Transition metal compounds are a rich source for anticancer drug development. Judicious application of coordination ligands is a critical success factor in the design of effective anti-tumor compounds. N-heterocyclic carbenes (NHC) are stable ligands that have strong donor strengths in stabilizing metal ions and versatility in structural modifications to provide diverse scaffolds for biological molecular targeting. Remarkable advances have been achieved in the development of metal NHC complexes as anticancer as well as theranostic agents. NHC complexes of gold, platinum and palladium have been designed to elicit potent cancer cell cytotoxicity, effective anti-tumor activities in animal models as well as selective binding to molecular targets (e.g. protein thiols, DNA G-quadraplexes, mismatched DNA). The mechanisms of action of some of these complexes have been elucidated.
Taotao Zou Chunnam Lok Wan Pui-Ki Zhang Zhi Feng Fung Sin Ki 支志明
Current Opinion in Chemical Biology
2018
An iron(III)-BPsalan complex was found to efficiently catalyze the asymmetric chlorination reaction of cyclic β-keto esters and N -Boc oxindoles, affording the corresponding chlorinated products in high yield and up to 92% ee with NCS as chlorination reagent under mild reaction conditions.
Luo Yong Heng Ping Yuan Ji Li Zong Rui Gu Xin 徐镇江 支志明
Synthesis (Germany)
2018
Photocatalytic hydrogen evolution from pure water is successfully realized by using interstitial P-doped CdS with rich S vacancies (CdS-P) as the photocatalyst in the absence of any electron sacrificial agents. Through interstitial P doping, the impurity level of S vacancies is located near the Fermi level and becomes an effective electron trap level in CdS-P, which can change dynamic properties of photogenerated electrons and thus prolong their lifetimes. The long-lived photogenerated electrons are able to reach the surface active sites to initiate an efficient photocatalytic redox reaction. Moreover, the photocatalytic activity of CdS-P can be further improved through the loading of CoP as a cocatalyst.
Shi Rui Ye Hui-Fang Liang Fei Wang Zhuan Li Kai Weng Yu-Xiang Zheshuai Lin Wenfu Fu 支志明 Yong Chen
Advanced Materials
2018
Thermally induced transition from ordinary phosphorescence to delayed fluorescence in two kinds of luminescent copper(i) complexes is comprehensively investigated by using variable-temperature time-integrated and time-resolved photoluminescence measurements as well as model analysis. A pronounced impact of the molecular structure on exciton transfer from the lowest excited triplet spin states to the singlet spin states with higher energy is firmly demonstrated. Moreover, several fundamental photophysical processes including triplet localization, triplet harvesting, and reverse intersystem crossing are explored using theoretical models. Temperature dependence abnormalities of the emission intensity are quantitatively interpreted. Raman spectral characterization and theoretical calculations of vibronic emission transitions reveal that the molecules' thermal vibrations play an essential role in the fluorescence process.
Su Zheng Cheng G. 支志明 徐士杰
Journal of Materials Chemistry C
2017
Two classes of cationic palladium(II) acetylide complexes containing pincer-type ligands, 2,2′:6′,2′′-terpyridine (terpy) and 2,6-bis(1-butylimidazol-2-ylidenyl)pyridine (C^N^C), were prepared and structurally characterized. Replacing terpy with the strongly σ-donating C^N^C ligand with two N-heterocyclic carbene (NHC) units results in the Pd acetylide complexes displaying phosphorescence at room temperature and stronger intermolecular interactions in the solid state. X-ray crystal structures of [Pd(terpy)(C≡CPh)]PF (1) and [Pd(C^N^C)(C≡CPh)]PF (7) reveal that the complex cations are arranged in a one-dimensional stacking structure with pair-like Pd⋅⋅⋅Pd contacts of 3.349 Å for 1 and 3.292 Å for 7. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations were used to examine the electronic properties. Comparative studies of the [Pt(L)(C≡CPh)] analogs by H NMR spectroscopy shed insight on the intermolecular interactions of these Pd acetylide complexes. The strong Pd−C bonds render 7 and its derivative sufficiently stable for investigation of photo-cytotoxicity under cellular conditions.
Hung Faan-Fung Wu Shuixing Wai pong To Kwong Wai-Lun Xiangguo Guan Wei Lu Low Kam-Hung 支志明
Chemistry - An Asian Journal
2017
The CoP nanoparticle catalyst had excellent catalytic activity and a short catalytic induction period in the presence of anions, and high sustainability in ammonia borane hydrolysis, with an initial turnover frequency of 72.2 mol mol min at ambient temperature. This value is unprecedented for noble-metal-free catalytic systems.
Fu Zi-Cheng Xu Yong Sharon lai fung Chan Wang Wei Wei Li Fang Liang Fei Yong Chen Zheshuai Lin Wenfu Fu 支志明
Chemical Communications
2017
A unique ruthenium-thiolate molecular rhomboid (⋄)-[Ru(SAr)(CO)], which consists of eight octahedra linked by alternate face- and vertex-sharing, was produced by isomerization of the molecular wheel (○)-[Ru(SAr)(CO)] at elevated temperature. The use of a (○)-[Ru(SAr)(CO)] wheel for catalytic aziridination of alkenes via nitrene transfer is also described.
Tso Ken Chi-Hang Sharon lai fung Chan Jie sheng Huang 支志明
Chemical Communications
2017
Metal N-heterocyclic carbene (NHC) complexes are a promising class of anti-cancer agents displaying potent in vitro and in vivo activities. Taking a multi-faceted approach employing two clickable photoaffinity probes, herein we report the identification of multiple molecular targets for anti-cancer active pincer gold(III) NHC complexes. These complexes display potent and selective cytotoxicity against cultured cancer cells and in vivo anti-tumor activities in mice bearing xenografts of human cervical and lung cancers. Our experiments revealed the specific engagement of the gold(III) complexes with multiple cellular targets, including HSP60, vimentin, nucleophosmin, and YB-1, accompanied by expected downstream mechanisms of action. Additionally, Pt and Pd analogues can also bind the cellular proteins targeted by the gold(III) complexes, uncovering a distinct pincer cyclometalated metal–NHC scaffold in the design of anti-cancer metal medicines with multiple molecular targets.
Fung Sin Ki Taotao Zou Bei Cao Lee Pui Yan Fung Y.M. Eva Hu Di Chunnam Lok 支志明
Angewandte Chemie - International Edition
2017
Gold(iii) porphyrin-PEG conjugates [Au(TPP-COO-PEG-OCH)]Cl (1) and [Au(TPP-CONH-PEG-OCH)]Cl (2) have been synthesized and characterized. Based on the amphiphilic character of the conjugates, they were found to undergo self-assembly into nanostructures with size 120-200 nm and this did not require the presence of other surfactants or components for nano-assembly, unlike most conventional drug nano-formulations. With a readily hydrolyzable ester linkage, chemotherapeutic [Au(TPP-COOH)] exhibited triggered release from the conjugate 1 in acidic buffer solution as well as in vitro and in vivo without the formation of toxic side products. The nanostructures of 1 showed higher cellular uptake into cancer cells compared to non-tumorigenic cells, owing to their energy-dependent uptake mechanism. This, together with a generally higher metabolic rate and more acidic nature of cancer cells which can lead to faster hydrolysis of the ester bond, afforded 1 with excellent selectivity in killing cancer cells compared with non-tumorigenic cells in vitro. This was corroborated by fluorescence microscopy imaging and flow cytometric analysis of co-culture model of colon cancer (HCT116) and normal colon (NCM460) cells. In vivo experiments showed that treatment of nude mice bearing HCT116 xenografts with 1 resulted in significant inhibition of tumor growth and, more importantly, minimal systemic toxicity as revealed by histopathological analysis of tissue sections and blood biochemisty. The latter is explained by a lower accumulation of 1 in organs of treated mice at its effective dosage, as compared to that of other gold(iii) porphyrin complexes. Co-assembly of 1 and doxorubicin resulted in encapsulation of doxorubicin by the nanostructures of 1. The nanocomposites demonstrated a strong synergism on killing cancer cells and could overcome efflux pump-mediated drug-resistance in a doxorubicin-resistant ovarian cancer cell line (A2780adr) which was found in cells incubated with doxorubicin alone. Also, the nanocomposites accumulated more slowly in non-tumorigenic cells, resulting in a lower toxicity toward non-tumorigenic cells. These results indicate the potential application of 1 not only as an anti-cancer agent but also as a nanoscale drug carrier for chemotherapy.
Chung Clive Yik-Sham Fung Sin Ki Tong Ka-Chung Wan Pui-Ki Chunnam Lok Huang Yanyu Tianfeng Chen 支志明
Chemical Science
2017
The photophysical properties of a series of gold(i) [LAu(C≡CR)] (L = PCy (1a-4a), RNC (5a), NHC (6a)) and gold(iii) complexes [Au(C^N^C)(C≡CR)] (1b-4b) bearing heterocyclic arylacetylide ligands with narrow band-gap are compared. The luminescence of both series are derived from an intraligand transition localized on the arylacetylide ligand (ππ*(C≡CR)) but 1a-3a displayed prompt fluorescence (τ = 2.7-12.0 ns) while 1b-3b showed mainly phosphorescence (τ = 104-205 μs). The experimentally determined intersystem crossing (ISC) rate constants (k) are on the order of 10 to 10 s for the gold(i) series (1a-3a) but 10 to 10 s for the gold(iii) analogues (1b-3b). DFT/TDDFT calculations have been performed to help understand the difference in the k between the two series of complexes. Owing to the different oxidation states of the gold ion, the Au(i) complexes have linear coordination geometry while the Au(iii) complexes are square planar. It was found from DFT/TDDFT calculations that due to this difference in coordination geometries, the energy gap between the singlet and triplet excited states (ΔE) with effective spin-orbit coupling (SOC) for Au(i) systems is much larger than that for the Au(iii) counterparts, thus resulting in the poor ISC efficiency for the former. Time-resolved spectroscopies revealed a minor contribution (<2.9%) of a long-lived delayed fluorescence (DF) (τ = 4.6-12.5 μs) to the total fluorescence in 1a-3a. Attempts have been made to elucidate the mechanism for the origins of the DF: the dependence of the DF intensity with the power of excitation light reveals that triplet-triplet annihilation (TTA) is the most probable mechanism for the DF of 1a while germinate electron-hole pair (GP) recombination accounts for the DF of 2a in 77 K glassy solution (MeOH/EtOH = 4 : 1). Both 4a and 4b contain a BODIPY moiety at the acetylide ligand and display only IL(ππ*) fluorescence with negligible phosphorescence being observed. Computational analyses attributed this observation to the lack of low-lying triplet excited states that could have effective SOC with the S excited state.
Chan Kaai-Tung Glenna so ming Tong Wai pong To Yang Chen Du Lili Phillips David 支志明
Chemical Science
2017