Fluorophilicity of alkyl and polyfluoroalkyl nicotinic acid ester prodrugs

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• 作者：Vivian Ojogun ; Barbara L. Knutson ; S ; hya Vyas ; Hans-Joachim Lehmler
• 关键词：Fluorophilicity ; Fluorinated solutes ; Nicotinates ; Phase behavior ; Prodrug
• 刊名：Journal of Fluorine Chemistry
• 出版年：2010
• 出版时间：July 2010
• 年：2010
• 卷：131
• 期：7
• 页码：784-790
• 全文大小：298 K

文摘

The fluorophilicity of a series of hydrocarbon and fluorocarbon-functionalized nicotinic acid esters (nicotinates) is measured from their partitioning behavior (log K_p) 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 log K_p values 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 (log K_p = 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.