Dipartimento di Chimica Inorganica, Chimica Analitica e Chimica Fisica, Università di Messina, Viale Ferdinando Stagno d'Alcontres, 31, I-98166 Messina (Vill. S. Agata), Italy.
Eur J Pharm Sci. 2012 Nov 20;47(4):661-77. doi: 10.1016/j.ejps.2012.08.005. Epub 2012 Aug 15.
The total solubility of three penicillin derivatives was determined, in pure water and NaCl aqueous solutions at different salt concentrations (from ∼0.15 to 1.0 mol L(-1) for ampicillin and amoxicillin, and from ∼0.05 to 2.0 mol L(-1) for (+)6-aminopenicillanic acid), using the shake-flask method for generating the saturated solutions, followed by potentiometric analysis. The knowledge of the pH of solubilization and of the protonation constants determined in the same experimental conditions, allowed us to calculate, by means of the mass balance equations, the solubility of the neutral species at different ionic strength values, to model its dependence on the salt concentration and to determine the corresponding values at infinite dilution. The salting parameter and the activity coefficients of the neutral species were calculated by the Setschenow equation. The protonation constants of ampicillin and amoxicillin, determined at different temperatures (from T=288.15 to 318.15K), from potentiometric and spectrophotometric measurements, were used to calculate, by means of the Van't Hoff equation, the temperature coefficients at different ionic strength values and the corresponding protonation entropies. The protonation enthalpies of the (+)6-aminopenicillanic acid were determined by isoperibol calorimetric titrations at T=298.15K and up to I=2.0 mol L(-1). The dependence of the protonation constants on ionic strength was modeled by means of the Debye-Hückel and SIT (Specific ion Interaction Theory) approaches, and the specific interaction parameters of the ionic species were determined. The hydrolysis of the β-lactam ring was studied by spectrophotometric and H NMR investigations as a function of pH, ionic strength and time. Potentiometric measurements carried out on the hydrolyzed (+)6-aminopenicillanic acid allowed us to highlight that the opened and the closed β-lactam forms of the (+)6-aminopenicillanic acid have quite different acid-base properties. An analysis of literature solubility, protonation constants, enthalpies and activity coefficients is reported too.
三种青霉素衍生物在纯水中和不同盐浓度的 NaCl 水溶液中的总溶解度（氨苄西林和阿莫西林的盐浓度从 ∼0.15 到 1.0 mol L(-1)，(+)6-氨基青霉烷酸的盐浓度从 ∼0.05 到 2.0 mol L(-1)）通过摇瓶法生成饱和溶液，然后进行电位分析。在相同实验条件下测定的溶度积和质子化常数的知识，使我们能够通过质量平衡方程计算不同离子强度值下中性物质的溶解度，对其与盐浓度的关系进行建模，并确定无限稀释时的相应值。盐参数和中性物质的活度系数由 Setschenow 方程计算。通过电位法和分光光度法在不同温度（T=288.15 到 318.15K）下测定的氨苄西林和阿莫西林的质子化常数，通过 Van't Hoff 方程计算不同离子强度值下的温度系数和相应的质子化熵。在 T=298.15K 和 I=2.0 mol L(-1)下，通过等压量热滴定法测定 (+)6-氨基青霉烷酸的质子化焓。通过 Debye-Hückel 和 SIT（特定离子相互作用理论）方法对质子化常数与离子强度的关系进行建模，并确定离子物种的特定相互作用参数。通过分光光度法和 H NMR 研究作为 pH、离子强度和时间的函数，研究了β-内酰胺环的水解。对水解的 (+)6-氨基青霉烷酸进行的电位测量使我们能够强调，(+)6-氨基青霉烷酸的开环和闭环β-内酰胺形式具有截然不同的酸碱性质。还报告了文献溶解度、质子化常数、焓和活度系数的分析。
