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External‐Radiation‐Induced Local Hydroxylation Enables Remote Release of Functional Molecules in Tumors
Author(s) -
Fu Qunfeng,
Li Hongyu,
Duan Dongban,
Wang Changlun,
Shen Siyong,
Ma Huimin,
Liu Zhibo
Publication year - 2020
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202005612
Subject(s) - chemistry , hydroxylation , in vivo , prodrug , radical , fluorophore , molecule , functional group , combinatorial chemistry , photochemistry , small molecule , biophysics , organic chemistry , biochemistry , fluorescence , enzyme , physics , microbiology and biotechnology , quantum mechanics , biology , polymer
Abstract Radiation‐induced cleavage for controlled release in vivo is yet to be established. We demonstrate the use of 3,5‐dihydroxybenzyl carbamate (DHBC) as a masking group that is selectively and efficiently removed by external radiation in vitro and in vivo. DHBC reacts mainly with hydroxyl radicals produced by radiation to afford hydroxylation at para / ortho positions, followed by 1,4‐ or 1,6‐elimination to rescue the functionality of the client molecule. The reaction is rapid and can liberate functional molecules under physiological conditions. This controlled‐release platform is compatible with living systems, as demonstrated by the release of a rhodol fluorophore derivative in cells and tumor xenografts. The combined benefits of the robust caging group, the good release yield, and the independence of penetration depth make DHBC derivatives attractive chemical caging moieties for use in chemical biology and prodrug activation.