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Aryl-urea substituted fatty acids are protonophores and mitochondrial uncouplers that utilise a urea-based synthetic anion transport moiety to carry out the protonophoric cycle. Herein we show that replacement of the urea group with carbamate, a functional group not previously reported to possess anion transport activity, produces analogues that retain the activity of their urea counterparts. Thus, the aryl-carbamate substituted fatty acids uncouple oxidative phosphorylation and inhibit ATP production by collapsing the mitochondrial proton gradient. Proton transport proceeds via self-assembly of the deprotonated aryl-carbamates into membrane permeable dimeric species, formed by intermolecular binding of the carboxylate group to the carbamate moiety. These results highlight the anion transport capacity of the carbamate functional group.

Sorafenib maintenance improves outcome after hematopoietic cell transplant (HCT) for patients with FLT3-ITD acute myeloid leukemia (AML). Although promising outcomes have been reported for sorafenib plus intensive chemotherapy, randomized data are limited. This placebo-controlled, phase 2 study (ACTRN12611001112954) randomized 102 patients 18-65 years (2:1) to sorafenib vs placebo (days 4-10) combined with intensive induction; idarubicin 12mg/m2 days 1-3 plus cytarabine 1.5g/m2 twice daily on days 1,3,5,7 (18-55 years) or 100mg/m2 days 1-7 (56-65 years), consolidation therapy, followed by maintenance treatment for 12 months (post-HCT excluded) in newly diagnosed FLT3-ITD AML. Four patients were excluded from modified intention-to-treat final analysis (3 not dosed and 1 later found to be FLT3-ITD negative). Rates of complete remission (CR)/CR with incomplete hematologic recovery (CR/CRi) were high in both arms (sorafenib 78%/9%, placebo 70%/24%). With 49.1 months median follow-up, the primary endpoint of event-free survival (EFS) was not improved by sorafenib (2-year EFS 47.9% vs 45.4%)(hazard ratio [HR] 0.87;95% confidence interval [CI] 0.51-1.51, p=0.61). Two-year overall survival (OS) was 67% in the sorafenib arm and 58% in the placebo arm (HR 0.76; 95% CI 0.42-1.39). For patients transplanted in first remission, 2-year OS was 84% and 67% in the sorafenib and placebo arms, respectively (HR 0.45;95% CI 0.18-1.12, p=0.08). In exploratory analyses, FLT3-ITD measurable residual disease negative status (<0.001%) post-induction was associated with improved 2-year OS (83% vs 60%) (HR 0.4;95% CI 0.17-0.93, p=0.028). In conclusion, routine use of pre-transplant sorafenib plus chemotherapy in unselected patients with FLT3-ITD AML is not supported by this study.

In respiring mitochondria, the proton gradient across the inner mitochondrial membrane is used to drive ATP production. Mitochondrial uncouplers, which are typically weak acid protonophores, can disrupt this process to induce mitochondrial dysfunction and apoptosis in cancer cells. We have shown that bisaryl urea-based anion transporters can also mediate mitochondrial uncoupling through a novel fatty acid-activated proton transport mechanism, where the bisaryl urea promotes the transbilayer movement of deprotonated fatty acids and proton transport. In this paper, we investigated the impact of replacing the urea group with squaramide, amide and diurea anion binding motifs. Bisaryl squaramides were found to depolarise mitochondria and reduce MDA-MB-231 breast cancer cell viability to similar extents as their urea counterpart. Bisaryl amides and diureas were less active and required higher concentrations to produce these effects. For all scaffolds, the substitution of the bisaryl rings with lipophilic electron-withdrawing groups was required for activity. An investigation of the proton transport mechanism in vesicles showed that active compounds participate in fatty acid-activated proton transport, except for a squaramide analogue, which was sufficiently acidic to act as a classical protonophore and transport protons in the absence of free fatty acids.

Understanding the cellular mechanisms by which amphiphilic ionic liquids (AmILs) induce cytotoxicity is an important step in the development of task-specific AmILs for safe industrial applications or as cytotoxic anticancer agents. Accumulated evidence suggests that AmILs kill cells by disrupting cellular membranes and/or inducing mitochondrial dysfunction. The cation of AmILs is lipophilic due to alkyl substitution, and lipophilic cations are a group of compounds known to accumulate in mitochondria in response to the membrane potential across the inner mitochondrial membrane (IMM). We therefore hypothesised that AmILs exert their cytotoxic effects by disrupting the IMM, the integrity of which is critical to several important cellular processes. Using fluorescence microscopy we show that a quinolinium-based AmIL rapidly accumulates in the mitochondria of HeLa cells. In a panel of AmILs we found that cytotoxicity correlates with their capacity to disrupt lipid bilayers, and that AmILs produce a range of cellular effects consistent with permeabilisation of the IMM at cytotoxic concentrations. Thus, AmILs depolarise the IMM, inhibit oxidative phosphorylation and ATP synthesis, and induce ROS formation. These effects were only induced by AmILs with aromatic cations substituted with long (decyl) alkyl chains, as these features promote accumulation in, and permeabilisation of, the IMM. These mechanistic insights help explain the structure-activity relationship governing AmILs cytotoxicity and may be used to rationally design either safe or cytotoxic AmILs.

Mitochondria in tumor cells are functionally different from those in normal cells and could be targeted to develop new anticancer agents. We showed recently that the aryl-ureido fatty acid CTU is the prototype of a new class of mitochondrion-targeted agents that kill cancer cells by increasing the production of reactive oxygen species (ROS), activating endoplasmic reticulum (ER)-stress and promoting apoptosis. However, prolonged treatment with high doses of CTU were required for in vivo anti-tumor activity. Thus, new strategies are now required to produce agents that have enhanced anticancer activity over CTU. In the present study we prepared a novel aryl-urea termed 3-thiaCTU, that contained an in-chain sulfur heteroatom, for evaluation in tumor cell lines and in mice carrying tumor xenografts. The principal finding to emerge was that 3-thiaCTU was several-fold more active than CTU in the activation of aryl-urea mechanisms that promoted cancer cell killing. Thus, in in vitro studies 3-thiaCTU disrupted the mitochondrial membrane potential, increased ROS production, activated ER-stress and promoted tumor cell apoptosis more effectively than CTU. 3-ThiaCTU was also significantly more active than CTUin vivo in mice that carried MDA-MB-231 cell xenografts. Compared to CTU, 3-thiaCTU prevented tumor growth more effectively and at much lower doses. These findings indicate that, in comparison to CTU, 3-thiaCTU is an aryl-urea with markedly enhanced activity that could now be suitable for development as a novel anticancer agent.

Uveal melanoma (UM) is the primary ocular cancer with upto 50% of patients dying from metastasis. Although rare, it is deadly as patients with metastatic UM seldom survive beyond 18 months after diagnosis. Chemotherapeutics have no proven efficacy, including immunotherapies that have been tried as current treatment options but produce marginal improvement in overall survival for UM patients. While therapeutics are low in efficacy, there is an urgent need to explore novel targets in the treatment of UM. This review provides an update on the contribution of inflammation to UM with a focus on exploring potential therapeutic targets related to the inflammatory tumour microenvironment. As a tumour promoting event, inflammation is one of the hallmarks of cancers. The presence of the inflammatory phenotype characterised by the abundance of immune mediators and proinflammatory cytokines surrounding UM tumours, is a potential area to explore novel therapeutic targets. Despite decades of investigation regarding the role UM tumour microenvironment has played, that of inflammation in UM progression remains poorly understood. With advancement of technologies, an understanding of the prognosis of UM has been accelerated. Excitingly, novel therapeutic targets related to the inflammatory tumour microenvironment have been identified and relevant studies are underway in their preliminary phases, illustrating optimistic results.

AusGeochem [1] is an open access geochemical data repository supported by AuScope via funding from the Australian National Collaborative Infrastructure Research Infrastructure Strategy (NCRIS). The AusGeochem concept was developed in response to open community workshops held around Australia during a 2018-19 consultation process involving academia, industry and geoscience surveys. Key issues identified where the need for improvements in: (1) collaboration between geochemistry laboratories in the areas of asset procurement, maintenance and end user support; (2) cooperation between universities, geoscience surveys and industry in creating geochronology and isotopic maps at a national scale; and (3) curation and preservation of sample and data collections of national/global significance. To address some of these issues, AuScope supported a new, grassroots community network project led by a consortium of geochemistry laboratories at Curtin University, Macquarie University and the University of Melbourne. The consortium partnered with Lithodat Pty Ltd, an Australian company specialising in spatial geoscience data management, to build a collaborative platform for collating, preserving, and disseminating geochronology and isotopic data aligned with FAIR principles. The broader geochemistry community was consulted via the establishment of Expert Advisory Groups in the areas of SHRIMP U-Pb geochronology, Ar-Ar geochronology, LA-ICP-MS and low temperature thermochronology (fission track and (U-Th)/He). The AusGeochem platform was successfully launched for community use in December 2021 [2]. During 2022-23, the AuScope Geochemistry Network (AGN) consortium will expand by including new “data partner” laboratories at several universities across Australia. Museums Victoria will also join as a “collections partner” by registering its unique collection of rock and mineral samples for the purpose of making it discoverable and accessible to the research community. The AGN+ team will

To promote a more efficient and transparent geochemistry data ecosystem, a consortium of Australian university research laboratories called the AuScope Geochemistry Network assembled to build a collaborative platform for the express purpose of preserving, disseminating and collating geochronology and isotopic data. In partnership with geoscience-data-solutions company Lithodat Pty Ltd, the open, cloud-based AusGeochem platform (https://ausgeochem.auscope.org.au) was developed to simultaneously serve as a geosample registry, a geochemical data repository and a data analysis tool. Informed by method-specific groups of geochemistry experts and established international data reporting practices, community-agreed database schemas were developed for rock and mineral geosample metadata and secondary ion mass spectrometry U-Pb analysis, with additional models for laser ablation-inductively coupled-mass spectrometry U-Pb and Lu-Hf, Ar-Ar, fission-track and (U-Th-Sm)/He under development. Collectively, the AusGeochem platform provides the geochemistry community with a new, dynamic resource to help facilitate FAIR (Findable, Accessible, Interoperable, Reusable) data management, streamline data dissemination and advanced quantitative investigations of Earth system processes. By systematically archiving detailed geochemical (meta-)data in structured schemas, intractably large datasets comprising thousands of analyses produced by numerous laboratories can be readily interrogated in novel and powerful ways. These include rapid derivation of inter-data relationships, facilitating on-the-fly data compilation, analysis and visualisation.

Targeting the cancer cell mitochondrion is a promising approach for developing novel anticancer agents. The experimental anticancer agent N,N'-bis(3,5-dichlorophenyl)urea (SR4) induces apoptotic cell death in several cancer cell lines by uncoupling mitochondrial oxidative phosphorylation (OxPhos) using a protein-free mechanism. However, the precise mechanism by which SR4 depolarizes mitochondria is unclear because SR4 lacks an acidic functional group typically found in protein-independent uncouplers. Recently, it was shown that structurally related thioureas can facilitate proton transport across lipid bilayers by a fatty acid-activated mechanism, in which the fatty acid acts as the site of protonation/deprotonation and the thiourea acts as an anion transporter that shuttles deprotonated fatty acids across the phospholipid bilayer to enable proton leak. In this paper, we show that SR4-mediated proton transport is enhanced by the presence of free fatty acids in the lipid bilayer, indicating that SR4 uncouples mitochondria through the fatty acid-activated mechanism. This mechanistic insight was used to develop a library of substituted bisaryl ureas for structure-activity relationship studies and subsequent cell testing. It was found that lipophilic electron-withdrawing groups on bisaryl ureas enhanced electrogenic proton transport via the fatty acid-activated mechanism and had the capacity to depolarize mitochondria and reduce the viability of MDA-MB-231 breast cancer cells. The most active compound in the series reduced cell viability with greater potency than SR4 and was more effective at inhibiting adenosine triphosphate production.

Brutal university cuts are putting at risk an industry crucial to addressing climate change Down Under and around the world. Saving geoscience will require a community reckoning.

The role of lipids in modulating membrane protein function is an emerging and rapidly growing area of research. The rational design of lipids that target membrane proteins for the treatment of pathological conditions is a novel extension in this field and provides a step forward in our understanding of membrane transporters. Bioactive lipids show considerable promise as analgesics for the treatment of chronic pain and bind to a high-affinity allosteric binding site on the human glycine transporter 2 (GlyT2 or SLC6A5). Here we use a combination of medicinal chemistry, electrophysiology, and computational modelling to develop a rational structure activity relationship for lipid inhibitors and demonstrate the key role of the lipid tail interactions for GlyT2 inhibition. Specifically, we examine how lipid inhibitor head group stereochemistry, tail length and double bond position promote enhanced inhibition. Overall, the L-stereoisomer is generally a better inhibitor than the D-stereoisomer, longer tail length correlates with greater potency, and the position of the double bond influences the activity of the inhibitor. We propose that the binding of the lipid inhibitor deep into the allosteric binding pocket is critical for inhibition. Furthermore, this provides insight into the mechanism of inhibition of GlyT2 and highlights how lipids can modulate the activity of membrane proteins by binding to cavities between helices. The principles identified in this work have broader implications for the development of a larger class of compounds that could target SLC6 transporters for disease treatment.

Glycine neurotransmission in the dorsal horn of the spinal cord plays a key role in regulating nociceptive signaling, but in chronic pain states reduced glycine neurotransmission is associated with the development of allodynia and hypersensitivity to painful stimuli. This suggests that restoration of glycine neurotransmission may be therapeutic for the treatment of chronic pain. Glycine transporter 2 inhibitors have been demonstrated to enhance glycine neurotransmission and provide relief from allodynia in rodent models of chronic pain. In recent years, photoswitchable compounds have been developed to provide the possibility of controlling the activity of target proteins using light. In this study we have developed a photoswitchable noncompetitive inhibitor of glycine transporter 2 that has different affinities for the transporter at 365 nm compared to 470 nm light.

Omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) play crucial and often opposing regulatory roles in health and in pathological conditions. n-3 and n-6 PUFA undergo biotransformation to parallel series of lipid mediators that are potent modulators of many cellular processes. A wide range of biological actions have been attributed to lipid mediators derived from n-6 PUFA, and these mediators have served as lead compounds in the development of numerous clinically approved drugs, including latanoprost (Xalatan: Pfizer), which is listed on the WHO Model List of Essential Medicines. n-3 PUFA-derived mediators have received less attention, in part because early studies suggested that n-3 PUFA act simply as competitive substrates for biotransformation enzymes and decrease the formation of n-6 PUFA-derived lipid mediators. However, more recent studies suggest that n-3 PUFA-derived mediators are biologically important in their own right. It is now emerging that many n-3 PUFA-derived lipid mediators have potent and diverse activities that are distinct from their n-6 counterparts. These findings provide new opportunities for drug discovery. Herein, we review the biosynthesis of n-3 PUFA-derived lipid mediators and highlight their biological actions that may be exploited for drug development. Lastly, we provide examples of medicinal chemistry research that has utilized n-3 PUFA-derived lipid mediators as novel lead compounds in drug design.

© 2019 American Chemical Society. Inhibitors that target the glycine transporter 2, GlyT2, show promise as analgesics, but may be limited by their toxicity through complete or irreversible binding. Acyl-glycine inhibitors, however, are selective for GlyT2 and have been shown to provide analgesia in animal models of pain with minimal side effects, but are comparatively weak GlyT2 inhibitors. Here, we modify the simple acyl-glycine by synthesizing lipid analogues with a range of amino acid head groups in both l- and d-configurations, to produce nanomolar affinity, selective GlyT2 inhibitors. The potent inhibitor oleoyl-d-lysine (33) is also resistant to degradation in both human and rat plasma and liver microsomes, and is rapidly absorbed following an intraperitoneal injection to rats and readily crosses the blood-brain barrier. We demonstrate that 33 provides greater analgesia at lower doses, and does not possess the severe side effects of the very slowly reversible GlyT2 inhibitor, ORG25543 (2).

© 2019 Elsevier B.V. We recently developed a novel aryl-urea fatty acid (CTU; 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that impaired the viability of MDA-MB-231 breast cancer cells in vitro and in mouse xenograft models in vivo. At present there is a deficiency of information on the structural requirements for the activity of CTU. Our initial study suggested that electron withdrawing groups were required on the aryl ring, and in this study we further evaluated the influence of the electronic properties of aromatic substitution on the capacity of CTU analogues to decrease MDA-MB-231 breast cancer cell viability. Analogues that contained strong electron-withdrawing groups in the meta- and para-positions of the aryl ring exhibited improved activity over CTU. Effective analogues down-regulated the cyclins D1, E1 and B1, and the cyclin-dependent kinases (CDKs) 4 and 6, that form complexes to coordinate cell cycle progression. Active CTU analogues also stimulated the phosphorylation and activation of the p38 MAP kinase signalling pathway in cells and both decreased proliferation (5-bromo-2′-deoxyuridine (brdU) incorporation) and activated apoptosis (executioner caspase-3/7 activity). These agents offer a new approach to target the cell cycle at multiple phases in order to efficiently prevent cancer cell expansion. Inclusion of the present structural information in drug design approaches could enhance the development of optimal analogues of aryl-urea fatty acids as potential anti-cancer agents.

© Mostyn et al. The treatment of chronic pain is poorly managed by current analgesics, and there is a need for new classes of drugs. We recently developed a series of bioactive lipids that inhibit the human glycine transporter GlyT2 (SLC6A5) and provide analgesia in animal models of pain. Here, we have used functional analysis of mutant transporters combined with molecular dynamics simulations of lipid-transporter interactions to understand how these bioactive lipids interact with GlyT2. This study identifies a novel extracellular allosteric modulator site formed by a crevice between transmembrane domains 5, 7, and 8, and extracellular loop 4 of GlyT2. Knowledge of this site could be exploited further in the development of drugs to treat pain, and to identify other allosteric modulators of the SLC6 family of transporters.

© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Selective targeting of the tumor cell mitochondrion is a viable approach for the development of anticancer agents because the organelle is functionally different from the mitochondria of normal cells. We recently developed a novel aryl-urea fatty acid, 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid (1) that was found to disrupt mitochondria and to activate apoptosis in MDA-MB-231 breast cancer cells. However, there is currently little information on the structural requirements for the activity of compound 1 analogues. The present study evaluated the role of the carboxylic acid group on the anticancer activity of 1. Bioisosteric replacement of the carboxylate in 1 maintained activity. Thus, like 1, the sulfonic acid analogue 1-SA and the oxo-thiadiazole analogue 1-OT were also found to target the mitochondrion and to activate cell killing capacity. The hydroxamic acid analogue 1-HA also killed MDA-MB-231 cells, but its onset of action was slower than that of 1-SA and 1-OT. In contrast, replacement of the carboxylate with non-bioisosteric amido and methylamido groups produced analogues that minimally altered mitochondrial function and showed little capacity to decrease tumor cell viability. These findings suggest that the carboxylate moiety in the novel mitochondrially targeted agent 1 is an important determinant of the kinetics and efficacy of anticancer cell activities of compound 1 analogues. Further development of carboxylate-modified analogues of aryl-urea fatty acids as potential anticancer agents could now be warranted.

© 2017 American Chemical Society. Cancer cell mitochondria are promising anticancer drug targets because they control cell death and are structurally and functionally different from normal cell mitochondria. We synthesized arylurea fatty acids and found that the analogue 16-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid (13b) decreased proliferation and activated apoptosis in MDA-MB-231 breast cancer cells in vitro and in vivo. In mechanistic studies 13b emerged as the prototype of a novel class of mitochondrion-targeted agents that deplete cardiolipin and promote cancer cell death.

© 2014 by The American Society for Pharmacology and Experimental Therapeutics. Solute carrier (SLC) transporters regulate the cellular influx and disposition of endogenous and xenobiotic compounds, including anticancer agents such as the multikinase inhibitors (MKIs). Recent evidence suggests that MKIs may also inhibit SLC-dependent transport of coadministered drugs, although present information on the relative susceptibilities of multiple SLC transporters is limited. This study evaluated 18 MKI drugs and metabolites as inhibitors of prototypic substrate uptake by 13 SLC transporters that were overexpressed in human embryonic kidney cells. Organic anion transporting polypeptides (OATPs) 1A2, 1B3, and 2B1, organic anion transporter 3 (OAT3), and organic cation transporter 1 (OCT1) were inhibited by most MKIs, whereas substrate uptake by OATP1B1, OAT1, 2, and 4, OCT2 and 3, and organic zwitterion/cation transporter 1 (OCTN1) was less susceptible to inhibition; OCTN2 was also inhibited by cediranib. In further studies, IC50 values were determined for the most effective MKIs, and erlotinib and cediranib were found to be potent competitive inhibitors of OATP2B1 (Ki= 41 nM) and OATP1A2 (Ki= 33 nM), respectively. From predictive approaches, several MKI-SLC interactions were found to be of potential in vivo significance. Copyright

Intercellular communication is essential to maintain vital physiological activities and to regulate the organism's phenotype. There are a number of ways in which cells communicate with one another. This can occur via autocrine signaling, endocrine signaling or by the transfer of molecular mediators across gap junctions. More recently communication via microvesicular shedding has gained important recognition as a significant pathway by which cells can coordinate the spread and dominance of selective traits within a population. Through this communication apparatus, cells can now acquire and secure a survival advantage, particularly in the context of malignant disease. This review aims to highlight some of the functions and implications of microparticles in physiology of various disease states, and present a novel therapeutic strategy through the regulation of microparticle production.

The tyrosine kinase inhibitor drug sorafenib is used in the treatment of liver and renal cancers but adverse effects may necessitate dose interruption and under-dosage may lead to therapeutic failure. Sorafenib also undergoes cytochrome P450 (CYP)-dependent biotransformation to the N-oxide and other metabolites. However, although CYPs are major determinants of efficacy and toxicity the roles of these enzymes in the formation of multiple sorafenib metabolites are unclear. In the present study CYP-mediated pathways of sorafenib oxidation in human liver were evaluated. cDNA-expressed CYP3A4 was the major catalyst in the formation of the principal N-oxide and N-hydroxymethyl metabolites of sorafenib, as well as the minor N-desmethyl metabolite. In contrast, CYP3A5 exhibited only ∼5% of the activity of CYP3A4 and eleven other CYPs and three flavin-containing monooxygenases were inactive. In human hepatic microsomes metabolite formation was correlated with CYP3A4-mediated midazolam 1′-hydroxylation, but not with other CYP-specific substrate oxidations. In accord with these findings the CYP3A4 inhibitor ketoconazole selectively inhibited microsomal sorafenib oxidation pathways. From computational modeling studies atoms in the structure of sorafenib that undergo biotransformation were within ∼5.4 of the CYP3A4 heme. Important hydrogen bonding interactions between sorafenib and amino acids Ser-119 and Glu-374 in the active center of CYP3A4 were identified. These findings indicate that sorafenib is oxidized selectively by human CYP3A4. This information could be adapted in individualized approaches to optimize sorafenib safety and efficacy in cancer patients. © 2012 Elsevier Inc.

Mitogen-activated protein kinase phosphatases (MKPs) are dual specificity protein phosphatases (DUSPs) that dephosphorylate both phospho-tyrosine and phospho-threonine residues on mitogen-activated protein kinases (MAPKs). Because the MAPK family of signalling molecules (phospho-p38 MAPK, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)) play essential roles in cell signalling pathways that regulate cell growth and inflammation, controlling MAPK-mediated pathways is a therapeutically attractive strategy. While small molecule MAPK inhibitors have utility, in this review we will focus on exploring the potential of targeting the endogenous MAPK deactivator - MKP-1. Importantly, there is a strong justification for developing both inhibitors and upregulators of MKP-1 because of the diverse roles played by MAPKs in disease: for example, in cancer, MKP-1 inhibitors may prove beneficial, as MKP-1 is overexpressed and is considered responsible for the failure of JNK-driven apoptotic pathways induced by chemotherapeutics; conversely, in inflammatory diseases such as asthma and arthritis, MKP-1 reduces MAPKmediated signalling and developing novel ligands to upregulate MKP-1 levels would be a therapeutically attractive anti-inflammatory strategy. Thus, in this review we utilise MKP-1 homology modeling to highlight the structural features of MKP-1 inhibitors that permit potent and selective inhibition, and to provide insights into the structural requirements for selective MKP-1 upregulators. © 2012 Bentham Science Publishers.

Element response variations under different laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) operating conditions were investigated to identify important factors for selecting an internal standard (IS) for quantitative elemental bio-imaging. Analytes covering a range of atomic masses and first ionisation potentials (FIP) were selected to investigate the signal response variation with changes in laser spot diameter, mass bias and cell sampling position. In all cases, an IS improved experimental precision regardless of a close match in element mass or FIP but optimal analyte/IS combinations depended on the difference in masses of the analyte and IS. Particular attention was paid to 13C as this isotope is typically used as an IS in elemental bio-imaging applications. Despite its non-ideal IS characteristics (often different mass and FIP to many analytes), possibility of abundance sensitivity effects and poor signal-to-background ratio, 13C was a suitable IS candidate exhibiting a linear response with respect to the mass ablated, apparent independence from the high abundance of the adjacent 14N mass peak and effective analyte normalisation after background subtraction as long as the 13C signal from the sample was at least 6% of the gross signal. © 2011 The Royal Society of Chemistry.

The photodegradation rate of a perylene dye (Lumogen F Yellow 083) in methyl isobutyrate was found to increase with ketone concentration for two different ketones. Of the ketones employed, methyl pyruvate, an impurity in methyl methacrylate, was found to be particularly deleterious to dye stability. In agreement with other published studies, the addition of the anti-oxidant DABCO (1,4-diazabicyclo-[2.2.2] octane) to the dye matrix was found to increase dye stability; however when ketones were present, DABCO lead to increased photodegradation. These results highlight the importance of removing ketone impurities from dye matrices during production of Luminescent Solar Concentrators (LSCs). © 2009 Elsevier Ltd. All rights reserved.

Thin films of a new dimeric ruthenium phthalocyanine complex bearing a thioester-functionalized axial ligand were formed on gold surfaces. Characterization of the thin films by laser ablation-inductively coupled-mass spectrometry and scanning tunneling microscopy revealed that the films do not have any long-range order. © 2009 Elsevier B.V. All rights reserved.

Facile syntheses of the monounsaturated omega-3 fatty acids, (Z)-15-octadecenoic acid and (Z)-16-nonadecenoic acid, are presented. Commercially available hydroxy fatty acids were esterified and oxidised, followed by the Wittig reaction to introduce the omega-3 olefinic bond; hydrolysis yielded the omega-3 fatty acids in high purity. An examination of different reaction conditions for the Wittig step found that THF as solvent and coupling temperatures of -78 °C gave optimal stereoselectivity, affording the omega-3 olefins in Z:E ratios 97:3. The syntheses have overall yields of ~43%, and utilise straightforward, robust chemistry, that may be readily scaled up and reproduced. Also presented is a method for accurately determining the double bond geometry and isomeric purity of the fatty acid products using 1H-13C-HSQC NMR and GC-MS, respectively. © 2010 AOCS.

Four new ruthenium phthalocyanine complexes bearing axial ligands with thioacetate groups that facilitate thin film formation on gold surfaces are presented. Scanning tunnelling microscopy (STM) images and surface coverage data obtained by solution inductively coupled plasma mass spectrometry (ICP-MS) experiments show that peripheral and axial ligand substituents on the complexes have a significant effect on their surface coverage. A laser ablation ICP-MS technique that provides information about thin films across macro-sized areas is described here for the first time. Using the technique, the maximum surface coverage of a ruthenium phthalocyanine complex was found to occur within one minute of gold substrate immersion in the complex-containing solution. © Tsinghua University Press and Springer-Verlag 2009.