Redox-Click Chemistry for Disulfide Formation from Thiols

Abstract

The dynamic disulfide linkage plays a vital role in various biological processes as well as drugs and biomaterials. Oxidation of thiols is a widely utilized approach for disulfide synthesis; however, achieving both optimal reactivity and selectivity continues to pose a significant challenge. Here, we report the redox-click chemistry for disulfide formation from thiols by sulfonyl fluorides in both batch and flow-mode. Sulfuryl fluoride is a potent oxidant with exceptional selectivity toward thiols. This reaction's unique characteristics satisfy click chemistry's stringent criteria with its high thermodynamic driving force, simple reaction conditions, wide scope, quantitative yields, exceptional chemoselectivity, and non-chromatographic purification process. Furthermore, the redox click chemistry's ability to joining various modular thiol units was showcased in the synthesis of symmetrical, unsymmetrical and cyclic disulfides, poly(disulfide)s, and the in vivo disulfide cross-linked biomedical hydrogels.

Ultrabright NIR-IIb Fluorescence Quantum Dots for Targeted Imaging-Guided Surgery

“…Fourier transform infrared (FT-IR) spectroscopy was used to characterize the chemical composition of PbS@CdS@PEG NPs, PbS@CdS QDs, and mPEG-SH. As shown in Figure g and Figure S2, comparing with (iii) PbS@CdS QDs, (i) PbS@CdS@PEG NPs and (ii) mPEG-SH exhibited characteristic spectral peaks at 3420 cm –1 /3572 cm –1 (terminal thiol groups, −SH), 1112 cm –1 /1087 cm –1 (C–O–C stretching), and 515 cm –1 (−S–S– stretching), confirming the successful modification of PEG on the surface of PbS@CdS QDs. − In this case, −S–S– (disulfide bonds) were formed by the oxidation of mPEG-SH by ammonium hydroxide during PEGylation of NPs …”

“…49−51 In this case, −S−S− (disulfide bonds) were formed by the oxidation of mPEG-SH by ammonium hydroxide during PEGylation of NPs. 52 The PbS@CdS@PEG NPs, meticulously encapsulated in mPEG-SH, exhibited an impressive ability to evade the immune response typically triggered by scavenger receptors recognition during in vivo testing. 39 This unique trait significantly prolonged the fluorescence contrast time, enhancing the potential utility of these NPs in a variety of clinical applications.…”

Application of Iodine as a Catalyst in Aerobic Oxidations: A Sustainable Approach for Thiol Oxidations

“…Disulfide bonds are a valuable functional group known for their remarkable biological significance. They are widely prevalent in various natural compounds, biological formulations, biomaterials, and pharmaceuticals in Figure 1 [ [1][2][3][4][5][6]. The oxidation of thiols offers a straightforward and viable approach for synthesizing disulfides.…”