Using light scattering to assess how phospholipid-protein interactions affect complex I functionality in liposomes.

Complex I is an essential membrane protein in respiration, oxidising NADH and reducing ubiquinone to contribute to the proton-motive force that powers ATP synthesis. Liposomes provide an attractive platform to investigate complex I in a phospholipid membrane with the native hydrophobic ubiquinone substrate and proton transport across the membrane, but without convoluting contributions from other proteins present in the native mitochondrial inner membrane. Here, we use dynamic and electrophoretic light scattering techniques (DLS and ELS) to show how physical parameters, in particular the zeta potential (ζ-potential), correlate strongly with the biochemical functionality of complex I-containing proteoliposomes. We find that cardiolipin plays a crucial role in the reconstitution and functioning of complex I and that, as a highly charged lipid, it acts as a sensitive reporter on the biochemical competence of proteoliposomes in ELS measurements. We show that the change in ζ-potential between liposomes and proteoliposomes correlates linearly with protein retention and catalytic oxidoreduction activity of complex I. These correlations are dependent on the presence of cardiolipin, but are otherwise independent of the liposome lipid composition. Moreover, changes in the ζ-potential are sensitive to the proton motive force established upon proton pumping by complex I, thereby constituting a complementary technique to established biochemical assays. ELS measurements may thus serve as a more widely useful tool to investigate membrane proteins in lipid systems, especially those that contain charged lipids.

Homogeneous Gold Catalysis Using Complexes Recovered from Waste Electronic Equipment.

Despite the greater awareness of elemental sustainability and the benefits of the circular economy concept, much waste electrical and electronic equipment (WEEE) is still destined for landfill. Effective methods for valorizing this waste within our society are therefore imperative. In this contribution, two gold(III) complexes obtained as recovery products from WEEE and their anion metathesis products were investigated as homogenous catalysts. These four recovery products were successfully applied as catalysts for the cyclization of propargylic amides and the condensation of acetylacetone with o-iodoaniline. Impressive activity was also observed in the gold-catalyzed reaction between electron-rich arenes (2-methylfuran, 1,3-dimethoxybenzene, and azulene) and α,ß-unsaturated carbonyl compounds (methyl vinyl ketone and cyclohexenone). These recovered compounds were also shown to be effective catalysts for the oxidative cross-coupling reaction of aryl silanes and arenes. When employed as Lewis acid catalysts for carbonyl-containing substrates, the WEEE-derived gold complexes could also be recovered at the end of the reaction and reused without loss in catalytic activity, enhancing still further the sustainability of the process. This is the first direct application in homogeneous catalysis of gold recovery products sourced from e-waste.

From Waste to Green Applications: The Use of Recovered Gold and Palladium in Catalysis.

The direct use in catalysis of precious metal recovery products from industrial and consumer waste is a very promising recent area of investigation. It represents a more sustainable, environmentally benign, and profitable way of managing the low abundance of precious metals, as well as encouraging new ways of exploiting their catalytic properties. This review demonstrates the feasibility and sustainability of this innovative approach, inspired by circular economy models, and aims to stimulate further research and industrial processes based on the valorisation of secondary resources of these raw materials. The overview of the use of recovered gold and palladium in catalytic processes will be complemented by critical appraisal of the recovery and reuse approaches that have been proposed.

Strategies for the functionalisation of gold nanorods to reduce toxicity and aid clinical translation.

Gold nanorods (GNRs) show great promise as photothermal therapy agents due to their remarkable ability to convert light into heat. In most cases, gold nanorods are synthesised via a seed-mediated method assisted by surfactants. However, the toxicity of these surfactants, principally cetrimonium ions, has prevented GNRs from being used more widely in vivo. To address this issue, various detoxification and functionalisation approaches have been proposed in recent years to replace or cover surfactant coatings on the gold surface. In this short review, the advantages and limitations of each approach are examined in the context of the recent progress made towards the design of GNRs suitable for use in the body.

Gold nanomaterials in the management of lung cancer.

Lung cancer (LC) is one of the most deadly cancers worldwide, with very low survival rates, mainly due to poor management, which has barely changed in recent years. Nanomedicines, especially gold nanomaterials, with their unique and size-dependent properties offer a potential solution to many challenges in the field. The versatility afforded by the shape, size, charge and surface chemistry of gold nanostructures allows them to be adapted for many applications in the diagnosis, treatment and imaging of LC. In this review, a survey of the most recent advances in the field is presented with an emphasis on the optical properties of gold nanoscale materials and their use in cancer management. Gold nanoparticle toxicology has also been a focus of interest for many years but the studies have also sometimes arrived at contradictory conclusions. To enable extrapolation and facilitate the development of medicines based on gold nanomaterials, it must be assumed that each design will have its own unique characteristics that require evaluation before translation to the clinic. Advances in the understanding and recognition of the molecular signatures of LC have aided the development of personalised medicines. Tailoring the treatment to each case should, ideally increase the survival outcomes as well as reduce medical costs. This review seeks to present the potential of gold nanomaterials in LC management and to provide a unified view, which will be of interest to those in the field as well as researchers considering entering this highly important area of research.

Simultaneous Detection of Carbon Monoxide and Viscosity Changes in Cells.

A new family of robust, non-toxic, water-compatible ruthenium(II) vinyl probes allows the rapid, selective and sensitive detection of endogenous carbon monoxide (CO) in live mammalian cells under normoxic and hypoxic conditions. Uniquely, these probes incorporate a viscosity-sensitive BODIPY fluorophore that allows the measurement of microscopic viscosity in live cells via fluorescence lifetime imaging microscopy (FLIM) while also monitoring CO levels. This is the first example of a probe that can simultaneously detect CO alongside small viscosity changes in organelles of live cells.

Metallostar Assemblies Based on Dithiocarbamates for Use as MRI Contrast Agents.

Two different octadentate gadolinium chelates based on DO3A and DOTAGA chelates (hydration number q = 1) have been used to prepare a series of bi-, tri-, and tetrametallic d-f mixed-metal complexes. The piperazine-based dithiocarbamate linker ensures that rotation of the gadolinium chelates is restricted, leading to enhanced relaxivity (r1) values, which increase with the overall mass and number of gadolinium units. The r1 value (at 10 MHz, 25 °C) per gadolinium unit rises from 5.0 mM-1 s-1 for the Gd-DO3A-NH2 monogadolinium chelate to 9.2 mM-1 s-1 in a trigadolinium complex with a ruthenium(III) core. Using a 1.5 T clinical scanner operating at 63.87 MHz (25 °C), an 86% increase in the relaxivity per gadolinium unit is observed for this multimetallic compound compared to clinically approved Dotarem. The gadolinium complexes based on the DOTAGA chelate also performed well at 63.87 MHz, with a relaxivity value of 9.5 mM-1 s-1 per gadolinium unit being observed for the trigadolinium d-f mixed-metal complex with a ruthenium(III) core. The versatility of dithiocarbamate coordination chemistry thus provides access to a wide range of d-f hybrids with potential for use as high-performance MRI contrast agents.

Gold nanomaterials functionalised with gadolinium chelates and their application in multimodal imaging and therapy.

Over the last decade, much work has been dedicated to improving the performance of gadolinium-based magnetic resonance imaging (MRI) contrast agents by tethering them to biocompatible gold nanoparticles. The enhancement in performance (measured in terms of 'relaxivity') stems from the restriction in motion experienced by the gadolinium chelates on being attached to the gold nanoparticle surface. More recently, the unique properties of gold nanoparticles have been exploited to create very promising tools for multimodal imaging and MRI-guided therapies. This review addresses the progress made in the design of gadolinium-functionalised gold nanoparticles for use in MRI, multimodal imaging and theranostics. It also seeks to connect the chemical properties of these assemblies with potential application in the clinic.

Combined Magnetic Resonance Imaging and Photodynamic Therapy Using Polyfunctionalised Nanoparticles Bearing Robust Gadolinium Surface Units.

A robust dithiocarbamate tether allows novel gadolinium units based on DOTAGA (q=1) to be attached to the surface of gold nanoparticles (2.6-4.1 nm diameter) along with functional units offering biocompatibility, targeting and photodynamic therapy. A dramatic increase in relaxivity (r1 ) per Gd unit from 5.01 mm-1 s-1 in unbound form to 31.68 mm-1 s-1 (10 MHz, 37 °C) is observed when immobilised on the surface due to restricted rotation and enhanced rigidity of the Gd complex on the nanoparticle surface. The single-step synthetic route provides a straightforward and versatile way of preparing multifunctional gold nanoparticles, including examples with conjugated zinc-tetraphenylporphyrin photosensitizers. The lack of toxicity of these materials (MTT assays) is transformed on irradiation of HeLa cells for 30 minutes (PDT), leading to 75 % cell death. In addition to passive targeting, the inclusion of units capable of actively targeting overexpressed folate receptors illustrates the potential of these assemblies as targeted theranostic agents.

Synthesis and Application of Ruthenium(II) Alkenyl Complexes with Perylene Fluorophores for the Detection of Toxic Vapours and Gases.

A series of new ruthenium(II) vinyl complexes has been prepared incorporating perylenemonoimide (PMI) units. This fluorogenic moiety was functionalised with terminal alkyne or pyridyl groups, allowing attachment to the metal either as a vinyl ligand or through the pyridyl nitrogen. The inherent low solubility of the perylene compounds was improved through the design of poly-PEGylated (PEG=polyethylene glycol) units bearing a terminal alkyne or a pyridyl group. By absorbing the compounds on silica, vapours and gases could be detected in the solid state. The reaction of the complexes [Ru(CH=CH-PerIm )Cl(CO)(py-3PEG)(PPh3 )2 ] and [Ru(CH=CH-3PEG)Cl(CO)(py-PerIm )(PPh3 )2 ] with carbon monoxide, isonitrile or cyanide was found to result in modulation of the fluorescence behaviour. The complexes were observed to display solvatochromic effects and the interaction of the complexes with a wide range of other species was also studied. The study suggests that such complexes have potential for the detection of gases or vapours that are toxic to humans.

Rapid, High-Yield Fructose Dehydration to 5-Hydroxymethylfurfural in Mixtures of Water and the Noncoordinating Ionic Liquid [bmim][OTf].

The noncoordinating ionic liquid [bmim][OTf] (bmim=1-butyl-3-methylimidazolium) is an effective and versatile solvent for the high-yield dehydration of fructose to the platform chemical 5-hydroxymethylfurfural (HMF) over short reaction times. In contrast to prior studies in which low yields were obtained for this transformation in ionic liquids (ILs) with noncoordinating anions, this contribution reveals that the water content is an essential parameter for an efficient reaction in ILs. Achieving the optimum amount of water can increase the yield dramatically by regulating the acidity of the catalyst and partially suppressing the side reaction caused by self-condensation of HMF. Using acid catalysis in [bmim][OTf] with 3.5 % water content, yields above 80 % can be achieved at 100 °C in only 10 min, even at high (14 %) fructose loading. These results also suggest that [bmim][OTf] represents a superior medium for solvent extraction of HMF compared to halide-based ILs, allowing the option of isolation or further valorization of the HMF formed.

Polyfunctionalised Nanoparticles Bearing Robust Gadolinium Surface Units for High Relaxivity Performance in MRI.

The first example of an octadentate gadolinium unit based on DO3A (hydration number q=1) with a dithiocarbamate tether has been designed and attached to the surface of gold nanoparticles (around 4.4 nm in diameter). In addition to the superior robustness of this attachment, the restricted rotation of the Gd complex on the nanoparticle surface leads to a dramatic increase in relaxivity (r1 ) from 4.0 mm-1 s-1 in unbound form to 34.3 mm-1 s-1 (at 10 MHz, 37 °C) and 22±2 mm-1 s-1 (at 63.87 MHz, 25 °C) when immobilised on the surface. The one-pot synthetic route provides a straightforward and versatile way of preparing a range of multifunctional gold nanoparticles. The incorporation of additional surface units for biocompatibility (PEG and thioglucose units) and targeting (folic acid) leads to little detrimental effect on the high relaxivity observed for these non-toxic multifunctional materials. In addition to the passive targeting attributed to gold nanoparticles, the inclusion of a unit capable of targeting the folate receptors overexpressed by cancer cells, such as HeLa cells, illustrates the potential of these assemblies.

Highly Sensitive and Selective Molecular Probes for Chromo-Fluorogenic Sensing of Carbon Monoxide in Air, Aqueous Solution and Cells.

Optical sensing offers a low-cost and effective means to sense carbon monoxide in air and in solution. This contribution reports the synthesis of a new series of vinyl complexes [Ru(CH=CHR)Cl(CO)(TBTD)(PPh3 )2 ] (R=aryl, TBTD=5-(3-thienyl)-2,1,3-benzothiadiazole) and shows them to be highly sensitive and selective probes for carbon monoxide in both solution and air. Depending on the vinyl substituent, chromogenic and fluorogenic responses signalled the presence of this invisible, odourless, tasteless and toxic gas. Adsorbing the complexes on silica produced colorimetric probes for the 'naked eye' detection of CO in the gas phase with a limit of detection as low as 8 ppm in some cases, while the release of the TBTD fluorophore allowed detection at much lower concentrations through the fluorescence response. Structural data were obtained by single-crystal X-ray diffraction techniques, while the photophysical behaviour was explored computationally using TD-DFT experiments. The systems were also shown to be selective for CO over all other gases tested, including water vapour and common organic solvents. By introducing a poly(ethylene)glycol chain to the vinyl functionality, water compatibility was achieved and these non-cytotoxic complexes were employed in the sensing of CO in HeLa cells, offering a simple and rapid system for sensing this gasotransmitter in this challenging medium.

Ex Vivo Tracking of Endogenous CO with a Ruthenium(II) Complex.

A two-photon fluorescent probe based on a ruthenium(II) vinyl complex is capable of selectively detecting carbon monoxide in cells and ex vivo using mice with a subcutaneous air pouch as a model for inflammation. This probe combines highly selective and sensitive ex vivo detection of endogenous CO in a realistic model with facile, inexpensive synthesis, and displays many advantages over the widely used palladium-based systems.

Facile Preparation of Drug-Loaded Tristearin Encapsulated Superparamagnetic Iron Oxide Nanoparticles Using Coaxial Electrospray Processing.

Naturally occurring polymers are promising biocompatible materials that have many applications for emerging therapies, drug delivery systems, and diagnostic agents. The handling and processing of such materials still constitutes a major challenge, which can limit the full exploitation of their properties. This study explores an ambient environment processing technique: coaxial electrospray (CO-ES) to encapsulate genistein (an isoflavonoid and model drug), superparamagnetic iron oxide nanoparticles (SPIONs, 10-15 nm), and a fluorophore (BODIPY) into a layered (triglyceride tristearin shell) particulate system, with a view to constructing a theranostic agent. Mode mapping of CO-ES led to an optimized atomization engineering window for stable jetting, leading to encapsulation of SPIONs within particles of diameter 0.65-1.2 µm and drug encapsulation efficiencies of around 92%. Electron microscopy was used to image the encapsulated SPIONs and confirm core-shell triglyceride encapsulation in addition to further physicochemical characterization (AFM, FTIR, DSC, and TGA). Cell viability assays (MTT, HeLa cells) were used to determine optimal SPION loaded particles (∼1 mg/mL), while in vitro release profile experiments (PBS, pH = 7.4) demonstrate a triphasic release profile. Further cell studies confirmed cell uptake and internalization at selected time points (t = 1, 2, and 4 h). The results suggest potential for using the CO-ES technique as an efficient way to encapsulate SPIONs together with sensitive drugs for the development of multimodal particles that have potential application for combined imaging and therapy.

The stepwise generation of multimetallic complexes based on a vinylbipyridine linkage and their photophysical properties.

The versatile rhenium complex [ReCl(CO)3(bpyC[triple bond, length as m-dash]CH)] (HC[triple bond, length as m-dash]Cbpy = 5-ethynyl-2,2'-bipyridine) is used to generate a series of bimetallic complexes through the hydrometallation of [MHCl(CO)(BTD)(PPh3)2] (M = Ru, Os; BTD = 2,1,3-benzothiadiazole). The ruthenium complex [Ru{CH[double bond, length as m-dash]CH-bpyReCl(CO)3}Cl(BTD)(CO)(PPh3)2] was characterised structurally. Ligand exchange reactions with bifunctional linkers bearing oxygen and sulfur donors provide access to tetra- and pentametallic complexes such as [{M{CH[double bond, length as m-dash]CH-bpyReCl(CO)3}(CO)(PPh3)2}2(S2CNC4H8NCS2)] and Fe[C5H4CO2M{CH[double bond, length as m-dash]CH-bpyReCl(CO)3}(CO)(PPh3)2]2. The effect of the group 8 metal on the photophysical properties of the rhenium centre was investigated using the complexes [Ru{CH[double bond, length as m-dash]CH-bpyReCl(CO)3}Cl(BTD)(CO)(PPh3)2] and [M{CH[double bond, length as m-dash]CH-bpyReCl(CO)3}{S2P(OEt)2}(CO)(PPh3)2] (M = Ru, Os). This revealed the quenching of the rhenium-based emission in favour of weak radiative processes based on the Ru and Os centres. The potential for exploiting this effect is illustrated by the reaction of [Ru{CH[double bond, length as m-dash]CH-bpyReCl(CO)3}Cl(CO)(BTD)(PPh3)2] with carbon monoxide, which results in a 5-fold fluorescence enhancement in the dicarbonyl product, [Ru{CH[double bond, length as m-dash]CH-bpyReCl(CO)3}Cl(CO)2(PPh3)2], as the quenching effect is disrupted.

Bifunctional Chalcogen Linkers for the Stepwise Generation of Multimetallic Assemblies and Functionalized Nanoparticles.

The disulfide ligand (SC6H4CO2H-4)2 acts as a simple but versatile linker for a range of group 8 transition metals through reaction of the oxygen donors. This leads to a range of homobimetallic ruthenium and osmium alkenyl compounds, [{M(CH═CHR)(CO)(PPh3)2(O2CC6H4S-4)}2] (M = Ru, Os; R = C6H4Me-4). Additional metal-based functionality can be added through the use of precursors incorporating rhenium bipyridine units (R = (bpy)ReCl(CO)3). The more robust diphosphine ligands in [{Ru(dppm)2(O2CC6H4S-4)}2]2+ (dppm = diphenylphosphinomethane) allow reduction of the disulfide bond with sodium borohydride to yield the thiol complex [Ru(O2CC6H4SH-4)(dppm)2]+. This complex reacts with [AuCl(PPh3)] to afford the bimetallic compound [Ru(dppm)2(O2CC6H4S-4)Au(PPh3)]+. However, an improved route to the same and related heterobimetallic compounds is provided by the reaction of cis-[RuCl2(dppm)2] with [Au(SC6H4CO2H-4)(L)] (L = PPh3, PCy3, PMe3, IDip) in the presence of base and NH4PF6 (IDip = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene). The heterotrimetallic compound [Au(SC6H4CO2Ru(dppm)2)2]+ is accessible through the reaction of the homoleptic gold(I) dithiolate [Au(SC6H4CO2H-4)2]PPN (PPN = bis(triphenylphosphine)iminium) with cis-[RuCl2(dppm)2]. Without departure from the same methodology, greater complexity can be incorporated into the system to provide the penta- and heptametallic assemblies [(dppf){AuSC6H4CO2Ru(dppm)2}2]2+ and [(dppf){AuSC6H4CO2Os(CH═CH-bpyReCl(CO)3)(CO)(PPh3)2}2]. The same stepwise approach provides the dinuclear organometallic complexes [(L)Au(SC6H4CO2-4)M(CH═CHC6H4Me-4)(CO)(PPh3)2] (M = Ru, Os; L = PPh3, IDip). Complexes containing three metals from different groups of the periodic table [(L)Au(SC6H4CO2-4)M{CH═CH-bpyReCl(CO)3}(CO)(PPh3)2] (M = Ru, Os) can also be prepared, with one ruthenium example (L = PPh3) being structurally characterized. In order to illustrate the versatility of this approach, the synthesis and characterization (IR and NMR spectroscopy, TEM, EDS, and TGA) of the functionalized gold and palladium nanoparticles Au@[SC6H4CO2Ru(dppm)2]+ and Pd@[SC6H4CO2Ru(dppm)2]+ is reported.

The Highly Selective and Near-Quantitative Conversion of Glucose to 5-Hydroxymethylfurfural Using Ionic Liquids.

A number of ionic liquids have been shown to be excellent solvents for lignocellulosic biomass processing, and some of these are particularly effective in the production of the versatile chemical building block 5-hydroxymethylfurfural (HMF). In this study, the production of HMF from the simple sugar glucose in ionic liquid media is discussed. Several aspects of the selective catalytic formation of HMF from glucose have been elucidated using metal halide salts in two distinct ionic liquids, 1-butyl-3-methylimidazolium chloride and 1-butyl-3-methylimidazolium hydrogen sulfate as well as mixtures of these, revealing key features for accelerating the desired reaction and suppressing byproduct formation. The choice of ionic liquid anion is revealed to be of particular importance, with low HMF yields in the case of hydrogen sulfate-based salts, which are reported to be effective for HMF production from fructose. The most successful system investigated in this study led to almost quantitative conversion of glucose to HMF (90% in only 30 minutes using 7 mol% catalyst loading at 120°C) in a system which is selective for the desired product, has low energy intensity and is environmentally benign.

Chromo-fluorogenic probes for carbon monoxide detection.

The sensing of carbon monoxide (CO) using electrochemical cells or semiconducting metal oxides has led to inexpensive alarms for the home and workplace. It is now recognised that chronic exposure to low levels of CO also poses a significant health risk. It is perhaps surprising therefore that the CO is used in cell-signalling pathways and plays a growing role in therapy. However, the selective monitoring of low levels of CO remains challenging, and it is this area that has benefited from the development of probes which give a colour or fluorescence response. This feature article covers the design of chromo-fluorogenic probes and their application to CO sensing in air, solution and in cells.

Ruthenium(II) and osmium(II) vinyl complexes as highly sensitive and selective chromogenic and fluorogenic probes for the sensing of carbon monoxide in air.

The detection of carbon monoxide in solution and air has been achieved using simple, inexpensive systems based on the vinyl complexes [M(CHCHR)Cl(CO)(BTD)(PPh3 )2 ] (R=aryl, BTD=2,1,3-benzothiadiazole). Depending on the nature of the vinyl group, chromogenic and fluorogenic responses signalled the presence of this odourless, tasteless, invisible, and toxic gas. Solutions of the complexes in CHCl3 underwent rapid change between easily differentiated colours when exposed to air samples containing CO. More significantly, the adsorption of the complexes on silica produced colorimetric probes for the naked-eye detection of CO in the gas phase. Structural data for key species before and after the addition of CO were obtained by means of single X-ray diffraction studies. In all cases, the ruthenium and osmium vinyl complexes studied showed a highly selective response to CO with exceptionally low detection limits. Naked-eye detection of CO at concentrations as low as 5 ppb in air was achieved with the onset of toxic levels (i.e., 100 ppm), thus resulting in a remarkably clear colour change. Moreover, complexes bearing pyrenyl, naphthyl, and phenanthrenyl moieties were fluorescent, and greater sensitivities were achieved (through turn-on emission fluorescence) in the presence of CO both in solution and air. This behaviour was explored computationally using time-dependent density functional theory (TDDFT) experiments. In addition, the systems were shown to be selective for CO over all other gases tested, including water vapour and common organic solvents. Supporting the metal complexes on cellulose strips for use in an existing optoelectronic device allows numerical readings for the CO concentration to be obtained and provision of an alarm system.