ORCID Profile
0000-0003-1755-7991
Current Organisation
La Trobe University
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Analytical Chemistry | Transition Metal Chemistry | Solid State Chemistry | Organic Chemical Synthesis | Sensor Technology (Chemical aspects) | Physical Chemistry (Incl. Structural) | Electrochemistry | Structural Chemistry and Spectroscopy | Characterisation of Biological Macromolecules | Organic Chemistry | Physical Chemistry of Materials | Main Group Metal Chemistry | Optical Properties of Materials | Synthesis of Materials | Inorganic Chemistry | Bioinorganic Chemistry | Electroanalytical Chemistry | Analytical Spectrometry | Nanochemistry and Supramolecular Chemistry | Chemical Characterisation of Materials | F-Block Chemistry | Physical Organic Chemistry | Physical Chemistry not elsewhere classified | Analytical Biochemistry
ANZSRC Socio-Economic Objective (SEO)
Expanding Knowledge in the Chemical Sciences | Scientific Instruments | Expanding Knowledge in the Biological Sciences | Chemical sciences | Diagnostic Methods |
Related Links
Publications
Rhenium(i ) complexes of N-heterocyclic carbene ligands that bind to amyloid plaques of Alzheimer's disease
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C6CC10066J
Abstract: Rhenium( i ) complexes of tridentate N-heterocyclic carbene ligands that bind to amyloid plaques in human brain tissue are reported.
Luminescence Studies of the Intracellular Distribution of a Dinuclear gold(I) N-Heterocyclic Carbene Complex
Publisher: Wiley
Date: 05-09-2006
Antibacterial silver and gold complexes of imidazole and 1,2,4-triazole derived N-heterocyclic carbenes.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2DT01657E
Abstract: A series of gold(I) (4a-4h, 5a-5b) and silver(I) (3a-3h) complexes of 1,2,4-triazolylidene and imidazolylidene based N-heterocyclic carbene ligands were prepared and the antibacterial activities of these complexes have been evaluated. The complexes were characterised using
Cationic, linear Au(I) N-heterocyclic carbene complexes: synthesis, structure and anti-mitochondrial activity
Publisher: Royal Society of Chemistry (RSC)
Date: 2006
DOI: 10.1039/B602560A
Abstract: Six linear, two-coordinate cationic Au(I) N-heterocyclic carbene complexes of the form [(R2Im)2Au]+ (R = Me 1, Me, Et 2, i-Pr 3, n-Bu 4, t-Bu 5 and Cy 6) have been prepared by the reaction of two equivalents of the appropriate dialkylimidazol-2-ylidene (R2Im) with (Me2S)AuCl in dmf. Single crystal structural studies for 1.PF6, 2.PF6), 3.Cl and 4-6.PF6 show that for all six complexes the gold(I) centres have quasi-linear C-Au-C coordination, with quasi-parallel pairs of aromatic imidazole planes, except in 5.PF6 where they are quasi-normal in the latter, Au-C are 2.038(3), 2.033(3) A, cf. (e.g.) 2.027(2) A. Inter-cation Au...Au are close at 3.487(2), 3.525(2) A in 1PF6 and 2.PF6. The structural studies and low temperature NMR experiments provide no supportive evidence for the presence of pi back-bonding within this series of complexes. The lipophilicities of the six compounds, as estimated from the logarithm of the n-octanol-water partition coefficients (log P), varied across the series within the range -1.09 to 1.73. To investigate their potential as possible anti-mitochondrial anti-tumour agents, five of the compounds have been evaluated for their propensities to induce mitochondrial membrane permeabilization (MMP) in isolated rat liver mitochondria. At concentrations between 1-10 microM compounds 1.Br and 3-6.Cl induced dose-dependent, Ca2+-sensitive mitochondrial swelling at rates that increased with the lipophilicities of the complexes, with the most lipophilic compounds inducing the most rapid onset of swelling. The swelling was completely inhibited by cyclosporin A, the specific inhibitor of the mitochondrial permeability transition pore.
Chromium(V) peptide complexes: Synthesis and spectroscopic characterization
Publisher: American Chemical Society (ACS)
Date: 25-01-2005
DOI: 10.1021/IC048322H
Abstract: A series of stable Cr(V) model complexes that mimic the binding of Cr(V) to peptide backbones at the C-terminus of proteins have been prepared for N,N-dimethylurea derivatives of the tripeptides Aib3-DMF, AibLAlaAib-DMF, and AibDAlaAib-DMF (Aib = 2-amino-2-methylpropanoic acid, DMF = N,N-dimethylformamide). The Cr(ll) precursor complexes were synthesized by the initial deprotonation of the amide and acid groups of the peptide ligands in DMF with potassium tert-butoxide in the presence of CrCl2. The Cr(II) intermediates thus formed were then immediately oxidized to Cr(V) using tert-butyl hydroperoxide. Spectroscopic and mass-spectrometric analyses of the Cr(V) complexes showed that a new metal-directed organic transformation of the ligand had occurred. This involved a DMF solvent molecule becoming covalently bound to the amine group of the peptide ligand, yielding a urea group, and a third coordinated deprotonated urea nitrogen donor. A metal-directed oxidative coupling has been proposed as a possible mechanism for the organic transformation. The Cr(V/IV) reduction potential was determined for the three Cr(V) complexes using cyclic voltammetry, and in all cases it was quasi-reversible. These are the first isolated and fully characterized Cr(V) complexes with non-sulfur-containing peptide ligands.
Electrochemiluminescent Ruthenium(II) N-Heterocyclic Carbene Complexes: a Combined Experimental and Theoretical Study
Publisher: American Chemical Society (ACS)
Date: 18-06-2013
DOI: 10.1021/IC400263R
Abstract: A series of four Ru(II) complexes of the form [Ru(bpy)2(C(^)N)](2+) (where C(^)N is a bidentate pyridine-functionalized imidazolylidene- or benzimidazolylidene-based N-heterocyclic carbene (NHC) ligand and bpy is 2,2'-bipyridine) have been synthesized using a Ag(I) transmetalation protocol from the Ru(II) precursor compound, Ru(bpy)2Cl2. The synthesized azolium salts and Ru(II) complexes were characterized by elemental analysis, (1)H and (13)C NMR spectroscopy, cyclic voltammetry, and electronic absorption and emission spectroscopy. The molecular structures for two benzimidazolium salts and three Ru(II) complexes were determined by single crystal X-ray diffraction. The complexes display photoluminescence within the range 611-629 nm, with the emission wavelength of the benzimidazolylidene containing structures, slightly blue-shifted relative to the imidazolylidene containing complexes. All complexes exhibited a reversible, one-electron oxidation, which is assigned to the Ru(2+/3+) redox couple. When compared to [Ru(bpy)3](2+), complexes of imidazolylidene containing ligands were oxidized at more negative potentials, while those of the benzimidazolylidene containing ligands were oxidized at more positive potentials. All four complexes exhibited moderately intense electrochemiluminescence (ECL) with the obtained ECL spectra closely resembling the photoluminescence spectra. The ability to predictably fine-tune the highest occupied molecular orbital (HOMO) level of the Ru(II) complexes via the flexible synthetic strategy offered by NHCs is valuable for the design of ECL-based multiplexed detection strategies.
Synthesis, conformational analysis and antibacterial activity of Au(i)–Ag(i) and Au(i)–Hg(ii) heterobimetallic N-heterocyclic carbene complexes
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0DT02225J
Abstract: A family heterobimetallic Au( i )–Ag( i ) and Au( i )–Hg( ii ) complexes of bis-N-heterocyclic carbene ligands been prepared and their antibacterial properties evaluated.
Ablation of CD8+ T cell recognition of an immunodominant epitope in SARS-CoV-2 Omicron variants BA.1, BA.2 and BA.3
Publisher: Springer Science and Business Media LLC
Date: 27-10-2022
DOI: 10.1038/S41467-022-34180-1
Abstract: The emergence of the SARS-CoV-2 Omicron variant has raised concerns of escape from vaccine-induced immunity. A number of studies have demonstrated a reduction in antibody-mediated neutralization of the Omicron variant in vaccinated in iduals. Preliminary observations have suggested that T cells are less likely to be affected by changes in Omicron. However, the complexity of human leukocyte antigen genetics and its impact upon immunodominant T cell epitope selection suggests that the maintenance of T cell immunity may not be universal. In this study, we describe the impact that changes in Omicron BA.1, BA.2 and BA.3 have on recognition by spike-specific T cells. These T cells constitute the immunodominant CD8 + T cell response in HLA-A*29:02 + COVID-19 convalescent and vaccinated in iduals however, they fail to recognize the Omicron-encoded sequence. These observations demonstrate that in addition to evasion of antibody-mediated immunity, changes in Omicron variants can also lead to evasion of recognition by immunodominant T cell responses.
Therapeutic Gold Compounds
Publisher: Wiley
Date: 02-05-2014
Iridium Complexes of N-Heterocyclic Carbene Ligands: Investigation into the Energetic Requirements for Efficient Electrogenerated Chemiluminescence
Publisher: American Chemical Society (ACS)
Date: 27-05-2014
DOI: 10.1021/OM500076W
Rhenium complexes of bidentate, bis-bidentate and tridentate N-heterocyclic carbene ligands
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C5DT03295D
Abstract: Rhenium( i ) tricarbonyl complexes of a range of bidentate, bis-bidentate and tridentate NHC ligands have been prepared. These NHC ligands are of interest for possible applications in the development of Tc-99m or Re-186/188 radiopharmaceuticals and the stability of two complexes were evaluated in ligand challenge experiments using the metal binding amino acids l -histidine or l -cysteine.
Controlled Axial Coordination: Solid‐Phase Synthesis and Purification of Metallo‐Radiopharmaceuticals
Publisher: Wiley
Date: 15-10-2008
Triamidetriamine Bearing Macrobicyclic and Macrotricyclic Ligands: Potential Applications in the Development of Copper-64 Radiopharmaceuticals
Publisher: American Chemical Society (ACS)
Date: 16-12-2013
DOI: 10.1021/IC4024508
Abstract: A versatile and straightforward synthetic approach is described for the preparation of triamide bearing analogues of sarcophagine hexaazamacrobicyclic cage ligands without the need for a templating metal ion. Reaction of 1,1,1-tris(aminoethyl)ethane (tame) with 3 equiv of 2-chloroacetyl chloride, yields the tris(α-chloroamide) synthetic intermediate 6, which when treated with either 1,1,1-tris(aminoethyl)ethane or 1,4,7-triazacyclononane furnished two novel triamidetriamine cryptand ligands (7 and 8 respectively). The Co(III) and Cu(II) complexes of cryptand 7 were prepared however, cryptand 8 could not be metalated. The cryptands and the Co(III) complex 9 have been characterized by elemental analysis, (1)H and (13)C NMR spectroscopy, and X-ray crystallography. These studies confirm that the Co(III) complex 9 adopts an octahedral geometry with three facial deprotonated amido-donors and three facial amine donor groups. The Cu(II) complex 10 was characterized by elemental analysis, single crystal X-ray crystallography, cyclic voltammetry, and UV-visible absorption spectroscopy. In contrast to the Co(III) complex (9), the Cu(II) center adopts a square planar coordination geometry, with two amine and two deprotonated amido donor groups. Compound 10 exhibited a quasi-reversible, one-electron oxidation, which is assigned to the Cu(2+/3+) redox couple. These cryptands represent interesting ligands for radiopharmaceutical applications, and 7 has been labeled with (64)Cu to give (64)Cu-10. This complex showed good stability when subjected to L-cysteine challenge whereas low levels of decomplexation were evident in the presence of L-histidine.
Synthesis, X‐ray Crystallography, Spectroelectrochemistry and Computational Studies on Potential Copper‐Based Radiopharmaceuticals
Publisher: Wiley
Date: 17-07-2008
Synthesis, Radiolabelling and Confocal Fluorescence Microscopy of Styrene‐Derivatised Bis(thiosemicarbazonato)zinc and ‐copper Complexes
Publisher: Wiley
Date: 04-2008
Access to the Parent Tetrakis(pyridine)gold(III) Trication, Facile Formation of Rare Au(III) Terminal Hydroxides, and Preliminary Studies of Biological Properties
Publisher: American Chemical Society (ACS)
Date: 03-2016
DOI: 10.1021/ACS.INORGCHEM.5B02667
Abstract: In this paper we report on the use of [NO][BF4] to access tricationic tetrakis(pyridine)gold(III) from Au powder, a species inaccessible using the more traditional (tetrahydrothiophene)AuCl route. It is then demonstrated that this family of compounds can be used to access new terminal Au(III) hydroxides, a challenging class of compounds, and the first crystallographically characterized ex les employing bidentate ligands. Finally, preliminary biological studies indicate good activity for derivatives featuring polydentate ligands against the HeLa and PC3 cell lines but also strong inhibition of primary HUVEC cells.
Targeting the mitochondrial cell death pathway with gold compounds
Publisher: Elsevier BV
Date: 07-2007
Luminescent iridium(iii ) complexes of N-heterocyclic carbene ligands prepared using the ‘click reaction’
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9DT01362H
Abstract: Luminescent and electrochemiluminescent N-heterocyclic carbene-combined 1,2,3-triazole and 1,2,3-triazolylidene Ir( iii ) complexes have been prepared and their potential as luminescent probes in cell imaging has been evaluated.
Dinuclear Au(I) N-heterocyclic carbene complexes derived from unsymmetrical azolium cyclophane salts: Potential probes for live cell imaging applications
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6DT01409G
Abstract: Dinuclear Au–NHC complexes engineered to have short Au⋯Au distances are strongly luminescent and can be used as probes for live cell imaging applications.
Rhenium and Technetium Tricarbonyl Complexes of N-Heterocyclic Carbene Ligands
Publisher: American Chemical Society (ACS)
Date: 03-10-2014
DOI: 10.1021/IC500917S
Abstract: A strategy for the conjugation of N-heterocyclic carbene (NHC) ligands to biomolecules via amide bond formation is described. Both 1-(2-pyridyl)imidazolium or 1-(2-pyridyl)benzimidazolium salts functionalized with a pendant carboxylic acid group were prepared and coupled to glycine benzyl ester using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide. A series of 10 rhenium(I) tricarbonyl complexes of the form [ReX(CO)3(ĈN)] (ĈN is a bidentate NHC ligand, and X is a monodentate anionic ligand: Cl(-), RCO2(-)) were synthesized via a Ag2O transmetalation protocol from the Re(I) precursor compound Re(CO)5Cl. The synthesized azolium salts and Re(I) complexes were characterized by elemental analysis and by (1)H and (13)C NMR spectroscopy, and the molecular structures for one imidazolium salt and seven Re(I) complexes were determined by single-crystal X-ray diffraction. (1)H NMR and mass spectrometry studies for an acetonitrile-d3 solution of [ReCl(CO)3(1-(2-pyridyl)-3-methylimidazolylidene)] show that the monodentate chloride ligand is labile and exchanges with this solvent yielding a cationic acetonitrile adduct. For the first time the labeling of an NHC ligand with technetium-99m is reported. Rapid Tc-99m labeling was achieved by heating the imidazolium salt 1-(2-pyridyl)-3-methylimidazolium iodide and Ag2O in methanol, followed by the addition of fac-[(99m)Tc(OH2)3(CO)3](+). To confirm the structure of the (99m)Tc-labeled complex, the equivalent (99)Tc complex was prepared, and mass spectrometric studies showed that the formed Tc complexes are of the form [(99m/99)Tc(CH3CN)(CO)3(1-(2-pyridyl)-3-methylimidazolylidene)](+) with an acetonitrile molecule coordinated to the metal center.
Near‐Infrared Electrochemiluminescence from Bistridentate Ruthenium(II) Di(quinoline‐8‐yl)pyridine Complexes in Aqueous Media
Publisher: Wiley
Date: 02-2020
Synthetic, structural and spectroscopic studies of (pseudo)halo(1,3-di-tert-butylimidazol-2-ylidine)gold complexes
Publisher: Royal Society of Chemistry (RSC)
Date: 2005
DOI: 10.1039/B412540A
Abstract: A series of (pseudo)halo(1,3-di-tert-butylimidazol-2-ylidine)gold complexes [(But2Im)AuX](X = Cl, Br, I, CN, N3, NCO, SCN, SeCN, ONO2, OCOCH3, CH3) have been synthesized and characterised spectroscopically and structurally. 13C NMR chemical shifts for the carbene carbon vary widely with differing ancillary anion, correlating well with the sigma-donor ability of the latter and with the M-C(carbene) bond distance. These results reinforce the notion that N-heterocyclic carbene ligands are primarily sigma-donor ligands with little pi-acceptor ability.
Charge neutral rhenium tricarbonyl complexes of tridentate N-heterocyclic carbene ligands that bind to amyloid plaques of Alzheimer's disease
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/C9DT04687A
Abstract: Two tridentate ligand systems bearing N-heterocyclic carbene (NHC), amine and carboxylate donor groups coupled to benzothiazole- or stilbene-based amyloid binding moieties were synthesised.
Macrocyclic Diamide Ligand Systems: Potential Chelators for 64Cu- and 68Ga-Based Positron Emission Tomography Imaging Agents
Publisher: American Chemical Society (ACS)
Date: 09-07-2009
DOI: 10.1021/IC900307F
Mitochondrial permeability transition induced by dinuclear gold(I)-carbene complexes: potential new antimitochondrial antitumour agents
Publisher: Elsevier BV
Date: 10-2004
Nickel(II) and Palladium(II) Complexes with Chelating N-Heterocyclic Carbene Amidate Ligands: Interplay between Normal and Abnormal Coordination Modes
Publisher: American Chemical Society (ACS)
Date: 08-03-2013
DOI: 10.1021/OM4000133
Probing Conformational Variation in Luminescent Dinuclear Gold(I) N‐Heterocyclic Carbene Complexes
Publisher: Wiley
Date: 16-08-2017
Cytotoxic properties of rhenium(I) tricarbonyl complexes of N-heterocyclic carbene ligands.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2DT00447J
Abstract: A family of eight rhenium(I) tricarbonyl complexes bearing pyridyl-imidazolylidene or bis-imidazolylidene ligands in combination with a series of
Metal complexes with di(N-heterocyclic carbene) ligands bearing a rigid ortho-, meta or para-phenylene bridge
Publisher: Royal Society of Chemistry (RSC)
Date: 2016
DOI: 10.1039/C6DT01129B
Abstract: Ag( i ) complexes with diNHC ligands are efficient transmetalating agents towards transition metals.
Interactions between tripodal porphyrin hosts and single walled carbon nanotubes: an experimental and theoretical (DFT) account
Publisher: Royal Society of Chemistry (RSC)
Date: 2008
DOI: 10.1039/B719494C
Tuning the electrochemiluminescent properties of iridium complexes of N-heterocyclic carbene ligands
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C8DT04433C
Abstract: A series of electrochemiluminescent iridium( iii ) N-heterocyclic carbene complexes have been prepared to tune electrochemical and spectroscopic behaviour.
Bioenergetic differences selectively sensitize tumorigenic liver progenitor cells to a new gold(I) compound
Publisher: Oxford University Press (OUP)
Date: 15-04-2008
Abstract: A hallmark of cancer cells is their ability to evade apoptosis and mitochondria play a critical role in this process. Delineating mitochondrial differences between normal and cancer cells has proven challenging due to the lack of matched cell lines. Here, we compare two matched liver progenitor cell (LPC) lines, one non-tumorigenic [p53-immortalized liver (PIL) 4] and the other tumorigenic (PIL2). Analysis of these cell lines and a p53 wild-type non-tumorigenic cell line [bipotential murine oval liver (BMOL)] revealed an increase in expression of genes encoding the antiapoptotic proteins cellular inhibitor of apoptosis protein (cIAP) 1 and yes associate protein in the PIL2 cells, which resulted in an increase in the protein encoded by these genes. PIL2 cells have higher mitochondrial membrane potential (Deltapsi(m)) compared with PIL4 and BMOL and had greater levels of reactive oxygen species, despite the fact that the mitochondrial antioxidant enzyme, manganese superoxide disumutase, was elevated at transcript and protein levels. Taken together, these results may account for the observed resistance of PIL2 cells to apoptotic stimuli compared with PIL4. We tested a new gold compound to show that hyperpolarized Deltapsi(m) led to its increased accumulation in mitochondria of PIL2 cells. This compound selectively induces apoptosis in PIL2 cells but not in PIL4 or BMOL. The gold compound depolarized the Deltapsi(m), depleted the adenosine triphosphate pool and activated caspase-3 and caspase-9, suggesting that apoptosis was mediated via mitochondria. This investigation shows that the non-tumorigenic and tumorigenic LPCs are useful models to delineate the role of mitochondrial dysfunction in tumorigenesis and for the future development of mitochondria-targeted chemotherapeutics that selectively target tumor cells.
Electronic absorption spectroscopy and time-dependent density functional theory calculations on the nickel(II) complex of 1,4-bis(pyrrol-2-ylmethyleneamino)butane
Publisher: Elsevier BV
Date: 2009
A spectroscopic investigation of the self-association and DNA binding properties of a series of ternary ruthenium(II) complexes
Publisher: Elsevier BV
Date: 05-2005
DOI: 10.1016/J.JINORGBIO.2005.01.007
Abstract: Six ruthenium(II) complexes of the general form cis-alpha-[Ru(N4-tetradentate)(N2-bidentate)]Cl2 have been synthesized from the two related tetradentate ligands 1,6-di(2'-pyridyl)-2,5-dimethyl-2,5-diazahexane (picenMe2) and 1,6-di(2'-pyridyl)-2,5-dibenzyl-2,5-diazahexane (picenBz2) and the bidentate ligands 2,2'-bipyridine (bipy), 1,10-phenanthroline (phen) and dipyrido[3,2-f:2'3'-h]quinoxaline (dpq). Synthetic intermediate species of the general form cis-alpha-[Ru(II)(N4-tetradentate)(DMSO)Cl][PF6] were isolated. The N4-tetradentate ligand picenMe2 formed only the cis-alpha stereoisomer, while picenBz2 formed both the cis-alpha and cis-beta stereoisomers. These latter stereoisomers were resolved by fractional crystallisation. Dimer self-association constants, K(D), were estimated from the concentration dependence of the 1H NMR shifts for some of these complexes in aqueous solutions at 25 degrees C. The values of K(D) ranged from 0.6 to 7.9 M(-1) and a relationship was observed between the aromatic surface area of the bidentate component and the degree to which self-association occurred, whereby a greater level of self-association correlates with a larger surface area for the bidentate ligand. Some of these complexes demonstrate an ability to bind to DNA that is consistent with intercalation of the bidentate molecular component between the base pairs of the DNA molecule. Using calf-thymus DNA, the equilibrium binding constants, K(B), were determined for some of the complexes using intrinsic methods and these ranged from 3.32 to 5.11 M(-1), the intercalating abilities of the different bidentate ligands being in the order dp q > phen > bipy. This relationship between aromatic surface area of the bidentate ligand and the degree of DNA binding activity is the same as that observed in the self-association study.
Spectroelectrochemical and Computational Studies on the Mechanism of Hypoxia Selectivity of Copper Radiopharmaceuticals
Publisher: Wiley
Date: 27-06-2008
Abstract: Detailed chemical, spectroelectrochemical and computational studies have been used to investigate the mechanism of hypoxia selectivity of a range of copper radiopharmaceuticals. A revised mechanism involving a delicate balance between cellular uptake, intracellular reduction, reoxidation, protonation and ligand dissociation is proposed. This mechanism accounts for observed differences in the reported cellular uptake and washout of related copper bis(thiosemicarbazonato) complexes. Three copper and zinc complexes have been characterised by X-ray crystallography and the redox chemistry of a series of copper complexes has been investigated by using electronic absorption and EPR spectroelectrochemistry. Time-dependent density functional theory (TD-DFT) calculations have also been used to probe the electronic structures of intermediate species and assign the electronic absorption spectra. DFT calculations also show that one-electron oxidation is ligand-based, leading to the formation of cationic triplet species. In the absence of protons, metal-centred one-electron reduction gives the reduced anionic copper(I) species, [CuIATSM](-), and for the first time it is shown that molecular oxygen can reoxidise this anion to give the neutral, lipophilic parent complexes, which can wash out of cells. The electrochemistry is pH dependent and in the presence of stronger acids both chemical and electrochemical reduction leads to quantitative and rapid dissociation of copper(I) ions from the mono- or diprotonated complexes, [CuIATSMH] and [Cu(I)ATSMH2]+. In addition, a range of protonated intermediate species have been identified at lower acid concentrations. The one-electron reduction potential, rate of reoxidation of the copper(I) anionic species and ease of protonation are dependent on the structure of the ligand, which also governs their observed behaviour in vivo.
The Fate of NHC‐Stabilized Dicarbon
Publisher: Wiley
Date: 14-01-2015
Abstract: The attempted synthesis of NHC-stabilized dicarbon (NHC=C=C=NHC) through deprotonation of a doubly protonated precursor ([NHC-CH=CH-NHC](2+) ) is reported. Rather than deprotonation, a clean reduction to NHC=CH-CH=NHC is observed with a variety of bases. The apparent resistance towards deprotonation to the target compound led to a reinvestigation of the electronic structure of NHC→CC←NHC, which showed that the highest occupied molecular orbital/lowest unoccupied molecular orbital (HOMO/LUMO) gap is likely too small to allow for isolation of this species. This is in contrast to the recent isolation of the cyclic alkylaminocarbene analogue (cAAC=C=C=cAAC), which has a large HOMO-LUMO gap. A detailed theoretical study illuminates the differences in electronic structures between these molecules, highlighting another case of the potential advantages of using cAAC rather than NHC as a ligand. The bonding analysis suggests that the dicarbon compounds are well represented in terms of donor-acceptor interactions L→C2 ←L (L=NHC, cAAC).
Increased glutaminyl cyclase activity in brains of Alzheimer's disease individuals.
Publisher: Wiley
Date: 20-07-2020
DOI: 10.1111/JNC.15114
Abstract: Glutaminyl cyclases (QC) catalyze the formation of neurotoxic pGlu‐modified amyloid‐β peptides found in the brains of people with Alzheimer's disease (AD). Reports of several‐fold increases in soluble QC (sQC) expression in the brain and peripheral circulation of AD in iduals has prompted the development of QC inhibitors as potential AD therapeutics. There is, however, a lack of standardized quantitative data on QC expression in human tissues, precluding inter‐laboratory comparison and validation. We tested the hypothesis that QC is elevated in AD tissues by quantifying levels of sQC protein and activity in post‐mortem brain tissues from AD and age‐matched control in iduals. We found a modest but statistically significant increase in sQC protein, which paralleled a similar increase in enzyme activity. In plasma s les sourced from the Australian Imaging, Biomarker and Lifestyle study we determined that QC activity was not different between the AD and control group, though a modest increase was observed in female AD in iduals compared to controls. Plasma QC activity was further correlated with levels of circulating monocytes in AD in iduals. These data provide quantitative evidence that alterations in QC expression are associated with AD pathology. image
Luminescent iridium(iii)–boronic acid complexes for carbohydrate sensing
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0DT02177F
Abstract: A family of four Ir( iii ) complexes with either pyridyl-1,2,4-triazole or pyridyl-1,3,4-oxadiazole ligands bearing boronic acid groups have been prepared as potential luminescent sensors for carbohydrates.
Facile Formation of Homoleptic Au(III) Trications via Simultaneous Oxidation and Ligand Delivery from [PhI(pyridine)2]2+
Publisher: American Chemical Society (ACS)
Date: 21-08-2014
DOI: 10.1021/JA506365M
Abstract: We report the first ex les of Au(III) tricationic complexes bound only by neutral monodentate ligands, which are a new class of gold reagents. Oxidative addition to the bis-pyridine Au(I) cation, [Au(4-DMAP)2](+), using a series of dicationic I(III) oxidants of the general form [PhI(L)2](2+) (L = pyridine, 4-DMAP, 4-cyanopyridine) allows ready access to homoleptic and pseudo-homoleptic Au(III) complexes [Au(4-DMAP)2(L)2](3+). The facile oxidative addition of Au(I) species additionally demonstrates the efficacy of PhI(L)2](2+) reagents as halide-free oxidants for Au(I). Comparisons are made via attempts to oxidize NHC-Au(I)Cl, where introduction of the chloride anion results in complex mixtures via ligand and chloride exchange, demonstrating the advantage of using the pyridine-based homoleptic compounds. The new Au(III) trications show intriguing reactivity with water, yielding dinuclear oxo-bridged and rare terminal Au(III)-OH complexes.
Bromide ion binding by a dinuclear gold(i ) N-heterocyclic carbene complex: a spectrofluorescence and X-ray absorption spectroscopic study
Publisher: Royal Society of Chemistry (RSC)
Date: 2013
DOI: 10.1039/C2DT31817B
Abstract: Fluorescence and X-ray absorption spectroscopy were used to investigate the anion binding properties of a luminescent, dinuclear Au(I) N-heterocyclic carbene (NHC) complex ([1](2+)) with a short Au(I)···Au(I) contact. The addition of Br(-) ions to a DMSO solution of [1](PF(6))(2) caused a red-shift in the fluorescence emission band from 396 nm to 496 nm. Similarly, the addition of Br(-) ions to [1](PF(6))(2) caused a decrease in the energy of the Au L(3)-edge in the X-ray absorption spectrum, consistent with the formation of an association complex between the cation [1](2+) and Br(-) ions. Solution-based structural studies of the association complex were carried out using extended X-ray absorption fine structure (EXAFS) modelling of the Au(I)···Au(I) core of the cation. These studies indicate that the association complex results from Au(I)···Br(-) interactions, with the Br(-) ions occupying two partially occupied sites at ~2.9 and 3.9 Å from the Au(I) atoms.
Selective Synthesis of Ni(II) and Pd(II) Complexes with either ‘Normal’ or ‘Abnormal’ N‐Heterocyclic Carbene Coordination Modes
Publisher: Wiley
Date: 13-03-2018
Mitochondria-targeted chemotherapeutics : the rational design of gold(I) N-Heterocyclic Carbene complexes that are selectively toxic to cancer cells and target protein selenols in preference to thiols
Publisher: American Chemical Society (ACS)
Date: 26-08-2008
DOI: 10.1021/JA804027J
Abstract: A family of lipophilic, cationic Au(I) complexes of N-heterocyclic carbenes (NHCs) have been designed as new mitochondria-targeted antitumor agents that combine both selective mitochondrial accumulation and selective thioredoxin reductase inhibition properties within a single molecule. Two-step ligand exchange reactions with cysteine (Cys) and selenocysteine (Sec) occur with release of the NHC ligands. At physiological pH the rate constants for the reactions with Sec are 20- to 80-fold higher than those with Cys. The complexes are selectively toxic to two highly tumorigenic breast cancer cell lines and not to normal breast cells, and the degree of selectivity and potency are optimized by modification of the substituent on the simple imidazolium salt precursor. The lead compound is shown to accumulate in mitochondria of cancer cells, to cause cell death through a mitochondrial apoptotic pathway and to inhibit the activity of thioredoxin reductase (TrxR) but not the closely related and Se-free enzyme glutathione reductase.
Iridium(iii ) N-heterocyclic carbene complexes: an experimental and theoretical study of structural, spectroscopic, electrochemical and electrogenerated chemiluminescence properties
Publisher: Royal Society of Chemistry (RSC)
Date: 2015
DOI: 10.1039/C4DT03378G
Abstract: Theoretical and experimental studies of a series of iridium N-heterocyclic carbene complexes.
Understanding Electrogenerated Chemiluminescence Efficiency in Blue-Shifted Iridium(III)-Complexes: An Experimental and Theoretical Study
Publisher: Wiley
Date: 03-03-2014
Abstract: Compared to tris(2-phenylpyridine)iridium(III) ([Ir(ppy)3 ]), iridium(III) complexes containing difluorophenylpyridine (df-ppy) and/or an ancillary triazolylpyridine ligand [3-phenyl-1,2,4-triazol-5-ylpyridinato (ptp) or 1-benzyl-1,2,3-triazol-4-ylpyridine (ptb)] exhibit considerable hypsochromic shifts (ca. 25-60 nm), due to the significant stabilising effect of these ligands on the HOMO energy, whilst having relatively little effect on the LUMO. Despite their lower photoluminescence quantum yields compared with [Ir(ppy)3 ] and [Ir(df-ppy)3 ], the iridium(III) complexes containing triazolylpyridine ligands gave greater electrogenerated chemiluminescence (ECL) intensities (using tri-n-propylamine (TPA) as a co-reactant), which can in part be ascribed to the more energetically favourable reactions of the oxidised complex (M(+) ) with both TPA and its neutral radical oxidation product. The calculated iridium(III) complex LUMO energies were shown to be a good predictor of the corresponding M(+) LUMO energies, and both HOMO and LUMO levels are related to ECL efficiency. The theoretical and experimental data together show that the best strategy for the design of efficient new blue-shifted electrochemiluminophores is to aim to stabilise the HOMO, while only moderately stabilising the LUMO, thereby increasing the energy gap but ensuring favourable thermodynamics and kinetics for the ECL reaction. Of the iridium(III) complexes examined, [Ir(df-ppy)2 (ptb)](+) was most attractive as a blue-emitter for ECL detection, featuring a large hypsochromic shift (λmax =454 and 484 nm), superior co-reactant ECL intensity than the archetypal homoleptic green and blue emitters: [Ir(ppy)3 ] and [Ir(df-ppy)3 ] (by over 16-fold and threefold, respectively), and greater solubility in polar solvents.
Heterobinietallic N-Heterocyclic Carbene Complexes: A Synthetic, Spectroscopic, and Theoretical Study
Publisher: American Chemical Society (ACS)
Date: 26-03-2016
DOI: 10.1021/ACS.INORGCHEM.6B00222
Abstract: A new synthetic methodology has been developed for the preparation of heterobimetallic group 11 and group 12 complexes of a symmetrical bis-NHC "pincer" ligand. The synthetic route involved the initial preparation of a mononuclear [Au(NHC)2](+) complex with pendent imidazole moieties on the NHC ligands. Subsequent alkylation of the imidazole groups with Et3OBF4 and metalation with a second metal ion (Ag(I) or Hg(II)) provided two heterobimetallic complexes. Four homobimetallic (Cu(I)2, Ag(I)2, Au(I)2, and Hg(II)2) complexes of the same bis-NHC "pincer" ligand were also prepared. The homobimetallic Cu(I)2, Au(I)2, and Hg(II)2 complexes and heterobimetallic Au(I)-Ag(I) and Au(I)-Hg(II) complexes and the synthetic intermediates for the heterobimetallic complexes were characterized by X-ray crystallography. These X-ray structures show that the bimetallic complexes adopt "twisted" conformations in the solid state, supporting short M···M interactions. Crystalline s les of the homobimetallic Ag(I)2 and Au(I)2 and heterobimetallic Au(I)-Ag(I) and Au(I)-Hg(II) complexes were emissive at room temperature and at 77 K. The geometries of the synthesized complexes were optimized at the M06-L/def2-SVP level of theory, and the electronic nature of the M···M interactions for all synthesized complexes was investigated using natural bond orbital (NBO) calculations.
(2-Hydroxyphenylimido-κN)(methanolato-κO)[2-(2-oxidobenzylideneamino)phenolato-κ2O,N,O′](triphenylphosphine-κP)rhenium(V)
Publisher: International Union of Crystallography (IUCr)
Date: 03-05-2008
A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection
Publisher: Springer Science and Business Media LLC
Date: 19-07-2023
DOI: 10.1038/S41586-023-06331-X
Abstract: Studies have demonstrated that at least 20% of in iduals infected with SARS-CoV-2 remain asymptomatic 1–4 . Although most global efforts have focused on severe illness in COVID-19, examining asymptomatic infection provides a unique opportunity to consider early immunological features that promote rapid viral clearance. Here, postulating that variation in the human leukocyte antigen ( HLA ) loci may underly processes mediating asymptomatic infection, we enrolled 29,947 in iduals, for whom high-resolution HLA genotyping data were available, in a smartphone-based study designed to track COVID-19 symptoms and outcomes. Our discovery cohort ( n = 1,428) comprised unvaccinated in iduals who reported a positive test result for SARS-CoV-2. We tested for association of five HLA loci with disease course and identified a strong association between HLA-B*15:01 and asymptomatic infection, observed in two independent cohorts. Suggesting that this genetic association is due to pre-existing T cell immunity, we show that T cells from pre-pandemic s les from in iduals carrying HLA-B*15:01 were reactive to the immunodominant SARS-CoV-2 S-derived peptide NQKLIANQF. The majority of the reactive T cells displayed a memory phenotype, were highly polyfunctional and were cross-reactive to a peptide derived from seasonal coronaviruses. The crystal structure of HLA-B*15:01–peptide complexes demonstrates that the peptides NQKLIANQF and NQKLIANAF (from OC43-CoV and HKU1-CoV) share a similar ability to be stabilized and presented by HLA-B*15:01. Finally, we show that the structural similarity of the peptides underpins T cell cross-reactivity of high-affinity public T cell receptors, providing the molecular basis for HLA-B*15:01 -mediated pre-existing immunity.
Synthesis and structural characterisation of linear Au(I) N-heterocyclic carbene complexes: New analogues of the Au(I) phosphine drug Auranofin
Publisher: Elsevier BV
Date: 12-2005
In Vitro and In Vivo Evaluations of a Hydrophilic 64Cu-Bis(Thiosemicarbazonato)–Glucose Conjugate for Hypoxia Imaging
Publisher: Society of Nuclear Medicine
Date: 16-10-2008
DOI: 10.2967/JNUMED.108.054015
Abstract: A water-soluble glucose conjugate of the hypoxia tracer 64Cu-diacetyl-bis(N4-methylthiosemicarbazone) (64Cu-ATSM) was synthesized and radiolabeled (64Cu-ATSE/A-G). Here we report our initial biological experiments with 64Cu-ATSE/A-G and compare the results with those obtained for 64Cu-ATSM and 18F-FDG. The uptake of 64Cu-ATSE/A-G and 64Cu-ATSM into HeLa cells in vitro was investigated at a range of dissolved oxygen concentrations representing normoxia, hypoxia, and anoxia. Small-animal PET with 64Cu-ATSE/A-G was performed in male BDIX rats implanted with P22 syngeneic carcinosarcomas. Images of 64Cu-ATSM and 18F-FDG were obtained in the same model for comparison. 64CuATSE/A-G showed oxygen concentration-dependent uptake in vitro and, under anoxic conditions, showed slightly lower levels of cellular uptake than 64Cu-ATSM uptake levels under hypoxic conditions were also lower. Whereas the normoxic uptake of 64Cu-ATSM increased linearly over time, 64Cu-ATSE/A-G uptake remained at low levels over the entire time course. In the PET study, 64CuATSE/A-G showed good tumor uptake and a biodistribution pattern substantially different from that of each of the controls. In marked contrast to the findings for 64Cu-ATSM, renal clearance and accumulation in the bladder were observed. 64Cu-ATSE/A-G did not display the characteristic brain and heart uptake of 18F-FDG. The in vitro cell uptake studies demonstrated that 64Cu-ATSE/A-G retained hypoxia selectivity and had improved characteristics when compared with 64Cu-ATSM. The in vivo PET results indicated a difference in the excretion pathways, with a shift from primarily hepatointestinal for 64Cu-ATSM to partially renal with 64Cu-ATSE/A-G. This finding is consistent with the hydrophilic nature of the glucose conjugate. A comparison with 18F-FDG PET results revealed that 64Cu-ATSE/A-G was not a surrogate for glucose metabolism. We have demonstrated that our method for the modification of Cu-bis(thiosemicarbazonato) complexes allows their biodistribution to be modified without negating their hypoxia selectivity or tumor uptake properties.
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