Gold compounds for catalysis and metal-mediated transformations in biological systems

One of the challenges of modern inorganic chemistry is translating the potential of metal catalysts to living systems to achieve controlled non-natural transformations. This field poses numerous issues associated with the metal compounds biocompatibility, stability, and reactivity in complex aqueous environment. Moreover, it should be noted that although referring to ‘metal catalysis’, turnover has not yet been fully demonstrated in most of the examples within living systems. Nevertheless, transition metal catalysts offer an opportunity of modulating bioprocesses through reactions that are complementary to enzymes. In this context, gold complexes, both coordination and organometallic, have emerged as promising tools for bio-orthogonal transformations, endowed with excellent reactivity and selectivity, compatibility within aqueous reaction medium, fast kinetics of ligand exchange reactions, and mild reaction conditions. Thus, a number of examples of gold-templated reactions in a biologically relevant context will be presented and discussed here in relation to their potential applications in biological and medicinal chemistry

Manipulating nanoscale structure to control functionality in printed organic photovoltaic, transistor and bioelectronic devices.

Printed electronics is simultaneously one of the most intensely studied emerging research areas in science and technology and one of the fastest growing commercial markets in the world today. For the past decade the potential for organic electronic (OE) materials to revolutionize this printed electronics space has been widely promoted. Such conviction in the potential of these carbon-based semiconducting materials arises from their ability to be dissolved in solution, and thus the exciting possibility of simply printing a range of multifunctional devices onto flexible substrates at high speeds for very low cost using standard roll-to-roll printing techniques. However, the transition from promising laboratory innovations to large scale prototypes requires precise control of nanoscale material and device structure across large areas during printing fabrication. Maintaining this nanoscale material control during printing presents a significant new challenge that demands the coupling of OE materials and devices with clever nanoscience fabrication approaches that are adapted to the limited thermodynamic levers available. In this review we present an update on the strategies and capabilities that are required in order to manipulate the nanoscale structure of large area printed organic photovoltaic (OPV), transistor and bioelectronics devices in order to control their device functionality. This discussion covers a range of efforts to manipulate the electroactive ink materials and their nanostructured assembly into devices, and also device processing strategies to tune the nanoscale material properties and assembly routes through printing fabrication. The review finishes by highlighting progress in printed OE devices that provide a feedback loop between laboratory nanoscience innovations and their feasibility in adapting to large scale printing fabrication. The ability to control material properties on the nanoscale whilst simultaneously printing functional devices on the square metre scale is prompting innovative developments in the targeted nanoscience required for OPV, transistor and biofunctional devices

Professionals’ views on the use of smartphone technology to support children and adolescents with memory impairment due to acquired brain injury

Purpose: To identify from a health-care professionals’ perspective whether smartphones are used by children and adolescents with acquired brain injury as memory aids; what factors predict smartphone use and what barriers prevent the use of smartphones as memory aids by children and adolescents. Method: A cross-sectional online survey was undertaken with 88 health-care professionals working with children and adolescents with brain injury. Results: Children and adolescents with brain injury were reported to use smartphones as memory aids by 75% of professionals. However, only 42% of professionals helped their clients to use smartphones. The only factor that significantly predicted reported smartphone use was the professionals’ positive attitudes toward assistive technology. Several barriers to using smartphones as memory aids were identified, including the poor accessibility of devices and cost of devices. Conclusion: Many children and adolescents with brain injury are already using smartphones as memory aids but this is often not facilitated by professionals. Improving the attitudes of professionals toward using smartphones as assistive technology could help to increase smartphone use in rehabilitation

New AMD3100 derivatives for CXCR4 chemokine receptor targeted molecular imaging studies: synthesis, anti-HIV-1 evaluation and binding affinities

CXCR4 is a target of growing interest for the development of new therapeutic drugs and imaging agents as its role in multiple disease states has been demonstrated. AMD3100, a CXCR4 chemokine receptor antagonist that is in current clinical use as a haematopoietic stem cell mobilising drug, has been widely studied for its anti-HIV properties, potential to inhibit metastatic spread of certain cancers and, more recently, its ability to chelate radiometals for nuclear imaging. In this study, AMD3100 is functionalised on the phenyl moiety to investigate the influence of the structural modification on the anti-HIV-1 properties and receptor affinity in competition with anti-CXCR4 monoclonal antibodies and the natural ligand for CXCR4, CXCL12. The effect of complexation of nickel(II) in the cyclam cavities has been investigated. Two amino derivatives were obtained and are suitable intermediates for conjugation reactions to obtain CXCR4 molecular imaging agents. A fluorescent probe (BODIPY) and a precursor for 18F (positron emitting isotope) radiolabelling were conjugated to validate this route to new CXCR4 imaging agents

A systematic review of the efficacy of acceptance and commitment therapy for Posttraumatic Stress Disorder, and an empirical study of the associations of empathy and psychological flexibility with burnout and psychological distress in frontline homelessness staff

This thesis is submitted in partial fulfilment of the requirement for the degree of Doctorate of Clinical Psychology (DClinPsy) and is made up of two papers, the systematic review and empirical report. The systematic review aimed to understand the efficacy of Acceptance and Commitment Therapy (ACT) interventions for Posttraumatic Stress Disorder (PTSD). ACT aims to increase psychological flexibility, an openness to experiencing internal experiences such as thoughts and feelings, allowing flexible responses to the current situation while pursuing personally meaningful goals and values. ACT posits that psychological inflexibility, being guided by or attempting to control thoughts and feelings, even when this impacts upon the pursuit of personally meaningful goals and values, underlies psychological distress, including PTSD. Four databases were searched, with 1,454 articles screened resulting in nine papers describing ten studies being included in the systematic review. The Psychotherapy Outcome Study Methodology Rating Form (POMRF) was used to assess the quality of these papers. Results indicated that there is preliminary evidence to suggest ACT may be an efficacious intervention for PTSD. However, the quality of the studies was low, so more methodologically rigorous and large-scale trials are required to provide an evidence base for ACT interventions for PTSD. The empirical paper aimed to investigate the roles of individual factors (psychological flexibility and empathy) associated with burnout (measured by three variables: emotional exhaustion, depersonalisation, and personal accomplishment) and psychological distress (secondary traumatic stress, burnout, depression, anxiety and stress) in individuals working in homelessness organisations. Burnout and psychological distress can negatively impact the individual as well as those they are supporting, but little research has investigated factors associated with these difficulties. The current research was therefore a unique contribution to the homelessness services literature. A total of 139 participants completed an online survey, with results suggesting that higher psychological flexibility is associated with lower burnout across the three measured domains, and all psychological distress variables. Higher empathy was associated with two burnout factors (lower depersonalisation and higher personal accomplishment). Further analyses suggested that the results tentatively support that interventions to increase psychological flexibility, and for some, empathic concern, may reduce vulnerability to psychological distress and burnout in frontline homelessness staff. Experimental investigations of the outcome of interventions to increase psychological flexibility and empathic concern are recommended in order to support homelessness staff

FACS purification and transcriptome analysis of drosophila neural stem cells reveals a role for Klumpfuss in self-renewal

Drosophila neuroblasts (NBs) have emerged as a model for stem cell biology that is ideal for genetic analysis but is limited by the lack of cell-type-specific gene expression data. Here, we describe a method for isolating large numbers of pure NBs and differentiating neurons that retain both cell-cycle and lineage characteristics. We determine transcriptional profiles by mRNA sequencing and identify 28 predicted NB-specific transcription factors that can be arranged in a network containing hubs for Notch signaling, growth control, and chromatin regulation. Overexpression and RNA interference for these factors identify Klumpfuss as a regulator of self-renewal. We show that loss of Klumpfuss function causes premature differentiation and that overexpression results in the formation of transplantable brain tumors. Our data represent a valuable resource for investigating Drosophila developmental neurobiology, and the described method can be applied to other invertebrate stem cell lineages as well

The beauty of gold: knowledge of mechanisms leads to different applications of organogold compounds in medicine and catalysis

This review is aimed at providing a concise overview of the results obtained by our group in the field of organometallic chemistry of gold. Therefore, a selection of examples amongst the most extensively explored families of bioactive gold complexes — Au(I) N-heterocyclic carbenes and cyclometalated Au(III) compounds — is presented. Insights into the bio-inorganic mechanisms of reactivity of organogold compounds obtained by an integrated investigational approach, and knowledge of structure-activity relationships are discussed also in relation to novel applications of gold-based catalysts and metal-mediated transformations in aqueous environment

PrFeO3 Photocathodes Prepared Through Spray Pyrolysis

Perovskite oxides are receiving wide interest for photocatalytic and photoelectrochemical devices, owing to their suitable band gaps for solar light absorption and stability in aqueous applications. Herein, we assess the activity of PrFeO3 photocathodes prepared by using spray pyrolysis and calcination temperatures between 500 and 700 °C. Scanning electron microscopy shows corrugated films of high surface coverage on the conductive glass substrate. The electrochemically active surface area shows slight decreases with temperature increases from 500 to 600 and 700 °C. However, transient photocurrent responses and impedance spectroscopy data showed that films calcined at higher temperatures reduced the probabilities of recombination due to trap states, resulting in faster rates of charge extraction. In this trade‐off, a calcination temperature of 600 °C provided a maximum photocurrent of ‐130±4 μA cm−2 at +0.43 VRHE under simulated sunlight, with an incident photon‐to‐current conversion efficiency of 6.6 % at +0.61 VRHE and 350 nm and an onset potential of +1.4 VRHE for cathodic photocurrent

A functional description of CymA, an electron-transfer hub supporting anaerobic respiratory flexibility in Shewanella

CymA (tetrahaem cytochrome c) is a member of the NapC/NirT family of quinol dehydrogenases. Essential for the anaerobic respiratory flexibility of shewanellae, CymA transfers electrons from menaquinol to various dedicated systems for the reduction of terminal electron acceptors including fumarate and insoluble minerals of Fe(III). Spectroscopic characterization of CymA from Shewanella oneidensis strain MR-1 identifies three low-spin His/His co-ordinated c-haems and a single high-spin c-haem with His/H2O co-ordination lying adjacent to the quinol-binding site. At pH 7, binding of the menaquinol analogue, 2-heptyl-4-hydroxyquinoline-N-oxide, does not alter the mid-point potentials of the high-spin (approximately −240 mV) and low-spin (approximately −110, −190 and −265 mV) haems that appear biased to transfer electrons from the high- to low-spin centres following quinol oxidation. CymA is reduced with menadiol (Em=−80 mV) in the presence of NADH (Em=−320 mV) and an NADH–menadione (2-methyl-1,4-naphthoquinone) oxidoreductase, but not by menadiol alone. In cytoplasmic membranes reduction of CymA may then require the thermodynamic driving force from NADH, formate or H2 oxidation as the redox poise of the menaquinol pool in isolation is insufficient. Spectroscopic studies suggest that CymA requires a non-haem co-factor for quinol oxidation and that the reduced enzyme forms a 1:1 complex with its redox partner Fcc3 (flavocytochrome c3 fumarate reductase). The implications for CymA supporting the respiratory flexibility of shewanellae are discussed.</jats:p

Towards a comprehensive understanding of the structural dynamics of a bacterial diterpene synthase during catalysis

Terpenes constitute the largest and structurally most diverse natural product family. Most terpenoids exhibit a stereochemically complex macrocyclic core, which is generated by C–C bond forming of aliphatic oligo-prenyl precursors. This reaction is catalysed by terpene synthases (TPSs), which are capable of chaperoning highly reactive carbocation intermediates through an enzyme-specific reaction. Due to the instability of carbocation intermediates, the proteins’ structural dynamics and enzyme:substrate interactions during TPS catalysis remain elusive. Here, we present the structure of the diterpene synthase CotB2, in complex with an in crystallo cyclised abrupt reaction product and a substrate-derived diphosphate. We captured additional snapshots of the reaction to gain an overview of CotB2’s catalytic mechanism. To enhance insights into catalysis, structural information is augmented with multiscale molecular dynamic simulations. Our data represent fundamental TPS structure dynamics during catalysis, which ultimately enable rational engineering towards tailored terpene macrocycles that are inaccessible by conventional chemical synthesis