School of Chemistry - Research Publications
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ItemAn Engineered Nanosugar Enables Rapid and Sustained Glucose-Responsive Insulin Delivery in Diabetic Mice(WILEY-V C H VERLAG GMBH, 2023-03-12)Glucose-responsive insulin-delivery platforms that are sensitive to dynamic glucose concentration fluctuations and provide both rapid and prolonged insulin release have great potential to control hyperglycemia and avoid hypoglycemia diabetes. Here, biodegradable and charge-switchable phytoglycogen nanoparticles capable of glucose-stimulated insulin release are engineered. The nanoparticles are "nanosugars" bearing glucose-sensitive phenylboronic acid groups and amine moieties that allow effective complexation with insulin (≈95% loading capacity) to form nanocomplexes. A single subcutaneous injection of nanocomplexes shows a rapid and efficient response to a glucose challenge in two distinct diabetic mouse models, resulting in optimal blood glucose levels (below 200 mg dL-1 ) for up to 13 h. The morphology of the nanocomplexes is found to be key to controlling rapid and extended glucose-regulated insulin delivery in vivo. These studies reveal that the injected nanocomplexes enabled efficient insulin release in the mouse, with optimal bioavailability, pharmacokinetics, and safety profiles. These results highlight a promising strategy for the development of a glucose-responsive insulin delivery system based on a natural and biodegradable nanosugar.
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ItemDeconstructed beetles: Bilayered composite materials produce green coloration with remarkably high near-infrared reflectance(Elsevier BV, 2023-06-01)Beetle elytra (hardened forewings) are a promising source of inspiration to develop or enhance the performance of human-fabricated composite materials. The structures responsible for optical properties in the ultra-violet to visible spectrum (300–700 nm) have been extensively characterised, but we have limited knowledge of optical properties and their physical origin in the near-infrared (NIR; 700–1700 nm). We examined the elytra of three species of green scarab beetles (Xylonichus eucalypti, Anoplognathus prasinus and Paraschizognathus olivaceus) with very high NIR reflectance. We manually separated layers in the elytra to disambiguate their contributions to the overall optical response. We show that unlike other scarabs, nanostructures within the cuticle layer do not produce notable reflectance. Instead, the cuticle resembles a pigment-based filter with 50% transmittance in the NIR and absorption in the visible spectrum contributing to the green appearance. Each species has a layer below the cuticle that appears white to the naked eye and produces broadband reflectance, particularly in the near-infrared; however, the structure of the white underlay differs markedly between the three species. In A. prasinus and P. olivaceus, the structure is disordered (no regular, repeated elements at optical length scales); whereas in Xylonichus eucalypti, the white underlay was notably thinner and comprised quasi-ordered hollow cylindrical structures embedded in a chitin matrix. We modelled the coherent scattering produced by this structure to demonstrate that it is responsible for broadband visible and NIR reflectance. We discuss biological implications and technological applications of the composite structure of beetle elytra.
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ItemNo Preview AvailableUltrasonics in polymer science: applications and challenges(Elsevier BV, 2023-07-01)Ultrasonic waves in a liquid media generate both chemical and mechanistic effects that are actively used to perform chemical reactions, polymer synthesis, nanoparticle synthesis, colloids, food processing and so on. The application of sonochemistry in polymer science has been an interesting topic of research in the recent years. Ultrasonication acts as an external stimulus to initiate free radical polymerization (FRP) by the homolysis of the solvent, thereby generating radicals. The recent utilization of high frequency ultrasound (>100 KHz) for polymer synthesis has evoked new interest in the use of sonochemistry in the field of polymer chemistry, especially in chain growth polymerization reactions including reversible-deactivation radical polymerization (RDRP) techniques and novel applications. This review presents the principles of sonochemisty and the fundamental aspects governing the cavitation process and the radical generation process. A historical overview of the development of ultrasound-assisted polymerization with a focus on chain-growth polymerizations operating under pseudo-“living” conditions including nitroxide-mediated polymerization (NMP), atom transfer radical polymerization (ATRP) and reversible addition–fragmentation chain transfer (RAFT) polymerization is provided. The utilization of ultrasound in polymer applications such as hydrogels, biomedical nanostructures, drug delivery, nanocomposite synthesis is also discussed. Unlike conventional FRP, ultrasound-initiated polymerization does not involve any external toxic chemical initiators, adds temporal control to the polymerization process, offers excellent control over the molecular weight and the microstructure of the final polymers, etc. The ultrasound assisted polymerization is a novel, clean and green technology, which can be investigated further by coupling with thermo-, mechano- or photochemical stimuli or flow chemistry. It has the potential to be scaled up into an industrial process.
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ItemA photo-switchable molecular capsule: sequential photoinduced processes(ROYAL SOC CHEMISTRY, 2022-10-24)The metastable trilacunary heteropolyoxomolybdate [PMo9O31(py)3]3- - {PMo9}; py = pyridine) and the ditopic pyridyl bearing diarylethene (DAE) (C25H16N2F6S2) self-assemble via a facile ligand replacement methodology to yield the photo-active molecular capsule [(PMo9O31)2(DAE)3]6-. The spatial arrangement and conformation of the three DAE ligands are directed by the surface chemistry of the molecular metal oxide precursor with exclusive ligation of the photo-active antiparallel rotamer to the polyoxometalate (POM) while the integrity of the assembly in solution has been verified by a suite of spectroscopic techniques. Electrocyclisation of the three DAEs occurs sequentially and has been investigated using a combination of steady-state and time-resolved spectroscopies with the discovery of a photochemical cascade whereby rapid photoinduced ring closure is followed by electron transfer from the ring-closed DAE to the POM in the latent donor-acceptor system on subsequent excitation. This interpretation is also supported by computational and detailed spectroelectrochemical analysis. Ring-closing quantum yields were also determined using a custom quantum yield determination setup (QYDS), providing insight into the impact of POM coordination on these processes.
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ItemElectro-Microfluidic Assembly Platform for Manipulating Colloidal Structures inside Water-in-Oil Emulsion Droplets.(Wiley, 2022-11)Colloidal assembly is a key strategy in nature and artificial device. Hereby, an electromicrofluidic assembly platform (eMAP) is proposed and validated to achieve 3D colloidal assembly and manipulation within water droplets. The water-in-oil emulsion droplets autoposition in the eMAP driven by dielectrophoresis, where the (di)electrowetting effect induces droplet deformation, facilitating quadratic growth of the electric field in water droplet to achieve "far-field" dielectrophoretic colloidal assembly. Reconfigurable 3D colloidal configurations are observed and dynamically programmed via applied electric fields, colloidal properties, and droplet size. Binary and ternary colloidal assemblies in one droplet allow designable chemical and physical anisotropies for functional materials and devices. Integration of eMAP in high throughput enables mass production of functional microcapsules, and programmable optoelectronic units for display devices. This eMAP is a valuable reference for expanding fundamental and practical exploration of colloidal systems.
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ItemExcited-State Barrier Controls E ? Z Photoisomerization in p-Hydroxycinnamate Biochromophores(AMER CHEMICAL SOC, 2022-09-23)Molecules based on the deprotonated p-hydroxycinnamate moiety are widespread in nature, including serving as UV filters in the leaves of plants and as the biochromophore in photoactive yellow protein. The photophysical behavior of these chromophores is centered around a rapid E → Z photoisomerization by passage through a conical intersection seam. Here, we use photoisomerization and photodissociation action spectroscopies with deprotonated 4-hydroxybenzal acetone (pCK-) to characterize a wavelength-dependent bifurcation between electron autodetachment (spontaneous ejection of an electron from the S1 state because it is situated in the detachment continuum) and E → Z photoisomerization. While autodetachment occurs across the entire S1(ππ*) band (370-480 nm), E → Z photoisomerization occurs only over a blue portion of the band (370-430 nm). No E → Z photoisomerization is observed when the ketone functional group in pCK- is replaced with an ester or carboxylic acid. The wavelength-dependent bifurcation is consistent with potential energy surface calculations showing that a barrier separates the Franck-Condon region from the E → Z isomerizing conical intersection. The barrier height, which is substantially higher in the gas phase than in solution, depends on the functional group and governs whether E → Z photoisomerization occurs more rapidly than autodetachment.
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ItemIn-cell DNP NMR reveals multiple targeting effect of antimicrobial peptide(ELSEVIER, 2022-01-01)Dynamic nuclear polarization NMR spectroscopy was used to investigate the effect of the antimicrobial peptide (AMP) maculatin 1.1 on E. coli cells. The enhanced 15N NMR signals from nucleic acids, proteins and lipids identified a number of unanticipated physiological responses to peptide stress, revealing that membrane-active AMPs can have a multi-target impact on E. coli cells. DNP-enhanced 15N-observed 31P-dephased REDOR NMR allowed monitoring how Mac1 induced DNA condensation and prevented intermolecular salt bridges between the main E. coli lipid phosphatidylethanolamine (PE) molecules. The latter was supported by similar results obtained using E. coli PE lipid systems. Overall, the ability to monitor the action of antimicrobial peptides in situ will provide greater insight into their mode of action.
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ItemSynthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds(BEILSTEIN-INSTITUT, 2023-01-31)Nine new fluorinated analogues were synthesised by late-stage functionalisation using Diversinate™ chemistry on the Open Source Malaria (OSM) triazolopyrazine scaffold (Series 4). The structures of all analogues were fully characterised by NMR, UV and MS data analysis; three triazolopyrazines were confirmed by X-ray crystal structure analysis. The inhibitory activity of all compounds against the growth of the malaria parasite Plasmodium falciparum (3D7 and Dd2 strains) and the cytotoxicity against a human embryonic kidney (HEK293) cell line were tested. Some of the compounds demonstrated moderate antimalarial activity with IC50 values ranging from 0.2 to >80 µM; none of the compounds displayed any cytotoxicity against HEK293 cells at 80 µM. Antimalarial activity was significantly reduced when C-8 of the triazolopyrazine scaffold was substituted with CF3 and CF2H moieties, whereas incorporation of a CF2Me group at the same position completely abolished antiplasmodial effects.
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ItemHigh-resolution structural study on pyridin-3-yl ebselen and its N-methylated tosylate and iodide derivatives.(International Union of Crystallography (IUCr), 2023-02-01)The crystal structure of the pyridine-substituted benzisoselenazolinone 2-(pyridin-3-yl)-2,3-dihydro-1,2-benzoselenazol-3-one (C12H8N2OSe, 2), related to the antioxidant ebselen [systematic name: 2-phenyl-1,2-benzoselenazol-3(2H)-one, 1], is characterized by strong intermolecular N...Se(-N) chalcogen bonding, where the N...Se distance of 2.3831 (6) Å is well within the sum of the van der Waals radii for N and Se (3.34 Å). This strong interaction results in significant lengthening of the internal N-Se distance, consistent with significant population of the Se-N σ* antibonding orbital. Much weaker intermolecular O...Se chalcogen bonding occurs between the amide-like O atom in 2 and the less polarized C-Se bond in this structure. Charge density analysis of 2 using multipole refinement of high-resolution data allowed the electrostatic surface potential for 2 to be mapped, and clearly reveals the σ-hole at the extension of the Se-N bond as an area of positive electrostatic potential. Topological analysis of the electron-density distribution in 2 was carried out within the Quantum Theory of Atoms in Molecules (QTAIM) framework and revealed bond paths and (3,-1) bond critical points (BCPs) for the N...Se-N moiety consistent with a closed-shell interaction; however, the potential energy term is suggestive of electron sharing. Analysis of the electron localization function (ELF) for the strong N...Se and the weak O...Se chalcogen-bonding interactions in the structure of 2 suggest significant electron sharing in the former interaction, and a largely electrostatic interaction in the latter. Conversion of 2 to its N-methylated derivatives by reaction with methyl iodide [1-methyl-3-(3-oxo-2,3-dihydro-1,2-benzoselenazol-2-yl)pyridin-1-ium iodide, C13H11N2OSe+·I-] and methyl tosylate [1-methyl-3-(3-oxo-2,3-dihydro-1,2-benzoselenazol-2-yl)pyridin-1-ium toluenesulfonate trihydrate, C13H11N2OSe+·C7H7O3S-·3H2O] removes the possibility of N...Se chalcogen bonding and instead structures are obtained where the iodide and tosylate counter-ions fulfill the role of chalcogen-bond acceptors, with a strong I-...Se interaction in the iodide salt and a weaker p-Tol-SO3-...Se interaction in the tosylate salt.
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ItemA Census of Hsp70-Mediated Proteome Solubility Changes upon Recovery from Heat Stress(AMER CHEMICAL SOC, 2022-05-06)Eukaryotic cells respond to heat shock through several regulatory processes including upregulation of stress responsive chaperones and reversible shutdown of cellular activities through formation of protein assemblies. However, the underlying regulatory mechanisms of the recovery of these heat-induced protein assemblies remain largely elusive. Here, we measured the proteome abundance and solubility changes during recovery from heat shock in the mouse Neuro2a cell line. We found that prefoldins and translation machinery are rapidly down-regulated as the first step in the heat shock response. Analysis of proteome solubility reveals that a rapid mobilization of protein quality control machineries, along with changes in cellular energy metabolism, translational activity, and actin cytoskeleton are fundamental to the early stress responses. In contrast, longer term adaptation to stress involves renewal of core cellular components. Inhibition of the Hsp70 family, pivotal for the heat shock response, selectively and negatively affects the ribosomal machinery and delays the solubility recovery of many nuclear proteins. ProteomeXchange: PXD030069.