title: Extraordinary modulation of disulfide redox-responsiveness by cooperativity of twin-disulfide bonds.
abstract: Disulfide bonds have frequently been incorporated into synthetic materials to promote sensitivity of the systems towards different redox environments. Although many strategies have been developed to rationally tune the stability of disulfide linkers, methods to tune their responsiveness towards different redox environments remain elusive. In this work we have developed and explored a disulfide linker bearing two independent disulfide bonds, referred to as a twin-disulfide linker. We have demonstrated that the twin-disulfide linker displays an ultrahigh stability at lower concentrations of reducing agent or in weakly reducing environments without a significant compromise in the sensitivity of its response to highly reducing environments such as cytoplasm, a feature that is in remarkable contrast to the traditional single disulfide bonds. Such an extraordinary responsiveness arises from the cooperativity of the twin-disulfide bonds, which should be of particular interest for applications such as controlled drug delivery and sensing, because relatively large differences in disulfide stability in different redox environments is desired in these applications.
authors.affiliation: The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation, State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005 (P. R. China).
authors.forename: Linxiang
authors.initials: L
authors.lastname: Zhai
authors.forename: Jingjing
authors.initials: J
authors.lastname: Liang
authors.forename: Xiangqun
authors.initials: X
authors.lastname: Guo
authors.forename: Yibing
authors.initials: Y
authors.lastname: Zhao
authors.forename: Chuanliu
authors.initials: C
authors.lastname: Wu
mesh_terms: D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D004220:Disulfides / Q000737:chemistry*; D016503:Drug Delivery Systems; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D004220:Disulfides; D013438:Sulfhydryl Compounds
keywords: conjugation; cooperative effects; disulfide bonds; redox chemistry; thiol-disulfide exchange