Tuning Cerium(IV)‐Assisted Hydrolysis of Phosphatidylcholine Liposomes under Mildly Acidic and Neutral Conditions

With the goal of designing a lysosomal phospholipase mimic, we optimized experimental variables to enhance Ce^IV‐assisted hydrolysis of phosphatidylcholine (PC) liposomes. Our best result was obtained with the chelating agent bis–tris propane (BTP). Similar to the hydrolytic enzyme, Ce^IV‐assisted hydrolysis of PC phosphate ester bonds was higher at lysosomal pH (～4.8) compared to pH 7.2. In the presence of BTP, the average cleavage yield at ～pH 4.8 and 37 °C was: 67±1 %, 5.7‐fold higher than at ～pH 7.2 and roughly equivalent to the percent of phospholipid found on the metal‐accessible exo leaflet of small liposomes. No Ce^IV precipitation was observed. When BTP was absent, there was significant turbidity, and the amount of cleavage at ～pH 4.8 (69±1 %) was 2.1‐fold higher than the yield obtained at ～pH 7.2. Our results show that BTP generates homogenous solutions of Ce^IV that hydrolyze phosphatidylcholine with enhanced selectivity for lysosomal pH.