Two cytotoxic iron(II) complexes [Fe(L)(CH3 CN)n ](ClO4 )2 (L=qpy for Fe-1 a, Py5 -OH for Fe-2 a) were synthesized. Both complexes are stable against spontaneous demetalation and oxidation in buffer solutions. Cyclic voltammetry measurements revealed the higher stability of Fe-2 a (+0.82 V vs Fc) against Fe(II) to Fe(III) oxidation than Fe-1 a (+0.57 V vs Fc). These two complexes display potent cytotoxicity at micromolar level against a panel of cancer cell lines (Fe-1 a=0.8-3.1 μM; Fe-2 a=0.6-3.4 μM), and induce apoptosis that involves caspase activation. Transcriptomic and Connectivity Map analyses revealed that the changes of gene expression induced by Fe-1 a and Fe-2 a are similar to that induced by ciclopirox, an antifungal compound whose mode of action involves formation of intracellular cytotoxic iron chelates. Both Fe-1 a and Fe-2 a caused cellular nuclear DNA damage, as revealed by Comet assay and H2 AX immunofluorescence experiments. The cytotoxicity is associated with production of reactive oxygen species (for Fe-1 a), cell cycle regulation, and stress kinase pathways. The relative contributions of these to the overall cytotoxic mechanism is significantly affected by the structure of penta-N-donor ligand.
Kwong Wai-Lun Chunnam Lok Tse Chun-Wai Wong Ella L.ai-Ming 支志明
Chemistry (Weinheim an der Bergstrasse, Germany)
2015
The effects of La incorporation in three transition-metal (TM = Y, Zr, and Nb) oxides as gate dielectric of pentacene organic thin-film transistor (OTFT) have been investigated. La incorporated in Zr oxide and Nb oxide greatly decreases their trap density (as confirmed by low-frequency noise measurement) by passivating their oxygen vacancies, resulting in larger pentacene grains grown on them (as shown by atomic force microscopy) and thus higher carrier mobility for the OTFT due to less grain-boundary scattering. The carrier mobility of the ZrLaO- and NbLaO-OTFTs is about 70 times and 300 times higher than that of their counterparts based on ZrO₂ and Nb₂O₅, respectively. However, La incorporated in Y₂O₃ increases its trap density by roughening its surface, causing smaller pentacene grains grown and thus lower carrier mobility. On the other hand, all the three TM elements incorporated in La₂O₃ can result in more moisture-resistant gate dielectric with smoother surface, resulting in larger pentacene grains grown and thus higher carrier mobility for the OTFT.
Han Chuan Yu Wingman Tang Leung Cheung Hoi 支志明 Lai Peter T.
IEEE Transactions on Electron Devices
2015
A germline mutation (A339V) in thyroid transcription factor-1 ( TITF1/. NKX2.1) was shown to be associated with multinodular goiter (MNG) and papillary thyroid carcinoma (PTC) pathogenesis. The overexpression of A339V TTF1 significantly promoted hormone-independent growth of the normal thyroid cells, representing a cause of MNG and/or PTC. Nevertheless, the underlying mechanism still remains unclear. In this study, we used liquid chromatography (LC)-tandem mass spectrometry (MS/MS)-based shotgun proteomics comparing the global protein expression profiles of normal thyroid cells (PCCL3) that overexpressed the wild-type or A339V TTF1 to identify key proteins implicated in this process. Proteomic pathway analysis revealed that the aberrant activation of epidermal growth factor (EGF) signaling is significantly associated with the overexpression of A339V TTF1 in PCCL3, and clathrin heavy chain (Chc) is the most significantly up-regulated protein of the pathway. Intriguingly, dysregulated Chc expression facilitated a nuclear accumulation of pStat3, leading to an enhanced cell proliferation of the A339V clones. Down-regulation and abrogation of Chc-mediated cellular trafficking, respectively, by knocking-down Chc and ectopic expression of a dominant-negative (DN) form of Chc could significantly reduce the nuclear pStat3 and rescue the aberrant cell proliferation of the A339V clones. Subsequent expression analysis further revealed that CHC and pSTAT3 are co-overexpressed in 66.7% (10/15) MNG. Taken together, our results suggest that the A339V TTF1 mutant protein up-regulates the cellular expression of Chc, resulting in a constitutive activation of Stat3 pathway, and prompting the aberrant growth of thyroid cells. This extensive growth signal may promote the development of MNG.
Lau Sin-Ting Zhou Tingwen Liu Jessica Ai-Jia Fung Y.M. Eva 支志明 Brian Lang Elly sau wai Ngan
Biochimica et Biophysica Acta - Molecular Basis of Disease
2015
Upon switching the counter-ion to a highly lipophilic anion, a series of phosphorescent cationic organoplatinum(ii) salts are rendered soluble in non-polar solvents and can further self-organize into lamellar nanostructures, breath-figure arrays and smectic mesophases. This journal is
Yong Chen 支志明 Wei Lu
Chemical Communications
2015
We have performed theoretical analyses of the photophysical properties of a series of cyclometalated gold(III) arylacetylide complexes, [(C∧N∧C)AuIIIC≡CPh-4-OMe], with different extents of π-conjugation at the doubly C-deprotonated [C∧N∧C] ligand via replacement of one of the phenyl moieties in the non-conjugated C
Ming Tong Glenna So Chan Kaai-Tung Chang Xiaoyong 支志明
Chemical Science
2015
Here we describe a luminescent cyclometalated Au(iii)-avidin conjugate that exhibits a 520 nm emission with a lifetime of 1.8 μs in PBS solution in open air. The conjugate stains proteins and DNA and can inhibit cancer cell proliferation. This journal is
Tsai Johnson Lui-Lui Chan Anna On-Yee 支志明
Chemical Communications
2015
Covering: 2000 to 2014 Cancer is one of the leading causes of death worldwide. Ginseng, a key ingredient in traditional Chinese medicine, shows great promise as a new treatment option. As listed by the U.S. National Institutes of Health as a complementary and alternative medicine, its anti-cancer functions are being increasingly recognized. This review covers the mechanisms of action of ginsenosides and their metabolites, which can modulate signaling pathways associated with inflammation, oxidative stress, angiogenesis, metastasis, and stem/progenitor-like properties of cancer cells. The emerging use of structurally modified ginsenosides and recent clinical studies on the use of ginseng either alone or in combination with other herbs or Western medicines which are exploited as novel therapeutic strategies will also be explored. This journal is
Alice sze tsai Wong 支志明 Karwah Leung
Natural Product Reports
2015
The macrocyclic [Fe(L1)Cl] (1, L1 = N,N′-dimethyl-2,11-diaza[3,3](2,6)pyridinophane) complex is an active catalyst for the oxidation of water to oxygen using [NH][Ce(NO)] (CAN), NaIO, or Oxone as the oxidant. The mechanism of 1-catalysed water oxidation was examined by spectroscopic methods and by O-labelling experiments, revealing that FeO and/or FeO species are likely to be involved in the reaction. The redox behaviour of 1 and these high-valent FeO species of L1 has been examined by both cyclic voltammetry and density functional theory (DFT) calculations. In aqueous solutions, the cyclic voltammograms of 1 at different pH show a pH-dependent reversible couple (E = +0.46 V vs. SCE at pH 1) and an irreversible anodic wave (E = +1.18 V vs. SCE at pH 1) assigned to the Fe/Fe couple and the Fe to Fe oxidation, respectively. DFT calculations showed that the E value of the half reaction involving [Fe(L1)(O)(OH)]/[Fe(L1)(O)(OH)] is +1.42 V vs. SCE at pH 1. Using CAN as the oxidant at pH 1, the formation of an FeO reaction intermediate was suggested by ESI-MS and UV-vis absorption spectroscopic measurements, and the rate of oxygen evolution was linearly dependent on the concentrations of both 1 and CAN. Using NaIO or Oxone as the oxidant at pH 1, the rate of oxygen evolution was linearly dependent on the concentration of 1, and a reactive FeO species with formula [Fe(L1)(O)] generated by oxidation with NaIO or Oxone was suggested by ESI-MS measurements. DFT calculations revealed that [Fe(L1)(O)] is capable of oxidizing water to oxygen with a reaction barrier of 15.7 kcal mol.
Wai pong To Wai-Shan Chow Toby Tse Chun-Wai Xiangguo Guan Jie sheng Huang 支志明
Chemical Science
2015
Self-assembled functional nanoarchitectures are employed as important nanoscale building blocks for advanced materials and smart miniature devices to fulfi ll the increasing needs of high materials usage effi ciency, low energy consumption, and high-performance devices. One-dimensional (1D) crystalline nanostructures, especially molecule-composed crystalline nanostructures, attract signifi cant attention due to their fascinating infusion structure and functionality which enables the easy tailoring of organic molecules with excellent carrier mobility and crystal stability. In this review, we discuss the recent progress of 1D crystalline self-assembled nanostructures of functional molecules, which include both a small molecule-derived and a polymer-based crystalline nanostructure. The basic principles of the molecular structure design and the process engineering of 1D crystalline nanostructures are also discussed. The molecular building blocks, self-assembly structures, and their applications in optical, electrical, and photoelectrical devices are overviewed and we give a brief outlook on crucial issues that need to be addressed in future research endeavors.
Yanbing Guo Xu Liang Huibiao Liu Yongjun Li 支志明 李玉良
Advanced Materials
2015
The effects of La incorporation in three transition-metal (TM = Y, Zr, and Nb) oxides as gate dielectric of pentacene organic thin-film transistor (OTFT) have been investigated. La incorporated in Zr oxide and Nb oxide greatly decreases their trap density (as confirmed by low-frequency noise measurement) by passivating their oxygen vacancies, resulting in larger pentacene grains grown on them (as shown by atomic force microscopy) and thus higher carrier mobility for the OTFT due to less grain-boundary scattering. The carrier mobility of the ZrLaO- and NbLaO-OTFTs is about 70 times and 300 times higher than that of their counterparts based on ZrO and NbO, respectively. However, La incorporated in YO increases its trap density by roughening its surface, causing smaller pentacene grains grown and thus lower carrier mobility. On the other hand, all the three TM elements incorporated in LaO can result in more moisture-resistant gate dielectric with smoother surface, resulting in larger pentacene grains grown and thus higher carrier mobility for the OTFT.
Chuanyu Han Tang Wing-Man Leung 支志明 Pui to Lai
IEEE Transactions on Electron Devices
2015