RECENT PUBLICATIONS

Fluorescent labeling and biodistribution of latex nanoparticles formed by surfactant-free RAFT emulsion polymerization

Associate Professor Brian Hawkett

A/Prof Brian Hawkett

Cheuk Ka Poon, Byung Kim, Brian Hawkett* and Sebastien Perrier. Macromolecular Bioscience, 17 (10), 1600366, 2017. DOI: 10.1002/mabi.201600366

Abstract
The authors report the preparation of a novel range of functional polyacrylamide stabilized polystyrene nanoparticles, obtained by surfactant-free reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization, their fluorescent tagging, cellular uptake, and biodistribution. The authors show the versatility of the RAFT emulsion process for the design of functional nanoparticles of well-defined size that can be used as drug delivery vectors. Functionalization with a fluorescent tag offers a useful visualization tool for tracing, localization, and clearance studies of these carriers in biological models. The studies are carried out by labeling the sterically stabilized latex particles chemically with rhodamine B. The fluorescent particles are incubated in a healthy human renal proximal tubular cell line model, and intravenously injected into a mouse model. Cellular localization and biodistribution of these particles on the biological models are explored.


Quantum chemical prediction of equilibrium acidities of ureas, deltamides, squaramides, and croconamides

Professor Kate Jolliffe

Prof Kate Jolliffe

Junming Ho, Vincent Zwicker, Karen Yuen and Kate Jolliffe*. The Journal of Organic Chemistry, 82 (19), 10732-10736, 2017. DOI: 10.1021/acs.joc.7b02083

Abstract
Robust quantum chemical methods are employed to predict the pKa’s of several families of dual hydrogen-bonding organocatalysts/anion receptors, including deltamides and croconamides as well as their thio derivatives. The average accuracy of these predictions is -1 pKa unit and allows for a comparison of the acidity between classes of receptors and for quantitative studies of substituent effects. These computational insights further explain the relationship between pKa and chloride anion affinity of these receptors that will be important for designing future anion receptors and organocatalysts.


Structure and phase transition in BaThO3: A combined neutron and synchrotron X-ray diffraction study

Professor Brendan Kennedy

Prof Brendan Kennedy

Gabriel Murphy and Brendan Kennedy* et al. Journal of Alloys and Compounds, 727, 1044-1049, 2017. DOI: 10.1016/j.jallcom.2017.08.200

Abstract
The structure of BaThO3, obtained by solid state synthesis, was refined for the first time by the Rietveld method using a combination of synchrotron X-ray and neutron powder diffraction data. BaThO3 has an orthorhombic structure at room temperature, in space group Pbnm with a ¼ 6.3491(5), b ¼ 6.3796(4) and c ¼ 8.9907(7) Å. Heating BaThO3 to above 700 oC results in a continuous transition to a second orthorhombic structure, in space group Ibmm, demonstrated by both in situ neutron and synchrotron X-ray powder diffraction measurements. The coefficient of volumetric thermal expansion for BaThO3 is determined to be 1.04 x 10-5 oC-1 from 50 to 625 oC (Pbnm phase), and 9.43 x 10-6 oC-1 from 800 to 1000 oC (Ibmm phase). BaThO3 was found to decompose upon exposure to atmospheric moisture resulting in the formation of ThO2. The thermal expansion of ThO2, which invariably co-exists with BaThO3, is also described.


Self-assembly behaviour of hetero-nuclear Janus dumbbells

Dr Toby Hudson

Dr Toby Hudson

Patrick O'Toole* and Toby Hudson et al. Soft Matter, 13 (39), 7141-7153, 2017. DOI: 10.1039/c7sm01401e

Abstract
We investigate the fluid structure and self-assembly of a system of Janus dumbbells by means of aggregation-volume-bias Monte Carlo simulations and Simulated Annealing techniques. In our approach, Janus dumbbells model asymmetric colloidal particles constituted by two tangent (touching) spheres (labelled as h and s) of different sizes and interaction properties: specifically, the h spheres interact with all other spheres belonging to different dumbbells via hard-sphere potentials, whereas two s spheres interact via a square-well potential. By introducing a parameter a A [0,2] that controls the size ratio between the h and s spheres, we are able to investigate the overall phase behaviour of Janus dumbbells as a function of a. In a previous paper (O’Toole et al., Soft Matter, 2017, 13, 803) we focused on the region where the s sphere is larger than the h sphere (a 4 1), documenting the presence of a variety of phase behaviours. Here we investigate a different regime of size ratios, predominantly where the hard sphere is larger than (or comparable to) the attractive one. Under these conditions, we observe the onset of many different self-assembled super-structures. Depending on the specific value of a we document the presence of spherical clusters (micelles) progressively evolving into more exotic structures including platelets, filaments, networks and percolating fluids, sponge structures and lamellar phases. We find no evidence of a gas liquid phase separation for a r 1.1, since under these conditions it is pre-empted by the development of self-assembled phases.


Targeting the genome-stability hub Ctf4 by stapled-peptide design

Dr Yu Heng Lau

Dr Yu Heng Lau

Yu Heng Lau et al. Angew. Chem. Int. Ed.,, 56 (42), 12866-12872, 2017. DOI: 10.1002/anie.201705611

Abstract
The exploitation of synthetic lethality by smallmolecule targeting of pathways that maintain genomic stability is an attractive chemotherapeutic approach. The Ctf4/AND-1 protein hub, which links DNA replication, repair, and chromosome segregation, represents a novel target for the
synthetic lethality approach. Herein, we report the design, optimization, and validation of double-click stapled peptides encoding the Ctf4-interacting peptide (CIP) of the replicative helicase subunit Sld5. By screening stapling positions in the Sld5 CIP, we identified an unorthodox i,i+6 stapled peptide with improved, submicromolar binding to Ctf4. The mode of interaction with Ctf4 was confirmed by a crystal structure of the stapled Sld5 peptide bound to Ctf4. The stapled Sld5 peptide was able to displace the Ctf4 partner DNA polymerase a from the replisome in yeast extracts. Our study provides proof-ofprinciple evidence for the development of small-molecule inhibitors of the human CTF4 orthologue AND-1.


Structural requirements of flavonoids to induce heme oxygenase-1 expression

Prof Richard Payne

Prof Rich Payne

Richard Payne et al. Free Radical Biology and Medicine, 113, 165-175, 2017. DOI: 10.1016/j.freeradbiomed.2017.09.030

Abstract
Population studies suggest cardiovascular health benefits of consuming fruits and vegetables rich in polyphenolic compounds such as flavonoids. We reported previously that the flavonoid quercetin protects arteries from oxidant-induced endothelial dysfunction and attenuates atherosclerosis in apolipoprotein E gene knockout mice, with induction of heme oxygenase-1 (Hmox1) playing a critical role. The present study investigated the structural requirements of flavonoids to induce Hmox1 in human aortic endothelial cells (HAEC). We identified ortho-dihydroxyl groups and an α,β-unsaturated system attached to a catechol as the key structural requirements for Hmox1 induction. Active but not inactive flavonoids had a low oxidation potential and prevented ascorbate autoxidation, suggesting that Hmox1 inducers readily undergo oxidation and that oxidized, rather than reduced, flavonoids may be the biological inducer of Hmox1. To test this hypothesis, we synthesized stable derivatives of caffeic acid (3-(3,4-dihyroxyphenyl)-2-propenoic acid) containing either ortho-dihydroxy or ortho-dioxo groups. Compared with the dihydroxy compound, the quinone analog induced Hmox1 more potently in HAEC and also provided enhanced protection to arteries of wild type animals against oxidant-induced endothelial dysfunction. In contrast, the quinone analog failed to provide protection against oxidant-induced endothelial dysfunction in arteries of Hmox1–/– mice, establishing a key role for Hmox1 in vascular protection. These results suggest that oxidized forms of dietary polyphenols are the likely inducers of Hmox1 and may explain in part the protective cardiovascular effects of diets rich in these compounds.


A coordination polymer for the site-specific integration of semiconducting sequences into DNA-based materials

David Smith

Dr David Smith

David Smith et al. Nature Communications, 8 (1), 1-7, 2017 (Open Access) DOI: 10.1038/s41467-017-00852-6

Abstract
Advances in bottom-up material design have been significantly progressed through DNA-based approaches. However, the routine integration of semiconducting properties, particularly long-range electrical conduction, into the basic topological motif of DNA remains challenging. Here, we demonstrate this with a coordination polymer derived from 6-thioguanosine (6-TG-H), a sulfur-containing analog of a natural nucleoside. The complexation reaction with Au(I) ions spontaneously assembles luminescent one-dimensional helical chains, characterized as {AuI(μ-6-TG)} n , extending many μm in length that are structurally analogous to natural DNA. Uniquely, for such a material, this gold-thiolate can be transformed into a wire-like conducting form by oxidative doping. We also show that this self-assembly reaction is compatible with a 6-TG-modified DNA duplex and provides a straightforward method by which to integrate semiconducting sequences, site-specifically, into the framework of DNA materials, transforming their properties in a fundamental and technologically useful manner.


Extracts from cotton over the whole growing season induce Orobanche cumana (sunflower broomrape) germination with significant cultivar interactions

Associate Professor Chris McErlean

A/Prof Chris McErlean

Chris McErlean et al. Frontiers of Agricultural Science and Engineering, 4 (2), 228-236, 2017. DOI: 10.15302/J-FASE-2017150

Abstract
Five cotton cultivars and their parents were tested for induction of germination of Orobanche Cumana Wallr. (sunflower broomrape) seeds in pot and field experiments. Germination rates induced by cotton root extracts were the highest followed by stem extracts then leaf extracts. Cotton seedlings at the six-leaf stage induced higher germination than seedling at the two- and four-leaf stage, in all five cotton cultivars and their parents. In the field, the highest concentration of cotton root extracts gave the highest germination rate of O. cumana, and the lowest concentration of cotton root extracts gave the lowest germination rate. Methanol extracts of cotton rhizosphere soil gave the highest germination of O. cumana. In general, the root, stem and leaf extracts were more active at the sixleaf stage than other seedling stages. In conclusion, extracts of cotton rhizosphere soil and tissues have high activity in the seedling stage. Extracts of cotton across the whole growing season were able to induce O. Cumana germination but displayed significant cultivar interactions.


Untangling complex redox chemistry in zeolitic imidazolate frameworks using Fourier transformed alternating current voltammetry

Associate Professor Deanna D

A/Prof Deanna D'Alessandro

Pavel Usov, Michael Murphy and Deanna D'Alessandro et al. Analytical Chemistry, 89 (19), 10181-10187, 2017. DOI: 10.1021/acs.analchem.7b01224

Abstract
Two zeolitic imidazolate frameworks, ZIF-67 and ZIF-8, were interrogated for their redox properties using Fourier transformed alternating current voltammetry, which revealed that the 2-methylimidazolate ligand is responsible for multiple redox transformations. Further insight was gained by employing discrete tetrahedral complexes, [M(DMIM)4]2+ (DMIM = 1,2-dimethylimidazole, M = CoII or ZnII) which have similar structural motifs to ZIFs. In this work we demonstrate a multidirectional approach that enables the complex electrochemical behavior of ZIFs to be unraveled.


A new approach to understand the adsorption of thiophene on different surfaces: An atom probe investigation of self-assembled monolayers

Professor Thomas Maschmeyer

Prof Thomas Maschmeyer

Tony Masters and Thomas Maschmeyer et al. Langmuir, 33 (38), 9573-9581, 2017. DOI: 10.1021/acs.langmuir.7b01820

Abstract
Atom probe tomography was used to analyze self-assembled monolayers of thiophene on different surfaces, including tungsten, platinum, and aluminum, where the tungsten was examined in both pristine and oxidized forms. A glovebag with controlled atmospheres was used to alter the level of oxidation for tungsten. It was shown that different substrates lead to substantial changes in the way thiophene adsorbs on the surface. Furthermore, the oxidation of the surface strongly influenced the adsorption behavior of the thiophene molecules, leading to clear differences in the amounts and compositions of field evaporated ions and molecular ions.


The critical role of the transition-state cusp diameter in understanding adiabatic and non-adiabatic electron transfer

Emeritus Professor Noel Hush

E/Prof Noel Hush

Jeffrey Reimers* and Noel Hush**. Russian Journal of Electrochemistry, 53 (9), 1042-1053, 2017. DOI: 10.1134/S1023193517090105

Abstract
The equation of Levich and Dogonadze describing the rate of electron-transfer processes in the weak-coupling “non-adiabatic” limit is understood in terms of the properties of general adiabatic electron-transfer theory. The cusp diameter describing the continuous changeover of Born-Oppenheimer adiabatic surfaces from donor-like to acceptor-like character is shown to be the critical property controlling reaction rates and intervalence spectra. Their work is presented in the context of general Born-Oppenheimer breakdown phenomena and linked to the overarching cusp catastrophe.


Fluorescent sensing arrays for cations and anions

Professor Kate Jolliffe

Prof Kate Jolliffe

David Smith, Inga Topolnicki, Vincent Zwicker, Kate Jolliffe*, and Liz New* et al. Analyst, 142 (19), 3549-3563, 2017. DOI: 10.1039/c7an01200d

Abstract
Array-based sensing methods can be used to distinguish sets of similar analytes, by using a number of non-specific or cross-reactive probes. Following subsequent statistical analysis, patterns or components can be isolated that can be used to unambiguously identify the specific analyte(s) present. Over the past two decades, various arrays for the identification of cations and anions have been reported. These often employ fluorescence methods, owing to good sensitivity and a versatile, easy to read output. The past few years have seen an increase in the number of such studies reported in the literature. This critical review will summarise this recent work, and identify the criteria required for a successful array system. In particular, it will focus on the different types of molecular structures that can be used, the breadth of ions that can be distinguished in a single array, the sensitivity and dynamic range to which they can be identified, and how successfully these aims have been met.


Multi-scale structural analysis of the A-site and oxygen deficient perovskite Sr(11)Mo(4)O(23)

Professor Brendan Kennedy

Prof Brendan Kennedy

Ilyas Qasim, Qingi Zhou and Brendan Kennedy* et al. Dalton Transactions, 46 (37), 12466-12473, 2017. DOI: 10.1039/c7dt02087b

Abstract
The long range average crystal structure, as well as the short and medium range structural features, of the A-site deficient and oxygen deficient perovskite Sr11Mo4O23 have been determined. Rietveld refinement of synchrotron X-ray and neutron powder diffraction data show that this compound is cubic with space group Fd[3 with combining macron]m and a lattice parameter of a = 16.4108 Å. These findings contradict earlier reports of a tetragonal crystal structure. Sr11Mo4O23 appears to be isostructural with Ba11W4O23, except that the disordered coordination environment around one of the Mo sites seems to be a mixture of octahedral and square pyramidal instead of octahedral and tetrahedral. The short and medium range structural features have been inspected using the neutron pair distribution function (PDF). Short range correlations between the oxygen polyhedra surrounding the Mo(2) atom exist to avoid short O-O contacts. A model has been constructed which contains such correlations and is verified by reverse Monte Carlo (RMC) modeling of the PDF. The RMC refinements also give the distribution of inter-atomic distances in this compound which reveals how the various atomic positions are correlated and over what length scales. These results are important for understanding the ionic conduction pathways.


Ticks from diverse genera encode chemokine-inhibitory evasin proteins

Professor Richard Payne

Prof Rich Payne

Richard Payne et al. Journal of Biological Chemistry, 292 (38), 15670-15680, 2017. DOI: 10.1074/jbc.M117.807255

Abstract
To prolong residence on their hosts, ticks secrete many salivary factors that target host defense molecules. In particular, the tick Rhipicephalus sanguineus has been shown to produce three salivary glycoproteins named “evasins,” which bind to host chemokines, thereby inhibiting the recruitment of leukocytes to the location of the tick bite. Using sequence similarity searches, we have identified 257 new putative evasin sequences encoded by the genomes or salivary or visceral transcriptomes of numerous hard ticks, spanning the genera Rhipicephalus, Amblyomma, and Ixodes of the Ixodidae family. Nine representative sequences were successfully expressed in Escherichia coli, and eight of the nine candidates exhibited high-affinity binding to human chemokines. Sequence alignments enabled classification of the evasins into two subfamilies: C8 evasins share a conserved set of eight Cys residues (four disulfide bonds), whereas C6 evasins have only three of these disulfide bonds. Most of the identified sequences contain predicted secretion leader sequences, N-linked glycosylation sites, and a putative site of tyrosine sulfation. We conclude that chemokine-binding evasin proteins are widely expressed among tick species of the Ixodidae family, are likely to play important roles in subverting host defenses, and constitute a valuable pool of anti-inflammatory proteins for potential future therapeutic applications.


Tuneable pressure effects in graphene oxide layers

Emeritus Professor Len Lindoy

E/Prof Len Lindoy

Len Lindoy et al. Scientific Reports, 7 (1), 12159, 2017. DOI: 10.1038/s41598-017-12444-x

Abstract
Tuneable pressure effects associated with changing interlayer distances in two-dimensional graphene oxide (GO)/reduced GO (rGO) layers are demonstrated through monitoring the changes in the spin-crossover (SCO) temperature (T1/2) of [Fe(Htrz)2(trz)](BF4) nanoparticles (NPs) incorporated in the interlayer spaces of the GO/rGO layers. The interlayer separation along the GO to GO/rGO-NP composites to rGO series decreases smoothly from 9.00 Å (for GO) to 3.50 Å (for rGO) as the temperature employed for the thermal reduction treatments of the GO-NP composites is increased. At the same time, T1/2 increases from 351 K to 362 K along the series. This T1/2 increment of 11 K corresponds to that observed for pristine [Fe(Htrz)2(trz)](BF4) NPs under a hydrostatic pressure of 38 MPa. The influence of the stacked layer structures on the pseudo-pressure effects has been further probed by investigating the differences in T1/2 for [Fe(Htrz)2(trz)](BF4) that is present in the composite as larger bulk particles rather than as NPs.


Spin-state patterning in an iron(II) tripodal spin-corssover complex

Professor Cameron Kepert

Prof Cameron Kepert

Natasha Sciortino, Cameron Kepert and Len Lindoy et al. ACS Omega, 2 (7), 3349-3353, 2017. DOI: 10.1021/acsomega.7b00630

Abstract
A mononuclear iron(II) complex that displays a gradual two-step spin-crossover (SCO) transition is reported. The intermediate plateau (IP) occurs between HS0.40LS0.60 and HS0.30LS0.70 (HS = high spin; LS = low spin) ratios over the region of ca. 190-170 K. A phase change occurs at the IP, breaking the symmetry, resulting in six independent SCO sites compared to one at the 100% HS and LS plateau regions, respectively. Variable-temperature X-ray photoelectron spectroscopy shows that the SCO behavior is completely reversible among the HS, IP, and LS regions. The results both confirm and extend the related results for the above system described by Halcrow et al. (Kulmaczewski, R.; Cespedes, O.; Halcrow, M. A.Gradual Thermal Spin-Crossover Mediated By a Reentrant Z' = 1 –> Z' = 6 –> Z' = 1 Phase Transition, Inorg. Chem. 2017, 56, 3144-3148) in a recent report.


Synchrotron X-ray diffraction studies of beta-Ca(2-x)M(x)SiO(4) (M = Mg and Sr)

Professor Brendan Kennedy

Prof Brendan Kennedy

Brendan Kennedy et al. Turkish Journal of Chemistry, 41 (4), 548-558, 2017. DOI: 10.3906/kim-1701-28

Abstract
The structures of Mg- and Sr-doped beta-Ca2 SiO4 have been established from high-resolution synchrotron X-ray powder diffraction. These silicates are all isostructural and the structures have been refined in the monoclinic space group, P 21 /n. As expected based on size arguments, the cell parameters increase as the amount of Sr increases and likewise decrease as the amount of Mg increases due the size effects of the dopant cation. In all cases the SiO4 tetrahedra are essentially regular.


Editorial: A patent review of oxytocin receptor antagonists 2013-2017

Professor Michael Kassiou

Prof Michael Kassiou

Timothy Katte and Michael Kassiou*. Expert Opinion on Therapeutic Patents, online, 2017. DOI: 10.1080/13543776.2017.1379992

Introduction
Preterm births result in higher levels of neonatal morbidity and mortality and have been proven to result in further complications later in the infant’s life [1]. It has also been shown that preterm births are the largest single contributor to the cause of neonatal deaths [2]. Interventions such as dietary changes, habitual changes, and tocolytic agents have all been explored (for review see Goldenberg et al. [3]). Tocolytic agents are compounds that can prevent or interrupt uterine contractions. Current tocolytic agents include β-receptor agonists (ritodrine) [4], progesterone [5,6], calcium channel blockers (nifedipine) [7], and at the forefront of current research, oxytocin receptor (OTR) antagonists. Read more.


Synthesis and characterisation of new tripodal lanthanide complexes and investigation of their optical and magnetic properties

Emeritus Professor Len Lindoy

E/Prof Len Lindoy

Len Lindoy et al. Dalton Transactions, 46 (36), 12177-12184, 2017. DOI: 10.1039/c7dt02556d

Abstract
This paper presents the synthesis of a tripodal ligand (H3L) via the Schiff base condensation of N,N-diethylsalicylaldehyde and tris(2-aminoethyl)amine. The neutral complexes of type [EuL], [GdL] and [DyL] were synthesized and characterized by FT-IR, SEM-EDS, PXRD, single crystal X-ray diffraction, CHN analysis and high resolution ESI-MS. X-ray crystallographic studies demonstrated that the heptadentate ligand incorporating a cavity pre-organized by hydrogen bonding binds the Ln(III) ions to yield a face capped octahedral coordination geometry with three-fold symmetry. Photoluminescence studies show a typical Ln(III) absorption character for the three complexes, with [EuL] demonstrating considerably stronger lanthanide-based luminescence peaks, and a Eu(III) centered luminescence lifetime of 0.144 ± 0.01 ms. Temperature/field-dependent DC and temperature/frequency-dependent AC magnetic measurements carried out for the Dy(III) complex indicated obvious magnetic anisotropy and suggested slow relaxation behaviour with considerable quantum tunnelling of the magnetization contribution.


Large area optical mapping of surface contact angle

Professor John Canning

Prof John Canning

John Canning and Whayne Padden et al. Optics Express, 25 (18), 21127, 2017. DOI: 10.1364/OE.25.021127

Abstract
Top-down contact angle measurements have been validated and confirmed to be as good if not more reliable than side-based measurements. A range of samples, including industrially relevant materials for roofing and printing, has been compared. Using the top-down approach, mapping in both 1-D and 2-D has been demonstrated. The method was applied to study the change in contact angle as a function of change in silver (Ag) nanoparticle size controlled by thermal evaporation. Large area mapping reveals good uniformity for commercial Aspen paper coated with black laser printer ink. A demonstration of the forensic and chemical analysis potential in 2-D is shown by uncovering the hidden CsF initials made with mineral oil on the coated Aspen paper. The method promises to revolutionize nanoscale characterization and industrial monitoring as well as chemical analyses by allowing rapid contact angle measurements over large areas or large numbers of samples in ways and times that have not been possible before.


Pyrophosphate recognition and sensing in water using bis[zinc(II)dipicolylamino]-functionalized peptides

Professor Kate Jolliffe

Prof Kate Jolliffe

Kate Jolliffe*. Accounts of Chemical Research, 50 (9), 2254-2263, 2017. DOI: 10.1021/acs.accounts.7b00252

Conspectus
Phosphate oxoanions and phosphorylated biomolecules (such as nucleotides, lipids, and proteins) play key roles in a wide range of biological processes. The ability to selectively detect these ions in the presence of each other has numerous applications in biochemistry and biomedicine. However, receptors and sensors that can discriminate between polyphosphate species with high selectivity and in biologically relevant conditions are rare.

In this Account, we show how peptides (both cyclic and linear) can be used to position two zinc(II)dipicolylamine [Zn(II)DPA] binding sites in an appropriate arrangement to provide selective binding of pyrophosphate (PPi) in the presence of other polyphosphate species, including ATP, and in complex media such as cell growth buffer.

The use of peptide scaffolds to position the Zn(II)DPA anion binding sites allowed the synthesis of small receptor libraries in which the arrangement of the two binding sites could be subtly altered to evaluate the factors affecting both binding selectivity and affinity for PPi. We altered a number of structural elements including peptide length, cyclic peptide ring size, amino acid composition, the positioning of the binding sites with respect to one another, and the relative stereochemistry of the peptides. Backbone modified cyclic peptides based on the Lissoclinum class of natural products were initially employed to provide an added degree of preorganization to the receptors, although it was subsequently found that short, flexible bis[Zn(II)DPA]-functionalized linear peptides are also effective scaffolds for selective pyrophosphate recognition.

The peptidic receptors were successfully employed for the detection of PPi in aqueous media by indicator displacement assays using both colorimetric and fluorescent indicators, with the best compounds able to bind to PPi selectively in both cell growth media and artificial urine and also allow the accurate determination of PPi concentrations in physiologically relevant ranges (micromolar concentrations) in these complex media. Improved pyrophosphate selectivity was observed upon increasing the complexity of the media from HEPES buffer to cell growth media (Krebs saline).

Pyrophosphate sensors in which a fluorescent indicator was covalently attached to either a linear or cyclic peptide scaffold through a flexible linker were then constructed. When the Zn(II)DPA binding sites and the indicator were suitably placed with respect to one another on the peptide scaffold, these ‘intramolecular indicator displacement assays’ showed improved selectivity for PPi over other polyphosphate anions, such as ATP, when compared to the intermolecular indicator displacement assays. This observation provides the basis for the design and application of future PPi sensors in biochemistry and biomedicine.


Imaging of vanadium in microfossils: A new potential biosignature

Professor Peter Lay

Prof Peter Lay

Jade Aitken and Peter Lay et al. Astrobiology, 17 (11), 1-8, 2017. DOI: 10.1089/ast.2017.1709

Abstract
The inability to unambiguously distinguish the biogenicity of microfossil-like structures in the ancient rock record is a fundamental predicament facing Archean paleobiologists and astrobiologists. Therefore, novel methods for discriminating biological from nonbiological chemistries of microfossil-like structures are of the utmost importance in the search for evidence of early life on Earth. This, too, is important for the search for life on Mars by in situ analyses via rovers or sample return missions for future analysis here on Earth. Here, we report the application of synchrotron X-ray fluorescence imaging of vanadium, within thermally altered organic-walled microfossils of bona fide biological origin. From our data, we demonstrate that vanadium is present within microfossils of undisputable biological origin. It is well known in the organic geochemistry literature that elements such as vanadium are enriched and contained within crude oils, asphalts, and black shales that have been formed by diagenesis of biological organic material. It has been demonstrated that the origin of vanadium is due to the diagenetic alteration of precursor chlorophyll and heme porphyrin pigment compounds from living organisms. We propose that, taken together, microfossil-like morphology, carbonaceous composition, and the presence of vanadium could be used in tandem as a biosignature to ascertain the biogenicity of putative microfossil-like structures.


Terminally truncated isopenicillin N synthase generates a dithioester product: Evidence for a thioaldehyde intermediate during catalysis and a new mode of reaction for non-heme iron oxidases

Associate Professor Peter Rutledge

A/Prof Peter Rutledge

Peter Rutledge* et al. Chemistry: A European Journal, 23 (52), 12815-12824, 2017. DOI: 10.1002/chem.20170159

Abstract
Isopenicillin N synthase (IPNS) catalyses the four-electron oxidation of a tripeptide, l-δ-(α-aminoadipoyl)-l-cysteinyl-d-valine (ACV), to give isopenicillin N (IPN), the first-formed β-lactam in penicillin and cephalosporin biosynthesis. IPNS catalysis is dependent upon an iron(II) cofactor and oxygen as a co-substrate. In the absence of substrate, the carbonyl oxygen of the side-chain amide of the penultimate residue, Gln330, co-ordinates to the active-site metal iron. Substrate binding ablates the interaction between Gln330 and the metal, triggering rearrangement of seven C-terminal residues, which move to take up a conformation that extends the final α-helix and encloses ACV in the active site. Mutagenesis studies are reported, which probe the role of the C-terminal and other aspects of the substrate binding pocket in IPNS. The hydrophobic nature of amino acid side-chains around the ACV binding pocket is important in catalysis. Deletion of seven C-terminal residues exposes the active site and leads to formation of a new type of thiol oxidation product. The isolated product is shown by LC-MS and NMR analyses to be the ene-thiol tautomer of a dithioester, made up from two molecules of ACV linked between the thiol sulfur of one tripeptide and the oxidised cysteinyl β-carbon of the other. A mechanism for its formation is proposed, supported by an X-ray crystal structure, which shows the substrate ACV bound at the active site, its cysteinyl β-carbon exposed to attack by a second molecule of substrate, adjacent. Formation of this product constitutes a new mode of reaction for IPNS and non-heme iron oxidases in general.


Reversible pressure-controlled depolymerization of a copper(II)-containing coordination polymer

Emeritus Professor Len Lindoy

E/Prof Len Lindoy

Kate Jolliffe and Len Lindoy* et al. Chemistry: A European Journal, 23 (51), 12480-12483, 2017. DOI: 10.1002/chem.201703115

Abstract
A unique pressure-induced Cu-N bond breaking/bond forming reaction is reported. The variation of pressure on a single crystal of a one-dimensional copper- (II)-containing coordination polymer (Cu2L2(1-methylpiperazine)2]n, where H2L is 1,1'-(1,3-phenylene)-bis(4,4-dimethylpentane-1,3-dione)), was monitored using single crystal X-ray diffraction with the aid of a diamond anvil cell. At a very low elevated pressure (approximately equal to 0.05 GPa) a remarkable reversible phase change was observed. The phase change results in the depolymerization of the material through the cleavage and formation of axial Cu-N bonds as well as "ring flips" of individual axially coordinated 1-methylpiperazine ligands. Overall, the pressure-induced phase change is associated with a surprising (and non-intuitive) shift in structure-from a 1-dimensional coordination polymer to a discrete dinuclear complex.


Semisynthetic prion protein (PrP) variants carrying glycan mimics at position 181 and 197 do not form fibrils

Professor Richard Payne

Prof Richard Payne

Robert Thompson, Siyao Wang and Richard Payne et al. Chemical Science, 8 (9), 2017 (Online). DOI: 10.1039/c7sc02719b

Abstract
The prion protein (PrP) is an N-glycosylated protein attached to the outer leaflet of eukaryotic cell membranes via a glycosylphosphatidylinositol (GPI) anchor. Different prion strains have distinct glycosylation patterns and the extent of glycosylation of potentially pathogenic misfolded prion protein (PrPSc) has a major impact on several prion-related diseases (transmissible spongiform encephalopathies, TSEs). Based on these findings it is hypothesized that posttranslational modifications (PTMs) of PrP influence conversion of cellular prion protein (PrPC) into PrPSc and, as such, modified PrP variants are critical tools needed to investigate the impact of PTMs on the pathogenesis of TSEs. Here we report a semisynthetic approach to generate PrP variants modified with monodisperse polyethyleneglycol (PEG) units as mimics of N-glycans. Incorporating PEG at glycosylation sites 181 and 197 in PrP induced only small changes to the secondary structure when compared to unmodified, wildtype PrP. More importantly, in vitro aggregation was abrogated for all PEGylated PrP variants under conditions at which wildtype PrP aggregated. Furthermore, the addition of PEGylated PrP as low as 10 mol% to wildtype PrP completely blocked aggregation. A similar effect was observed for synthetic PEGylated PrP segments comprising amino acids 179–231 alone if these were added to wildtype PrP in aggregation assays. This behavior raises the question if large N-glycans interfere with aggregation in vivo and if PEGylated PrP peptides could serve as potential therapeutics.