“Two Birds with One Stone” Ruthenium(II) Complex Probe for Biothiols Discrimination and Detection In Vitro and In Vivo

Abstract

In this work, a “two birds with one stone” ruthenium(II) complex probe, Ru‐NBD, is proposed as an effective tool for biothiols detection and discrimination in vitro and in vivo. Ru‐NBD is nonluminescent due to the quenching of Ru(II) complex emission by photoinduced electron transfer (PET) from Ru(II) center to NBD and the quenching of NBD emission through 4‐substitution with “O” ether bond. Ru‐NBD is capable of reacting with Cys/Hcy to form long‐lived red‐emitting Ru‐OH and short‐lived green‐emitting NBD‐NR, while reacting with GSH to produce Ru‐OH and nonemissive NBD‐SR. The long lifetime emission of Ru(II) complex allows elimination of short lifetime background and NBD‐NR fluorescence for total biothiols detection (“bird” one) by time‐gated luminescence (TGL) analysis, and the remarkable difference in luminescence color response allows discrimination GSH and Cys/Hcy (“bird” two) through steady‐state luminescence analysis. Ru‐NBD features high sensitivity and selectivity, rapid luminescence response, and low cytotoxicity, which enables it to be used as the probe for luminescence and background‐free TGL detection and visualization of biothiols in live cells, zebrafish, and mice. The successful development of this probe is anticipated to contribute to the future biological studies of biothiols roles in various diseases.

Determination and Imaging of Small Biomolecules and Ions Using Ruthenium(II) Complex-Based Chemosensors

“…In 2020, Liu et al reported a “Two Birds with One Stone” Ru(II) complex 54 for the detection and discrimination of biothiols in vitro and in vivo (Fig. 26 A) [ 224 ]. Complex 54 was developed through coupling of two different signaling units (Ru(II) complex and NBD) through a “luminophore-responsive linker-luminophore” approach.…”

Time‐Resolved Luminescent Sensing and Imaging for Enzyme Catalytic Activity Based on Responsive Probes

“…To distinguish three different biothiols, Zhang et al designed and synthesized a bifunctional Ru(II) complex (Ru3), which could detect the total content of biothiols and discriminate GSH and Cys/Hcy simultaneously (Figure 13a). [53] The probe consisted of a longlived luminescent Ru(II) complex and a short-lived fluorescent 7-nitro-2,1,3-benzoxadiazoles (NBD) unit with an ether bond as a linker. The PET effect from Ru(II) complex to NBD quenched the long-lived luminescence of Ru(II) complex and the shortlived fluorescence of NBD simultaneously.…”

Advances in the development of fluorescence probes for cell plasma membrane imaging

“…< Fig. 6 is here > Luminescent transition metal complexes have recently attracted enormous interests in the development of probes for biosensing and imaging due to their abundant photo-physical/-chemical properties and controllable cytotoxicity [47][48][49][50][51][52][53]. Among various metal complexes, luminescent platinum(II) (Pt(II)), ruthenium (II) (Ru(II)), rhenium(I) (Re(I)), and iridium(III) (Ir(III)) are contributing significantly to this field [54][55][56][57][58][59].…”