Iridium(III) Complexes of Bifunctional 2-(2-Pyridyl)imidazole Ligands: Electrochemiluminescent Emitters in Aqueous Media.

A series of electrochemiluminescent (ECL) iridium(III) complexes with the general formula [Ir(CN)(pim)] (where CN = cyclometalating ligands 2-phenylpyridinato (ppy) or 2-(2,4-difluorophenyl)pyridinato (dFppy), and pim = 2-(2-pyridyl)imidazole) have been synthesized. In each case, the 2-(2-pyridyl)imidazole ancillary ligand has been modified to facilitate bioconjugation and ECL label development. All complexes exhibit blue-shifted optical and electro-generated phosphorescence relative to the archetypal complex [Ir(ppy)(bpy)] (bpy = 2,2'-bipyridine).

Experimental and theoretical studies of pH-responsive iridium(III) complexes of azole and N-heterocyclic carbene ligands.

A series of nine luminescent iridium(III) complexes with pH-responsive imidazole and benzimidazole ligands have been prepared and characterized. The first series of complexes were of the form [Ir(ppy)(N^N)] or [Ir(ppy)(C^N)] (where ppy is 2-phenylpyridine and N^N is 2-(2-pyridyl)imidazole or 2-(2-pyridyl)benzimidazole and C^N represents a pyridyl-triazolylidene-based N-heterocyclic carbene ligand). For these complexes, the benzimidazole group was either unsubstituted or substituted with electron-withdrawing (Cl) or electron-donating (Me) groups.

A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection.

Studies have demonstrated that at least 20% of individuals infected with SARS-CoV-2 remain asymptomatic. Although most global efforts have focused on severe illness in COVID-19, examining asymptomatic infection provides a unique opportunity to consider early immunological features that promote rapid viral clearance. Here, postulating that variation in the human leukocyte antigen (HLA) loci may underly processes mediating asymptomatic infection, we enrolled 29,947 individuals, for whom high-resolution HLA genotyping data were available, in a smartphone-based study designed to track COVID-19 symptoms and outcomes.

Ablation of CD8 T cell recognition of an immunodominant epitope in SARS-CoV-2 Omicron variants BA.1, BA.2 and BA.3.

The emergence of the SARS-CoV-2 Omicron variant has raised concerns of escape from vaccine-induced immunity. A number of studies have demonstrated a reduction in antibody-mediated neutralization of the Omicron variant in vaccinated individuals. Preliminary observations have suggested that T cells are less likely to be affected by changes in Omicron.

Antibacterial silver and gold complexes of imidazole and 1,2,4-triazole derived N-heterocyclic carbenes.

A series of gold(I) (4a-4h, 5a-5b) and silver(I) (3a-3h) complexes of 1,2,4-triazolylidene and imidazolylidene based N-heterocyclic carbene ligands were prepared and the antibacterial activities of these complexes have been evaluated. The complexes were characterised using H-NMR, C-NMR, HRMS and in the cases of 3a, 3c, 4b and 5b by X-ray crystallography. The gold(I) complexes with phenyl substituents (4a-4d) were found to have potent antibacterial activity against Gram-positive bacteria, with the complexes of the 1,2,4-triazolylidene ligands being more active (4c, MIC = 4-8 μg mL against and 2 μg mL against ) than the analogous imidazolylidene complexes 4a and 4b (4a, MIC = 64 μg mL against and 2-4 μg mL against ).

Cytotoxic properties of rhenium(I) tricarbonyl complexes of N-heterocyclic carbene ligands.

A family of eight rhenium(I) tricarbonyl complexes bearing pyridyl-imidazolylidene or bis-imidazolylidene ligands in combination with a series of -acetyl amino acids ligands (glycine, isoleucine, and proline) and an acetate have been synthesised and characterised. These complexes are of interest as potential anticancer agents, where the oxygen bound carboxylate ligand can exchange with water giving rise to cytotoxic cationic complexes. The pseudo-first-order aquation rate constants for the complexes were evaluated using H NMR time-course experiments and for the complexes of the bis-imidazolylidene ligand the average value was 6.

Luminescent iridium(iii)-boronic acid complexes for carbohydrate sensing.

A family of four Ir(iii) complexes of the form [Ir(ppy)2(L)]Cl (where ppy = 2-phenyl-pyridine and L = a pyridyl-1,2,4-triazole or pyridyl-1,3,4-oxadiazole ligand bearing a boronic acid group) have been prepared as potential luminescent sensors for carbohydrates. A modular eight step procedure was developed to synthesise the complexes, and this was initiated with the preparation of two benzhydrazide and three S-ethylated pyridine-2-thiocarboxamides precursors. Reaction of these precursors produced three new 1,2,4-triazole- and one 1,3,4-oxadiazole-based ligands substituted with boronic acid pinacol ester groups.

Increased glutaminyl cyclase activity in brains of Alzheimer's disease individuals.

Glutaminyl cyclases (QC) catalyze the formation of neurotoxic pGlu-modified amyloid-β peptides found in the brains of people with Alzheimer's disease (AD). Reports of several-fold increases in soluble QC (sQC) expression in the brain and peripheral circulation of AD individuals has prompted the development of QC inhibitors as potential AD therapeutics. There is, however, a lack of standardized quantitative data on QC expression in human tissues, precluding inter-laboratory comparison and validation.

Charge neutral rhenium tricarbonyl complexes of tridentate N-heterocyclic carbene ligands that bind to amyloid plaques of Alzheimer's disease.

Two tridentate ligand systems bearing N-heterocyclic carbene (NHC), amine and carboxylate donor groups coupled to benzothiazole- or stilbene-based amyloid binding moieties were synthesised. Reaction of the imidazolium salt containing pro-ligands with Re(CO)5Cl yielded the corresponding rhenium metal complexes which were characterised by NMR, and X-ray crystallography. These ligands are of interest for the potential preparation of technetium-99m imaging agents for Alzheimer's disease and the capacity of these rhenium complexes bind to amyloid fibrils composed of amyloid-β peptide and amyloid plaques in human frontal cortex brain tissue was evaluated using fluorescence microscopy.

A luminescent lipid mimetic iridium(III) N-heterocyclic carbene complex for membrane labelling.

Labelling phospholipid membranes with luminophores without altering the biophysical characteristics of the system is particularly challenging due to the small size of the phospholipid molecules and the sensitivity of membrane properties to the presence of fused heterocyclic molecules. Here the design and synthesis of a luminescent lipid mimetic Ir(III) N-heterocyclic carbene complex of the form [Ir(ppy)(C^N)] (where ppy = 2-(phenyl)-pyridine and C^N is a N-heterocyclic carbene ligand) conjugated to stearic acid is described. This complex was synthesised by the reaction of an acetate functionalised Ir(III) precursor complex with tert-butyl N-(2-aminoethyl)carbamate (mono-BOC protected ethylene diamine) and after deprotection of the amine group this complex was coupled to stearic acid using the peptide coupling reagent 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC).

Near-Infrared Electrochemiluminescence from Bistridentate Ruthenium(II) Di(quinoline-8-yl)pyridine Complexes in Aqueous Media.

We report the synthesis, photophysics, electrochemistry and electrochemiluminescence (ECL) of two dqp (dqp=2,6-di(quinoline-8-yl)pyridine) based ruthenium(II) complexes, bearing either a n-butyl ester (1) or the corresponding carboxylic acid functionality (2). The complexes were prepared from [Ru(dqp)(MeCN) ][PF ] by reaction with the dqp precursor using microwave irradiation. In both cases, photoluminescence spectra present strong MLCT-based red/near-infrared (NIR) emissions centred at about 710 nm.

Luminescent iridium(iii) complexes of N-heterocyclic carbene ligands prepared using the 'click reaction'.

A series of imidazolium salt, N-heterocyclic carbene (NHC) ligand precursors, combined with 1,2,3-triazoles were synthesized using the Cu(i) catalyzed azide-alkyne cycloaddition 'click reaction'. These pro-ligands were prepared from imidazolium molecules that were functionalized with either a terminal alkyne or azide group. Methylation of the triazole unit with methyl iodide produced a series of imidazolium/triazolium NHC pro-ligands.

Stepwise Synthesis of -imidazolium Macrocycles and Their -Heterocyclic Carbene Metal Complexes.

A modular stepwise synthetic method has been developed for the preperation of -imidazolium macrocycles. Initially a series of three (imidazolylmethyl)benzene precursors were alkylated with 1,2-dibromoethane to produce the corresponding -bromoethylimidazolium bromide salts. In the second step the -bromoethylimidazolium bromide salts were reacted with selected (imidazolylmethyl)benzene molecules to produce a series of two symmetrical and three asymmetrical -imidazolium macrocycles.

Tuning the electrochemiluminescent properties of iridium complexes of N-heterocyclic carbene ligands.

A series of five heteroleptic Ir(iii) complexes of the general form Ir(dfppy)2(C^C) have been prepared (where dfppy represents 2-(2,4-difluorophenyl)pyridine and C^C represents a bidentate cyclometalated phenyl substituted imidazolylidene ligand). The cyclometalated phenyl ring of the imidazolylidene ligand was either unsubstituted or substituted with electron donating (OMe and Me) or electron withdrawing (Cl and F) groups in the 2 and 4 positions. The synthesised Ir(iii) complexes have been characterised by elemental analysis, NMR spectroscopy, cyclic voltammetry and electronic absorption and emission spectroscopy.

Unusually Strong Electrochemiluminescence from Iridium-Based Redox Polymers Immobilized As Thin Layers or Polymer Nanoparticles.

A new class of redox metallopolymer based on cyclometalated iridium(III) centers is described, with unusually intense luminescence properties in aqueous media. We report the facile synthesis, photophysical and electrochemical characterization, supported by DFT calculations and their electrochemiluminescence (ECL) properties which, under some circumstances, are significantly greater than the analogous ruthenium-based materials. The photoluminescence (PL) and ECL of these materials are further dramatically enhanced when dispersed or immobilized as polymeric nanoparticles (PNPs).

Rhenium(i) complexes of N-heterocyclic carbene ligands that bind to amyloid plaques of Alzheimer's disease.

A series of [Re(i)L(CO)] complexes (where L is a bifunctional bis(NHC)-amine ligand) that are analogues of potential Tc-99m diagnostic imaging agents for Alzheimer's disease have been synthesised. One of the complexes bound to amyloid plaques in human frontal cortex brain tissue from subjects with Alzheimer's disease.

Dinuclear Au(i) N-heterocyclic carbene complexes derived from unsymmetrical azolium cyclophane salts: potential probes for live cell imaging applications.

We have synthesized a new series of azolium cyclophanes and used them as precursors of inherently luminescent dinuclear Au(i)-N-heterocyclic carbene (NHC) complexes. The azolium cyclophanes contained two azolium groups (either imidazolium or benzimidazolium), an o-xylyl group, and an alkyl linker chain (either C2, C3 or C4). All of the azolium cyclophanes were characterised by X-ray diffraction studies and VT NMR studies, and all were fluxional in solution on the NMR timescale.

Metal complexes with di(N-heterocyclic carbene) ligands bearing a rigid ortho-, meta or para-phenylene bridge.

Three novel dinuclear bis-dicarbene silver(i) complexes of general formula [Ag2(MeIm-phenylene-MeIm)2](PF6)2 (Im = imidazol-2-ylidene) were synthesized. The corresponding copper(i) and gold(i) complexes were obtained by transmetalation of the di(N-heterocyclic carbene) ligand from the silver(i) species, and both coordination geometry and stoichiometry are maintained for all three group 11 metals as expected. The photophysical properties of the Ag(i) and Au(i) complexes were also investigated and discussed; in particular the most strongly emitting complex was also studied via DFT calculations.

Heterobimetallic N-Heterocyclic Carbene Complexes: A Synthetic, Spectroscopic, and Theoretical Study.

A new synthetic methodology has been developed for the preparation of heterobimetallic group 11 and group 12 complexes of a symmetrical bis-NHC "pincer" ligand. The synthetic route involved the initial preparation of a mononuclear [Au(NHC)2](+) complex with pendent imidazole moieties on the NHC ligands. Subsequent alkylation of the imidazole groups with Et3OBF4 and metalation with a second metal ion (Ag(I) or Hg(II)) provided two heterobimetallic complexes.

Access to the Parent Tetrakis(pyridine)gold(III) Trication, Facile Formation of Rare Au(III) Terminal Hydroxides, and Preliminary Studies of Biological Properties.

In this paper we report on the use of [NO][BF4] to access tricationic tetrakis(pyridine)gold(III) from Au powder, a species inaccessible using the more traditional (tetrahydrothiophene)AuCl route. It is then demonstrated that this family of compounds can be used to access new terminal Au(III) hydroxides, a challenging class of compounds, and the first crystallographically characterized examples employing bidentate ligands. Finally, preliminary biological studies indicate good activity for derivatives featuring polydentate ligands against the HeLa and PC3 cell lines but also strong inhibition of primary HUVEC cells.

Rhenium complexes of bidentate, bis-bidentate and tridentate N-heterocyclic carbene ligands.

A series of eight Rhenium(I)-N-heterocyclic carbene (NHC) complexes of the general form [ReCl(CO)3(C^C)] (where C^C is a bis(NHC) bidentate ligand), [ReCl(CO)3(C^C)]2 (where C^C is a bis-bidentate tetra-NHC ligand) and [Re(CO)3(C^N^C)](+)[X](-) (where C^N^C is a bis(NHC)-amine ligand and the counter ion X is either the ReO4(-) or PF6(-)) have been synthesised using a Ag2O transmetallation protocol. The novel precursor imidazolium salts and Re(I) complexes were characterized by elemental analysis, (1)H and (13)C NMR spectroscopy and the molecular structures for two imidazolium salt and six Re(I) complexes were determined by single crystal X-ray diffraction. These NHC ligand systems are of interest for possible applications in the development of Tc-99m or Re-186/188 radiopharmaceuticals and as such the stability of two complexes of the form [ReCl(CO)3(C^C)] and [Re(CO)3(C^N^C)][ReO4] were evaluated in ligand challenge experiments using the metal binding amino acids L-histidine or L-cysteine.

Iridium(III) N-heterocyclic carbene complexes: an experimental and theoretical study of structural, spectroscopic, electrochemical and electrogenerated chemiluminescence properties.

Four cationic heteroleptic iridium(III) complexes have been prepared from methyl- or benzyl-substituted chelating imidazolylidene or benzimidazolylidene ligands using a Ag(I) transmetallation protocol. The synthesised iridium(III) complexes were characterised by elemental analysis, (1)H and (13)C NMR spectroscopy and the molecular structures for three complexes were determined by single crystal X-ray diffraction. A combined theoretical and experimental investigation into the spectroscopic and electrochemical properties of the series was performed in order to gain understanding into the factors influencing photoluminescence and electrochemiluminescence efficiency for these complexes, with the results compared with those of similar NHC complexes of iridium and ruthenium.

The fate of NHC-stabilized dicarbon.

The attempted synthesis of NHC-stabilized dicarbon (NHC=C=C=NHC) through deprotonation of a doubly protonated precursor ([NHC-CH=CH-NHC](2+) ) is reported. Rather than deprotonation, a clean reduction to NHC=CH-CH=NHC is observed with a variety of bases. The apparent resistance towards deprotonation to the target compound led to a reinvestigation of the electronic structure of NHC→CC←NHC, which showed that the highest occupied molecular orbital/lowest unoccupied molecular orbital (HOMO/LUMO) gap is likely too small to allow for isolation of this species.

Rhenium and technetium tricarbonyl complexes of N-heterocyclic carbene ligands.

A strategy for the conjugation of N-heterocyclic carbene (NHC) ligands to biomolecules via amide bond formation is described. Both 1-(2-pyridyl)imidazolium or 1-(2-pyridyl)benzimidazolium salts functionalized with a pendant carboxylic acid group were prepared and coupled to glycine benzyl ester using 1-ethyl-3-(3-(dimethylamino)propyl)carbodiimide. A series of 10 rhenium(I) tricarbonyl complexes of the form [ReX(CO)3(ĈN)] (ĈN is a bidentate NHC ligand, and X is a monodentate anionic ligand: Cl(-), RCO2(-)) were synthesized via a Ag2O transmetalation protocol from the Re(I) precursor compound Re(CO)5Cl.