Photocleavage of o-nitrobenzyl ether derivatives for rapid biomedical release applications.
The externally controlled cleavage of covalently linked prodrugs, proteins, or solid-phase formulation vehicles offers potential advantages for controlled drug or gene delivery. A series of o-nitrobenzyl ester compounds (1-8) were synthesized to allow a systematic study of photolability. The o-nitrobenzyl ester was strictly required for photolability, while imido esters were not photolabile. The degradation kinetics of 1-o-phenylethyl ester was an order of magnitude faster than that of o-nitrobenzyl ester. Tosylate, phosphate, and benzoate derivatives of 1-o-nitrophenylethyl displayed similar photolability (>80% decomposition within 10 min at 3.5 mW/cm2 at 365 nm). O-o-Nitrobenzyl O',O''-diethyl phosphate displayed the fastest decomposition at photoirradiation condition (3.5 mW/cm2, 365 nm) suitable for biological systems. We report the synthesis and photo-decomposition of 1-o-nitrophenylethyl derivatives amenable for the creation of photolabile prodrugs or formulation particles for drug depots, DNA condensation, or tissue engineering applications.
Kim
Moon Suk
MS
Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, 1024 Vagelos Research Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA.
Diamond
Scott L
SL
D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D004987:Ethers / Q000737:chemistry*; D010777:Photochemistry; D013056:Spectrophotometry, Ultraviolet
D004337:Drug Carriers; D004987:Ethers