Lee Peng Foo, Peter
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- PublicationOpen AccessCopper (II) complexes of substituted salicylaldehyde dibenzyl semicarbazones: Synthesis, cytotoxicity and interaction with quadruplex DNAA series of substituted salicylaldehyde dibenzyl semicarbazones [RC6H3(OH)CH=NNHCON(CH2Ph)2] and their copper(II) complexes were synthesized and characterized. The chloridocopper(II) complexes of the 4- OH and 5-OH substituted ligands (complexes 9 and 7) show modest affinity and good selectivity (over duplex DNA) for the quadruplex formed from the 22AG human telomeric (HTelo) DNA sequence. Substitution of the chlorido ligands of these two complexes with pyridine yielded derivatives (7-py and 9-py) with increased affinity for HTelo. These derivatives also show good selectivity for HTelo over calf-thymus DNA (170- and 211-fold, respectively). The X-ray crystal structures of 9 and 9-py were determined. Molecular docking studies based on these structures show that the complexes stack on the 5′-end of the HTelo quadruplex, with the hydroxyl group forming a hydrogen bond with a guanine residue. Complexes 7, 9, 7-py and 9-py display significant cytotoxicity against MOLT-4 human leukaemia cells. Interestingly, they have low to negligible cytotoxicity against the non- cancerous IMR-90 human fibroblasts.
327 381WOS© Citations 35
- PublicationMetadata onlyWhat types of feedback do undergraduate chemistry students give each other? A case study from SingaporeThis study was part of a larger project to improve learning of undergraduate chemistry in Singapore through the use of self-authored three-tier multiple-choice questions (3TMCQs) and the giving/receiving of peer feedback. Specifically, we examined the quality of written feedback based on the classification by Hattie and Timperley (2007) that year 2 to 4 learners (N=31) gave each other on responses in their 3TMCQs (N=466 administered). It was found that the most common type of voluntary feedback given by test-makers was task (& self), followed by process (& self), self alone, and lastly regulation (& self) levels over seven chemistry courses. In addition, question type (based on revised Bloom’s Taxonomy) had a marginal effect on the quality of feedback received; instead, items answered incorrectly garnered higher quality feedback and were four times more important than the cognitive level of questions. Feedback quality given by more experienced students was also no better than those given by less experienced ones. While there is growing evidence supporting the self-authoring of questions and giving/receiving peer feedback to enhance learning at undergraduate levels, further research is warranted into the types of peer feedback that learners may receive when attempting different question formats.
- PublicationOpen Access
- PublicationOpen AccessDownregulation of oncogenic RAS and c-Myc expression in MOLT-4 leukaemia cells by a salicylaldehyde semicarbazone copper(II) complexCopper complexes with potent anti-tumor effect have been extensively developed. Most investigations of their modes of action focused on the biomolecular targets but not the signal transduction between target binding and cell death. We have previously shown that the cytotoxic complex pyridine(2,4-dihydroxybenzaldehyde dibenzyl semicarbazone)copper(II) (complex 1) shows selective binding to human telomeric G-quadruplex DNA over double-stranded DNA in vitro. Herein, we elucidate the mechanism of action by which complex 1 induces apoptosis in MOLT-4 cells. Complex 1 accumulates in the nuclei and differentially downregulates the expression of c-Myc, c-Kit and KRAS oncogenes. Chemical affinity capture assay results show that the complex is associated with c-Myc and KRAS quadruplex sequences in MOLT-4 cells. We further showed that the reduction in Ras protein expression resulted in attenuated MEK-ERK and PI3K-Akt signalling activities, leading to the activation of caspase dependent apoptosis. Notably, complex 1 increased the sensitivity of MOLT-4 cells to cisplatin and vice versa. Overall, we demonstrated that complex 1 induces apoptosis, at least in part, by suppressing KRAS, c-Kit and c-Myc oncogene expression and the pro-survival MEK-ERK and PI3K-Akt signalling pathways.
173 153Scopus© Citations 12WOS© Citations 12
- PublicationOpen AccessCurrent sheath formation in the plasma focusThe shaping and formation of the current sheath takes place in the breakdown phase of a plasma focus device. Achieving a clear understanding of the current sheath formation process is important because the plasma focus device performance depends on the quality of this sheath. In this paper, we created and successfully run an electromagnetic particle in cell code to simulate the breakdown phase. Magnetic effects are self-consistently incorporated in this formalism, allowing us to carry the simulation all the way to the point prior to breakdown.
- PublicationMetadata onlyRuthenium arene complexes with chalcone ligands incorporating pyridyl and anthryl units: Synthesis, aqueous stability and interaction with quadruplex DNA(Elsevier, 2023)
;Tan, Alan K. X. ;Chia, Jing Kang ;Teng, Jia Jun Zen ;Chiow, Steve Yan Cheng ;Zhai, Weiting ;Wu, Simin ;Lee, Xuan Peng ;Guo, Xingtong ; ;Rakesh GangulyTan, Kelvin Yong LengTwelve ruthenium(II) arene complexes incorporating chalcone ligands with pyridyl and anthryl units, as well as chlorido or oxalato ancillary ligands, have been synthesized and structurally characterized by 1H NMR spectroscopy, ESI mass spectrometry and elemental analysis. Compared to the oxalato compounds, the chlorido complexes were less stable and more susceptible to aquation in solution; the dissociation was suppressed in the presence of chloride ions. All six of the chlorido complexes and three of the oxalato complexes were able to bind to quadruplex DNA, exhibiting greater selectivity for HTelo over c-myc. The cationic species 3f, in which the chalcone chelates to the metal center, was found to bind to HTelo most strongly. These results indicate that the ancillary ligand, the location of the N-donor atom in the pyridyl ring, the position of the α,β-unsaturated ketone relative to the pyridyl and anthryl entities in the chalcone moiety, as well as the presence of the metal center all play significant roles in improving the binding of such complexes to quadruplex DNA. 10
- PublicationOpen AccessEducating science teachers in the 21st century: Implications for pre-service teacher educationThis study examines the verbal interactions among a group of pre-service teachers as they engaged in scientific discussions in a medicinal chemistry course. These discussions were part of the course that encompassed an explicit instruction of scientific argumentation structures as well as an applied component, whereby the pre-service teachers learned the content of medicinal chemistry through cases developed using the strategy of competing theories. By adopting a case study approach using sociocultural framework of learning, we examined the interactions between the pre-service teachers using video data. We describe 12 possible forms of interactions during discussions ─ (1) seeking clarification, (2) figuring out loud, (3) sharing information, (4) agreement, (5) asking questions, (6) providing explanations, (7) raising strategic and procedural issues, (8) stating claims, (9) disagreement, (10) sharing perspectives, (11) offering alternatives, and (12) persuasion. The pre-service teachers engaged in figuring out aloud and seeking clarifications frequently, and used persuasion least in their discussions. To clarify their ideas and thoughts, pre-service teachers commonly rebut their counterparts and used warrants to support their own assertions. A similar pattern was also observed when figuring their thoughts out loud. Our findings suggest that pre-service teachers were able to carry out rebuttals in the argumentation process. However, the quality and function of their rebuttals can be improved by deepening their understanding of the subject matter knowledge and the science argumentation structure. Implications are discussed.
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- PublicationOpen AccessOptimization of neon soft X-ray emission from 200 J plasma focus device for application in soft X-ray lithographyThe Fast Miniature Plasma Focus (FMPF) device is basically made up of coaxial electrodes with centrally placed anode and six cathode rods surrounding them concentrically. They are enclosed in a vacuum chamber, filled with low pressure operating gas. However, in our experiments, these cathode rods were removed to investigate the influence of them on neon soft X-ray (SXR) and hard X-ray (HXR) emission from the device. On removal of cathode rods, the cathode base plate serves as cathode and the plasma sheath is formed between the anode and the base plate of cathode. Neon was used as the operating gas for our experiments and the FMPF device used is of 235 J energy capacities. The experimental results showed that the FMPF device was able to focus better and the SXR emission efficiency was five times higher without cathode rods than with cathode rods. On the contrary, HXR emission did not vary with and without cathode rods. This observed phenomenon was further cross-checked through imaging of plasma dynamics, with and without cathode rods. FMPF device consists of 4 Pseudo Spark Gap (PSG) switches, which need to operate synchronously to deliver high voltage from capacitors to the anode. It was also seen that, the presence or absence of cathode rods also influence the synchronous operation of PSG switches. It also implies that this is one definite way to optimize the SXR emission from the FMPF device. This study reveals an important finding that, cathode rods play a vital role in the formation of plasma sheath with consequential influence on the radiation emission from plasma focus devices. Enhancement of the X-ray emission from this device is definitely a stepping stone in the realization of this device for industrial applications such as X-ray lithography for semiconductor industries.