Kim Moon Suk, Diamond Scott L
Institute for Medicine and Engineering, Department of Chemical and Biomolecular Engineering, 1024 Vagelos Research Laboratory, University of Pennsylvania, Philadelphia, PA 19104, USA.
Bioorg Med Chem Lett. 2006 Aug 1;16(15):4007-10. doi: 10.1016/j.bmcl.2006.05.013. Epub 2006 May 19.
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.
对共价连接的前药、蛋白质或固相制剂载体进行外部控制的裂解，为可控药物或基因递送提供了潜在优势。合成了一系列邻硝基苄酯化合物（1-8），以便对光解性进行系统研究。光解性严格要求有邻硝基苄酯，而亚胺酯没有光解性。1-邻苯乙基酯的降解动力学比邻硝基苄酯快一个数量级。1-邻硝基苯乙基的甲苯磺酸酯、磷酸酯和苯甲酸酯衍生物表现出相似的光解性（在365nm下3.5mW/cm2照射10分钟内分解>80%）。邻-邻硝基苄基O′，O″-二乙基磷酸酯在适合生物系统的光照射条件（3.5mW/cm2，365nm）下分解最快。我们报道了1-邻硝基苯乙基衍生物的合成及光分解，这些衍生物适用于制备光不稳定前药或用于药物库、DNA缩合或组织工程应用的制剂颗粒。
