烷醇哌嗪类化合物SIPI5357与α-环糊精(α-CD)和β-环糊精(β-CD)制备得到的非共价复合物。质谱分析结果显示,SIPI5357分子可以与环糊精分子以1∶1的关系生成非共价复合物。使用紫外分光光度法对液相中非共价复合物的形成进行了辅助研究,得到了同样的结果。溶解度实验表明,这些非共价复合物的形成可以显著地提高此哌嗪类化合物在水溶液中的溶解度,使得它作为高效的口服或注射药物成为可能。此外,根据溶解度实验的结果,还计算了SIPI5357和两种环糊精分子在液相中的生成常数,它们分别为β-环糊精-SIPI5357:262L/mol/L,α-环糊精-SIPI5357:63.4L/mol/L。两种非共价复合物的稳定程度为β-环糊精-SIPI5357>α-环糊精-SIPI5357。

The non-covalent complexes of α-cyclodextrin and β-cyclodextrin （α-CD, β-CD） with an antidepressant compound-aralkyl hydroxyl piperazine derivative, 1 - （ 1 -chloro-2-methoxynaphthalene-6yl ） -2- （ 4- （ 1 - phenylethyl）piperazin-1-yl） pentan-l-ol dihydrochloride dihydrate （SIPI5357）, have been investigated. The complexes of α-CD, and β-CD with SIPI5357 have been prepared and studied by electrospray ionization mass spectrometry （ESI-MS） and ultraviolet （UV） spectrometry. The mass spectrometry results revealed that SIPI5357 （guest） and α-CD, and β-CD （host） formed 1：1 complexes in water solution. Furthermore, the α-CD/β-CD-SIPI5357 complexes exhibited different features and properties in UV spectroscopy from the reactants, which are coincidence with the results of ESI-MS. According to the solubility measurement, the formation of the non-covalent complexes could prominently increase the solubility of SIPI5357 in aqueous solution that has great significance in the study of the antidepressant drugs. The formation constant of the complexes have also been estimated by phase solubility studies. The calculated apparent formation constants of SIPI5357-β-CD and SIPI5357-α-CD are 262 L/mol and 63.4 L/mol, respectively.