N,N'-Substituted thioureas and their metal complexes: syntheses, structures and electronic properties.

The synthesis of six N,N'-substituted thiourea ligands (L1a-L3b) was achieved in two steps. A corresponding extensive series of Cu(I), Cu(II), Ni(II) and Zn(II) complexes (1-24) with varying formulations were synthesised from these ligands by the reaction of a 1 : 1 or a 1 : 2 mixture of Cu(II), Ni(II) and Zn(II) perchlorate or chloride salts. Complexes 1-24 have been comprehensively characterised by mass spectrometry, elemental analysis, UV-vis., IR, and 1H and 13C{1H} NMR spectroscopies where applicable. The X-ray crystal structures were obtained for eight examples: [(L1a)2Cu]ClO4 (1), [(L1c)2Zn](ClO4)2 (4), [(L2a)2Cu]ClO4 (6), [(L2c)2Ni](ClO4)2 (7), [(L1b)2Cu](ClO4) (15), [(L1b)CuCl] (16), [(L4)2CuCl2] (19) and [(L3b)CuClO4] (21). These studies reveal that L1c and L2c represent ligands that have undergone cleavage during reaction with the metal salt; L4 represents an intramolecular rearrangement (via a Hugershoff reaction) of L2b; and in most cases Cu(II) is reduced to Cu(I) during the ligand reaction. The X-ray crystal structures also reveal that 1, 4, 6, 15 and 16 are monometallic species in the solid state; that Cu(I) in 1, 6, 15 and 16 and Zn(II) in 4 are arranged in a distorted tetrahedral geometry; that Cu(I) in 21 adopts a trigonal planar geometry; and that in 7 and 19 the Ni(II) and Cu(II) centres, respectively, possess square planar geometry. Preliminary studies on the biological activity (using the Malaria Sybr Green I Fluorescence assay) of the thiourea containing complexes suggests that the d10 complexes, and increased ligand stoichiometries, may afford higher potency.

Shaping and enforcing coordination spheres: probing the ability of tripodal ligands to favour trigonal prismatic geometry.

We report two tripodal frameworks, mono(2,2'-bipyrid-6-yl)bis(2-pyridyl)methanol () and bis(2,2'-bipyrid-6-yl)mono(2-pyridyl)methanol () which have one and two bipyridyl arms, respectively. Both ligands form complexes with the first row transition metals. Both ligands appear to overcome the steric strain involved in twisting the ligand to produce an octahedral complex and the solid state structures in general show more octahedral character than complexes of the related ligand, tris(2,2'-bipyrid-6-yl)methanol (). Continuous Shape Mapping (CShM) calculations based on crystallographic data reveal that is incapable of enforcing a trigonal prismatic (TP) co-ordination geometry in the solid state, surprisingly even upon co-ordination to metals with no stereochemical preference such as cadmium (S(TP) = 7.15 and S(Oh) = 3.95). However, ligand clearly maintains an ability to enforce a trigonal prismatic conformation which is demonstrated in the crystal structures of the Mn(II) and Cd(II) complexes (S(TP) = 0.75 and 1.09, respectively). While maintains near-TP configurations in the presence of metal ions with strong octahedral preferences, distorts towards predominantly octahedral co-ordination geometries, increasing in the order Co(II) < Ni(II) < Fe(II) and no trigonal prismatic structures.

Co-ordination behaviour of a novel tristhiourea tripodal ligand; structural variations in a series of transition metal complexes.

The co-ordination chemistry of a tristhiourea tris(2-pyridylmethyl)amine ligand () with a series of transition metal ions has been investigated. Crystallographic data show that large metal ions, with no geometrical preferences, such as Mn(ii) and Cd(ii), will form seven co-ordinate monocapped octahedral complexes, while smaller metal ions such as Zn(ii) favour five co-ordinate trigonal bipyramidal structures. In a similar manner to the related bisthiourea complexes, the Ni(ii) complex shows a strong preference for octahedral geometries resulting in the ligand binding asymmetrically. Spectroscopic (IR and NMR), spectrometric (MS) as well as electrochemical data for these complexes are reported.

Heteronuclear Ir(III)-Ln(III) Luminescent Complexes: Small-Molecule Probes for Dual Modal Imaging and Oxygen Sensing.

Luminescent, mixed metal d-f complexes have the potential to be used for dual (magnetic resonance imaging (MRI) and luminescence) in vivo imaging. Here, we present dinuclear and trinuclear d-f complexes, comprising a rigid framework linking a luminescent Ir center to one (Ir·Ln) or two (Ir·Ln2) lanthanide metal centers (where Ln = Eu(III) and Gd(III), respectively). A range of physical, spectroscopic, and imaging-based properties including relaxivity arising from the Gd(III) units and the occurrence of Ir(III) → Eu(III) photoinduced energy-transfer are presented. The rigidity imposed by the ligand facilitates high relaxivities for the Gd(III) complexes, while the luminescence from the Ir(III) and Eu(III) centers provide luminescence imaging capabilities. Dinuclear (Ir·Ln) complexes performed best in cellular studies, exhibiting good solubility in aqueous solutions, low toxicity after 4 and 18 h, respectively, and punctate lysosomal staining. We also demonstrate the first example of oxygen sensing in fixed cells using the dyad Ir·Gd, via two-photon phosphorescence lifetime imaging (PLIM).

Near-IR luminescent lanthanide complexes with 1,8-diaminoanthraquinone-based chromophoric ligands.

Three new chromophoric anthraquinone-based multidentate ligands have been synthesised in a step-wise manner from 1,8-dichloroanthraquinone. The ligands each comprise two dipicolyl amine units and react with trivalent lanthanide ions to form monometallic complexes of the form [Ln(L)](OTf)3 as indicated by MS studies and elemental analyses. Supporting DFT studies show that the monometallic species are highly favoured (>1000 kJ mol(-1)) over the formation of a 2 : 2 dimetallic congener. Both ligands and complexes absorb light efficiently (ε ∼ 10(4) M(-1) cm(-1)) in the visible part of the spectrum, with λabsca. 535-550 nm through an intramolecular charge transfer (ICT) transition localised on the substituted anthraquinone unit. In all cases the complexes show a fluorescence band at ca. 675 nm due to the ICT emitting state. The corresponding Nd(iii), Yb(iii) and Er(iii) complexes also reveal sensitised near-IR emission characteristic of each ion following excitation of the ICT visible absorption band at 535 nm.

Water soluble, cyclometalated Pt(ii)-Ln(iii) conjugates towards novel bimodal imaging agents.

Facile conjugation of a luminescent cyclometalated Pt(II) complex with a DO3A-derived Gd(III) moiety yields a hybrid species with visible luminescence and enhanced relaxivity.

Using lanthanide ions in molecular bioimaging.

Trivalent lanthanide ions offer remarkable opportunities in the design of bioimaging agents: this review presents an accessible discussion of their application in both optical and magnetic resonance imaging. Aspects of molecular design, control over key physical properties and biological compatibility are discussed in this context, together with developments and opportunities as responsive probes and in multimodal imaging.

Co-ordinative properties of a tripodal trisamide ligand with a capped octahedral preference.

An investigation into the co-ordination chemistry of tris(6-pivaloylamino-2-pyridylmethyl)amine (TPPA) shows a preference for capped octahedral geometry when no additional donors are present. This tripodal ligand yields capped octahedral complexes upon co-ordination to a series of first row transition metals when the counter-ion is a perchlorate, bromide or iodide ion. The exact geometry has been confirmed by shape mapping calculations. The largest variation from the capped octahedral geometry is observed in the case of nickel(ii), indicating a greater octahedral preference of this metal ion.

Synthesis, characterisation and evaluation of a novel copper-64 complex with selective uptake in EMT-6 cells under hypoxic conditions.

The radiometal (64)Cu is now widely used in the development of diagnostic imaging agents for positron emission tomography (PET). The present study has led to the development and evaluation of a novel chelating agent for (64)Cu: the new monothiourea tripodal ligand 1-benzoyl-3-{6-[(bis-pyridin-2-ylmethyl-amino)-methyl]-pyridin-2-yl}-thiourea (MTUBo). X-ray crystallographic analysis has shown this ligand forms a mononuclear complex with copper(II) and co-ordinates via a trigonal bipyramidal N4S array of donor atoms. Promisingly, cell uptake studies revealed that (64)Cu-MTUBo selectively accumulates in EMT-6 cells incubated under hypoxic conditions which may result from its relatively high Cu(II/I) redox potential. Small-animal PET imaging and ex vivo biodistribution studies in EMT-6 tumor bearing BALB/c mice revealed significant tumor uptake after 1 h p.i., yielding tumor-to-muscle (T/M) and tumor-to-blood (T/B) ratios of 8.1 and 1.1, respectively. However, injection of (64)Cu-acetate resulted in similar uptake indicating that the observed uptake was most likely non-specific. Despite showing high in vitro stability, it is likely that in vivo the complex undergoes transchelation to proteins within the blood in a relatively short timeframe. For comparison, the hypoxia imaging agent (64)Cu-ATSM was also evaluated in the same murine tumor model and showed about 60% higher tumor uptake than (64)Cu-MTUBo.

Co-ordination behaviour of a novel bisthiourea tripodal ligand: structural, spectroscopic and electrochemical properties of a series of transition metal complexes.

The synthesis of a thiourea substituted derivative of tris(pyridyl-2-methyl)amine (TPA) is reported. Two of the three pyridine rings are substituted in the 6-position with benzoylthiourea groups. These thiourea groups undergo intramolecular hydrogen bonding to form six-membered rings which leaves one N-H group available to form hydrogen bonds with other molecules. This reports details how the complexation of this new ligand with transition metal ions yields complexes with differing geometries. Seven co-ordinate Mn(II) and Cd(II), six co-ordinate Ni(II) and five co-ordinate Co(II), Cu(II) and Zn(II) complexes have been isolated.

Bimodal, dimetallic lanthanide complexes that bind to DNA: the nature of binding and its influence on water relaxivity.

UV-visible titrations, (1)H NMRD experiments and molecular docking studies show that emissive anthraquinone appended dimetallic lanthanide complexes bind to DNA. The strength of binding and the observed relaxivity behaviour depend on the nature of the substituted anthraquinone core.

A facile one-pot synthesis of a new cryptand via a Pd(II)-catalysed carbonylation reaction.

We report the facile and efficient synthesis of a novel cryptand using a one-pot method involving a Pd(II)-catalysed carbonylation reaction. The crystal structure of the corresponding Cu(II) cryptate is also described.

The co-ordination chemistry of bis(2,2'-bipyrid-6'-yl)ketone with first row transition metals: the reversible interconversion of a mononuclear complex and a dinuclear hemiketal containing species.

Bis(2,2'-bipyrid-6'-yl)ketone has been shown to co-ordinate to Zn(II) to form either a dinuclear hemiketal complex in methanol solutions or mononuclear complexes in acetonitrile. The ligand readily complexes to the late transition metals in acetonitrile to yield mononuclear complexes (Mn(II), Co(II), Ni(II),Zn(II) and Cd(II)) however for Fe(II) only dinuclear complexes [Fe(2){(2-bipy)(2)C(OMe)O(-)}(2)][ClO(4)](2) could be isolated. The solid state structures of the mononuclear complexes exhibit varying degrees of distortion compared to an anticipated planar array of bipyridyl donors.

Uptake and localisation of rhenium fac-tricarbonyl polypyridyls in fluorescent cell imaging experiments.

The synthesis of a series of rhenium fac tricarbonyl bisimine complexes and their application as lumophores in fluorescence imaging of yeast and human adenocarcinoma cells is reported. A wide range of complexes are synthesised with varying charges and lipophilicities, all of which have photophysical properties which make them suitable as cell imaging agents. After attempts to apply these as imaging agents in various strains of yeast which showed limited uptake, an investigation was undertaken of their applications as imaging agents in mammalian cells. In general the uptake was high and short-term toxicity and photobleaching appear to be low. The patterns of uptake and localisation are correlated with structural and electronic features of the complexes in an attempt to establish ground-rules for the design and application of rhenium complexes in imaging of eukaryotes.

Functionalisation of terpyridine complexes containing the Re(CO)3(+) moiety.

The investigation into the substitution and addition chemistry of Re(sigma(2)-terpy)(CO)(3)Cl shows that the chloride in Re(sigma(2)-terpy)(CO)(3)Cl (1) may be substituted for acetonitrile to give [Re(sigma(2)-terpy)(CO)(3)(CH(3)CN)][PF(6)] (2), but in the cationic complex [Re(sigma(2)-terpyMe)(CO)(3)Cl][PF(6)] (4), where the pendant pyridine has been methylated, substitution of the chloride could not be achieved using standard conditions. However, use of [Re(sigma(2)-terpyMe)(CO)(3)I][PF(6)] (3) results in the formation of [Re(sigma(2)-terpyMe)(CO)(3)(CH(3)CN)][PF(6)](2) (5). The acetonitrile ligand in complex 2 was found to be labile and could be substituted by pyridine donors.

Responsive, di-metallic lanthanide complexes of a piperazine-bridged bis-macrocyclic ligand: modulation of visible luminescence and proton relaxivity.

The synthesis of a new functionalised bis-macrocyclic ligand (L1) is described together with the corresponding Ln(III) complexes, Ln(2)- (Ln = Gd(III), Eu(III)). Phosphorescence measurements on Gd(2)- at 77 K allowed the ligand-centred triplet state ((3)pi-pi*) to be estimated at ca. 28500 cm(-1). Steady state and time-resolved measurements confirmed emission from the f-centred excited state ((5)D(0)) for Eu(2)-. (1)H NMRD profiles revealed the longitudinal proton relaxivity (r(1)) of Gd(2)- to be 8.3 mM(-1)s(-1)(30 MHz, 25 degrees C). The interaction of Cu(II) and Hg(II) with the lanthanide complexes was probed using luminescence and relaxivity measurements. Addition of Cu(II) (10 eq.) resulted in quenching of the Eu(III) emission, but no increase in r(1) of the Gd(III) dimer. Addition of Hg(II) (10 eq.) caused changes to the hypersensitive emission bands of Eu(III) together with an increase in r(1) of Gd(2)- to be 10.3 mM(-1)s(-1)(30 MHz, 25 degrees C) suggesting a net increase in hydration at the Gd(III) centres.

A novel bipyridine-based hexadentate tripodal framework with a strong preference for trigonal prismatic co-ordination geometries.

The synthesis of the novel ligand tris(2,2'-bipyrid-6-yl) methanol (L(1)) is described. Co-ordination of the ligand to the first row transition metals (Mn(2+)-Zn(2+)) as well as Cd(2+) showed that the ligand formed complexes close to trigonal prismatic in geometry in the solid state. Analysis of the geometry of the co-ordination spheres showed varying degrees of trigonal prismatic and octahedral character. For each d-electron configuration, this could be related to the relative differences in ligand field stabilisation energies for the two geometries.

The synthesis and coordination chemistry of a tris-8-aminoquinoline tripodal ligand.

A tripodal tris-8-aminoquinoline ligand was synthesised in high yield via the Bucherer reaction. The septa-dentate ligand was found to give isolable complexes when coordinated with transition metals. Complexes of zinc(ii), cadmium(ii) and cobalt(iii) were isolated and their solid state structures were determined by single crystal X-ray diffraction. The solid state structures of these complexes were compared to the solution (1)H NMR data which was obtained for each complex. The two first row metals both gave octahedral six coordinate structures, although the two metals were coordinated by a differing donor set of heteroatoms. The cadmium complex was found to contain a seven coordinate cadmium centre in the solid state. DFT calculations were carried out in order to give an indication as to why the two different six coordinate binding modes were encountered.

Jahn-Teller distortions of six-coordinate CuII compounds: cis or trans?

Unlike their octahedral analogues, copper(II) compounds with trigonal prismatic stereochemistry undergo an elongation of two bonds in cis positions due to a Jahn-Teller effect, a behavior that can also occur in slightly twisted octahedra.

rac-N-{6-[Bromo-(hydr-oxy)meth-yl]-2-pyrid-yl}pivalamide.

The title compound, C(11)H(15)BrN(2)O(2), contains an amide group which is close to coplanar with the adjacent pyridine ring, the dihedral angle between the planes being 9.0 (5)°. The mol-ecular packing reveals a mutual hydrogen-bond inter-action between centrosymmetrically related hydroxyl O atoms. Further hydrogen bonding involving O-H⋯Br and N-H⋯Br inter-actions also appears to consolidate the packing.