title: Photocleavage of o-nitrobenzyl ether derivatives for rapid biomedical release applications.
abstract: 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.
authors.affiliation: Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, 1024 Vagelos Research Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Moon Suk
authors.initials: MS
authors.lastname: Kim
authors.forename: Scott L
authors.initials: SL
authors.lastname: Diamond
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers; D004987:Ethers / Q000737:chemistry*; D010777:Photochemistry; D013056:Spectrophotometry, Ultraviolet
chemical_list: D004337:Drug Carriers; D004987:Ethers