Fluorophilicity of alkyl and polyfluoroalkyl nicotinic acid ester prodrugs

Vivian Ojogun; Barbara L Knutson; Sandhya Vyas; Hans-Joachim Lehmler

doi:10.1016/j.jfluchem.2010.04.001

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Fluorophilicity of alkyl and polyfluoroalkyl nicotinic acid ester prodrugs

Journal article

Peer reviewed

Fluorophilicity of alkyl and polyfluoroalkyl nicotinic acid ester prodrugs

Vivian Ojogun, Barbara L Knutson, Sandhya Vyas and Hans-Joachim Lehmler

Journal of fluorine chemistry, Vol.131(7), pp.784-790

2010

DOI: 10.1016/j.jfluchem.2010.04.001

PMID: 20567608

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Abstract

The fluorophilicity of hydrocarbon and fluorocarbon-functionalized nicotinates is measured and predicted from their partitioning in biphasic perfluoro(methylcyclohexane)/toluene solvents. Varying the hydrocarbon or fluorocarbon alkyl chain length of the ester (one–twelve carbon atoms) provides a systematic comparison of the effect of molecule structure on fluorophilicity. 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.

Nicotinates

Prodrug

Phase behavior

Fluorinated solutes

Fluorophilicity

Details

Title: Subtitle: Fluorophilicity of alkyl and polyfluoroalkyl nicotinic acid ester prodrugs
Creators: Vivian Ojogun - Chemical and Materials Engineering Department, 177 Anderson Hall, University of Kentucky, Lexington, KY 40506-0046, United States
Barbara L Knutson - Chemical and Materials Engineering Department, 177 Anderson Hall, University of Kentucky, Lexington, KY 40506-0046, United States
Sandhya Vyas - Department of Occupational and Environmental Health, 100 Oakdale Campus, #124 IREH, University of Iowa, Iowa City, IA 52242-5000, United States
Hans-Joachim Lehmler - Department of Occupational and Environmental Health, 100 Oakdale Campus, #124 IREH, University of Iowa, Iowa City, IA 52242-5000, United States
Resource Type: Journal article
Publication Details: Journal of fluorine chemistry, Vol.131(7), pp.784-790
DOI: 10.1016/j.jfluchem.2010.04.001
PMID: 20567608
NLM abbreviation: J Fluor Chem
ISSN: 0022-1139
eISSN: 1873-3328
Publisher: Elsevier B.V
Language: English
Date published: 2010
Academic Unit: Occupational and Environmental Health; Iowa Neuroscience Institute
Record Identifier: 9984000921502771

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