Lipophilic cations: Synthesis, analysis and HPLC of novel arylphosphonium salts

CHED 269

Dennis Bennett, dbennett_9348@ric.edu and John C. Williams Jr., jcwilliams@ric.edu. Physical Sciences Department, Rhode Island College, 600 Mt. Pleasant Ave., Providence, RI 02908
Arylphosphonium salts have shown some promise as novel anti-cancer agents. They are also bactericidal and acetylcholinesterase inhibitors. These salts tend to accumulate in the mitochondria of malignant cells in vitro, but getting the salts into cells in vivo has proven challenging. We report synthesis of these salts conjugated to lipophilic groups and screening analysis of the compounds in vitro. We have demonstrated a three-step synthesis, two of which are performed in the same vessel, with overall good yields. The logP values of the compounds have been calculated by QSAR, from measured partition coefficients and HPLC. An alternative method is to use calibrated HPLC retention times to calculate these values. We report the application of a newly available column, Waters AT-3, to determine HPLC LogP values for a set of these compounds.