Fluorophilicity of Alkyl and Polyfluoroalkyl 1 Nicotinic Acid Ester Prodrugs.
Fluorophilicity of Alkyl and Polyfluoroalkyl 1 Nicotinic Acid Ester Prodrugs.
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烷基和多氟烷基 1 烟酸酯前药的亲氟性。
DOI：
10.1016/j.jfluchem.2010.04.001
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发表时间：
2010
影响因子：
1.9
通讯作者：
Lehmler,Hans-Joachim
中科院分区：
文献类型：
--
作者：
Ojogun,Vivian;Knutson,BarbaraL;Vyas,Sandhya;Lehmler,Hans-Joachim
一系列的烃和碳氟化合物官能化的烟酸酯（烟酸酯）的亲氟性测量从他们的分配行为（logKp）在全氟（甲基环己烷）（PFMC）和甲苯的两相溶剂系统。酯的烃或氟碳烷基的链长为1至12个碳原子。这些溶质的亲氟性的知识与这些用于基于氟碳化合物的药物递送的前药的设计相关。碳氢化合物烟酸酯的实验logKp值范围为-1.72至-3.40，氟化烟酸酯的实验logKp值范围为-1.64至0.13，其中只有具有最长氟化链的前药（2，2，3，3，4，4，5，5，6，6，7，7，8，8，8-十五氟辛基烟酸酯）优先分配到氟化相中（logKp=0.13）。使用从基团贡献技术或分子动力学模拟计算的溶解度参数的分配系数的预测是在合理的协议为全烃烟酸酯和短链全氟烟酸酯（10.3 -39%的偏差）。观察到最长链全氟烷基烟酸酯与实验分配系数的显著偏差（大于100%）。
The fluorophilicity of a series of hydrocarbon and fluorocarbon-functionalized nicotinic acid esters (nicotinates) is measured from their partitioning behavior (logKp) in the biphasic solvent system of perfluoro(methylcyclohexane) (PFMC) and toluene. The chain length of the hydrocarbon or fluorocarbon alkyl group of the ester ranges from one to twelve carbon atoms. Knowledge of the fluorophilicity of these solutes is relevant to the design of these prodrugs for fluorocarbon-based drug delivery. The experimental logKpvalues range from −1.72 to −3.40 for the hydrocarbon nicotinates and −1.64 to 0.13 for the fluorinated nicotinates, where only the prodrug with the longest fluorinated chain (2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctyl nicotinic acid ester) partitions preferentially into the fluorinated phase (logKp=0.13). Predictions of the partition coefficients using solubility parameters calculated from group contribution techniques or molecular dynamics simulation are in reasonable agreement for the perhydrocarbon nicotinates and short chained perfluorinated nicotinates (≈0.3–39% deviation). Significant deviations from experimental partition coefficients (greater than 100%) are observed for the longest chain perfluoroalkyl nicotinates.