Acidity constants of sparingly water-soluble drugs from potentiometric determinations in aqueous dimethyl sulfoxide.
Acidity constants of sparingly water-soluble drugs from potentiometric determinations in aqueous dimethyl sulfoxide.
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通过电位滴定法测定二甲亚砜水溶液中的难溶性药物的酸度常数。
DOI：
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发表时间：
1987
期刊：
影响因子：
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通讯作者：
L. Varoli
中科院分区：
文献类型：
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作者：
A. Fini;P. De Maria;A. Guarnieri;L. Varoli
本文报道了在纯有机溶剂和/或它们的含水混合物中的酸碱平衡的简要分析，目的是测定微溶于水的酸性药物的离解常数。在含水有机混合物中，含水Me 2SO（80%w/w）呈现出特别适合于酸碱研究的性质，并且只要玻璃电极被适当地校准，就可以通过电位技术获得具有化学意义的酸度常数。在此混合溶剂中，在25 ℃下用电位法测定了100多种酸的热力学酸度常数，并根据酸基的性质（COOH，OH，SH）和酸的结构（脂肪族，芳香族，杂环）将所选系列酸分为四类。已发现在水溶液中的实验pKa值与Me_2SO水溶液（80%w/w）中的pKa值之间的线性关系在单一类别内，并已导出一组方程（星号表示在混合溶剂中的无限稀释被视为标准状态的pKa值）。对于羧酸类，已发现以下“通用”方程：pKa（H2O）= -0.80 +0.67 pKa（Me 2SO; 80%w/w）。作为应用，报告了代表性数量的微溶酸在水中的pKa值。这些值已通过“通用”方程计算，使用在Me 2SO水溶液（80% w/w）中实验测定的pKa值。计算值与酸结构预期值吻合良好。
A brief analysis of the acid-base equilibria in pure organic solvents and/or in their aqueous mixtures is reported with the aim of determining dissociation constants of acidic drugs that are sparingly soluble in water. Among aqueous organic mixtures, aqueous Me2SO (80% w/w) presents properties particularly suitable for acid-base studies, and thermodynamically meaningful acidity constants can be obtained by a potentiometric technique, provided that the glass electrode is properly calibrated. Thermodynamic acidity constants of more than 100 acids have been potentiometrically determined at 25 degrees C in this mixed solvent, and the selected series of acids has been divided into four classes according to the nature of the acidic group (COOH, OH, SH) and the structure of the acid (aliphatic, aromatic, heterocyclic). A linear relationship between the experimental pKa values in water and pKa values in aqueous Me2SO (80% w/w) has been found within the single classes and a group of equations has been derived (the asterisk denotes pKa values in which infinite dilution in the mixed solvent is taken as a standard state). For the carboxylic acid class, the following "common" equation has been found: pKa(H2O) = -0.80 + 0.67 pKa (Me2SO; 80% w/w). As an application, pKa values in water are reported for a representative number of sparingly soluble acids. These values have been calculated by means of the "common" equation, using pKa values experimentally determined in aqueous Me2SO (80% w/w). The calculated values are in good agreement with those expected from the acid structures.