A5039894660- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Asymmetric Hydrogenation and Catalysis
- Metal complexes synthesis and properties
- Trace Elements in Health
- Click Chemistry and Applications
- Nanomaterials for catalytic reactions
- Ferrocene Chemistry and Applications
- Advanced biosensing and bioanalysis techniques
- Drug Transport and Resistance Mechanisms
- Catalysis for Biomass Conversion
- Protein Interaction Studies and Fluorescence Analysis
- Lanthanide and Transition Metal Complexes
- Organometallic Complex Synthesis and Catalysis
- Synthesis and Biological Evaluation
- Carbon dioxide utilization in catalysis
- Supramolecular Self-Assembly in Materials
- Chemical Synthesis and Analysis
- Heavy Metal Exposure and Toxicity
- Nanoparticle-Based Drug Delivery
- Radiopharmaceutical Chemistry and Applications
- Nanocluster Synthesis and Applications
- Nanoplatforms for cancer theranostics
- Magnetism in coordination complexes
- Mass Spectrometry Techniques and Applications
University of Warwick
2015-2024
University of Birmingham
2021-2024
Supra-Regional Assay Service
2023-2024
Coventry (United Kingdom)
2017-2021
Universidade Federal de São Carlos
2019
After nearly 20 years of research on the use ruthenium in fight against cancer, only two Ru(III) coordination complexes have advanced to clinical trials. During this time, field has produced excellent candidate drugs with outstanding vivo and vitro activity; however, we yet find a complex that would be viable alternative platinum currently used clinic. We aimed explore what learned from most prominent area, challenge new concepts chemical design. Particularly relevant are studies involving...
A photoactivatable dopamine-conjugated platinum(IV) anticancer complex (Pt-DA) has been incorporated into G-quadruplex G4K+ borate hydrogels by using ester linkages (Pt-G4K+B hydrogel). These were characterized 11B NMR, attenuated total reflection Fourier transform infrared spectroscopy, circular dichroism, scanning electron microscopy and transmission microscopy. Microscopy investigations revealed the transformation of an extended fiber assembly discrete flakes after incorporation Pt-DA....
Functional drug carrier systems have potential for increasing solubility and potency of drugs while reducing side effects. Complex polymeric materials, particularly anisotropic structures, are especially attractive due to their long circulation times. Here, we conjugated cyclic peptides the biocompatible polymer poly(2-hydroxypropyl methacrylamide) (pHPMA). The resulting conjugates were functionalized with organoiridium anticancer complexes. Small angle neutron scattering static light...
We report the synthesis and characterization of four neutral organometallic tethered complexes, [Ru(η6-Ph(CH2)3-ethylenediamine-N-R)Cl], where R = methanesulfonyl (Ms, 1), toluenesulfonyl (Ts, 2), 4-trifluoromethylbenzenesulfonyl (Tf, 3), 4-nitrobenzenesulfonyl (Nb, 4), including their X-ray crystal structures. These complexes exhibit moderate antiproliferative activity toward human ovarian, lung, hepatocellular, breast cancer cell lines. Complex 2 in particular exhibits a low...
Mitochondria generate energy but malfunction in many cancer cells, hence targeting mitochondrial metabolism is a promising approach for therapy. Here we have designed cyclometallated iridium(iii) complexes, containing one TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) spin label [C43H43N6O2Ir1·PF6]˙ (Ir-TEMPO1) and two labels [C52H58N8O4Ir1·PF6]˙ (Ir-TEMPO2). Electron paramagnetic resonance (EPR) spectroscopy revealed spin-spin interactions between the units Ir-TEMPO2. Both Ir-TEMPO1 Ir-TEMPO2...
Platinum drugs are widely used for cancer treatment. Other precious metals promising, but their clinical progress depends on achieving different mechanisms of action to overcome Pt-resistance. Here, we evaluate 13 organo-Os complexes: 16-electron sulfonyl-diamine catalysts [(η6-arene)Os(N,N′)], and 18-electron phenylazopyridine complexes [(η6-arene)Os(N,N')Cl/I]+ (arene = p-cymene, biphenyl, or terphenyl). Their antiproliferative activity does not depend p21 p53 status, unlike cisplatin,...
Organometallic complexes with novel activation mechanisms are attractive anticancer drug candidates.
New palladium complexes exhibit potent antiproliferative activity against A2780 and cisplatin-resistant A2780C is human ovarian cancer cells.
Abstract Most metallodrugs are prodrugs that can undergo ligand exchange and redox reactions in biological media. Here we have investigated the cellular stability of anticancer complex [Os II [(η 6 ‐ p ‐cymene)( RR / SS ‐MePh‐DPEN)] [ 1 ] (MePh‐DPEN=tosyl‐diphenylethylenediamine) which catalyses enantioselective reduction pyruvate to lactate cells. The introduction a bromide tag at an unreactive site on phenyl substituent Ph‐DPEN allowed us probe fate this Os human cancer cells by...
Abstract Asymmetric transfer hydrogenation (ATH) is an important process in organic synthesis for which the Noyori‐type Ru II catalysts [(arene)Ru(Tsdiamine)] are now well established and widely used. We demonstrate first time catalytic activity of osmium analogues. X‐ray crystal structures 16‐electron Os almost identical to those . Intriguingly precursor complex was isolated as a dichlorido with monodentate amine ligand. The readily synthesised (within 1 h) exhibit excellent...
Serum albumin is the major zinc carrier in blood plasma. Fatty acid binding to regulates its zinc-binding ability and alters plasma speciation.
Cyclometallated palladium(<sc>ii</sc>) and platinum(<sc>ii</sc>) pyrenyl-derived thiosemicarbazone (H<sub>2</sub>PrR) complexes of the type [M<sub>4</sub>(μ-S-PrR-κ<sup>3</sup>-<italic>C</italic>,<italic>N</italic>,<italic>S</italic>)<sub>4</sub>] (M = Pd<sup>II</sup>, Pt<sup>II</sup>; R ethyl, cyclohexyl) have been synthesised in good yields fully characterised.
Anticancer agents that exhibit catalytic mechanisms of action offer a unique multi-targeting strategy to overcome drug resistance. Nonetheless, many in-cell catalysts in development are hindered by deactivation endogenous nucleophiles. We have synthesised highly potent, stable Os-based 16-electron half-sandwich ('piano stool') catalyst introducing permanent covalent tether between the arene and chelated diamine ligand. This exhibits antiproliferative activity comparable clinical cisplatin...
Drug resistance to existing anticancer agents is a growing clinical concern, with many first line treatments showing poor efficacy in treatment plans of some cancers. Resistance platinum agents, such as cisplatin, particularly prevalent the ovarian cancer, one most common cancers amongst women developing world. Therefore, there an urgent need develop next generation which can overcome therapies. We report new series organoruthenium(II) complexes bearing structurally modified pyrithione...
Abstract Objectives Assessment of Wilson disease is complicated, with neither ceruloplasmin, nor serum or urine copper, being reliable. Two new indices, accurate non-ceruloplasmin copper (ANCC) and relative ANCC were developed applied to a cohort 71 patients, as part Disease Registry Study. Methods Elemental copper-protein speciation was for holo-ceruloplasmin quantitation using strong anion exchange chromatography coupled triple quadrupole inductively plasma mass spectrometry. The proteins...
Organo-ruthenium complexes catalyse formate reduction of NAD<sup>+</sup>, and enhances their antiproliferative activity in cancer cells.
A novel photoactivatable Pt(IV) diazido anticancer agent, Pt-succ-DFO, bearing a pendant deferoxamine (DFO) siderophore for radiometal chelation, has been synthesized the study of its in vivo behavior with radionuclide imaging. Pt-succ-DFO complexation Fe(III) and Ga(III) ions yielded new heterobimetallic complexes that maintain photoactivation properties photocytotoxicity parent Pt complex human cancer cell lines. Radiolabeled Pt-succ-DFO-68Ga (t1/2 = 68 min, positron emitter) was readily...
Abstract Marine cyanobacteria are critical players in global nutrient cycles that crucially depend on trace metals metalloenzymes, including zinc for CO 2 fixation and phosphorus acquisition. How strains proliferating the vast oligotrophic ocean gyres thrive at ultra-low concentrations is currently unknown. Using Synechococcus sp. WH8102 as a model we show its zinc-sensor protein Zur differs from all other known bacterial proteins overall structure location of sensory site. Uniquely,...
Fatty acids alter zinc speciation in plasma, increasing influx into endothelial cells.
Abstract Synthetic anticancer catalysts offer potential for low-dose therapy and the targeting of biochemical pathways in novel ways. Chiral organo-osmium complexes, example, can catalyse asymmetric transfer hydrogenation pyruvate, a key substrate energy generation, cells. However, small-molecule synthetic are readily poisoned there is need to optimise their activity before this occurs, or avoid occurring. We show that organometallic redox catalyst [Os( p -cymene)(TsDPEN)] ( 1 ), which...