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Item Open Access The Oxidation of Oxygen and Sulfur-Containing Heterocycles by Cytochrome P450 Enzymes(Wiley-VCH GmbH, 2023) Podgorski, M.N.; Keto, A.B.; Coleman, T.; Bruning, J.B.; De Voss, J.J.; Krenske, E.H.; Bell, S.G.The cytochrome P450 (CYP) superfamily of monooxygenase enzymes play important roles in the metabolism of molecules which contain heterocyclic, aromatic functional groups. Here we study how oxygen- and sulfur-containing heterocyclic groups interact with and are oxidized using the bacterial enzyme CYP199A4. This enzyme oxidized both 4-(thiophen-2-yl)benzoic acid and 4-(thiophen-3-yl)benzoic acid almost exclusively via sulfoxidation. The thiophene oxides produced were activated towards Diels-Alder dimerization after sulfoxidation, forming dimeric metabolites. Despite X-ray crystal structures demonstrating that the aromatic carbon atoms of the thiophene ring were located closer to the heme than the sulfur, sulfoxidation was still favoured with 4-(thiophen-3-yl)benzoic acid. These results highlight a preference of this cytochrome P450 enzyme for sulfoxidation over aromatic hydroxylation. Calculations predict a strong preference for homodimerization of the enantiomers of the thiophene oxides and the formation of a single major product, in broad agreement with the experimental data. 4-(Furan-2-yl)benzoic acid was oxidized to 4-(4'-hydroxybutanoyl)benzoic acid using a whole-cell system. This reaction proceeded via a g-keto-α,β-unsaturated aldehyde species which could be trapped in vitro using semicarbazide to generate a pyridazine species. The combination of the enzyme structures, the biochemical data and theoretical calculations provides detailed insight into the formation of the metabolites formed from these heterocyclic compounds.Item Metadata only Efficient biocatalytic C-H bond oxidation: an engineered heme-thiolate peroxygenase from a thermostable cytochrome P450(Royal Society of Chemistry, 2023) Gee, A.R.; Stone, I.; Stockdale, T.P.; Pukala, T.L.; De Voss, J.J.; Bell, S.G.A highly sought after reaction in chemical synthesis is the activation of unactivated carbon–hydrogen bonds. We demonstrate the hydroxylation of fatty acids using an engineered thermostable archaeal cytochrome P450 enzyme. By replacing a seven amino acid section of the I-helix, the nicotinamide cofactor-dependent monooxygenase was converted into a hydrogen peroxide using peroxygenase, enabling the efficient biocatalytic oxidation of C–H bonds at room temperature to 90 °C.Item Metadata only Exploiting Chemical Protein Synthesis to Study the Role of Tyrosine Sulfation on Anticoagulants from Hematophagous Organisms(American Chemical Society, 2023) Maxwell, J.W.C.; Hawkins, P.M.E.; Watson, E.E.; Payne, R.J.CONSPECTUS: Tyrosine sulfation is a post-translational modification (PTM) that modulates function by mediating key protein−protein interactions. One of the early proteins shown to possess this PTM was hirudin, produced in the salivary glands of the medicinal leech Hirudo medicinalis, whereby tyrosine sulfation led to a ∼10-fold improvement in α- thrombin inhibitory activity. Outside of this pioneering discovery, the involvement of tyrosine sulfation in modulating the activity of salivary proteins from other hematophagous organisms was unknown. We hypothesized that the intrinsic instability of the tyrosine sulfate functionality, particularly under the acidic conditions used to isolate and analyze peptides and proteins, has led to poor detection during the isolation and/or expression of these molecules. Herein, we summarize our efforts to interrogate the functional role of tyrosine sulfation in the thrombin inhibitory and anticoagulant activity of salivary peptides and proteins from a range of different blood feeding organisms, including leeches, ticks, mosquitoes, and flies. Specifically, we have harnessed synthetic chemistry to efficiently generate homogeneously sulfated peptides and proteins for detailed structure−function studies both in vitro and in vivo. Our studies began with the leech protein hirudin P6 (from Hirudinaria manillensis), which is both sulfated on tyrosine and Oglycosylated at a nearby threonine residue. Synthetically, this was achieved through solid-phase peptide synthesis (SPPS) with a latestage on-resin sulfation, followed by native chemical ligation and a folding step to generate six differentially modified variants of hirudin P6 to assess the functional interplay between O-glycosylation and tyrosine sulfation. A one-pot, kinetically controlled ligation of three peptide fragments was used to assemble homogeneously sulfoforms of madanin-1 and chimadanin from the tick Haemaphysalis longicornis. Dual tyrosine sulfation at two distinct sites was shown to increase the thrombin inhibitory activity by up to 3 orders of magnitude through a novel interaction with exosite II of thrombin. The diselenide-selenoester ligation developed by our lab provided us with a means to rapidly assemble a library of different sulfated tick anticoagulant proteins: the andersonins, hyalomins, madanin-like proteins, and hemeathrins, thus enabling the generation of key structure−activity data on this family of proteins. We have also confirmed the presence of tyrosine sulfation in the anticoagulant proteins of Anopheles mosquitoes (anophelins) and the Tsetse fly (TTI) via insect expression and mass spectrometric analysis. These molecules were subsequently synthesized and assessed for thrombin inhibitory and anticoagulant activity. Activity was significantly improved by the addition of tyrosine sulfate modifications and led to molecules with potent antithrombotic activity in an in vivo murine thrombosis model. The Account concludes with our most recent work on the design of trivalent hybrids that tandemly occupy the active site and both exosites (I and II) of α-thrombin, with a TTI-anophelin hybrid (Ki= 20 fM against α-thrombin) being one of the most potent protease inhibitors and anticoagulants ever generated. Taken together, this Account highlights the importance of the tyrosine sulfate post-translational modification within salivary proteins from blood feeding organisms for enhancing anticoagulant activity. This work lays the foundation for exploiting native or engineered variants as therapeutic leads for thrombotic disorders in the future.Item Open Access UV emission from lanthanide-doped upconversion nanoparticles in super-resolution microscopy: potential for cellular damage(American Chemical Society, 2023) Karami, A.; de Prinse, T.J.; Spooner, N.A.; Kidd, S.P.; Sumby, C.J.; Bi, J.Upconversion nanoparticles (UCNPs) co-doped with lanthanide ions have recently attracted significant attention as fluorescent probes for super-resolution microscopy (SRM). This is due to the advantages of UCNPs over other fluorescence probes, such as fluorescent proteins, owing to their unique optical properties, limited photobleaching, and sharp emissions. However, the concurrent emission of ultraviolet (UV) wavelength radiation by UCNPs and the potential for cell photodamage, which may limit useful live-cell analysis, have been overlooked. Here, UCNPs synthesized with eight commonly used combinations of Yb/Tm and Yb/Tm/Gd dopants were excited by either pulsed- or continuous-wave (CW) lasers to evaluate their UV emission. The ratio of emitted UV-A and UV-B was measured relative to blue emission at 475 nm, which is traditionally used for imaging during SRM. We demonstrate that most UCNP samples emit UV light and that the dopant concentration has a key role in generating UV emissions. In addition, the use of pulsed or CW lasers for excitation can lead to a large variation in the amount of UV emitted. This work highlights the importance of considering upconversion dopant composition and concentration, as well as analyzing the emission of synthesized UCNPs before their use to prevent unwanted cell photodamage during live-cell imaging by SRM. Moreover, it established a need to improve the visible light emission of UCNPs with respect to UV emission for SRM applications.Item Open Access Dual Laser Study of Non-Degenerate Two Wavelength Upconversion Demonstrated in Sensitizer-Free NaYF₄:Pr Nanoparticles(Wiley, 2021) de Prinse, T.J.; Karami, A.; Moffatt, J.E.; Payten, T.B.; Tsiminis, G.; Teixeira, L.D.S.; Bi, J.; Kee, T.W.; Klantsataya, E.; Sumby, C.J.; Spooner, N.A.Understanding the upconversion pathways of a rare-earth dopant is crucial to furthering the use of that material, either toward applications in imaging or elsewhere. This work outlines a new analysis approach that consists of using two synchronized widely-tunable laser sources to explore the properties of upconverting materials. By examining sensitizer-free rare-earth nanoparticles based on a matrix of hexagonal sodium yttrium tetrafluoride (β-NaYF4) doped with praseodymium but no ytterbium sensitizer, a “non-degenerate” two-color upconversion fluorescence at a combined excitation of 1020–850 nm is shown. This insight demonstrates the ability of this technique to locate and interrogate novel upconversion pathways. The dopant level of the nanoparticles could be modified without altering other factors, such as the particle's shape or size, that would also change optical properties and this allows investigation of the dopant-level dependency of the optical properties. The approach also allows exploration of the time delay domain between the arrival times of the two non-degenerate excitation pulses, which allows modulation of the brightness from the visible light emissions. This work opens up the parameter space for the systematic synthesis and characterization of new materials with non-degenerate upconversion emission.Item Open Access Investigating the Potential of Flexible and Pre-Organized Tetraamide Ligands to Encapsulate Anions in One-Dimensional Coordination Polymers: Synthesis, Spectroscopic Studies and Crystal Structures(MDPI AG, 2021) Haris, N.S.H.; Mansor, N.; Mohd Yusof, M.S.; Sumby, C.J.; Abdul Kadir, M.The synthesis of amide-based molecules, possessing pre-organized structures, has received significant attention due to their potential applications as molecular receptors and as components of nanomaterials. In this study, four extended tetraamide ligands incorporating ethylene and propylene spacers, namely 1,2-bis[N,N′-6-(3-pyridylmethylamido)pyridyl-2-carboxyamido]ethane (L1), 1,2-bis[N,N′-6-(4-pyridylmethylamido)pyridyl-2-carboxyamido]ethane (L2), 1,2-bis[N,N′-6-(3-pyridylmethylamido)pyridyl-2-carboxyamido]propane (L3) and 1,2-bis[N,N′-6-(4-pyridylmethylamido)pyridyl-2-carboxyamido]propane (L4), were successfully synthesized. Further, reaction of L2 and L4, incorporating pendant 4-pyridyl donors as the metal coordinating sites, with cadmium salts, produced two close-packed one-dimensional coordination polymers, {[Cd3(L2)4(H2O)10](NO3)6·12H2O·CH3OH}n and {[Cd(SO4)(L4)(H2O)2]·4H2O·CH3OH}n. X-ray crystallography reveals that the flexible tetraamide ligands fold upon themselves in the coordination polymer structure. As a consequence, the anion pocket in {[Cd(SO4)(L4)(H2O)2]·4H2O·CH3OH}n incorporating the ligand with the propylene spacer was blocked from encapsulating charge-balancing anions, which were involved in bridging the di-cadmium units. Interestingly, a strong interaction between the 2,6-pyridine dicarboxamide moiety with the nitrate anions was found in {[Cd3(L2)4(H2O)10](NO3)6·12H2O·CH3OH}n, showing potential for materials made from these ligands to serve as anion receptors.Item Metadata only Vortex Fluidics Improved Morphology of CH₃NH₃PbI₃-⨯Cl⨯ Films for Perovskite Solar Cells(Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2017) Sudchanham, J.; Batmunkh, M.; Reutrakul, V.; Shapter, J.G.; Raston, C.L.; Pakawatpanurut, P.We report the use of a vortex fluidic device (VFD) to prepare the precursor solution for CH₃NH₃PbI₃-⨯Cl⨯ perovskite films. These films exhibited improved surface coverage and enhanced light absorption relative to conventional batch processing used for preparing the precursor solution. This VFD-assisted perovskite solar cell displayed a power conversion efficiency of 11.65 %, which is significantly higher than 9.26% of the control device.Item Open Access Stoichiometric Control of Guest Recognition of Self-Assembled Palladium(II)-Based Supramolecular Architectures(Wiley, 2023) Algar, J.L.; Phillips, J.E.; Evans, J.D.; Preston, D.We report flexible [Pd(L)2 ]2+ complexes where there is self-recognition, driven by π-π interactions between electron-rich aromatic arms and the cationic regions they are tethered to. This self-recognition hampers the association of these molecules with aromatic molecular targets in solution. In one case, this complex can be reversibly converted to an 'open' [Pd2 (L)2 ]4+ macrocycle through introduction of more metal ion. This is accomplished by the ligand having two bidentate binding sites: a 2-pyridyl-1,2,3-triazole site, and a bis-1,2,3-triazole site. Due to favourable hydrogen bonding, the 2-pyridyl-1,2,3-triazole units reliably coordinate in the [Pd(L)2 ]2+ complex to control speciation: a second equivalent of Pd(II) is required to enforce coordination to bis-triazole sites and form the macrocycle. The macrocycle interacts with a molecular substrate with higher affinity. In this fashion we are able to use stoichiometry to reversibly switch between two different species and regulate guest binding.Item Open Access Exploring Photoswitchable Binding Interactions with Small Molecule- and Peptide-Based Inhibitors of Trypsin(Wiley, 2023) Palasis, K.; Peddie, V.; Turner, D.; Zhang, X.; Yu, J.; Abell, A.D.The ability to photochemically activate a drug, both when and where needed, requires optimisation of the difference in biological activity between each isomeric state. As a step to this goal, we report small molecule and peptide-based inhibitors of the same protease - trypsin - to better understand how photoswitchable drugs interact with their biological target. The best peptidic inhibitor displayed a >5-fold difference in inhibitory activity between isomeric states, whereas the best small molecule inhibitor only showed a 3.4-fold difference. Docking and molecular modelling suggests this result is due to a large change in 3D structure in the key binding residues of the peptidic inhibitor upon isomerisation, which is not observed for the small molecule inhibitor. Hence, we demonstrate that significant structural changes in critical binding motifs upon irradiation are essential for maximising the difference in biological activity between isomeric states. This is an important consideration in the design of future photoswitchable drugs for clinical applications.Item Open Access Studying manganese carbonyl photochemistry in a permanently porous metal–organic framework(Royal Society of Chemistry, 2023) Young, R.J.; Huxley, M.T.; Wu, L.; Hart, J.; O'Shea, J.; Doonan, C.J.; Champness, N.R.; Sumby, C.J.Mn(diimine)(CO)₃X (X = halide) complexes are critical components of chromophores, photo- and electrocatalysts, and photoactive CO-releasing molecules (photoCORMs). While these entities have been incorporated into metal–organic frameworks (MOFs), a detailed understanding of the photochemical and chemical processes that occur in a permanently porous support is lacking. Here we site-isolate and study the photochemistry of a Mn(diimine)(CO)₃Br moiety anchored within a permanently porous MOF support, allowing for not only the photo-liberation of CO from the metal but also its escape from the MOF crystals. In addition, the high crystallinity and structural flexibility of the MOF allows crystallographic snapshots of the photolysis products to be obtained. We report these photo-crystallographic studies in the presence of coordinating solvents, THF and acetonitrile, showing the changing coordination environment of the Mn species as CO loss proceeds. Using time resolved experiments, we report complementary spectroscopic studies of the photolysis chemistry and characterize the final photolysis product as a possible Mn(II) entity. These studies inform the chemistry that occurs in MOF-based photoCORMs and where these moieties are employed as catalysts.Item Metadata only Optimizing Arsenic Therapy by Selectively Targeting Leukemia Cells(American Chemical Society (ACS), 2023) Carrall, J.A.; Lie, W.; Lambert, J.M.; Harris, H.H.; Lai, B.; Dillon, C.T.Arsenic, in the simple form of arsenic trioxide, is currently marketed for the treatment of acute promyelocytic leukemia. Due to the multifaceted mechanisms of action of arsenic, it has also shown promise in other types of leukemias but is hindered by its toxic effects toward normal cells. This research has aimed to determine whether tumor-homing peptide complexes of arsenic can be designed and developed to strategically target specific cancers. The end goal is to achieve dose reduction and decreased side effects of the resultant arsenic therapeutic agent. In this article, we present the synthesis, characterization, and stability studies of a new class of As-peptide complexes designed to target leukemia. In vitro biological studies of the most stable complex show 1000 times greater toxicity toward leukemia cells over human blood cells, indicating potential for progression to in vivo studies.Item Metadata only Bioinspired Total Synthesis of Hyperireflexolides A and B(American Chemical Society (ACS), 2023) zur Bonsen, A.B.; Sumby, C.J.; George, J.H.Hyperireflexolides A and B were synthesized in six steps via the dearomatization and fragmentation of a simple acylphloroglucinol starting material. The dearomatized acylphloroglucinol undergoes a sequence of oxidative radical cyclization, retro-Dieckmann fragmentation, stereodivergent intramolecular carbonyl-ene reactions, and final α-hydroxy-β-diketone rearrangements to give the target natural products. This sequence is based on a biosynthetic proposal that claims the hyperireflexolides as highly rearranged polycyclic polyprenylated acylphloroglucinols (PPAPs), which is supported by the structural revision of hyperireflexolide B.Item Metadata only Smart Wearable Patches Using Light-Controlled Activation and Delivery of Photoswitchable Antimicrobial Peptides(Wiley, 2023) Kalyvas, J.T.; Marina, P.F.; Stachura, D.L.; Horsley, J.; Abell, A.D.A novel strategy to treat Staphylococcus aureus (S. aureus) skin infections is presented, where UV light is used to facilitate concomitant light-controlled activation and delivery of an antimicrobial therapeutic agent. Specifically, a new photoswitchable gramicidin S analogue was immobilized onto a polymeric wearable patch via a photocleavable linker that undergoes photolysis at the same wavelength of light required for activation of the peptide. Unlike toxic gramicidin S, the liberated active photoswitchable peptide exhibits antimicrobial activity against S. aureus while being ostensibly non-haemolytic to red blood cells. Moreover, irradiation with visible light switches off the antimicrobial properties of the peptide within seconds, presenting an ideal strategy to regulate antibiotic activity for localized bacterial infections with the potential to mitigate resistance.Item Metadata only A tetranuclear polypyridylruthenium(II) complex as a selective stain for extracellular vesicle penetration through brain microvascular endothelium(Royal Society of Chemistry, 2023) Wardhani, K.; Levina, A.; Sun, B.; Grau, G.E.R.; Keene, F.R.; Collins, J.G.; Lay, P.A.A new photoluminescent polypyridylruthenium(II) stain for extracellular vesicles (EVs) released from lipopolysaccharide-stimulated THP-1 monocytes enabled important new insights into how the bacteria-induced immune system affects the blood-brain barrier (BBB). These included previously unknown aspects of EV interactions with BBB microvascular endothelial cells and the extracellular matrix relevant to human brain diseases.Item Metadata only Selective carbon-hydrogen bond hydroxylation using an engineered cytochrome P450 peroxygenase(Elsevier, 2023) Akter, J.; Stockdale, T.P.; Child, S.A.; Lee, J.H.Z.; De Voss, J.J.; Bell, S.G.The cytochrome P450 enzyme CYP102A1 (P450BM3) is a versatile monooxygenase enzyme which has been adapted and engineered for multiple applications in chemical synthesis. Mutation of threonine 268 to glutamate (Thr268Glu) converted the heme domain of this enzyme into a H2O2 utilizing peroxygenase. This variant displayed significantly increased peroxide driven hydroxylation activity towards the saturated linear fatty acids tested (undecanoic through to hexadecenoic acid) when compared to the wild-type heme domain. The product distributions arising from fatty acid oxidation using this peroxygenase variant were broadly similar to those obtained with the wild-type monooxygenase holoenzyme, with oxidation occurring predominantly at the ω-1 through to ω-3 positions. 10-Undecenoic acid was regioselectively hydroxylated at the allylic ω-2 carbon by the Thr268Glu peroxygenase. The effect of isotopic substitution were measured using [9,9,10,10-d4]-dodecanoic acid. The kinetic isotope effect for both the monooxygenase and peroxygenase systems ranged between 7.9 and 9.5, with that of the peroxygenase enzyme being marginally lower. This highlights that carbon‑hydrogen bond abstraction is important in the mechanism of both the monooxygenase and peroxygenase systems. This would infer that the ferryl-oxo radical cation intermediate, compound I, is the likely reactive intermediate in both systems. The peroxygenase variant offers the possibility of simpler cytochrome P450 systems for selective oxidations. To demonstrate this we used this system to oxidize tetradecanoic acid using light driven generation of H2O2 by a flavin.Item Open Access Fabrication of 3D Oriented MOF Micropatterns with Anisotropic Fluorescent Properties(Wiley, 2023) Velásquez-Hernández, M.D.J.; Linares-Moreau, M.; Brandner, L.A.; Marmiroli, B.; Barella, M.; Acuna, G.P.; Zilio, S.D.; Verstreken, M.F.K.; Kravchenko, D.E.; Linder-Patton, O.M.; Evans, J.D.; Wiltsche, H.; Carraro, F.; Wolinski, H.; Ameloot, R.; Doonan, C.; Falcaro, P.Micropatterning crystalline materials with oriented pores is necessary for the fabrication of devices with anisotropic properties. Crystalline and porous metal–organic frameworks (MOFs) are ideal materials as their chemical and structural mutability enables precise tuning of functional properties for applications ranging from microelectronics to photonics. Herein, a patternable oriented MOF film is designed: by using a photomask under X-ray exposure, the MOF film decomposes in the irradiated areas, remaining intact in the unexposed regions. The MOF film acts simultaneously as a resist and as functional porous material. While the heteroepitaxial growth from aligned Cu(OH)₂ nanobelts is used to deposit oriented MOF films, the sensitivity to radiation is achieved by integrating a brominated dicarboxylate ligand (Br₂BDC) into a copper-based MOF Cu₂L₂DABCO (DABCO = 1,4-diazabicyclo[2.2.2]octane; L = BDC/Br₂BDC). The lithographed samples act as diffraction gratings upon irradiation with a laser, thus confirming the quality of the extended MOF micropattern. Furthermore, the oriented MOF patterns are functionalized with fluorescent dyes. As a result, by rotating the polarization angle of the laser excitation, the alignment of the dye in the MOF is demonstrated. By controlling the functional response to light, this MOF patterning protocol can be used for the microfabrication of optical components for photonic devices.Item Metadata only Engineering C–C Bond Cleavage Activity into a P450 Monooxygenase Enzyme(American Chemical Society (ACS), 2023) Miller, J.C.; Lee, J.H.Z.; Mclean, M.A.; Chao, R.R.; Stone, I.S.J.; Pukala, T.L.; Bruning, J.B.; De Voss, J.J.; Schuler, M.A.; Sligar, S.G.; Bell, S.G.The cytochrome P450 (CYP) superfamily of heme monooxygenases has demonstrated ability to facilitate hydroxylation, desaturation, sulfoxidation, epoxidation, heteroatom dealkylation, and carbon−carbon bond formation and cleavage (lyase) reactions. Seeking to study the carbon− carbon cleavage reaction of α-hydroxy ketones in mechanistic detail using a microbial P450, we synthesized α-hydroxy ketone probes based on the physiological substrate for a well-characterized benzoic acid metabolizing P450, CYP199A4. After observing low activity with wild-type CYP199A4, subsequent assays with an F182L mutant demonstrated enzyme-dependent C−C bond cleavage toward one of the α-hydroxy ketones. This C−C cleavage reaction was subject to an inverse kinetic solvent isotope effect analogous to that observed in the lyase activity of the human P450 CYP17A1, suggesting the involvement of a species earlier than Compound I in the catalytic cycle. Co-crystallization of F182L-CYP199A4 with this α-hydroxy ketone showed that the substrate bound in the active site with a preference for the (S)-enantiomer in a position which could mimic the topology of the lyase reaction in CYP17A1. Molecular dynamics simulations with an oxy-ferrous model of CYP199A4 revealed a displacement of the substrate to allow for oxygen binding and the formation of the lyase transition state proposed for CYP17A1. This demonstration that a correctly positioned α-hydroxy ketone substrate can realize lyase activity with an unusual inverse solvent isotope effect in an engineered microbial system opens the door for further detailed biophysical and structural characterization of CYP catalytic intermediates.Item Metadata only Experimental and computational characterisation of an artificial light harvesting complex(Royal Society of Chemistry, 2023) Slimani, S.L.; Kostecki, R.; Kursunlu, A.N.; Kee, T.W.; Tapping, P.C.; Mak, A.M.; Quach, J.Q.Photosynthesis has been shown to be a highly efficient process for energy transfer in plants and bacteria. Like natural photosynthetic systems, the artificial light harvesting complex (LHC) BODIPY pillar[5]arene exhibits Fo¨rster resonance energy transfer (FRET). However, extensive characterisation of the BODIPY pillar[5]arene LHC to determine its suitability as an artificial LHC has yet to occur. In this paper we experimentally and computationally investigate the photophysical properties of the LHC by comparing the light absorption of the BODIPY LHC to individual BODIPY chromophores. Our results show evidence for quantum coherence, with oscillation frequencies of 100 cm1 and 600 cm1 , which are attributable to vibronic, or exciton–phonon type coupling. Computational analysis suggests strong couplings of the molecular orbitals of the LHC resulting from the stacking of neighbouring BODIPY chromophore units. Interestingly, we find a 40% reduction in the absorbance of light for the BODIPY LHC compared to the individual chromophores which we attribute to electronic interactions between the conjugated p-systems of the BODIPY chromophores and the pillar[5]arene backbone.Item Open Access A bioinspired, one-step total synthesis of peshawaraquinone(Royal Society of Chemistry (RSC), 2023) Vieira de Castro, T.; Huang, D.M.; Sumby, C.J.; Lawrence, A.L.; George, J.H.A concise synthesis of a stereochemically complex meroterpenoid, peshawaraquinone, via the unsymmetrical dimerization of its achiral precursor, dehydro-a-lapachone, is reported. Enabled by reversible oxa-6p-electrocyclizations of 2H-pyran intermediates, the base-catalyzed dimerization sets up an intramolecular (3 + 2) cycloaddition, with the formation of six stereocenters during the cascade. Combining the generation and in situ dimerization of dehydro-a-lapachone allows a one-step total synthesis of peshawaraquinone from lawsone and prenal.Item Open Access Micro-analytical and molecular approaches for understanding the distribution, biochemistry, and molecular biology of selenium in (hyperaccumulator) plants(Springer Science and Business Media LLC, 2023) Pinto Irish, K.; Harvey, M.A.; Harris, H.H.; Aarts, M.G.M.; Chan, C.X.; Erskine, P.D.; van der Ent, A.Selenium (Se) is not essential for plants and is toxic at high concentrations. However, Se hyperaccumulator plants have evolved strategies to both tolerate and accumulate>1000 µg Se g−1 DW in their living above-ground tissues. Given the complexity of the biochemistry of Se, various approaches have been adopted to study Se metabolism in plants. These include X-ray-based techniques for assessing distribution and chemical speciation of Se, and molecular biology techniques to identify genes implicated in Se uptake, transport, and assimilation. This review presents these techniques, synthesises the current state of knowledge on Se metabolism in plants, and highlights future directions for research into Se (hyper)accumulation and tolerance. We conclude that powerful insights may be gained from coupling information on the distribution and chemical speciation of Se to genome-scale studies to identify gene functions and molecular mechanisms that underpin Se tolerance and accumulation in these ecologically and biotechnologically important plants species. The study of Se metabolism is challenging and is a useful testbed for developing novel analytical approaches that are potentially more widely applicable to the study of the regulation of a wide range of metal(loid)s in hyperaccumulator plants.