
Peter A. Lay- BSc (Hon1), The University of Melbourne, PhD ANU
- Managing Director at University of Sydney and Research Portfolio
Peter A. Lay
- BSc (Hon1), The University of Melbourne, PhD ANU
- Managing Director at University of Sydney and Research Portfolio
About
392
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Introduction
Current institution
University of Sydney and Research Portfolio
Current position
- Managing Director
Additional affiliations
January 2018 - present
June 2016 - present
January 2014 - December 2017
Education
February 1978 - August 1981
February 1974 - November 1977
Publications
Publications (392)
Glioblastoma, an aggressive cancer, is difficult to treat due to its location, late detection, drug resistance, and poor absorption of chemotherapeutics. Intratumoral drug administration offers a promising potential treatment alternative with localized delivery and minimal systemic toxicity. Vanadium(V) coordination complexes, incorporating Schiff...
The current work demonstrated that a mixed-ligand vanadium coordination complex had high in vitro anti-proliferative activity against the human glioblastoma (T98G) cell line. The complex, [V V OL 1 L 2 ], contained two iron chelating ligands, 2-hydroxy-1-naphthylaldehyde isonicotinoylhydrazone (L 1 H2) and clioquinol (L 2 H) and was previously repo...
Selective staining of extracellular vesicles (EVs) is a major challenge for diagnostic and therapeutic applications. Herein, the EV labeling properties of a new class of tetranuclear polypyridylruthenium(II) complexes, Rubb7-TNL and Rubb7-TL, as phosphorescent stains are described. These new stains have many advantages over standard stains to detec...
This review focusses on the significance of fluorescent, phosphorescent labelling and tracking of extracellular vesicles (EVs) for unravelling their biology, pathophysiology, and potential diagnostic and therapeutic uses.
Rhenium(I) tricarbonyl complexes are widely studied for their cell imaging properties and anti-cancer and anti-microbial activities, but the complexes with S-donor ligands remain relatively unexplored. A series of six fac-[Re(CO)3(NN)(SR)]...
A series of non-innocent halogen substituted Schiff base vanadium catecholate added different electron donating and withdrawing substituents on the catecholate to investigate the electronic effects on the properties of this...
Two new series of complexes with pyridine‐containing Schiff bases, [VVO(SALIEP)L] and [VVO(Cl‐SALIEP)L] (SALIEP=N‐(salicylideneaminato)‐2‐(2‐aminoethylpyridine; Cl‐SALIEP=N‐(5‐chlorosalicylideneaminato)‐2‐(2‐aminoethyl)pyridine, L=catecholato(2−) ligand) have been synthesized. Characterization by ¹H and ⁵¹V NMR and UV‐Vis spectroscopies confirmed t...
As shown by IncuCyte Zoom imaging proliferation assays, invasive triple‐negative human breast MDA‐MB‐231 cancer cells treated with sub‐toxic doses (5.0–20 μM, 72 h) of [GaQ3] (Q=8‐hydroxyquinolinato) caused profound morphological changes and inhibition of cell migration, which were likely due to terminal cell differentiation or similar phenotypical...
Internationally, the value and usefulness of museum zoological specimens are compromised when supporting contextual data are lost or disconnected from the specimen. In this pilot study, twelve Macropodidae Thylogale (pademelon) skins with known provenance from the Australian Museum (Sydney) were analysed using portable X-ray fluorescence spectrosco...
A new photoluminecent polypyridylruthenium(II) stain for extracellular vesicles (EVs) released from lipopolysaccharide-stimulated THP-1 monocytes enabled important new insights into how bacteria-induced immune system affects the blood-brain barrier (BBB). These included...
The regular incremental secretion of enamel and dentine can be interrupted during periods of stress resulting in accentuated growth lines. These accentuated lines, visible under light microscopy, provide a chronology of an individual's stress exposure. Previously, we showed that small biochemical changes along accentuated growth lines detected by R...
Twelve Re(I) tricarbonyl diimine (2,2'-bipyridine and 1,10-phenanthroline) complexes with thiotetrazolato ligands have been synthesised and fully characterised. Structural characterisation revealed the capacity of the tetrazolato ligand to bind to the Re(I) centre through either the S atom or the N atom with crystallography revealing most complexes...
A hydrophobic Schiff base catecholate vanadium complex was recently discovered to have anticancer properties superior to cisplatin and suited for intratumoral administration. This [VO(HSHED)(DTB)] complex, where HSHED is N-(salicylideneaminato)-N'-(2-hydroxyethyl)-1,2-ethanediamine and the non-innocent catecholato ligand is di-t-butylcatecholato (D...
Imbalances in metal homeostasis have been implicated in the progression and drug response of cancer cells. Understanding these changes will enable identification of new treatment regimes and precision medicine approaches to cancer treatment. In particular, there has been considerable interest in the interplay between copper homeostasis and response...
Tumour cell heterogeneity affects cisplatin but not doxorubicin cytotoxicity in two phenotypes of the triple-negative breast cancer (TNBC) cell line, MDA-MB-231. A mesenchymal MDA-MB-231 phenotype was three times less sensitive to cisplatin than an epithelial-type phenotype from the same cell line, which has important implications in the success of...
Ruthenium complexes are at the forefront of developments in metal-based anticancer drugs, but many questions remain open regarding their reactivity in biological media, including the role of transferrin (Tf) in their transport and cellular uptake. A well-known anticancer drug, KP1019 ((IndH)[RuIIICl4(Ind)2], where Ind = indazole) and a reference co...
Injections of highly cytotoxic or immunomodulating drugs directly into the inoperable tumor is a procedure that is increasingly applied in the clinic and uses established Pt-based drugs. It is advantageous for less stable anticancer metal complexes that fail administration by the standard intravenous route. Such hydrophobic metal-containing complex...
Transferrin (Tf) is a crucial transporter protein for Fe(III), but its biological role in binding other metal ions and their delivery into cells remain highly controversial. The first systematic exploration of the effect of non-Fe(III) metal ion binding on Tf conformation has been performed by urea-polyacrylamide gel electrophoresis (urea-PAGE), wh...
Biochemical changes in specific organelles underpin cellular function, and studying these changes is crucial to understand health and disease. Fluorescent probes have become important biosensing and imaging tools as they can be targeted to specific organelles and can detect changes in their chemical environment. However, the sensing capacity of flu...
Zytotoxische Verbindungen In ihrer Zuschrift auf S. 15968 präsentieren D. C. Crans, P. A. Lay et al. einen hoch zytotoxischen Vanadium(V)‐Komplex als eine potenzielle Wirkstoffleitverbindung für die Behandlung von Gehirnkrebs.
Cytotoxic Compounds In their Communication on page 15834, D. C. Crans, P. A. Lay et al. present a highly cytotoxic vanadium(V) complex as a potential drug lead for brain cancer treatment.
The chemistry and short lifetimes of metal‐based anti‐cancer drugs can be turned into an advantage for direct injections into tumors, which then allow the use of highly cytotoxic drugs. The release of their less toxic decomposition products into the blood will lead to decreased toxicity and can even have beneficial effects. We present a ternary VV...
V for Vanadium: A drastic decrease in cytotoxicity of a mixed‐ligand VV complex 1 after its decomposition in biological media can be employed in intratumoral injections, particularly for brain cancer. The release of relatively non‐toxic V decomposition products into the blood is expected to reduce the side effects and may also be beneficial due to...
The role of vanadium binding to transferrin (Tf) in the biological activities of vanadium-based drugs is a matter of considerable debate. In order to determine whether V(V) and/or V(IV) binding to Tf (in apo, monoferric(III), and diferric(III) forms) enhances or inhibits biological activities, cellular V uptake and in vitro antiproliferative activi...
Objective
Damage to locus ceruleus neurons could play a part in the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis because of impairment of the blood-brain barrier and enhanced neuroinflammation. The locus ceruleus has connections throughout the brain and spinal cord, so the char...
RuII‐arene complexes provide a versatile scaffold for novel anticancer drugs. Seven new RuII‐arene‐thiocarboxylato dimers were synthesized and characterized. Three of the complexes (2 a, b and 5) showed promising antiproliferative activities in MDA‐MB‐231 (human invasive breast cancer) cells, and were further tested in a panel of fifteen cancerous...
Vanadium drugs have been known for more than a century, but clinical translation has been hampered by unfavorable pharmacokinetics and lack of reliable delivery systems. Because of considerable interest in hydroxyapatite (HAP; Ca10(PO4)6(OH)2) nanoparticle-based drug delivery vehicles, particularly for the treatment of bone disease, and the well-kn...
Vanadium complexes are intensively tested for anti-cancer activities, particularly for the novel treatment protocols involving injections of cytotoxic compounds directly into the tumor. This approach is increasingly applied to difficult-to-treat cancers, such as pancreatic cancer. The first study of in-vitro anti-cancer properties of a rare stable...
Rhodium(III) anticancer drugs can exert preferential antimetastatic or cytotoxic activities, which are dependent on subtle structural changes. In order to delineate factors affecting the biotransformations and speciation, mer,cis-[RhCl 3 (S-dmso) 2 (O-dmso)] (A1) and mer,cis-[RhCl 3 (S-dmso) 2 ( ² N-indazole)] (A2) have been studied by X-ray absorp...
Fe(III) delivery from blood plasma to cells via the transferrin (Tf) cycle is studied intensively due to its crucial role in Fe homeostasis. Tf-cycle disruptions are linked to anemia, infections, immunodeficiency and neurodegeneration. Bio-layer interferometry (BLI) enabled direct kinetic and thermodynamic measurements for all Tf-cycle steps in a s...
Anti-cancer activities of vanadium compounds have generated recent interest because of a combination of desirable properties for chemotherapy, i.e., strong cytotoxicities, anti-metastatic activities and relatively low systemic toxicities. Certain hydrophobic vanadium(V) Schiff base/catecholate compounds, which as shown herein, have increased stabil...
We deposited Ge layers on (001) Si substrates by molecular beam epitaxy and used them to fabricate suspended membranes with high uniaxial tensile strain. We demonstrate a CMOS-compatible fabrication strategy to increase strain concentration and to eliminate the Ge buffer layer near the Ge/Si hetero-interface deposited at low temperature. This is ac...
Lipids are important cellular components which can be significantly altered in a range of disease states including prostate cancer. Here, a unique systematic approach has been used to define lipid profiles of prostate cancer cell lines, using quantitative mass spectrometry (LC-ESI-MS/MS), FTIR spectroscopy and fluorescent microscopy. All three appr...
A Focal Plane Array FTIR microscope has successfully been coupled to the IRM beamline at the Australian Synchrotron, following the method pioneered at previous beamlines at the SRC and NSLS I synchrotrons, whereby a wide aperture of synchrotron light is split into multiple beams and spatially reconfigured to match the entrance aperture of the FTIR...
Microplastics and fibres occur in high concentrations along urban coastlines, but the occurrence of microplastic ingestion by fishes in these areas requires further investigation. Herein, the ingestion of debris (i.e., synthetic and natural fibres and synthetic fragments of various polymer types) by three benthic-foraging fish species Acanthopagrus...
The inability to unambiguously distinguish the biogenicity of microfossil-like structures in the ancient rock record is a fundamental predicament facing Archean paleobiologists and astrobiologists. Therefore, novel methods for discriminating biological from nonbiological chemistries of microfossil-like structures are of the utmost importance in the...
Metal ion speciation in various biological systems has been extensively studied to elucidate its biological role and the toxicity of the element of interest. In the present study, chromium speciation was performed by reacting Cr(III) nutritional supplements [Cr(pic)3], where pic = 2-pyridinecarboxylato(), and a Cr(III) propionate complex, [Cr3O(OC...
The current work is focused on the characterization of the chromium(III)-containing low-molecular-weight (LMW) fractions of blood serum by mass spectrometry. The LMW fractions of serum binding-Cr(III) were collected by organic solvent precipitation using acetonitrile. The chromium(III) compounds used were [Cr(pic) 3 ], where pic = 2-pyridinecarboxy...
Cytotoxic effects of Metvan (cis-[VIVO(OSO3)(Me2phen)2], where Me2phen = 4,7-dimethyl-1,10-phenanthroline) and its analogues with 1,10-phenanthroline (phen) and 2,2′-bipyridine (bpy) ligands in cultured human lung cancer (A549) cells have been re-investigated in conjunction with reactivity of the V(IV) complexes in neutral aerated aqueous solutions...
Diverse biological activities of vanadium(V) drugs mainly arise from their abilities to inhibit phosphate-dependent enzymes and to alter cell signaling. Initial interest focused on anti-diabetic activities but has shifted to anti-cancer and anti-parasitic drugs. V-based anti-diabetics are pro-drugs that release active components (e.g., H₂VO₄¯) in b...
RhIII(*Cp)Cl(X,Y)]n+ complexes (X,Y = Cl, PTA, n = 0 (2); X,Y = en, n = 1 (3, Cl- salt; 4, PF6- salt); X,Y = acac, n = 0 (5); X,Y = cur, n = 0 (6), where *Cp = pentamethylcyclopentadienato, curH = curcumin; PTA = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane; en = 1,2-ethanediamine; acac = acetylacetonato = 2,4-pentanedionato(1-)) were synthesized...
Microvesicles (MVs) are involved in cell-cell interactions, including disease pathogenesis. Nondestructive Fourier-transform infrared (FTIR) spectra from MVs were assessed as a technique to provide new biochemical insights into a LPS-induced monocyte model of septic shock. FTIR spectroscopy provided a quick method to investigate relative difference...
Studies of metal uptake, metabolism and excretion by single cells (including bacteria, yeast, plant and animal cells) is a widespread area of research, yet little is known about the reactivity and speciation of metal ions in the corresponding cell culture media, which dictates in-vitro activities. This review discusses: (i) composition requirements...
Background:
The ability of Zn(II) and Cu(II) metal complexes of non-steroidal anti-inflammatory drugs (NSAIDs) to inhibit acute arterial inflammation in vivo has been studied.
Results:
When acute vascular inflammation was induced in normocholesterolemic New Zealand White rabbits by inserting a non-occlusive silastic collar around the common caro...
The prevalence of diabetes, particularly with respect to type 2 diabetes, has reached epidemic proportions and continues to grow worldwide. One of the potential therapeutic targets in the treatment of type 2 diabetes involves the role of protein tyrosine phosphatases in the negative regulation of insulin signaling. The complexes of V(V/IV), Cr(III)...
Lipids have an important role in many aspects of cell biology, including membrane architecture/compartment formation, intracellular traffic, signalling, hormone regulation, inflammation, energy storage and metabolism. Lipid biology is therefore integrally involved in major human diseases, including metabolic disorders, neurodegenerative diseases, o...
Fluorometer of liposomes incubated with ReZolve-L1™.
Histogram showing fluorescence intensity 560-595nm of DMPC vesicles (A) and DMPC and cholesterol vesicles (DMPC:cholesterol 8:1 molar ratio) (B) incubated with ReZolve-L1™ when excited at 405nm and representative fluorescence and transmitted lights images of vesicles by flow cytometry. (C) Fluoro...
Raman spectra of ReZolve-L1™ and ReZolve-L1™ stained 3T3 cells.
(A) Structure and Raman spectrum of ReZolve-L1™ and (B) the second derivative of this spectrum. (C) Second derivatives of Raman spectra taken from a ReZolve-L1™ stained 3T3 adipocytes from a region of high (a) medium (b) and low (c) ReZolve-L1™ presence.
(TIF)
Raman spectra from Drosophila lipid droplet core.
Representative Raman spectra from the lipid droplet core of -4 h PF larval fat body tissue. Corresponding second derivatives are presented above each of the five spectra. Important lipid regions are shaded and assigned above.
(TIF)
ReZolve-L1™ and Oil Red O co-locate with Atg8a-autopahgic compartments in Drosophila fat body tissue during metamorphosis.
(A) Confocal micrographs of Drosophila fat body cells explanted from +2 h PF from pupae expressing Atg8a-GFP (green) and stained with ReZolve-L1™ (red). (B) Confocal micrographs of Drosophila fat body cells explanted from +2 h...
NAMI-A and KP1019 are Ru(III)-based anti-metastatic and cytotoxic anti-cancer drugs, respectively, and have been proposed to be activated by reduction to Ru(II). The potential reduction of NAMI-A and KP1019 in the hypoxic environment of a tumour model of neuroblastoma was examined. Normoxic, hypoxic and necrotic tumour tissues were modelled by mult...
Drug resistance and severe patient side-effects of Pt drugs have spurred research into other metal-based pharmaceuticals and recently Ru complexes have been identified as promising anti-cancer drugs. A series of RuII complexes [RuX2([9]aneS3)(S-dmso)] (X = Cl, Br, I, S-dmso = sulfur-bound dimethysulfoxide) containing the neutral face-capping sulfur...
Evidence is growing that metabolites of Cr(III) dietary supplements are partially oxidized to carcinogenic Cr(VI) and Cr(V) in vivo. Hence, we examined oxidations of Cr(III) peptide (triglycine, tetraglycine and pentaglycine) complexes to Cr(VI) and Cr(V) by PbO2 at 37°C and physiological pH values between 3.85 and 7.4. The products were characteri...
Fourier Transform Infrared (FTIR) microspectroscopy and confocal imaging have been used to demonstrate that the neutral rhenium(I) tricarbonyl phenanthroline species bound to 4-cyanophenyltetrazolate as the ancillary ligand is able to localise in regions with high concentrations of polar lipids such as phosphatidylethanolamine (PE), sphingomyelin,...
CrIII binding to transferrin (Tf; the main FeIII transport protein) has been postulated to mediate cellular uptake of CrIII to facilitate a purported essential role for this element. Experiments using HepG2 (human hepatoma) cells, which were chosen because of high levels of the transferrin receptor, showed that CrIII binding to vacant FeIII-binding...
Cr(III) binding to transferrin (Tf; the main Fe(III) transport protein) has been postulated to mediate cellular uptake of Cr(III) to facilitate a purported essential role for this element. Experiments using HepG2 (human hepatoma) cells, which were chosen because of high levels of the transferrin receptor, showed that Cr(III) binding to vacant Fe(II...
The design and operation of a low-volume spectroelectrochemical cell for X-ray absorption spectroscopy (XAS) of solutions at room temperature is described. Fluorescence XAS measurements are obtained from samples contained in the void space of a 50 µL reticulated vitreous carbon (sponge) working electrode. Both rapid electrosynthesis and control of...
Early life stress can disrupt development and negatively impact long-term health trajectories. Reconstructing histories of early life exposure to external stressors is hampered by the absence of retrospective time-specific biomarkers. Defects in tooth enamel have been used to reconstruct stress but the methods used are subjective and do not identif...
Cultures of Shewanella putrefaciens grown in medium containing 10mM 1,4-diamino-2-butanone (DBO) as an inhibitor of ornithine decarboxylase and 10mM 1,5-diaminopentane (cadaverine) showed the simultaneous biosynthesis of the macrocyclic dihydroxamic acids: putrebactin (pbH2), avaroferrin (avH2) and bisucaberin (bsH2). The level of DBO did not compl...
Chromium(III) nutritional supplements are widely consumed for their purported antidiabetic activities. X-ray fluorescence microscopy (XFM) and X-ray absorption near-edge structure (XANES) studies have now shown that non-toxic doses of [Cr3O(OCOEt)6(OH2)3]⁺ (A), a prospective antidiabetic drug that undergoes similar H2O2 induced oxidation reactions...
Chromium(III) nutritional supplements are widely consumed for their purported antidiabetic activities. X-ray fluorescence microscopy (XFM) and X-ray absorption near-edge structure (XANES) studies have now shown that non-toxic doses of [Cr3 O(OCOEt)6 (OH2 )3 ](+) (A), a prospective antidiabetic drug that undergoes similar H2 O2 induced oxidation rea...
Using a multimodal biospectroscopic approach, we settle several long-standing controversies over the molecular mechanisms that lead to brain damage in cerebral malaria, which is a major health concern in developing countries because of high levels of mortality and permanent brain damage. Our results provide the first conclusive evidence that import...
Background: Recent progress on metal-based chemotherapeutics suggested that precious metals other than Pt and Ru might also possess antitumor activities [1]. Although a number of Rh(III) coordination and organometallic complexes have been identified to exhibit promising anticancer properties, their clinical application was hampered by insufficient...
Intro: Recent progress on metal-based chemotherapeutics suggested that precious metal complexes other than Pt and Ru might also possess antitumor activities [1]. Although a number of Rh(III) coordination and organometallic complexes have been identified to exhibit promising anticancer properties, their clinical application was hampered by limited k...
Reactions with blood components are crucial for controlling the antidiabetic, anticancer, and other biological activities of V(V) and V(IV) complexes. Despite extensive studies of V(V) and V(IV) reactions with the major blood proteins (albumin and transferrin), reactions with whole blood and red blood cells (RBC) have been studied rarely. A detaile...
Recent investigations on metal-based chemotherapeutics suggested that
the precious metals other than Pt and Ru might also possess antitumor
activities [1]. A number of Rh(III)-dimethylsulfoxide complexes have
been reported to show antitumor activities in animal models that
comparable to the Ru analogues, although their mechanisms of action
hav...
The antidiabetic activities of vanadium(V) and -(IV) prodrugs are determined by their ability to release active species upon interactions with components of biological media. The first X-ray absorption spectroscopic study of the reactivity of typical vanadium (V) antidiabetics, vanadate ([V(V)O4](3-), A) and a vanadium(IV) bis(maltolato) complex (B...
Uncontrolled reactions in biological media are a main obstacle for clinical translation of V-based anti-diabetic or anti-cancer pro-drugs. We investigated the use of controlled-release pharmaceutical formulations to ameliorate this issue with a series of V(V) and (IV) complexes of anionic polysaccharides. Carboxymethyl cellulose, xanthan gum, or al...
The structures of trans-[CrIII(bpb)(OH2)2]⁺ and trans-[CrIII(bpb)(OH2)Cl] (bpb = N,N′-bis(2-pyridinecarboxamido)-1,2-benzene) have been determined by multiple-scattering analysis of their extended X-ray absorption fine structure (EXAFS) spectra. This is the first reported structural characterizations of these complexes, which have been used as cata...
A detailed review of coordination chemistry of Cr in the oxidation states 0 to VI is provided, with an emphasis on literature published during 2002–2012 (and partially 2013), and on new practical applications and biological roles of Cr complexes. This is an update of the Cr chapter in Comprehensive Coordination Chemistry II (2004) by the same autho...
The spectacular success of the Pt-based chemotherapeutics in clinical applications has inspired many investigations on the anticancer properties of adjacent metals [1]. In contrast, much less attention has been given to the biological properties of Rh compounds, although a number of Rh(III) coordination and organometallic complexes have been report...
Introduction: The spectacular success of the Pt-based chemotherapeutics in
clinical application inspired substantial investigations on the anticancer
properties of adjacent metals. The Ru complexes are the most promising
agents with either high tumour selectivity or remarkable anti-metastatic
activities. In contrast, much less attention has been gi...
While Cr(III) dietary supplements are widely consumed, some commercial supplements have yet to be structurally characterized. X-ray absorption spectroscopy and other spectroscopic methods were used to characterize Cr(III) nicotinato nutritional supplements that have long been used in complementary medicine. Different ratios of nicotinic acid and Cr...
A library of X-ray absorption near-edge structure (XANES) spectroscopic data for V(V), V(IV) and V(III) complexes with a broad range of biologically relevant ligand has been used to demonstrate that three-dimensional plots of key XANES parameters (pre-edge and edge energies; pre-edge and white line intensities) can be used for the prediction of V o...
The reactions of oral V(V/IV) anti-diabetic drugs within the gastrointestinal environment (particularly in the presence of food) are a crucial factor that affects their biological activities, but to date these have been poorly understood. In order to build up reactivity-activity relationships, the first detailed study of the reactivities of typical...
Metal ions play key roles in biology. Many are essential for catalysis, for electron transfer and for the fixation, sensing, and metabolism of gases. Others compete with those essential metal ions or have toxic or pharmacological effects.
This book is structured around the periodic table and focuses on the control of metal ions in cells. It address...
αSynuclein plays a central causative role in Parkinson's disease (PD). Increased expression of the P-type ATPase ion pump PARK9 / ATP13A2 suppresses αSynuclein toxicity in primary neurons. Our data indicates ATP13A2 encodes a zinc pump; neurospheres from a compound heterozygous ATP13A2(-/-) patient and ATP13A2 knockdown cells are sensitive to zinc,...
In the first application of bio-layer interferometry in medicinal inorganic chemistry, Fe(III)–transferrin (Tf) binds strongly to Tf receptor 1 (TfR1), but an apo–Tf adduct of the anti-metastatic prodrug, NAMI-A does not bind specifically to TfR1. Binding of NAMI-A to albumin affects its interactions with other blood proteins, such as immunoglobuli...
This chapter describes the current state of knowledge on the exposure, genotoxicities, and biochemistries of metals and metalloids that have been classified by The International Agency for Research on Cancer as group 1 carcinogens. In particular, this chapter focuses on the exposure routes, mechanisms of carcinogenesis, and procedures for minimizin...
The clinical success of platinum-based chemotherapeutics sparked substantial interest in the medical application of transition metal complexes. Of the most promising agents are Ru(III)/Ru(II) complexes with selective cytotoxicity to primary tumours or remarkably active against metastatic cancers 1. A number of Rh(III) organometallic and coordinatio...
In this work, transmission Fourier transform infrared spectroscopy (FTIR) has been used to study the native
oxides on the nitrogen doped tetrahedral amorphous carbon (ta-C:N) thin films deposited by a filtered
cathodic vacuum arc system, and the reactions of the oxides with 0.1 M NaOH aqueous solution. The native
oxides on ta-C:N films possess the...
α-Hemoglobin (αHb)-stabilizing protein (AHSP) is a molecular chaperone that assists hemoglobin assembly. AHSP induces changes
in αHb heme coordination, but how these changes are facilitated by interactions at the αHb·AHSP interface is not well understood.
To address this question we have used NMR, x-ray absorption spectroscopy, and ligand binding m...
The application of ion beam analysis (IBA) techniques to thin biological sections (ThBS) presents unique challenges in sample preparation, data acquisition and analysis. These samples are often the end product of expensive, time-consuming experiments, which involve many steps that require careful attention. Analysis via several techniques can maxim...
The stabilization of Cr(V) by biological 1,2-diolato ligands, including carbohydrates, glycoproteins, and sialic acid derivatives, is likely to play a crucial role in the genotoxicity of Cr(VI) and has also been implicated in the antidiabetic effect of Cr(III). Previously, such complexes have been observed by electron paramagnetic resonance (EPR) s...
Manganese porphyrin-based drugs are potent mimics of the enzyme superoxide dismutase. They exert remarkable efficacy in disease models and are entering clinical trials. Two lead compounds, MnTE-2-PyP(5+) and MnTnHex-2-PyP(5+), have similar catalytic rates, but differ in their alkyl chain substituents (ethyl vs n-hexyl). Herein we demonstrate that t...
An anti-metastatic drug, NAMI-A ((ImH)[Ru(III) Cl(4) (Im)(dmso)]; Im=imidazole, dmso=S-bound dimethylsulfoxide), and a cytotoxic drug, KP1019 ((IndH)[Ru(III) Cl(4) (Ind)(2) ]; Ind=indazole), are two Ru-based anticancer drugs in human clinical trials. Their reactivities under biologically relevant conditions, including aqueous buffers, protein solut...
SynonymsChromium and cancer; Chromium and diabetes; Chromium carcinogenicity; Hexavalent chromiumDefinitionChromium(VI) (Cr(VI), hexavalent chromium) is an established human carcinogen and a major occupational and environmental hazard. Toxic properties of Cr(VI) are related to its ability to enter cells easily and to form reactive high-valent (Cr(V...
Fourier transform infrared spectroscopy was used to characterize the biochemical composition of fungal cells. It also was applied to detect the differences between the biochemical constituents of spores and hyphae of A. fumigates species. FT-IR microscopy was used to monitor the fungal growth. Chemical markers of the fungal cell ultrastructures suc...