基于高斯过程对乙酰氨基酚在不同环境溶解机制的研究

Study on dissolution mechanism of paracetamol in different environments by Gaussian Process

目的探究对乙酰氨基酚在不同环境中的溶解过程及其作用机制。方法利用紫外分光光度法测定不同温度下(20、30、40、50、60、70、80℃)对乙酰氨基酚在水中的平衡溶解度,及在pH 4.98、pH 6.64磷酸缓冲液中的平衡溶解度。在DFT-B3LYP/6-311G(d p)水平下,求得不同温度及酸性溶液的对乙酰氨基酚与水二聚体势能面上的优化几何构型,并进行热力学性质分析。结果对乙酰氨基酚在20、30、40、50、60、70、80℃水中的溶解度分别为(11.347±0.212)、(14.791±0.046)、(22.918±0.158)、(31.574±0.315)、(48.210±0.497)、(63.401±0.262)、(103.538±1.666)mg/mL;pH 4.98、pH 6.64磷酸缓冲液和纯水的溶解度分别为(17.397±0.296)、(21.404±0.122)、(22.893±0.347)mg/mL。经振动频率计算,确定二聚体结构稳定。不同温度下,焓值变大,是吸热过程,焓变值随温度的升高而增大,分子间相互作用随温度升高而增强,体系熵值减小,减小值随温度升高而下降。在同一温度下(313.15 K),中性环境和酸性环境下的焓值增大值(△H_T)_(中性)>(△H_T)_(酸性),中性环境下的分子间相互作用强于酸性环境。结论不同环境下的对乙酰氨基酚与水分子形成二聚体的热力学变化规律与平衡溶解度变化规律相一致。

Objective To investigate the dissolution process and mechanism of paracetamol in different environments. Methods The equilibrium solubility of paracetamol was measured by UV spectrophotometry at different temperatures（ 20,30,40,50,60,70 and 80 ℃） in water and phosphate buffers of pH 4.98 and pH 6.64. The optimized geometries of paracetamol,water and stable dimer（ Ⅰ） were obtained at the DFTB3LYP/6-311G（ d p） level. The thermodynamic properties were also measured. Results The solubility of paracetamol in water at different temperatures and acidic environments were as follows：（ 11.347 ± 0.212）mg/mL at 20 ℃,（ 14.791± 0.046） mg/mL at 30 ℃,（ 22.918± 0.158） mg/mL at 40 ℃,（ 31.574± 0.315）mg/mL at 50 ℃,（ 48.210± 0.497） mg/mL at 60 ℃,（ 63.401± 0.262） mg/mL at 70 ℃,（ 103.538± 1.666）mg/mL at 80 ℃;（ 17.397± 0.296） mg/mL at pH 4. 98,（ 21. 404 ± 0. 122） mg/m L at pH 6. 64,（ 22. 893 ±0. 347） mg/m L in pure water. Vibrational frequency calculations ascertained the stabilization of the dimers.At different temperatures the enthalpy became larger and it was endothermic process. The enthalpy and intermolecular interaction increased with temperature. The system entropy decreased with temperature. At the same temperature（ 313.15 K） the enthalpy increased（ △HT）（neutral）（ △HT）（acid） in the neutral and acidic environments. The molecular interactions in neutral environments were stronger than in acidic environments.Conclusion The thermodynamic changes of dimers forming of paracetamol and water in different environments are consistent with the changes of equilibrium solubility.