Solubility enhancement of phenol and phenol derivatives in perfluoroocytl bromide

Perfluorinated solvents are gaining popularity as pulmonary ventilation flu ids, but they suffer from poor solvent quality in concurrent drug delivery applications. The present study examines the use of a hydrophobic solubiliz ing agent capable of interacting with model drug solutes by hydrogen bondin g with the purpose of enhancing solubility in perfluorooctyl bromide (PFOB) . A series of solubilizing agents containing a ketone carbonyl to act as a hydrogen bond acceptor and a perfluoroalkyl chain to maintain the solubilit y of the putative complex in PFOB are investigated. The solubility of pheno l in PFOB is enhanced to the greatest extent by 1-(4-perfluorobutyl phenyl) -1-hexanone (III) where the ketone carbonyl is protected from the electron withdrawing effects of the perfluorobutyl chain by a phenyl ring. Experimen ts with solubilizers lacking the ketone group suggest that pi-pi bond inter actions of III with phenol do not significantly enhance solubility. For a s eries of phenol derivatives, a rank-order correlation exists between the ma gnitude of solubility enhancement by III, as reflected by the calculated as sociation constants, and the Hammett sigma parameter of the phenols. Becaus e the O-methyl-substituted phenols do not have the ability to hydrogen bond , their solubility is not enhanced by the presence of III. The results of t he present study indicate that solubility of model drug hydrogen bond donat ing compounds can be enhanced in PFOB by the presence of fluorocarbon-solub le hydrogen bond accepters.