光谱法研究γ-环糊精及其两种衍生物与罗库溴铵和维库溴铵的相互作用

Spectroscopy study on the interaction of γ-cyclodextrin and its two derivatives with rocuronium and vecuronium

目的研究γ-环糊精(γ-CD)及其两种衍生物与罗库溴铵、维库溴铵的相互作用。方法采用等温滴定量热法研究γ-CD及其衍生物奥美克松钠Aom0498-16(HS-7)、舒更葡糖(Sugammadex)与罗库溴铵、维库溴铵的相互作用,测定其热力学常数及结合常数。采用紫外-可见分光光度法测定γ-CD与罗库溴铵、维库溴铵的包合比与结合常数,并采用核磁共振谱二维相关谱和氢谱表征γ-CD及其两种衍生物与罗库溴铵、维库溴铵的结合力大小。结果等温滴定量热法结果显示Sugammadex与HS-7均以1∶1结合罗库溴铵、维库溴铵,γ-CD以2∶1结合罗库溴铵;HS-7与罗库溴铵的结合常数k=(3.44±2.18)×107L/mol、与维库溴铵的结合常数k=(5.80±1.83)×106L/mol,Sugammadex与罗库溴铵的结合常数k=(1.04±0.34)×107L/mol、与维库溴铵的结合常数k=(2.53±1.07)×106L/mol,γ-CD与罗库溴铵的结合常数k=(2.84±3.41)×104L/mol。紫外-可见分光光度法结果表明γ-CD以2∶1结合罗库溴铵、维库溴铵,γ-CD与罗库溴铵的结合常数k=6.93×104L/mol,与维库溴铵的结合常数k=5.17×104L/mol。核磁共振法结果显示HS-7对罗库溴铵、维库溴铵的包合作用强于Sugammadex和γ-CD。结论 HS-7包合肌松药的能力大于Sugammadex及γ-CD。等温滴定量热法、紫外-可见分光光度法和核磁共振谱二维相关谱和氢谱法3种方法从不同的侧面表征了包合物的性质。

Objective To study the interaction of y-cyclodextrin （y-CD） and its two derivatives with rocuronium and vecuroniurn. Methods The interactions of y-CD and its two derivatives HS-7, Sugamrnadex with rocuronium and vecuronium were characterized by Isothermal Titration Calorimetry （ITC）, and the thermodynamic constant and the binding constant was determined. The binding constant and inclusion ratio of y-CD with rocuronium and vecuronium was observed by ultraviolet- visible spectrophotometry; the binding ability of three cyclodextrins with rocuronium and vecuronium was analyzed by nuclear magnetic resonance spectroscopy COSY and 1 HNMR. Results The results of ITC showed that HS-7, Sugammadex combined with rocuronium and vecuronium in a 1 ： 1 molar ratio, and y-CDs combined with rocuronium in a 2 ： 1 molar ratio, with the binding constant of HS-7 and rocuronium being （3. 44±2. 18）×10^7 L/mol, HS-7 and vecuronium being （5. 80±1. 83）×10^6 L/mol, Sugammadex and rocuronium being （1.04±0. 34） × 10^7 L/mol, Sugarnmadex and vecuronium being （2.53±1.07） × 10^6 L/mol, and y-CD and rocuronium being （2. 84±3. 41）×10^4L/mol. The results of ultraviolet-visible spectrophotometry revealed that y-CDs combined with rocuronium and vecuronium in a 2 ： 1 molar ratio, with the binding constant of y-CD and roeuronium being 6. 93 × 10^4L/mol, and of y-CD and vecuronium being 5. 17 × 10^4 L/mol. The results of nuclear magnetic resonance spectroscopy suggested that the binding ability of HS-7 with rocuronium and vecuronium was stronger than that of Sugammadex and y-CD. Conclusion The binding ability of HS-7 with rocuronium and vecuronium is stronger than that of Sugammadex and y-CD, and the three methods used in this study （ITC, ultraviolet-visible spectrophotometry and nuclear magnetic resonance spectroscopy） can characterize the inclusion complex from different perspectives.