Syntheses of phospholipids containing 2-nitrobenzyl ester moieties at the terminals of alkyl chains and properties of photodegradable liposomes from the lipids

Phospholipid la bearing 2-nitrobenzyl ester moieties as a photocleavable group at the terminal of alkyl chains was synthesized from the corresponding terminal carboxy-bearing phospholipid 2 by the reaction with 2-nitrophenyl-substituted diazomethane. Phospholipid, 1b bearing alpha-methyl-2-nitrobenzyl group, 1c bearing 4,5-dimethoxy-2-nitrobenzyl group, and 1d bearing alpha-methyl-4,5-dimethoxy-2-nitrobenzyl group were similarly synthesized by the use of the respective diazo compounds. The order of photolysis rates of 2-nitrobenzyl ester linkage of phospholipids by ultrahigh-pressure mercury lamp is 1b greater than or equal to 1d > 1a > 1c. Liposomes of 1a-1d containing calcein in the inner aqueous layer were prepared by vortexing, sonication, and gel-filtration. UV irradiation resulted in fast release of the entrapped fluorescence dye. The order of release rates : 1b greater than or equal to 1d > 1c > 1a is consistent with that of photolysis rates except for 1c, which has poor retention of the dye.