Daniel Wei-Jing Kwong

Dopamine receptor expression is correlated with certain types of cancers, including lung, breast and colon cancers. In this study, we report luminescent iridium(III) complexes (11–14) as intracellular dopamine receptor (D1R/D2R) cell imaging agents. Complexes 11 and 13, which are conjugated with a dopamine receptor agonist, showed superior cell imaging characteristics, high stability and low cytotoxicity (>100 μM) in A549 lung cancer cells. siRNA knockdown and dopamine competitive assays indicated that complexes 11 and 13 could selectively bind to dopamine receptors (D1R/D2R) in A549 cells. Fluorescence lifetime microscopy demonstrated that complex 13 has a longer luminescence lifetime at the wavelength of 560–650 nm than DAPI and other chromophores in biological fluids. The long luminescence lifetime of complex 13 not only provides an opportunity for efficient dopamine receptor tracking in biological media, but also enables the temporal separation of the probe signal from the intense background signal by fluorescence lifetime microscopy for efficient analysis. Complex 13 also shows high photostability, which could allow it to be employed for long-term cellular imaging. Furthermore, complex 13 could selectively track the internalization process of dopamine receptors (D1R/D2R) in living cells. To the best of our knowledge, complex 13 is the first metal-based compound that has been used to monitor intracellular dopamine receptors in living cells.

A novel luminescent cyclometalated iridium(iii) complex 1 was synthesized and employed as a chemosensor for the detection of Al³⁺ ions. 1 displays a long lifetime luminescence that allow 1 to detect Al³⁺ ions in strong fluorescence media.

The new amphiphilic BODPY‐porphyrin conjugate BZnPP and its precursor BZnPH were synthesised, and their linear and two‐photon photophysical properties, together with their cellular uptake and photo‐cytotoxicity, were studied. This amphiphilic conjugate consists of a hydrophobic BODIPY moiety and a hydrophilic tetra(ethylene glycol) chain bridging a cationic triphenylphosphonium group to an amphiphilic porphyrin ZnP through acetylide linkers at its meso positions. A large two‐photon absorption cross‐section (σ=1725 GM) and a high singlet oxygen quantum yield (0.52) were recorded. Intense linear‐ and two‐photon‐induced red emissions were also observed for both BZnPP and BZnPH. Further in vitro studies showed that BZnPP exhibited very efficient cellular uptake and strong photocytotoxic but weak dark cytotoxic properties towards human breast carcinoma MCF‐7 cells. In summary, the two‐photon‐induced emission and the potent photo‐cytotoxicity of BZnPP make it an efficacious dual‐purpose tumour‐imaging and photodynamic therapeutic agent in the tissue‐transparent spectral windows.

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.

A water-soluble light-responsive antitumor agent, PtEuL, based on a cisplatin-linked europium–cyclen complex has been synthesized and evaluated for controlled cisplatin release by linear/two-photon excitation in vitro with concomitant turn-on and long-lived europium emission as a responsive traceable signal.

Being one of the hallmarks of Alzheimer’s disease, β-amyloid (Aβ) aggregates induce complicated neurotoxicity. Evidences show that the underlying mechanism of neurotoxicity involves a glutamate receptor subtype, N-methyl-D-aspartate (NMDA) receptor, an increase in intracellular calcium( II) ion loading as well as an elevation in oxidation stress. In this work, among the 35 chemical components of Chinese herbal medicines (CHMs) being screened for inhibitors of Aβ aggregation, four of them, namely albiflorin, aloeemodin, neohesperidin and physcion, were found for the first time to exhibit a potent inhibitory effect on Aβ_1-40 and Aβ_1-42 aggregation. Their neuroprotective capability on primary hippocampal neuronal cells was also investigated by MTT assay, ROS assay and intracellular calcium(II) ion concentration measurement. It was interesting to find that physcion was rather toxic to neuronal cells while albiflorin, aloeemodin and neohesperidin reduced the toxicity and ROS induced by both monomeric and oligomeric Aβ species. In addition, albiflorin was particularly powerful in maintaining the intracellular Ca²⁺ concentration.

We report herein a novel iridium(III) complex 1 as an antitumour necrosis factor agent and the first metal-based inhibitor of TACE enzymatic activity. Complex 1 inhibited TNF-α secretion and p38 phosphorylation in human monocytic THP-1 cells.

We report herein the synthesis and application of a series of novel cyclometalated iridium(III) complexes 1−3 bearing a rhodamine-linked NˆN ligand for the detection of Cu²⁺ ions. Under the optimised conditions, the complexes exhibited high sensitivity and selectivity for Cu²⁺ ions over a panel of other metal ions and showed consistent performance in a pH value range of 6 to 8. Furthermore, the potential application of this system for the monitoring of Cu²⁺ ions in tap water or natural river water samples was demonstrated.