Bingyong He

An iridium(III) complex inhibits JMJD2 activities and acts as a potential epigenetic modulator

A novel iridium(III) complex was synthesized and evaluated for its ability to target JMJD2 enzymatic activity. The iridium(III) complex 1 can inhibit JMJD2 activity and was selective for JMJD2 activity over JARID, JMJD3, and HDAC activities. Moreover, 1 suppressed the trimethylation of the p21 promoter on H3K9me3 and interrupted the JMJD2D-H3K9me3 interactions in human cells, suggesting that it could act as an epigenetic modulator. To our knowledge, 1 represents the first metal-based JMJD2 inhibitor reported in the literature.

Development of an Aptamer-Based Sensing Platform for Metal Ions, Proteins, and Small Molecules through Terminal Deoxynucleotidyl Transferase Induced G-Quadruplex Formation

We report a label-free, structure-independent luminescent-sensing platform for metal ions, proteins, and small molecules utilizing an Ir(III) complex, terminal deoxynucleotidyl transferase (TdT), and a structure-folding aptamer. A novel G-quadruplex-selective Ir(III) complex was identified to detect the nascent G-quadruplex motifs with an enhanced luminescence response. Unlike most label-free DNA-based assays reported in the literature, this sensing platform does not require a specific secondary structure of aptamer, thus greatly simplifying DNA design. The detection platform was demonstrated by the detection of K(+) ions, thrombin, and cocaine as representative examples of metal ions, proteins, and small molecules.

A luminescent cocaine detection platform using a split G-quadruplex-selective iridium(III) complex and a three-way DNA junction architecture

In this study, a series of 10 in-house cyclometalated iridium(III) complexes bearing different auxiliary ligands were tested for their selectivity toward split G-quadruplex in order to construct a label-free switch-on cocaine detection platform employing a three-way junction architecture and a G-quadruplex motif as a signal output unit. Through two rounds of screening, we discovered that the iridium(III) complex 7 exhibited excellent selectivity toward the intermolecular G-quadruplex motif. A detection limit as low as 30 nM for cocaine can be achieved by this sensing approach with a linear relationship between luminescence intensity and cocaine concentration established from 30 to 300 nM. Furthermore, this sensing approach could detect cocaine in diluted oral fluid. We hope that our simple, signal-on, label-free oligonucleotide-based sensing method for cocaine using a three-way DNA junction architecture could act as a useful platform in bioanalytical research.

Development of a luminescent G-quadruplex-selective iridium(III) complex for the label-free detection of adenosine

A panel of six luminescent iridium(III) complexes were synthesized and evaluated for their ability to act as G-quadruplex-selective probes. The novel iridium(III) complex 1 was found to be highly selective for G-quadruplex DNA, and was employed for the construction of a label-free G-quadruplex-based adenosine detection assay in aqueous solution. Two different detection strategies were investigated for adenosine detection, and the results showed that initial addition of adenosine to the adenosine aptamer gave superior results. The assay exhibited a linear response for adenosine in the concentration range of 5 to 120 μM (R2 = 0.992), and the limit of detection for adenosine was 5 μM. Moreover, this assay was highly selective for adenosine over other nucleosides, and exhibited potential use for biological sample analysis.

Inhibition of the p53/hDM2 protein-protein interaction by cyclometallated iridium(III) compounds

Inactivation of the p53 transcription factor by mutation or other mechanisms is a frequent event in tumorigenesis. One of the major endogenous negative regulators of p53 in humans is hDM2, a ubiquitin E3 ligase that binds to p53 causing proteasomal p53 degradation. In this work, a library of organometallic iridium(III) compounds were synthesized and evaluated for their ability to disrupt the p53/hDM2 protein-protein interaction. The novel cyclometallated iridium(III) compound 1 [Ir(eppy)2(dcphen)](PF6) (where eppy = 2-(4-ethylphenyl)pyridine and dcphen = 4, 7-dichloro-1, 10-phenanthroline) blocked the interaction of p53/hDM2 in human amelanotic melanoma cells. Finally, 1 exhibited anti-proliferative activity and induced apoptosis in cancer cell lines consistent with inhibition of the p53/hDM2 interaction. Compound 1 represents the first reported organometallic p53/hDM2 protein-protein interaction inhibitor.

A G-triplex luminescent switch-on probe for the detection of mung bean nuclease activity

A cyclometallated Ir(iii) complex was synthesised and evaluated for the ability to act as a luminescent G-triplex probe. The iridium(iii) complex 1 [Ir(phq)2(2,9-dmphen)]PF6 (where phq = 2-phenylquinoline; 2,9-dmphen = 2,9-dimethyl-1,10-phenanthroline) exhibited high luminescence for G-triplex DNA over dsDNA and ssDNA, and was employed to construct a label-free G-triplex-based assay for mung bean nuclease activity in aqueous solution. This method was highly sensitive and selective for MB nuclease activity over other DNA-modifying enzymes.

A G-quadruplex-based platform for the detection of Hg2+ ions using a luminescent iridium(III) complex

We report herein the synthesis of a series of cyclometalated iridium(III) complexes as luminescent G-quadruplex-selective probes, which were used to construct an oligonucleotide-based platform for the dual detection and removal of Hg2+ ions.