ANSTO :: Browsing by Author "Yepuri, NR"

Browsing by Author "Yepuri, NR"

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Advancements in the provision of deuterated lipids for neutron applications from the National Deuteration Facility
(Australian Institute of Nuclear Science and Engineering (AINSE), 2020-11-11) Yepuri, NR; Moir, M; Krause-Heuer, AM; Klenner, MA; Darwish, TA
Molecular deuteration significantly increases the options for structure-function investigations using neutron scattering and diffraction techniques. Chemical deuteration activities, where catalysed 1H/2H exchange is followed by custom chemical synthesis, have led to diverse neutron scattering and reflectometry studies previously hampered by the lack of appropriate scattering contrast in multi-component samples. Deuteration of phospholipids is a common practice to elucidate membrane structure, dynamics and function, by providing selective visualisation in neutron scattering. Although analogous deuterium? (2H) and hydrogen? containing (1H) molecules have similar physicochemical properties, these isotopes of hydrogen result in vastly different for neutron scattering signals. Over the past few years the National Deuteration Facility (ANSTO) has increased its synthetic capability to produce complex deuterated molecules including lipids and phospholipids. Such synthetically challenging molecules are perdeuterated phytantriol1, tail deuterated POPC, and perdeuterated POPC.2 Phytantriol is an interfacially-active lipid that is chemically robust, non-digestible and forms particles with internal bicontinuous cubic phase structures (cubosomes) when dispersed with non-ionic surfactants at physiological temperatures. The tail-deuterated POPC, perdeuterated POPC and tail-deuterated GMO isotopologues would also provide suitable contrast for many neutron experiments and so these have been also our synthetic targets. Recently neutron reflection was employed to investigate the impact of phospholipid saturation (POPC-d64) and presence of cholesterol in cell model membranes on LDL and HDL lipid exchange and removal processes.3 Neutron reflection data that distinguish the effect of phospholipid acyl chain saturation and the presence of cholesterol on the ability of lipoproteins to exchange lipids to/from model membrane will be presented.
ANSTO’s National Deuteration Facility: recent advancements and an overview on molecular deuteration capabilities for neutron applications
(Australian Institute of Nuclear Science and Engineering (AINSE), 2020-11-11) Wilde, KL; Cagnes, MP; Duff, AP; Klenner, MA; Krause-Heuer, AM; Moir, M; Rekas, A; Russell, RA; Yepuri, NR; Darwish, TA
The National Deuteration Facility (NDF) at the Australian Nuclear Science and Technology Organisation (ANSTO) provides deuteration through both biological and chemical techniques for a diversity of molecules and applications and is the only facility of its type in the Southern Hemisphere with the specialised expertise and infrastructure for both biological and chemical molecular deuteration. Molecular deuteration of organic compounds and biomolecules significantly increases the options in complex structure function investigations using neutron scattering and reflectometry, nuclear magnetic resonance (NMR), mass spectrometry (MS) and other techniques. Deuteration (substitution of the naturally occurring hydrogen stable isotope deuterium (2H or D) for 1H (or H)) can provide contrast and improved resolution to assist investigations into the relationship between molecular structure and function of molecules of both biological and synthetic origin. By developing a suite of capabilities in both in vivo deuteration of biomolecules and chemical deuteration of small organic molecules, the NDF provides access to a broad range of deuterated molecules for research and industry. Variably deuterated proteins can be produced via recombinant expression in Escherichia coli and other microbial systems utilised to produce deuterated cellulose and cholesterol. By tailoring deuteration approaches with the ongoing development of chemical deuteration protocols for a broader range of molecular classes than available commercially, the NDF has increased the range of systems that can be investigated using deuterated molecules. Lipids, phospholipids (including head or tail or head/tail deuterated mono-unsaturated lipids such as POPC and DOPC), heterocyclics, aromatics, surfactants, ionic liquids, saturated and unsaturated fatty acids, sugars and match-out detergents have been deuterated. Common neutron applications include partially deuterated proteins for SANS experiments investigating multiprotein systems, neutron crystallography of perdeuterated proteins, neutron reflectometry of lipid bilayers systems and SANS using saturated lipid vesicles, or detergents amongst others. An overview and update on the NDF will be provided which will include details on the NDF User Program (e.g. information on the available modes of access), recent advancements in custom deuterated molecules available and brief highlights of deuterated molecule utilisation for neutron experiments at ANSTO’s Australian Centre for Neutron Scattering (ACNS). © 2020 The Authors.
The Australian National Deuteration Facility for structure function applications using neutrons
(International Conference on Neutron Scattering, 2017-07-12) Darwish, TA; Yepuri, NR; Heuer, AK; Duff, AP; Wilde, KL; Holden, PJ
There have been limited global initiatives in the field of molecular deuteration where the majority of these programs focus on biological deuteration of proteins and lipids, while more complex deuterated small molecules haven’t been widely available to the neutron community. This has limited the experiments that can be performed, and formed a bottle-neck for advancing the applications of neutron scattering. In this paper we will discuss the recent advancements and the impact of deuteration on the research outcomes achieved by using deuterated molecules produced by the National Deuteration Facility of the Australian Nuclear Science and Technology Organisation. Recent high-impact case studies in the fields of molecular electronics, structural biology, and biotechnology will be presented which reveal the exciting and diverse characterisation studies which are now available for the neutron community.
Cephalosporin-3'-diazeniumdiolates: targeted no-donor prodrugs for dispersing bacterial biofilms
(Wiley-V C H Verlag GMBH, 2012-01-01) Barraud, N; Kardak, BG; Yepuri, NR; Howlin, RP; Webb, JS; Faust, SN; Kjelleberg, S; Rice, SA; Kelso, MJ
Cereal starch granules with high (>50%) amylose content are a promising source of nutritionally desirable resistant starch, i.e. starch that escapes digestion in the small intestine, but the structural features responsible are not fully understood. We report the effects of partial enzyme digestion of maize starch granules on amylopectin branch length profiles, double and single helix contents, gelatinisation properties, crystallinity and lamellar periodicity. Comparing results for three maize starches (27, 57, and 84% amylose) that differ in both structural features and amylase-sensitivity allows conclusions to be drawn concerning the rate-determining features operating under the digestion conditions used. All starches are found to be digested by a side-by-side mechanism in which there is no major preference during enzyme attack for amylopectin branch lengths, helix form, crystallinity or lamellar organisation. We conclude that the major factor controlling enzyme susceptibility is granule architecture, with shorter length scales not playing a major role as inferred from the largely invariant nature of numerous structural measures during the digestion process (XRD, NMR, SAXS, DSC, FACE). Results are consistent with digestion rates being controlled by restricted diffusion of enzymes within densely packed granular structures, with an effective surface area for enzyme attack determined by external dimensions (57 or 84% amylose - relatively slow) or internal channels and pores (27% amylose - relatively fast). Although the process of granule digestion is to a first approximation non-discriminatory with respect to structure at molecular and mesoscopic length scales, secondary effects noted include (i) partial crystallisation of V-type helices during digestion of 27% amylose starch, (ii) preferential hydrolysis of long amylopectin branches during the early stage hydrolysis of 27% and 57% but not 84% amylose starches, linked with disruption of lamellar repeating structure and (iii) partial B-type recrystallisation after prolonged enzyme incubation for 57% and 84% amylose starches but not 27% amylose starch. © 2012, Wiley-VCH Verlag GmbH & Co. KGaA
Chemical deuteration and neutrons for structure function applications
(Australian Institute of Nuclear Science and Engineering, 2016-11-29) Darwish, TA; Yepuri, NR; Heuer, AK; Cagnes, MP; Holden, PJ
In small angle neutron scattering and neutron reflectometry studies, the use of mixtures of deuterated and hydrogenated solvents to manipulate scattering length density and achieve contrast variation is widespread. This approach, while useful is less effective for multicomponent organic systems containing molecules of similar scattering length densities. In such systems molecular deuteration is necessary to achieve contrast between the different components and it significantly increases the options in structure function investigations. There have been limited global initiatives in the field of molecular deuteration where the majority of these programs focus on biological deuteration of proteins and lipids, while more complex deuterated small molecules haven’t been widely available to the neutron community. This has limited the experiments that can be performed, and formed a bottle neck for advancing the applications of neutron scattering. In this paper we will discuss the recent advancements and the impact of deuteration on the research outcomes achieved by using deuterated molecules produced by the chemical deuteration laboratories at ANSTO’s National Deuteration Facility. Recent high-impact case studies will be presented which reveal the exciting and diverse characterisation studies which are now available for the neutron community. The chemical deuteration of surfactants, sugars, heterocyclic and aromatic compounds has made possible a wide range of investigations systems in the fields of molecular electronics, structural biology, and biotechnology.
Deuterated phospholipids to study the structure, function and dynamics of membrane proteins using neutron scattering
(Australian Nuclear Science and Technology Organisation, 2021-11-26) Yepuri, NR; Moir, M; Krause-Heuer, AM; Darwish, TA
Contrast matching and contrast variation in neutron scattering provide unparalleled power for understanding the structure, function, and dynamics of a selected component in a multicomponent system. A sophisticated contrast study often requires the availability of deuterated molecules in which deuterium atoms are introduced in a predictable and controlled fashion to replace protons. This can be achieved by direct deuteration of precursors followed by custom chemical synthesis, for which expertise and capabilities have been developed at facility (NDF), ANSTO. It this paper we will discuss recent high impact research output using deuterated phospholipids produced by NDF/ANSTO. We will describe the synthesis and applications of selectively or perdeuterated unsaturated phospholipids to contrast match out the whole lipid bilayer or nano disks within a multicomponent system. Further, we also describe their role in investigations related to membrane lipoproteins (ApoE) exchange in relation to lipid unsaturation,[1] effect of membrane composition,[2] and conformational analysis Mg+2 channel by neutron scattering techniques.[2, 3]
Deuteration for biological SANS: case studies, success and challenges in chemistry and biology
(Elsevier, 2022-11) Duff, AP; Cagnes, MP; Darwish, TA; Krause-Heuer, AM; Moir, M; Recsei, C; Rekas, A; Russell, RA; Wilde, KL; Yepuri, NR
Small angle neutron scattering is a powerful complementary technique in structural biology. It generally requires, or benefits from, deuteration to achieve its unique potentials. Molecular deuteration has become a mature expertise, with deuteration facilities located worldwide to support access to the technique for a wide breadth of structural biology and life sciences. The sorts of problems well answered by small angle scattering and deuteration involve large (> 10 Å) scale flexible movements, and this approach is best used where high-resolution methods (crystallography, NMR, cryo-EM) leave questions unanswered. This chapter introduces deuteration, reviewing biological deuteration of proteins, lipids and sterols, and then steps through the ever-expanding range of deuterated molecules being produced by chemical synthesis and enabling sophisticated experiments using physiologically relevant lipids. Case studies of recent successful use of deuteration may provide illustrative examples for strategies for future experiments. We discuss issues of nomenclature for synthesised molecules of novel labeling and make recommendations for their naming. We reflect on our experiences, with cost associated with achieving an arbitrary deuteration level, and on the benefits of experimental co-design by user scientist, deuteration scientist, and neutron scattering scientist working together. Although methods for biological and chemical deuteration are published in the public domain, we recommend that the best method to deuterate is to engage with a deuteration facility. © 2022 Elsevier
Fluorine-18 radiolabelling and in vitro / in vivo metabolism of [18F]D4-PBR111
(John Wiley & Sons, Inc, 2019-05-26) Wyatt, NA; Safavi-Naeini, M; Wotherspoon, ATL; Arthur, A; Nguyen, AP; Parmar, A; Hamze, H; Day, CM; Zahra, D; Matesic, L; Davis, E; Rahardjo, GL; Yepuri, NR; Shepherd, R; Murphy, RB; Pham, TQ; Nguyen, VH; Callaghan, PD; Holden, PJ; Grégoire, MC; Darwish, TA; Fraser, BH
Objectives The purinergic receptor P2X ligand-gated ion channel type 7 (P2X7R) is an adenosine triphosphate (ATP)-gated ion-channel, and P2X7R is a key player in inflammation. P2X7R is an emerging therapeutic target in central nervous system (CNS) diseases including Alzheimer's disease (AD) and Parkinson's disease (PD), because P2X7R also plays a pivotal role in neuroinflammation. P2X7R represents a potential molecular imaging target for neuroinflammation via biomedical imaging technique positron emission tomography (PET), and several radioligands targeting P2X7R have been developed and evaluated in animals. In our previous work, we have developed and characterized [11C]GSK1482160 as a P2X7R radioligand for neuroinflammation,2 clinical evaluation of [11C]GSK1482160 in healthy controls and patients is currently underway, and the estimation of radiation dosimetry for [11C]GSK1482160 in normal human subjects has been reported.3 Since the half-life (t1/2) of radionuclide carbon-11 is only 20.4 min, it is attractive for us to develop derivatives of [11C]GSK1482160, which can be labeled with the radionuclide fluorine-18 (t1/2, 109.7 min), and a fluorine-18 ligand would be ideal for widespread use.4 To this end, a series of [18F]fluoroalkyl including [18F]fluoromethyl (FM), [18F]fluoroethyl (FE), and [18F]fluoropropyl (FP) derivatives of GSK1482160 have been prepared and examined as new potential P2X7R radioligands. © 2019 The Authors
The influence of glass transitions on diffusion in OLED stacks
(Australian Institute of Nuclear Science and Engineering, 2016-11-29) McEwan, JA; Clulow, AJ; Shaw, PE; Nelson, A; Yepuri, NR; Darwish, TA; Burn, PL; Gentle, IR
Of all of the organic electronic devices thus far conceived, organic light emitting diodes (OLEDs) have been the most successfully applied in a commercial setting. With OLED displays now available in the television and portable device markets, the appetite for their continued development continues to garner considerable research interest. Optimised OLED device architectures typically comprise a number of organic layers with thicknesses between 10 nm and 100 nm sandwiched between inorganic electrodes. Each of the organic layers used in the device is sequentially deposited in an order that optimises charge transport and capture, and light emission from the devices. The fidelity and stability of these multilayer organic stacks is therefore of paramount importance in determining the efficiencies and operational lifetimes of OLED devices. Neutron reflectometry is a powerful technique for probing the layered structures found within OLEDs by utilising selective deuteration to provide contrast between or within the layers.1–3 Modelling the changes in the neutron reflectivity profiles of the OLED stacks deposited onto smooth substrates allows for the visualisation of changes in the layered structure in a non destructive manner. In this talk we will outline our recent efforts to relate the thermal properties of the organic materials used in OLED devices with their diffusion behaviour under thermal stress. Our collaboration with the National Deuteration Facility has led to the synthesis of a number of previously unobtainable deuterated analogues of semiconducting molecules typically used in OLEDs and that have a range of thermal characteristics.3–5 These molecules were used in time-resolved reflectometry experiments that have allowed us to systematically build up an understanding of the importance of glass transitions for the stability of OLED stacks.
Intrinsically disordered stress protein COR15A resides at the membrane surface during dehydration
(Biophysical Society, 2017-08-08) Bremer, A; Kent, B; Hauß, T; Thalhammer, A; Yepuri, NR; Darwish, TA; Garvey, CJ; Bryant, G; Hincha, DK
Plants from temperate climate zones are able to increase their freezing tolerance during exposure to low, above-zero temperatures in a process termed cold acclimation. During this process, several cold-regulated (COR) proteins are accumulated in the cells. One of them is COR15A, a small, intrinsically disordered protein that contributes to leaf freezing tolerance by stabilizing cellular membranes. The isolated protein folds into amphipathic α-helices in response to increased crowding conditions, such as high concentrations of glycerol. Although there is evidence for direct COR15A-membrane interactions, the orientation and depth of protein insertion were unknown. In addition, although folding due to high osmolyte concentrations had been established, the folding response of the protein under conditions of gradual dehydration had not been investigated. Here we show, using Fourier transform infrared spectroscopy, that COR15A starts to fold into α-helices already under mild dehydration conditions (97% relative humidity (RH), corresponding to freezing at −3°C) and that folding gradually increases with decreasing RH. Neutron diffraction experiments at 97 and 75% RH established that the presence of COR15A had no significant influence on the structure of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membranes. However, using deuterated POPC we could clearly establish that COR15A interacts with the membranes and penetrates below the headgroup region into the upper part of the fatty acyl chain region. This localization is in agreement with our hypothesis that COR15A-membrane interaction is at least, in part, driven by a hydrophobic interaction between the lipids and the hydrophobic face of the amphipathic protein α-helix. © 2017 Biophysical Society - Open access
Mild conditions for deuteration of primary and secondary arylamines for the synthesis of deuterated optoelectronic organic molecules
(Multidisciplinary Digital Publishing Institute, 2014-11-13) Krause-Heuer, AM; Yepuri, NR; Darwish, TA; Holden, PJ
Deuterated arylamines demonstrate great potential for use in optoelectronic devices, but their widespread utility requires a method for large-scale synthesis. The incorporation of these deuterated materials into optoelectronic devices also provides the opportunity for studies of the functioning device using neutron reflectometry based on the difference in the scattering length density between protonated and deuterated compounds. Here we report mild deuteration conditions utilising standard laboratory glassware for the deuteration of: diphenylamine, N-phenylnaphthylamine, N-phenyl-o-phenylenediamine and 1-naphthylamine (via H/D exchange in D2O at 80 °C, catalysed by Pt/C and Pd/C). These conditions were not successful in the deuteration of triphenylamine or N,N-dimethylaniline, suggesting that these mild conditions are not suitable for the deuteration of tertiary arylamines, but are likely to be applicable for the deuteration of other primary and secondary arylamines. The deuterated arylamines can then be used for synthesis of larger organic molecules or polymers with optoelectronic applications. © 2014, Creative Commons.
Monitoring the phase evolution in LiCoO2 electrodes during battery cycles using in-situ neutron diffraction technique
(John Wiley & Sons, Inc, 2019-12-03) Jena, A; Lee, PH; Pang, WK; Hsiao, KC; Peterson, VK; Darwish, TA; Yepuri, NR; Wu, SH; Chang, H; Liu, RS
LiCoO2 (LCO) with average particle distribution of 8 μm (LCO-A) and 11 μm (LCO-B) exhibit substantial differences in cycle performance. The half-cells have similar first-cycle discharge capacities of 173 and 175 mAh/g at 0.25 C, but after 100 cycles, the discharge capacities are substantially different, that is, 114 and 141 mAh/g for LCO-A and LCO-B, respectively. Operando neutron powder diffraction of full LCO||Li4Ti5O12 batteries show differences in the LCO reaction mechanism underpinning the electrochemical behavior. LCO-A follows a purely solid solution reaction during cycling compared to the solid solution and two-phase reaction mechanism in LCO-B. The absence of the two-phase reaction in LCO-A is consistent with a homogeneous distribution of Li throughout the particle. The two-phase reaction in LCO-B reflects two distinguishable distributions of Li within the particles. The faster capacity decay in LCO-A is correlated to an increase in electrode cracking during battery cycles. © 2019 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co.
New contrast options - diversity and specifity of deuteration
(Australian Institute of Nuclear Science and Engineering (AINSE), 2018-11-19) Holden, PJ; Cagnes, MP; Davydova, N; Duff, AP; Howard, JK; Krause-Heuer, AM; Yepuri, NR; Darwish, TA
The Australian National Deuteration Facility (NDF) continues to develop new capabilities in molecular deuteration. The tailoring of deuteration approach to solve specific contrast problems has greatly increased the range of systems that can be investigated and recent capability development and new applications will be described. The common problem of how to obtain good contrast during SANS of membrane proteins solubilised in detergent micelles has been solved by specific deuteration of detergent head groups and hydrophobic tails to different levels to contrast match at 100% D20 buffer. Likewise, in investigating the lo cation of a purely hydrophobic transmembrane peptide in bicontinuous cubic phase liquid crystals Page 25 ANBUG-AINSE Neutron Scattering Symposium, AANSS 2018 / Book of Abstracts suitable for drug delivery, a mixture of deuterated and hydrogenated phytanoyl monoethanolamide was used to perfectly contrast match out either gyroid or diamond phase lipids to pinpoint the peptides location. In Soft Matter, investigation of structure of the ligands in the shell layer of self-assembled monolayerprotected nanoparticles has been made possible by use of various combinations of immiscible deuterated or hydrogenated Phenylethanethiol (PET) and Dodecanethiol (DDT) and MONSA modelling of SANS data showed the janus and belt like distribution of the ligands on the surface and the effects of nanoparticle core size and ligand ratio on the patterning. Other case studies will include use of deuterated ionic liquids and new previously unavailable deuterated molecules will be highlighted. This work was supported by the National Collaborative Research Infrastructure Strategy © The Authors.
pH-dependent interactions of coacervate-forming histidine-rich peptide with model lipid membranes
(Frontiers Media, 2024-01-19) Gudler, S; Ferreira, FV; Ting, JSM; Domene, C; Maricar, S; Le Brun, AP; Yepuri, NR; Moir, M; Russell, RA; Darwish, TA; Miserez, A; Cárdenas, M
Peptide-based liquid droplets (coacervates) produced by spontaneous liquid-liquid phase separation (LLPS), have emerged as a promising class of drug delivery systems due to their high entrapping efficiency and the simplicity of their formulation. However, the detailed mechanisms governing their interaction with cell membranes and cellular uptake remain poorly understood. In this study, we investigated the interactions of peptide coacervates composed of HBpep—peptide derived from the histidine-rich beak proteins (HBPs) of the Humboldt squid—with model cellular membranes in the form of supported lipid bilayers (SLBs). We employed quartz crystal microbalance with dissipation monitoring (QCM-D), neutron reflectometry (NR) and atomistic molecular dynamics (MD) simulations to reveal the nature of these interactions in the absence of fluorescent labels or tags. HBpep forms small oligomers at pH 6 whereas it forms µm-sized coacervates at physiological pH. Our findings reveal that both HBpep oligomers and HBpep-coacervates adsorb onto SLBs at pH 6 and 7.4, respectively. At pH 6, when the peptide carries a net positive charge, HBpep oligomers insert into the SLB, facilitated by the peptide’s interactions with the charged lipids and cholesterol. Importantly, however, HBpep coacervate adsorption at physiological pH, when it is largely uncharged, is fully reversible, suggesting no significant lipid bilayer rearrangement. HBpep coacervates, previously identified as efficient drug delivery vehicles, do not interact with the lipid membrane in the same manner as traditional cationic drug delivery systems or cell-penetrating peptides. Based on our findings, HBpep coacervates at physiological pH cannot cross the cell membrane by a simple passive mechanism and are thus likely to adopt a non-canonical cell entry pathway. ©2024 Gudlur, Ferreira, Ting, Domene, Maricar, Le Brun, Yepuri, Moir, Russell, Darwish, Miserez and Cárdenas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).
A rapid MS/MS method to assess the deuterium kinetic isotope effect and associated improvement in the metabolic stability of deuterated biological and pharmacological molecules as applied to an imaging agent
(Elsevier B. V., 2019-08-08) Murphy, RB; Wyatt, AN; Fraser, BH; Yepuri, NR; Holden, PJ; Wotherspoon, ATL; Darwish, TA
The deuterium kinetic isotope effect has been known for a period of 40 years, but it is only relatively recently that new drug entities (NDEs) incorporating deuterium demonstrating beneficial pharmacokinetics, pharmacodynamics, and toxicology have arrived to market. Determination of the precise location to deuterate and subsequently any evaluation for a kinetic isotope effect (KIE) is challenging. Typically, such an evaluation would be performed in an in vitro metabolic assay (e.g. liver microsomes) in separate reaction media for both the deuterated and non-deuterated analogues. Here, we have devised an approach whereby we incubate a 1:1 ratio of both the deuterated and protio-form of an imaging agent together in the same liver microsomal assay and determine the relative rate of consumption of both moieties, based upon specific MS-MS transitions unique to both molecules without the need for liquid chromatography-mass spectrometry (LC-MS) separation and quantification. Any deviation of the ratio of the MS transitions from the initial starting point indicated an observable KIE. A site specific deuteration of PBR111, a neuroinflammation imaging agent, was chosen for a proof-of-concept study. Based upon prior mechanistic knowledge of PBR111, two locations were selected for deuteration; an active and inactive site, to corroborate that there was no significant KIE for the inactive site and confirm the efficacy of the developed methodology. Crown Copyright © 2019 Published by Elsevier B.V.
Realtime structural characterisation of thin film OLED stacks during thermally induced diffusion - the importance of glass transitions
(International Conference on Neutron Scattering, 2017-07-12) Nelson, A; McEwan, JA; Clulow, AJ; Shaw, PE; Darwish, TA; Yepuri, NR; Burn, PL; Gentle, IR
Organic Light Emitting Diode (OLED) devices are ubiquitous in the displays of many modern electronic devices, including televisions and mobile phones. High efficiency OLEDs are typically made as a sequentially deposited multilayer, with different organic semiconductor layers being required for hole/electron injection/transport, as well as light emission. The operational lifetime, efficiency and fidelity of these OLEDs depends on the structural stability of this multilayer stack, and understanding the factors that affect this stability are crucial in developing new devices. We have systematically characterised the kinetics of structural evolution in these systems as they experience thermally induced diffusion. These leading edge experiments are performed on the Platypus neutron reflectometer, which has been pioneering event mode acquisition techniques to capture quickly changing reflection signals as the multilayers inter-diffuse. Selective deuteration of these semiconductor materials is also critical in providing neutron contrast between each of the layers, without which the experiment could not be carried out. Our investigations reveal the importance of glass transition temperatures on the stability of these OLED systems and provide clear guidelines for material choices when designing new devices. Indeed, with knowledge of each of the T \'s one can predict the way in which diffusion occurs. For example, use of a high Tg emissive layer does not necessarily prevent diffusion from taking place.
Stereoselective synthesis of perdeuterated phytanic acid, its phospholipid derivatives and their formation into lipid model membranes for neutron reflectivity studies
(Elsevier, 2014-10-01) Yepuri, NR; Holt, SA; Moraes, G; Holden, PJ; Hossain, KR; Valenzuela, SM; Darwish, TA; James, M
We describe a straightforward method, for synthesis of large scale (gram quantities) of highly deuterated phytanic acid from commercially available phytol while preserving the stereochemistry around the chiral centres. The subsequent synthesis of tail-deuterated analogues of the archeabacterial membrane lipids 1,2-di(3RS,7R,11R-phytanyl)-sn-glycero-3-phosphocholine (DPEPC) and 1,2-di(3RS,7R,11R-phytanoyl)-sn-glycero-3-phosphocholine (DPhyPC) from perdeuterated phytanic acid is also described. Both lipids were employed in construction of two different model membranes, namely Langmuir monolayers and a tethered bilayer membrane (TBM) on a solid substrate, characterised by pressure area isotherm and neutron reflectometry techniques. At 10 mN/m pressure the head-group thickness of both monolayers was similar while the thickness of the tail region was significantly larger for tail-deuterated DPhyPC, which was evident from a smaller area per molecule. At 20 mN/m the thickness of the head and tail regions in both lipids was comparable, yet the area per molecule of tail-deuterated DPhyPC was 10% smaller than tail-deuterated DPEPC. In the TBM bilayer model membrane, the thickness of the lipid tails in both inner and outer leaflets was 8.2 Å, giving a total of 16.4 Å. Deuteration enabled unambiguous determination of the relative proportion of the hydrogenous tether, phospholipid and subphase. © 2014, Elsevier Ireland Ltd.
Synthesis of cephalosporin-3'-diazeniumdiolates: biofilm dispersing no-donor prodrugs activated by b-lactamase
(Royal Society of Chemistry, 2013-01-01) Yepuri, NR; Barraud, N; Mohammadi, NS; Kardak, BG; Kjelleberg, S; Rice, SA; Kelso, MJ
Use of biofilm dispersing NO-donor compounds in combination with antibiotics has emerged as a promising new strategy for treating drug-resistant bacterial biofilm infections. This paper details the synthesis and preliminary evaluation of six cephalosporin-3[prime or minute]-diazeniumdiolates as biofilm-targeted NO-donor prodrugs. Each of the compounds is shown to selectively release NO following reaction with the bacteria-specific enzyme [small beta]-lactamase and to trigger dispersion of Pseudomonas aeruginosa biofilms in vitro. © 2013, Royal Society of Chemistry
Synthesis of deuterated [D-32]oleic acid and its phospholipid derivative [D-64]dioleoyl-sn-glycero-3-phosphocholine
(Wiley-Blackwell, 2013-07-16) Darwish, TA; Luks, E; Moraes, G; Yepuri, NR; Holden, PJ; James, M
Oleic acid and its phospholipid derivatives are fundamental to the structure and function of cellular membranes. As a result, there has been increasing interest in the availability of their deuterated forms for many nuclear magnetic resonance, infrared, mass spectroscopy and neutron scattering studies. Here, we present for the first time a straightforward, large-scale (gram quantities) synthesis of highly deuterated [D32]oleic acid by using multiple, yet simple and high yielding reactions. The precursors for the synthesis of [D32]oleic acid are [D14]azelaic acid and [D17]nonanoic acid, which were obtained by complete deuteration (>98% D) of their 1H forms by using metal catalysed hydrothermal H/D exchange reactions. The oleic acid was produced with ca. 94% D isotopic purity and with no contamination by the trans-isomer (elaidic acid). The subsequent synthesis of [D64]dioleoyl-sn-glycero-3-phosphocholine from [D32]oleic acid is also described. Copyright © 2013 John Wiley & Sons, Ltd.© 2013, Wiley-Blackwell.
Synthesis of per-deuterated alkyl amines for the preparation of deuterated organic pyromellitamide gelators
(Pergamon-Elsevier Science Ltd, 2013-05-15) Yepuri, NR; Jamieson, SA; Darwish, TA; Rawal, A; Hook, JM; Thordarson, P; Holden, PJ; James, M
A general, direct and scalable synthesis of per-deuterated alkyl amines is reported, together with their incorporation into pyromellitamides, which form self-assembled gels in cyclohexane. The deuterium labelling of these gelators allows the study of the dynamic intermolecular interactions in these materials using solid-state 2H NMR spectroscopy.© 2013, Elsevier Ltd.

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