抗抑郁化合物SIPI5838和环糊精分子非共价复合物的研究

Non-Covalent Complexes of Cyclodextrins with Antidepressant Compound SIPI5838

报道了用电喷雾电离质谱(ESI-MS),并结合紫外分光光度法及溶解度实验,研究一种新型的具有自主知识产权的抗抑郁化合物SIPI5838与α-环糊精(CD)和β-环糊精(CD)分子生成的非共价复合物.质谱测量结果表明,在溶液中,SIPI5838分子可以与环糊精分子之间生成非共价复合物,且两者之间的配比关系为1∶1.这些非共价复合物的形成可以显著地提高这种抗抑郁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.另外,还用紫外分光光度法和溶解度实验对液相中非共价复合物的形成进行了辅助研究,这些结果均显示了非共价复合物的生成.根据溶解度实验结果,计算了SIPI5838和两种环糊精分子在液相中的生成常数,它们分别为SIPI5838-β-环糊精:1.83×103mol-1·L,SIPI5838-α-环糊精:3.15×101mol-1·L.两种非共价复合物的稳定程度为β-环糊精-SIPI5838>α-环糊精-SIPI5838.

The non-covalent complexes of α-, or β-cyclodextrins （α-,β-CD） with the newly developed antidepressant compound, SIPI5838, have been investigated. The complexes of α-, or β-CD with SIPI5838 have been prepared and characterized by electrospray ionization mass spectrometry （ESI-MS）, and ultraviolet （UV） spectrometry as well. The mass spectrometry results revealed that SIPI5838 （guest） and α-, or β-CD （host） formed a 1 ： 1 complex in aqueous solution. The formation of the non-covalent complexes could significantly increase the solubility of SIPI5838 in aqueous solution. Furthermore, α-/β-CD-SIPI5838 complexes exhibited different features and properties in UV-Vis spectroscopy from the reactants, which confirms the results of ESI-MS. The formation constant of the complexes have also been estimated by phase solubility studies. The calculated apparent formation constants of SIPI5838-β-CD and SIPI5838-α-CD are 1.83×10^3 and 3.15 × 10^1 mol^-1·L, respectively. The stability of these two complexes are in the order of β-CD-SIPI5838 〉 α-CD-SIPI5838.