Fluorescent probes for neuroscience: imaging brain tissue sections.

Neurobiological research relies heavily on imaging techniques, such as fluorescence microscopy, to understand neurological function and disease processes. However, the number and variety of fluorescent probes available for tissue section imaging limits the advance of research in the field. In this review, we outline the current range of fluorescent probes that are available to researchers for brain section imaging, including their physical and chemical characteristics, staining targets, and examples of discoveries for which they have been used.

Preliminary investigations into the use of the ancient pigments Han blue and Han purple as luminescent dusting powders for the detection of latent fingermarks.

Here we present our preliminary studies into the inorganic pigments Han blue (BaCuSiO) and Han purple (BaCuSiO) as near-infrared luminescent fingerprint dusting powders. These pigments were developed in ancient China around 800 BCE and both show luminescence in the NIR region. There remains, however, ambiguity in the literature concerning their photophysical properties.

Preclinical pharmacokinetics, pharmacodynamics, and toxicity of novel small-molecule GPR119 agonists to treat type-2 diabetes and obesity.

The escalating global prevalence of type-2 diabetes (T2D) and obesity necessitates the development of novel oral medications. Agonism at G-protein coupled receptor-119 (GPR119) has been recognized for modulation of metabolic homeostasis in T2D, obesity, and fatty liver disease. However, off-target effects have impeded the advancement of synthetic GPR119 agonist drug candidates.

Correlative multimodal optical and X-ray fluorescence imaging of brominated fluorophores.

Imaging with multiple modalities can maximise the information gained from the analysis of a single sample. probes for optical fluorescence and X-ray fluorescence microscopy based on brominated 4-amino-1,8-naphthalimide and BODIPY scaffolds have been successfully designed and synthesised. Herein we show that these prototype probes, based on each of these scaffolds, can be imaged in two different cancer cell lines, and that the respective optical fluorescence and X-ray fluorescence signals are well correlated in these images.

Elucidating the Mechanism of Efficient Eu(III) and Yb(III) Sensitisation from a Re(I) Tetrazolato Triangular Assembly.

The reaction of Re(CO)Br with deprotonated 1H-(5-(2,2':6',2''-terpyridine)pyrid-2-yl)tetrazole yields a triangular assembly formed by tricarbonyl Re(I) vertices. Photophysical measurements reveal blue-green emission with a maximum at 520 nm, 32 % quantum yield, and 2430 ns long-lived excited state decay lifetime in deaerated dichloromethane solution. Coordination of lanthanoid ions to the terpyridine units red-shifts the emission to 570 nm and also reveals efficient (90 %) and fast sensitisation of both Eu(III) and Yb(III) at room temperature, with a similar rate constant k on the order of 10 s.

Neutral rhenium(I) tricarbonyl complexes with sulfur-donor ligands: anti-proliferative activity and cellular localization.

Rhenium(I) tricarbonyl complexes are widely studied for their cell imaging properties and anti-cancer and anti-microbial activities, but the complexes with S-donor ligands remain relatively unexplored. A series of six -[Re(NN)(CO)(SR)] complexes, where (NN) is 2,2'-bipyridyl (bipy) or 1,10-phenanthroline (phen), and RSH is a series of thiocarboxylic acid methyl esters, have been synthesized and characterized. Cellular uptake and anti-proliferative activities of these complexes in human breast cancer cell lines (MDA-MB-231 and MCF-7) were generally lower than those of the previously described -[Re(NN)(CO)(OH)] complexes; however, one of the complexes, -[Re(CO)(phen)(SC(Ph)CHC(O)OMe)] (3b), was active (IC ∼ 10 μM at 72 h treatment) in thiol-depleted MDA-MB-231 cells.

Designing Ionic Ir(III) Cyclometalated Complexes as Photocatalysts for Light Assisted ATRP of MMA. A Combined Experimental and Mechanistic Study.

A new family of ionic Ir(III) cyclometalated complexes with general formula [Ir(CN)(NN)][Br], was designed and prepared to be assessed as photocalysts for the visible light assisted ATRP polymerization of MMA. To this purpose, our design strategy involved both: i) the decoration of the cyclometalating (CN) and the ancillary (NN) ligands with various electron withdrawing and/or electron donor substituents and, ii) the use of Br as the counter anion for these cationic Ir(III) species. After an extensive screening in which the [Ir(CN)(NN)][Br]-type compounds were compared to the model neutral complex fac-[Ir(ppy)], the "fully" amino-substituted ion pairs abbreviated as [10][Br] and [11][Br], exhibited the best photocatalytic performances under irradiation with CFL lamps.

Synthesis and cellular uptake of neutral rhenium(I) morpholine complexes.

Morpholine motifs have been used extensively as targeting moieties for lysosomes, primarily in fluorescence imaging agents. Traditionally these imaging agents are based on organic molecules which have several shortcomings including small Stokes shifts, short emission lifetimes, and susceptibility to photobleaching. To explore alternative lysosome targeting imaging agents we have used a rhenium based phosphorescent platform which has been previously demonstrated to have an improved Stokes shift, a long lifetime emission, and is highly photostable.

Ligand-Mediated Control of the Surface Oxidation States of Copper Nanoparticles Produced by Laser Ablation.

We report on studies that demonstrate how the chemical composition of the surface of copper nanoparticles (CuNPs) - in terms of percentage copper(I/II) oxides - can be varied by the presence of N-donor ligands during their formation via laser ablation. Changing the chemical composition thus allows systematic tuning of the surface plasmon resonance (SPR) transition. The trialed ligands include pyridines, tetrazoles, and alkylated tetrazoles.

Synthesis and the photophysical and biological properties of tricarbonyl Re(I) diimine complexes bound to thiotetrazolato ligands.

Twelve Re(I) tricarbonyl diimine (2,2'-bipyridine and 1,10-phenanthroline) complexes with thiotetrazolato ligands have been synthesised and fully characterised. Structural characterisation revealed the capacity of the tetrazolato ligand to bind to the Re(I) centre through either the S atom or the N atom with crystallography revealing most complexes being bound to the N atom. However, an example where the Re(I) centre is linked the S atom has been identified.

Elucidation of LMCT Excited States for Lanthanoid Complexes: A Theoretical and Solid-State Experimental Framework.

Photophysical and magnetic properties arising from both ground and excited states of lanthanoid ions are relevant for numerous applications. These properties can be substantially affected, both adversely and beneficially, by ligand-to-metal charge-transfer (LMCT) states. However, probing LMCT states remains a significant challenge in f-block chemistry, particularly in the solid state.

Luminescent Metal Complexes as Emerging Tools for Lipid Imaging.

Fluorescence microscopy is a key tool in the biological sciences, which finds use as a routine laboratory technique (e.g., epifluorescence microscope) or more advanced confocal, two-photon, and super-resolution applications.

2,7- and 4,9-Dialkynyldihydropyrene Molecular Switches: Syntheses, Properties, and Charge Transport in Single-Molecule Junctions.

This paper describes the syntheses of several functionalized dihydropyrene (DHP) molecular switches with different substitution patterns. Regioselective nucleophilic alkylation of a 5-substituted dimethyl isophthalate allowed the development of a workable synthetic protocol for the preparation of 2,7-alkyne-functionalized DHPs. Synthesis of DHPs with surface-anchoring groups in the 2,7- and 4,9-positions is described.

Reinterpreting the Fate of Iridium(III) Photocatalysts─Screening a Combinatorial Library to Explore Light-Driven Side-Reactions.

Photoredox catalysts are primarily selected based on ground and excited state properties, but their activity is also intrinsically tied to the nature of their reduced (or oxidized) intermediates. Catalyst reactivity often necessitates an inherent instability, thus these intermediates represent a mechanistic turning point that affords either product formation or side-reactions. In this work, we explore the scope of a previously demonstrated side-reaction that partially saturates one pyridine ring of the ancillary ligand in heteroleptic iridium(III) complexes.

Rhenium(I) conjugates as tools for tracking cholesterol in cells.

Cholesterol is vital to control membrane integrity and fluidity, but is also a precursor to produce steroid hormones, bile acids, and vitamin D. Consequently, altered cholesterol biology has been linked to many diseases, including metabolic syndromes and cancer. Defining the intracellular pools of cholesterol and its trafficking within cells is essential to understand both normal cell physiology and mechanisms of pathogenesis.

Photoactive Metal Carbonyl Complexes Bearing N-Heterocyclic Carbene Ligands: Synthesis, Characterization, and Viability as Photoredox Catalysts.

This report details the synthesis and characterization of a small family of previously unreported, structurally related chromium, molybdenum, tungsten, manganese, and iron complexes bearing N-heterocyclic carbene and carbonyl supporting ligands. These complexes have the general form [ML(CO)X] or [ML(CO)], where X = CO or Br and L = 1-phenyl-3-(2-pyridyl)imidazolin-2-ylidene. Where possible, the solid-state, spectroscopic, electrochemical, and photophysical properties of these molecules were studied using a combination of experiment and theory.

Pharmacological and structure-activity relationship studies of oleoyl-lysophosphatidylinositol synthetic mimetics.

Metabolic diseases, such as obesity and type 2 diabetes, are relentlessly spreading worldwide. The beginning of the 21st century has seen the introduction of mechanistically novel types of drugs, aimed primarily at keeping these pathologies under control. In particular, an important family of therapeutics exploits the beneficial physiology of the gut-derived glucagon-like peptide-1 (GLP-1), with important clinical benefits, from glycaemic control to cardioprotection.

Neutral Re(I) Complex Platform for Live Intracellular Imaging.

Luminescent metal complexes are a valuable platform for the generation of cell imaging agents. However, many metal complexes are cationic, a factor that can dominate the intracellular accumulation to specific organelles. Neutral Re(I) complexes offer a more attractive platform for the development of bioconjugated imaging agents, where charge cannot influence their intracellular distribution.

Structure illumination microscopy imaging of lipid vesicles in live bacteria with naphthalimide-appended organometallic complexes.

There is a lack of molecular probes for imaging bacteria, in comparison to the array of such tools available for the imaging of mammalian cells. Here, organometallic molecular probes have been developed and assessed for bacterial imaging, designed to have the potential to support multiple imaging modalities. The chemical structure of the probes is designed around a metal-naphthalimide structure.

Spectroscopic and Molecular Docking Study of the Interaction between Neutral Re(I) Tetrazolate Complexes and Bovine Serum Albumin.

Re(I) complexes have potential in biomedical sciences as imaging agents, diagnostics and therapeutics. Thus, it is crucial to understand how Re(I) complexes interact with carrier proteins, like serum albumins. Here, two neutral Re(I) complexes were used (fac-[Re(CO) (1,10-phenanthroline)L], in which L is either 4-cyanophenyltetrazolate (1) or 4-methoxycarbonylphenyltetrazole ester (2), to study the interactions with bovine serum albumin (BSA).

Mapping sub-cellular protein aggregates and lipid inclusions using synchrotron ATR-FTIR microspectroscopy.

Visualising direct biochemical markers of cell physiology and disease pathology at the sub-cellular level is an ongoing challenge in the biological sciences. A suite of microscopies exists to either visualise sub-cellular architecture or to indirectly view biochemical markers (e.g.

Accessing Lanthanide-to-Lanthanide Energy Transfer in a Family of Site-Resolved [Ln Ln '] Heterodimetallic Complexes.

The ligand H L (6-[3-oxo-3-(2-hydroxyphenyl)propionyl]pyridine-2-carboxylic acid), which exhibits two different coordination pockets, has been exploited to engender and study energy transfer (ET) in two dinuclear [Ln Ln '] analogues of interest, [EuYb] and [NdYb]. Their structural and physical properties have been compared with newly synthesised analogues featuring no possible ET ([EuLu], [NdLu], and [GdYb]) and with the corresponding homometallic [EuEu] and [NdNd] analogues, which have been previously reported. Photophysical data suggest that ET between Eu and Yb does not occur to a significant extent, whereas emission from Yb originates from sensitisation of the ligand.

In utero substrate restriction by placental insufficiency or maternal undernutrition decreases optical redox ratio in foetal perirenal fat.

Intrauterine growth restriction (IUGR) can result from reduced delivery of substrates, including oxygen and glucose, during pregnancy and may be caused by either placental insufficiency or maternal undernutrition. As a consequence of IUGR, there is altered programming of adipose tissue and this can be associated with metabolic diseases later in life. We have utilised two sheep models of IUGR, placental restriction and late gestation undernutrition, to determine the metabolic effects of growth restriction on foetal perirenal adipose tissue (PAT).

Rhenium N-heterocyclic carbene complexes block growth of aggressive cancers by inhibiting FGFR- and SRC-mediated signalling.

Background: Platinum-based anticancer drugs have been at the frontline of cancer therapy for the last 40 years, and are used in more than half of all treatments for different cancer types. However, they are not universally effective, and patients often suffer severe side effects because of their lack of cellular selectivity. There is therefore a compelling need to investigate the anticancer activity of alternative metal complexes.