A tri-functional vanadium(iv) complex to detect cysteine oxidation

Abstract

The development of effective molecular probes to detect and image the levels of oxidative stress in cells remains a challenge. Herein we report the design, synthesis and preliminary biological evaluation of a novel optical probe to monitor oxidation of thiol groups in cysteine-based phosphatases (CBPs). Following orthogonal protecting approaches we synthesised a new vanadyl complex designed to bind to CBPs. This complex is functionalised with a well-known dimedone derivative (to covalently trap sulfenic acids, SOHs) and a coumarin-based fluorophore for optical visualization. We show that this new probe efficiently binds to a range of phosphatases in vitro with nanomolar affinity. Moreover, preliminary flow cytometry and microscopy studies in live HCT116 cells show that this probe can successfully image cellular levels of sulfenic acids -one of the species resulting from protein oxidative damage.

Synthesis and Antiparasitic Activity of New Conjugates—Organic Drugs Tethered to Trithiolato-Bridged Dinuclear Ruthenium(II)–Arene Complexes

“…While the amide conjugate 18 was easily isolated in high yield (87%), the ester conjugate 17 could not be obtained in pure form, as it is prone to hydrolysis/solvolysis during purification. The N-Boc deprotection of 18 was realized in classical acidic conditions [85,86] (TFA, trifluoroacetic acid, Scheme 5), allowing the isolation of compound 19 in 64% yield.…”

Three-Photon AIE Pt(II) Complexes as Cysteine-Targeting Theranostic Agents for Tumor Imaging and Chemotherapy

“…10 μM) in cells . Intracellular Cys is found to be present in significantly higher levels in tumor tissues than in adjacent normal tissues. , Recently, a number of transition-metal complexes have been reported as Cys chemosensors. , They provide several advantages, such as significant Stokes shifts and large emission shifts that are responsive to deviations in the local environment. , These conventional fluorophores unavoidably face a problem of aggregation-caused quenching (ACQ), where their fluorescence is quenched at high concentrations. Aggregation-induced emission (AIE) as an abnormal fluorescence phenomenon, which is a counter activity to ACQ, has been discovered in recent years.…”

“…9,10 Recently, a number of transition-metal complexes have been reported as Cys chemosensors. 11,12 They provide several advantages, such as significant Stokes shifts and large emission shifts that are responsive to deviations in the local environment. 13,14 These conventional fluorophores unavoidably face a problem of aggregation-caused quenching (ACQ), where their fluorescence is quenched at high concentrations.…”