The reactions of pyrethrin I, cinerin I and jasmolin I with sodium hydroxide in ethanol afforded an approximately 1:1 ratio of two respective cyclopentadienone dimers, isolated in good yield. A combination of one-dimensional and two-dimensional NMR spectroscopic studies allowed determination of the structure and stereochemistry of the dimers. The dimers are formed by cycloaddition reactions of the less substituted alkene of the cyclopentadienone, and by regioisomeric endo transition states. Density functional theory calculations were in accord with the experimental findings showing the products formed by ambimodal transition states. One such transition state led to two initial products with the less stable product undergoing facile conversion to the other more stable, experimentally observed product. These studies clarify the structures of the altered pyrethrolone reported by Staudinger and Ruzicka in 1924.

Organic ionic plastic crystals (OIPCs) are promising for developing safer energy storage electrolytes. However, there remains a significant knowledge gap regarding how different cation-anion combinations influence their core properties, and cyclic ether-based cations have received limited attention. This study reports the synthesis and characterization of OIPCs based on the N -ethyl- N -methyl-oxazolidinium cation [C 2 moxa] + and demonstrates the first instance of oxazolidinium OIPCs being combined with lithium salts to create electrolytes. The [C 2 moxa] + cation was paired with [FSI] - , [TFSI] - , [BF 4 ] - , [PF 6 ] - and [FTFSI] - anions. A study of the thermal, transport and electrochemical properties was performed. Among the new salts developed, [C 2 moxa][BF 4 ] exhibited the most promising characteristics, including the lowest entropy of melting (ΔS = 7 J mol −1 K −1 ), an extended phase I range (10°C–130°C), the highest conductivity of 8 x 10 −6 S cm −1 at 30°C, and an electrochemical stability window of 4.8 V. When the [C 2 moxa][BF 4 ] and [C 2 moxa][FSI] were mixed with lithium salts (10, 20 and 50 mol% Li + ) of the same anion, the highest conductivity of 2 x 10 −3 S cm −1 at 30°C was found for the 20 mol% LiFSI/[C 2 moxa][FSI] electrolyte. Finally, preliminary lithium plating/stripping experiments and coulombic efficiency (CE) measurements demonstrate stability for lithium cycling for all four [C 2 moxa] + electrolytes.

To achieve malaria eradication, new preventative agents that act differently to front-line treatment drugs are needed. To identify potential chemoprevention starting points we screened a sub-set of the CSIRO Australia Compound Collection for compounds with slow-action in vitro activity against Plasmodium falciparum. This work identified N,N-dialkyl-5-alkylsulfonyl-1,3,4-oxadiazol-2-amines as a new antiplasmodial chemotype (e.g., 1 96 h IC50 550 nM; 3 96 h IC50 160 nM) with a different action to delayed-death slow-action drugs. A series of analogues were synthesized from thiotetrazoles and carbomoyl derivatives using Huisgen 1,3,4-oxadiazole synthesis followed by oxidation of the resultant thioethers to target sulfones. Structure activity relationship analysis of analogues identified compounds with potent and selective in vitro activity against drug-sensitive and multi-drug resistant Plasmodium parasites (e.g., 31 and 32 96 h IC50 <40 nM; SI > 2500). Subsequent studies in mice with compound 1, which had the best microsomal stability of the compounds assessed (T1/2 >255 min), demonstrated rapid clearance and poor oral in vivo efficacy in a P. berghei murine malaria model. These data indicate that while N,N-dialkyl-5-alkylsulfonyl-1,3,4-oxadiazol-2-amines are a novel class of slow-acting antiplasmodial agents, the further development of this chemotype for malaria chemoprophylaxis will require pharmacokinetic profile improvements.

Investigation of the thermodynamic and transport properties of four novel ether-functionalised piperidinium and morpholinium ionic liquids with LiFSI and LiTFSI salts, and Li-ion coordination in ionic liquids.

Two high-salt-content ionic liquid electrolytes with distinct cationic chemistries were compared. The one with a phosphonium cation showed superior characteristics, particularly in terms of its enhanced capacity when used in lithium metal batteries.

Sodium batteries are promising alternatives to state-of-the-art lithium batteries, owing to the cheaper resources and more sustainable materials. To realise this promise, the requirement for electrochemically and thermally stable electrolytes with low volatility and flammability to enable high-performance sodium batteries is crucial. In this work, we reported a unique family of salts through the synthesis of tris(amino)phosphonium cations [P1(DEA)3]+ and pairing with [FSI]- and [TFSI]- anions. The unique organic ionic plastic crystal (OIPC) [P1(DEA)3][FSI] displays high ionic conductivity which is several orders of magnitude greater than that of its counterpart [P1(DMA)3][FSI]. Electrolytes composed of 50 mol% NaFSI in [P1(DEA)3][FSI] showed a high conductivity value of 1.6 x 10-2 S cm-1 at 50 degrees C. The electrolyte supports stable Na plating/stripping with a small overpotential of 70 mV at 0.5 mA cm-2 with 2 h polarization. This electrolyte exhibits a satisfactory performance in sodium metal full cells (Na metal and NaFePO4 electrodes) with a stable cycling performance of 125 mA h g-1 at C/10, a high capacity retention of similar to 80% after 112 cycles and a coulombic efficiency close to 99.5%. A unique family of salts utilising the new tris(amino)phosphonium cation [P1(DEA)3]+, paired with [FSI]- anions, supports stable Na plating/stripping with a small overpotential and non-dendritic morphology.

ReSUMe Le MS2A etait une resine cetonique reduite et un vernis de predilection pour de nombreux conservateurs-restaurateurs de peinture jusqu'a l'arret de sa production en 2014. Afin d'y remedier, un nouveau procede de fabrication plus coherent a recemment ete developpe ; la nouvelle generation de resines concue avec une chimie repliquee s'appelle MS3. La comparaison directe entre la MS3 et la MS2A est limitee puisque aucun echantillon recent de la resine MS2A n'existe, de ce fait le travail presente ici se concentre principalement sur les performances et les caracteristiques de la resine MS3 en comparaison avec la documentation ecrite sur la MS2A et des echantillons plus anciens de MS2A. L'indice de refraction, la brillance, la temperature de transition vitreuse et le poids moleculaire sont presentes ici. La MS3 et d'autres resines a faible poids moleculaire ont ete artificiellement vieillies et par la suite examinees a l'aide de mesures IRTF et colorimetriques. La maniabilite et la performance ont ete evaluees en vernissant deux peintures a l'huile. Cette etude a demontre que la nouvelle resine MS3 montre une coherence avec les anciens echantillons de MS2A ainsi que des ameliorations dans la reduction des cetones, la couleur, le debit et la coherence d'un lot a l'autre. Lucile Berthelot. RESUMEN MS2A era una resina con bajo contenido de cetonas y un barniz preferido por muchos conservadores de pintura, pero su produccion ceso en el 2014. Para remediar esto, recientemente se desarrollo un nuevo proceso de fabricacion mas consistente y la proxima generacion de resina disenada replicando la quimica se llama MS3. La comparacion directa entre las resinas MS3 y MS2A es limitada ya que no existen muestras frescas de MS2A, por lo que el trabajo presentado aqui se centra principalmente en el rendimiento y las caracteristicas de MS3 en comparacion con informes sobre MS2A en la literatura y en comparaciones con muestras de referencia antiguas de MS2A. Se presentan el indice de refraccion, el brillo, la temperatura de transicion vitrea y el peso molecular. Muestras de MS3 y de resinas de barniz de bajo peso molecular comparativas se envejecieron artificialmente y se examinaron usando mediciones de color y de espectroscopia infraroja por transformada de Fourier (FTIR). El manejo practico y el rendimiento se evaluaron mediante el barnizado de dos pinturas al oleo. Este estudio ha demostrado que la nueva resina MS3 es consistente con las muestras mas antiguas de MS2A junto con mejoras en la reduccion del grupo ceto, el color, el flujo y la consistencia de lote a lote. traduccion: Silvia Centeno. RESUMO MS2A era uma resina de acetona reduzida e um verniz preferido para muitos conservadores de pintura, mas teve a producao intenropida em 2014. Para remediar isso, um novo processo de fabricacao mais consistente foi desenvolvido recentemente e a proxima geracao de resina projetada com quimica replicada, chamada MS3. A comparacao direta entre MS3 e MS2A e limitada, pois nao existem amostras novas de MS2A, portanto, o trabalho apresentado aqui se concentra principalmente no desempenho e nas caracteristicas do MS3 em comparacao com relatorios da literatura de MS2A e comparacoes com amostras de referencia mais antigas de MS2A. indice de refracao, brilho, temperatura de transicao vitrea e peso molecular sao apresentados. MS3 e resinas de verniz comparativas de baixo peso molecular foram envelhecidas artificialmente e examinadas usando FTIR e medicoes de cor. O manuseio pratico e o desempenho foram avaliados envernizando duas pinturas a oleo. Este estudo mostrou que a nova resina MS3 demonstra consistencia com amostras mais antigas de MS2A, juntamente com melhorias na reducao de ceto, cor, fluxo e consistencia de lote para lote. Traduzido por Beatriz Haspo.

Exploring highly concentrated (>50 mol% Li-salt) ionic liquids as electrolytes for lithium metal batteries can lead to the development of safer, high-performance batteries with increased energy density and improved cycling stability. However, at high concentrations of Li-salt, ionic liquid electrolytes can have high viscosity and slow ion transport kinetics. Here, we investigate the use of novel ether-functionalised cations as a promising approach for increasing fluidity and weakening Li+-anion interactions in highly concentrated ionic liquid electrolytes to facilitate faster transport of Li+. Three small ether-functionalised cations, namely 1-methoxymethyl-1,1,1-trimethylammonium ([N-111,N-1O1](+)), N-methoxymethyl-N-methylpiperidinium ([C(1O1)mpip](+)) and N-methoxymethyl-N-methylmorpholinium ([C(1O1)mmor](+)) are compared when paired with bis(fluorosulfonyl)imide ([FSI]-) anion at a 1:1 mol ratio with LiFSI. The study provides insights into the relationship between the structure of the ether-functionalised cations and the properties of the resulting electrolytes, including thermal behaviour, ionic conductivity, viscosity, ion diffusivity, Li plating/stripping behaviour and Li+-transference number. The performance of the electrolytes was tested in Li|LiFePO4 (LFP) cells (1.14 mAh cm(-2)) at 0.57 mA cm(-2) (C/2) for 100 cycles at 50 C. (LiFSI)(0.5)([C1O1mpip][FSI])(0.5) and (LiFSI)(0.5)([N-111,N-1O1][FSI])(0.5), have high Litransference numbers of 0.47 +/- 0.02 and 0.37 +/- 0.02, respectively, and both display 0.85 mAh cm(-2) areal discharge capacity after 100 cycles, with capacity retention over 98.5% (in comparison to the first cycle after preconditioning cycles), demonstrating the feasibility of these electrolytes in Li-metal cells.

The implementation of next-generation batteries requires the development of safe, compatible electrolytes that are stable and do not cause safety problems. The difluoro(oxalato)borate ([DFOB](-)) anion has been used as an electrolyte additive to aid with stability, but such an approach has most commonly been carried out using flammable solvent electrolytes. As an alternative approach, utilisation of the [DFOB](-) anion to make ionic liquids (ILs) or Organic Ionic Plastic Crystals (OIPCs) allows the advantageous properties of ILs or OIPCs, such as higher thermal stability and non-volatility, combined with the benefits of the [DFOB](-) anion. Here, we report the synthesis of new [DFOB](-)-based ILs paired with triethylmethylphosphonium [P-1222](+), and diethylisobutylmethylphosphonium [P-122i4](+). We also report the first OIPCs containing the [DFOB](-) anion, formed by combination with the 1-ethyl-1-methylpyrrolidinium [C(2)mpyr](+) cation, and the triethylmethylammonium [N-1222](+) cation. The traditional synthetic route using halide starting materials has been successfully replaced by a halide-free tosylate-based synthetic route that is advantageous for a purer, halide free product. The synthesised [DFOB](-)-based salts exhibit good thermal stability, while the ILs display relatively high ionic conductivity. Thus, the new [DFOB](-)-based electrolytes show promise for further investigation as battery electrolytes both in liquid and solid-state form.

A series of new salts with a small ether-functionalised trimethylammonium cation are synthesised and characterised to probe their unique structure–property relationships.

Zwitterionic materials can exhibit unique characteristics and are highly tunable by variation to the covalently bound cationic and anionic moieties. Despite the breadth of properties and potential uses reported to date, for electrolyte applications they have thus far primarily been used as additives or for making polymer gels. However, zwitterions offer intriguing promise as electrolyte matrix materials that are non-volatile and charged but non-migrating. Here we report a family of zwitterions that exhibit molecular disorder and plasticity, which allows their use as a solid-state conductive matrix. We have characterized the thermal, morphological and structural properties of these materials using techniques including differential scanning calorimetry, scanning electron microscopy, solid-state NMR and X-ray crystallography. We report the physical and transport properties of zwitterions combined with lithium salts and a lithium-functionalized polymer to form solid or high-salt-content liquid electrolytes. We demonstrate that the zwitterion-based electrolytes can allow high target ion transport and support stable lithium metal cell cycling. The ability to use disordered zwitterionic materials as electrolyte matrices for high target ion conduction, coupled with an extensive scope for varying the chemical and physical properties, has important implications for the future design of non-volatile materials that bridge the choice between traditional molecular and ionic solvent systems.

The synthesis and characterisation of a series of new oxazolidinium-based salts shows that ether functionality in the ring can have beneficial impacts on properties including ionic conductivity.

The readily available natural product stevioside provides a unique diterpene core structure that can be explored for small molecule library development by diversity-oriented synthesis and functional group transformations. Validation arrays were prepared from steviol, isosteviol, and related analogues, derived from stevioside, to produce over 90 compounds. These compounds were submitted to the NIH Molecular Libraries Small Molecule Repository for screening in the Molecular Libraries Screening Center Network. Micromolar hits were identified in multiple high-throughput assays for several library members. A cheminformatics analysis of the compounds was performed that verified the expected diversity and complexity of this set of compounds. The screening results indicate that scaffolds-derived natural products can provide screening hits against multiple target proteins.

The marine protozoan parasite Neoparamoeba perurans has been established as the causative agent for amoebic gill disease (AGD) in Atlantic salmon (Salmo salar). Freshwater bathing is the only routinely used treatment for AGD in Australia while hydrogen peroxide (H2O2) is used in countries with cooler water temperatures. The identification of new treatments that do not rely on either freshwater or H2O2 bathing is highly sought. However, in vitro based methods for high throughput screening of antiparasitic compounds have not been established for this parasite. To this end the present study evaluated two in vitro bioassays based on metabolic energy production and cellular membrane integrity to distinguish between amoebistatic (crenated or pseudocyst forms with recovery possible) and amoebicidal (death) activity. Amoebae were subject to either freshwater, H2O2 or chloramine-T for 4 h treatment and assessed 24 h after recovery. Visualization by microscopy and bioassay assessment 24 h post-treatment confirmed that H2O2 and freshwater are 95% amoebicidal albeit due to different mechanisms of action. These data are consistent with other studies where amoebae have been observed to recover following exposure to these compounds and provide evidence for the inclusion of a recovery component to differentiate between the mechanism of action of amoebicidal and amoebistatic treatments. Together these bioassays are a critical tool for high throughput screening of novel and more effective treatments against AGD.

Atovaquone-proguanil (Malarone®) is used for malaria prophylaxis and treatment. While the cytochrome bc1-inhibitor atovaquone has potent activity, proguanil's action is attributed to its cyclization-metabolite, cycloguanil. Evidence suggests that proguanil has limited intrinsic activity, associated with mitochondrial-function. Here we demonstrate that proguanil, and cyclization-blocked analogue tBuPG, have potent, but slow-acting, in vitro anti-plasmodial activity. Activity is folate-metabolism and isoprenoid biosynthesis-independent. In yeast dihydroorotate dehydrogenase-expressing parasites, proguanil and tBuPG slow-action remains, while bc1-inhibitor activity switches from comparatively fast to slow-acting. Like proguanil, tBuPG has activity against P. berghei liver-stage parasites. Both analogues act synergistically with bc1-inhibitors against blood-stages in vitro, however cycloguanil antagonizes activity. Together, these data suggest that proguanil is a potent slow-acting anti-plasmodial agent, that bc1 is essential to parasite survival independent of dihydroorotate dehydrogenase-activity, that Malarone® is a triple-drug combination that includes antagonistic partners and that a cyclization-blocked proguanil may be a superior combination partner for bc1-inhibitors in vivo.

Electrochemical activation of thiocarbonylthio reversible addition-fragmentation chain transfer (RAFT) agents (S=C(Z)S-R) is explored as a potential method for initiating RAFT polymerization under mild conditions without producing initiator-derived byproducts. Herein we apply cyclic voltammetry to establish a predominant reduction mechanism, where electrochemical reduction is coupled to an irreversible first-order chemical reaction. Structure-dependent trends in cyclic voltammograms (CVs), and comparison to absorption spectra, clarify the role of R- and Z-groups in determining reduction processes. The major reduction peak moves to more cathodic potentials in the series dithiobenzoates > trithiocarbonates > heteroaromatic dithiocarbamates > xanthates ∼ N-alkyl-N-aryldithiocarbamates, due to the Z-group influence on thiocarbonyl bond reactivity. More active (electron-withdrawing, radical stabilizing) R-groups shift the reduction peak anodically, in part due to their influence on the rate of the coupled chemical reaction. Analysis of CVs across a range of scan rates revealed that kinetic control over the reduction mechanism is influenced by both the charge transfer rate and chemical reaction rate.

A 54-member library of boronated octapeptides, with all but the boronated residue being proteinogenic, was tested for affinity to a set of saccharides commonly found on the terminus of mammalian glycans. After experimentation with a high-throughput dye-displacement assay, attention was focused on isothermal titration calorimetry as a tool to provide reliable affinity data, including enthalpy and entropy of binding. A small number of boronated peptides showed higher affinity and significant selectivity for N-acetylneuraminic acid over methyl-α-d-galactopyranoside, methyl-α/β-l-fucopyranoside and N-acetyl-d-glucosamine. Thermodynamic data showed that for most of the boronated peptides studied, saccharide binding was associated with a significant increase in entropy, presumably resulting from the displacement of semiordered water molecules from around the sugar and/or peptide.

The ability to modify the thiocarbonylthio end-groups of RAFT polymers is important for applications where an inert or highly functionalised material is required. Here we report a copper promoted cross-coupling reaction between RAFT polymer end-groups and aryl boronic acids. This method gives high conversion to the modified polymers, and is compatible with a wide variety of functional molecules.

Achieving efficient and targeted delivery of short interfering (siRNA) is an important research challenge to overcome to render highly promising siRNA therapies clinically successful. Challenges exist in designing synthetic carriers for these RNAi constructs that provide protection against serum degradation, extended blood retention times, effective cellular uptake through a variety of uptake mechanisms, endosomal escape, and efficient cargo release. These challenges have resulted in a significant body of research and led to many important findings about the chemical composition and structural layout of the delivery vector for optimal gene silencing. The challenge of targeted delivery vectors remains, and strategies to take advantage of nature's self-selective cellular uptake mechanisms for specific organ cells, such as the liver, have enabled researchers to step closer to achieving this goal. In this work, we report the design, synthesis, and biological evaluation of a novel polymeric delivery vector incorporating galactose moieties to target hepatic cells through clathrin-mediated endocytosis at asialoglycoprotein receptors. An investigation into the density of carbohydrate functionality and its distance from the polymer backbone is conducted using reversible addition-fragmentation chain transfer polymerization and postpolymerization modification.