Fluorophilicity of alkyl and polyfluoroalkyl nicotinic acid ester prodrugs

Vivian Ojogun, Barbara L. Knutson, Sandhya Vyas, Hans Joachim Lehmler

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


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

Original languageEnglish
Pages (from-to)784-790
Number of pages7
JournalJournal of Fluorine Chemistry
Issue number7
StatePublished - Jul 2010

Bibliographical note

Funding Information:
Special thanks to John May of the Environmental Research Training Laboratory (ERTL, University of Kentucky) for assistance with the GC analysis of the nicotinate partitioning. This work is funded by National Institute of Environmental Health Sciences, NIH , grants ES07380 and ES012475 .


  • Fluorinated solutes
  • Fluorophilicity
  • Nicotinates
  • Phase behavior
  • Prodrug

ASJC Scopus subject areas

  • Biochemistry
  • Environmental Chemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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