A series of [Re(I)L(CO)3]+ 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.

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. Four homobimetallic (Cu(I)2, Ag(I)2, Au(I)2, and Hg(II)2) complexes of the same bis-NHC “pincer” ligand were also prepared. The homobimetallic Cu(I)2, Au(I)2, and Hg(II)2 complexes and heterobimetallic Au(I)–Ag(I) and Au(I)–Hg(II) complexes and the synthetic intermediates for the heterobimetallic complexes were characterized by X-ray crystallography. These X-ray structures show that the bimetallic complexes adopt “twisted” conformations in the solid state, supporting short M···M interactions. Crystalline samples of the homobimetallic Ag(I)2 and Au(I)2 and heterobimetallic Au(I)–Ag(I) and Au(I)–Hg(II) complexes were emissive at room temperature and at 77 K. The geometries of the synthesized complexes were optimized at the M06-L/def2-SVP level of theory, and the electronic nature of the M···M interactions for all synthesized complexes was investigated using natural bond orbital (NBO) calculations.

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. In addition, the ruthenium(II) and iridium(III) complexes [RuCl(MeIm-(o-phenylene)-MeIm)(p-cym)](PF6) and [IrClCp*(MeIm-(o-phenylene)-MeIm)](PF6) were prepared and shown to present in these cases a chelating coordination of the di(N-heterocyclic carbene) ligand.

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, 1H and 13C 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 N^C coordination mode in these complexes is thought to stabilise thermally accessible non-emissive states relative to the case with analogous complexes with C^C coordinated NHC ligands, resulting in low quantum yields. As a result of this and the instability of the oxidised and reduced forms of the complexes, the electrogenerated chemiluminescence intensities for the compounds are also low, despite favourable energetics. These studies provide valuable insights into the factors that must be considered when designing new NHC-based luminescent complexes.

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, 1H and 13C 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. These studies showed that the former was unstable, with the chloride ligand being replaced by either cysteine or histidine, while no evidence for transchelation was observed for the latter suggesting that bis(NHC)-amine ligands of this type may be suitable for biological applications.

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. The synthesized azolium salts and Re(I) complexes were characterized by elemental analysis and by 1H and 13C NMR spectroscopy, and the molecular structures for one imidazolium salt and seven Re(I) complexes were determined by single-crystal X-ray diffraction. 1H NMR and mass spectrometry studies for an acetonitrile-d3 solution of [ReCl(CO)3(1-(2-pyridyl)-3-methylimidazolylidene)] show that the monodentate chloride ligand is labile and exchanges with this solvent yielding a cationic acetonitrile adduct. For the first time the labeling of an NHC ligand with technetium-99m is reported. Rapid Tc-99m labeling was achieved by heating the imidazolium salt 1-(2-pyridyl)-3-methylimidazolium iodide and Ag2O in methanol, followed by the addition of fac-[99mTc(OH2)3(CO)3]+. To confirm the structure of the 99mTc-labeled complex, the equivalent 99Tc complex was prepared, and mass spectrometric studies showed that the formed Tc complexes are of the form [99m/99Tc(CH3CN)(CO)3(1-(2-pyridyl)-3-methylimidazolylidene)]+ with an acetonitrile molecule coordinated to the metal center.

A versatile and straightforward synthetic approach is described for the preparation of triamide bearing analogues of sarcophagine hexaazamacrobicyclic cage ligands without the need for a templating metal ion. Reaction of 1,1,1-tris(aminoethyl)ethane (tame) with 3 equiv of 2-chloroacetyl chloride, yields the tris(α-chloroamide) synthetic intermediate 6, which when treated with either 1,1,1-tris(aminoethyl)ethane or 1,4,7-triazacyclononane furnished two novel triamidetriamine cryptand ligands (7 and 8 respectively). The Co(III) and Cu(II) complexes of cryptand 7 were prepared; however, cryptand 8 could not be metalated. The cryptands and the Co(III) complex 9 have been characterized by elemental analysis, 1H and 13C NMR spectroscopy, and X-ray crystallography. These studies confirm that the Co(III) complex 9 adopts an octahedral geometry with three facial deprotonated amido-donors and three facial amine donor groups. The Cu(II) complex 10 was characterized by elemental analysis, single crystal X-ray crystallography, cyclic voltammetry, and UV–visible absorption spectroscopy. In contrast to the Co(III) complex (9), the Cu(II) center adopts a square planar coordination geometry, with two amine and two deprotonated amido donor groups. Compound 10 exhibited a quasi-reversible, one-electron oxidation, which is assigned to the Cu2+/3+ redox couple. These cryptands represent interesting ligands for radiopharmaceutical applications, and 7 has been labeled with 64Cu to give 64Cu-10. This complex showed good stability when subjected to l-cysteine challenge whereas low levels of decomplexation were evident in the presence of l-histidine.

A series of five heteroleptic Ir(III) complexes of the general form Ir(ppy)2(C∧C:) have been prepared (C∧C represents a bidentate cyclometalated phenyl-substituted imidazolylidene ligand). The five complexes arise from the cyclometalated phenyl ring of the NHC ligand being unsubstituted or having electron-donating (OMe and Me) or electron-withdrawing (Cl and F) groups at the 2- and 4-positions of the ring. The synthesized phenyl-substituted imidazole precursors, imidazolium salts, and Ir(III) complexes have been characterized by elemental analysis, NMR spectroscopy, cyclic voltammetry, and electronic absorption and emission spectroscopy. The molecular structures for two imidazolium salts and two Ir(III) complexes were determined by single-crystal X-ray diffraction. Each of the Ir(III) complexes exhibited intense photoluminescence in acetonitrile solution at room temperature with quantum yields (ϕp) ranging from 42% to 68% and excited-state lifetimes on the order of 2 μs. Voltammetric experiments revealed one formal metal-based oxidation process and two ligand-based reductions for each complex. All complexes gave moderate to intense annihilation electrochemiluminescence (ECL); however, only the fluorinated complex produced significant coreactant ECL. The combined electrochemical, spectroscopic, and theoretical investigations offer insights into the reasons for this behavior and suggest useful strategies for the design of ECL emitters. A plot of oxidation potential versus emission color is proposed as a convenient reference guide to aid in the prediction of energy sufficiency in ECL reactions.

A series of four Ru(II) complexes of the form [Ru(bpy)2(C∧N)]2+ (where C∧N is a bidentate pyridine-functionalized imidazolylidene- or benzimidazolylidene-based N-heterocyclic carbene (NHC) ligand and bpy is 2,2′-bipyridine) have been synthesized using a Ag(I) transmetalation protocol from the Ru(II) precursor compound, Ru(bpy)2Cl2. The synthesized azolium salts and Ru(II) complexes were characterized by elemental analysis, 1H and 13C NMR spectroscopy, cyclic voltammetry, and electronic absorption and emission spectroscopy. The molecular structures for two benzimidazolium salts and three Ru(II) complexes were determined by single crystal X-ray diffraction. The complexes display photoluminescence within the range 611–629 nm, with the emission wavelength of the benzimidazolylidene containing structures, slightly blue-shifted relative to the imidazolylidene containing complexes. All complexes exhibited a reversible, one-electron oxidation, which is assigned to the Ru2+/3+ redox couple. When compared to [Ru(bpy)3]2+, complexes of imidazolylidene containing ligands were oxidized at more negative potentials, while those of the benzimidazolylidene containing ligands were oxidized at more positive potentials. All four complexes exhibited moderately intense electrochemiluminescence (ECL) with the obtained ECL spectra closely resembling the photoluminescence spectra. The ability to predictably fine-tune the highest occupied molecular orbital (HOMO) level of the Ru(II) complexes via the flexible synthetic strategy offered by NHCs is valuable for the design of ECL-based multiplexed detection strategies.

Fluorescence and X-ray absorption spectroscopy were used to investigate the anion binding properties of a luminescent, dinuclear Au(I) N-heterocyclic carbene (NHC) complex ([1]2+) with a short Au(I)⋯Au(I) contact. The addition of Br− ions to a DMSO solution of [1](PF6)2 caused a red-shift in the fluorescence emission band from 396 nm to 496 nm. Similarly, the addition of Br− ions to [1](PF6)2 caused a decrease in the energy of the Au L3-edge in the X-ray absorption spectrum, consistent with the formation of an association complex between the cation [1]2+ and Br− ions. Solution-based structural studies of the association complex were carried out using extended X-ray absorption fine structure (EXAFS) modelling of the Au(I)⋯Au(I) core of the cation. These studies indicate that the association complex results from Au(I)⋯Br− interactions, with the Br− ions occupying two partially occupied sites at ∼2.9 and 3.9 Å from the Au(I) atoms.

A series of six Ni(II) and Pd(II) complexes of two bidentate and two tetradentate N-heterocyclic carbene (NHC)/amidate ligands have been prepared. The complexes are uncharged, with square-planar coordination geometries, and the ligands are bound via the NHC groups and the deprotonated amide nitrogen atoms. Pd(II) complexes were prepared for the bidentate ligands, and in each case, two chelating bidentate ligands were bound to the metal center, yielding cis/trans geometric isomeric forms. The Pd(II) complexes of the tetradentate ligands were obtained as a series of constitutional isomeric forms that were separable by fractional crystallization. The constitutional isomers differed in the coordination mode of the NHC groups, which were bound as either “normal” (nNHC) or “abnormal” (aNHC) carbenes. Density functional theory (DFT) studies show that the energies of the isomeric forms increase in the order nNHC/nNHC < nNHC/aNHC < aNHC/aNHC and suggest that the “abnormal” NHC coordination mode occurs in kinetic rather than thermodynamic reaction products. The Ni(II) complexes of the tetradentate ligand showed only “normal” NHC coordination, suggesting that the mechanism by which aNHC binding occurs is metal dependent. The Ni(II) and Pd(II) complexes with nNHC donors displayed distorted-square-planar coordination geometries and axial chirality.

The N4-macrocyclic ligand 2,10-dioxo-1,4,8,11-tetraazabicyclo[11.4.0]1,12-heptadeca-1(12),14,16-triene H2L has been synthesized by the [1 + 1] condensation reaction between N,N′-bis(chloroacetyl)-1,2-phenylenediamine and 1,3-propylenediamine. The coordination chemistry of this ligand has been investigated with the metal ions Cu(II), Ni(II), Zn(II), and Ga(III) (complexes 1, 2, 3 and 4, respectively). H2L and its metal complexes have been fully characterized by the use of NMR, UV/vis, electron paramagnetic resonance, and elemental analysis where appropriate. The four metal complexes 1−4 have been structurally characterized by X-ray crystallography which confirmed that in all cases the amide nitrogen atoms are deprotonated and coordinated to the metal center. Complexes 3 and 4 are five-coordinate with a water molecule and chloride ion occupying the apical site, respectively. Cyclic voltammetric measurements on complex 1 show that this complex is oxidized reversibly with a half-wave potential, E1/2 = 0.47 V, and reduced irreversibly at EP = −1.84 V. Density functional theory calculations reproduce the geometries of the four complexes. The one-electron reduction and oxidation potentials for 1 were calculated by using two solvent models, DMF and H2O. The calculations indicated that the one electron oxidation of 1 may involve removal of an electron from the ligand as opposed to the metal center, producing a diradical. The diamide macrocyle is of interest for the development of new positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging agents, and a radiolabeled complex has been synthesized with the positron emitting isotope 64Cu. In vivo biodistribution studies for the 64Cu labeled complex, 64Cu-1, in male Lewis rats, showed that the activity is cleared rapidly from the blood within 1−2 h post-administration.

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, 1H and 13C 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 N^C coordination mode in these complexes is thought to stabilise thermally accessible non-emissive states relative to the case with analogous complexes with C^C coordinated NHC ligands, resulting in low quantum yields. As a result of this and the instability of the oxidised and reduced forms of the complexes, the electrogenerated chemiluminescence intensities for the compounds are also low, despite favourable energetics. These studies provide valuable insights into the factors that must be considered when designing new NHC-based luminescent complexes.

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. In addition, the ruthenium(II) and iridium(III) complexes [RuCl(MeIm-(o-phenylene)-MeIm)(p-cym)](PF6) and [IrClCp*(MeIm-(o-phenylene)-MeIm)](PF6) were prepared and shown to present in these cases a chelating coordination of the di(N-heterocyclic carbene) ligand.

Fluorescence and X-ray absorption spectroscopy were used to investigate the anion binding properties of a luminescent, dinuclear Au(I) N-heterocyclic carbene (NHC) complex ([1]2+) with a short Au(I)⋯Au(I) contact. The addition of Br− ions to a DMSO solution of [1](PF6)2 caused a red-shift in the fluorescence emission band from 396 nm to 496 nm. Similarly, the addition of Br− ions to [1](PF6)2 caused a decrease in the energy of the Au L3-edge in the X-ray absorption spectrum, consistent with the formation of an association complex between the cation [1]2+ and Br− ions. Solution-based structural studies of the association complex were carried out using extended X-ray absorption fine structure (EXAFS) modelling of the Au(I)⋯Au(I) core of the cation. These studies indicate that the association complex results from Au(I)⋯Br− interactions, with the Br− ions occupying two partially occupied sites at ∼2.9 and 3.9 Å from the Au(I) atoms.

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, 1H and 13C 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. These studies showed that the former was unstable, with the chloride ligand being replaced by either cysteine or histidine, while no evidence for transchelation was observed for the latter suggesting that bis(NHC)-amine ligands of this type may be suitable for biological applications.

A series of [Re(I)L(CO)3]+ 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.