Christopher M. Fitchett

4,5-Di(2-pyridyl)-1,2,3-triazolate: the elusive member of a family of bridging ligands that facilitate strong metal–metal interactions

The new click-adduct 4,5-di(2-pyridyl)-1,2,3-triazole acts as a doubly-chelating anionic bridging ligand that forms dinuclear ruthenium(II) complexes which exhibit strong metal-metal interactions.

Chiral heterocyclic ligands. Part 9. Homoconfigurational coordination polymers based on a C2-symmetric, linear-bridging ligand

The fusion of two bornane units to a pyrazine ring gives a sterically hindered C2-symmetric linear bridging ligand that readily assembles into one-dimensional coordination polymers; X-ray crystal structures are described for the free ligand and metallopolymers formed by reaction with silver(I) nitrate and copper(I) iodide.

[Fe2L3]4+ cylinders derived from bis(bidentate) 2-pyridyl-1,2,3- triazole "click" ligands: Synthesis, structures and exploration of biological activity

A series of metallosupramolecular [Fe2L3](BF4)4 “click” cylinders have been synthesized in excellent yields (90%–95%) from [Fe(H2O)6](BF4)2 and bis(bidentate) pyridyl-1,2,3-triazole ligands. All complexes were characterized by elemental analysis, IR, UV-vis, 1H-, 13C- and DOSY-NMR spectroscopies and, in four cases, the structures confirmed by X-ray crystallography. Molecular modeling indicated that some of these “click” complexes were of similar size and shape to related biologically active pyridylimine-based iron(II) helicates and suggested that the “click” complexes may bind both duplex and triplex DNA. Cell-based agarose diffusion assays showed that the metallosupramolecular [Fe2L3](BF4)4 “click” cylinders display no antifungal activity against S. cerevisiae. This observed lack of antifungal activity appears to be due to the poor stability of the “click” complexes in DMSO and biological media.

Discovery of a dual action first-in-class peptide that mimics and enhances CNS-mediated actions of thyrotropin-releasing hormone

Thyrotropin-releasing hormone (TRH) displays multiple CNS-mediated actions that have long been recognized to have therapeutic potential in treating a wide range of neurological disorders. Investigations of CNS functions and clinical use of TRH are hindered, however, due to its rapid degradation by TRH-degrading ectoenzyme (TRH-DE). We now report the discovery of a set of first-in-class compounds that display unique ability to both potently inhibit TRH-DE and bind to central TRH receptors with unparalleled affinity. This dual pharmacological activity within one molecular entity was found through selective manipulation of peptide stereochemistry. Notably, the lead compound of this set, L-pyroglutamyl-L-asparaginyl-L-prolyl-D-tyrosyl-D-tryptophan amide (Glp-Asn-Pro-D-Tyr-D-TrpNH(2)), is effective in vivo at producing and potentiating central actions of TRH without evoking release of thyroid-stimulating hormone (TSH). Specifically, this peptide displayed high plasma stability and combined potent inhibition of TRH-DE (K(i) 151 nM) with high affinity binding to central TRH receptors (K(i) 6.8 nM). Moreover, intraperitoneal injection of this peptide mimicked and augmented the effects of TRH on behavioural activity in rat. Analogous to TRH, it also antagonized pentobarbital-induced narcosis when administered intravenously. This discovery provides new opportunities for probing the role of TRH actions in the CNS and a basis for development of novel TRH-based neurotherapeutics.

Chiral Heterocyclic Ligands. XIII. Synthesis and X-Ray Crystal Structure of a Chiral, Unidirectional, Silver Coordination Polymer

The chiral bridging ligand 2 is shown to react with silver nitrate to produce a new type of chiral coordination polymer with a unidirectional ladder-like structure.

Synthesis and X-ray crystal structures of dinuclear silver(I) complexes of heteroaryl thioethers

Abstract The X-ray crystal structures of four complexes, obtained by reaction of silver nitrate with four different heteroaryl thioethers, are described. In these compounds the ligands act as dinuclear bridges between silver atoms, with coordination exclusively through the nitrogen donor atoms. All ligands form dinuclear complexes, either as discrete species or as higher aggregates involving additional nitrate bridges. π–π Stacking interactions provide extra stabilisation in some of the structures.

Cytotoxic and Antifungal Activities of 5-Hydroxyramulosin, a Compound Produced by an Endophytic Fungus Isolated from Cinnamomum mollisimum

An endophytic fungus isolated from the plant Cinnamomum mollissimum was investigated for the bioactivity of its metabolites. The fungus, similar to a Phoma sp., was cultured in potato dextrose broth for two weeks, followed by extraction with ethyl acetate. The crude extract obtained was fractionated by high-performance liquid chromatography. Both crude extract and fractions were assayed for cytotoxicity against P388 murine leukemic cells and inhibition of bacterial and fungal pathogens. The bioactive extract fraction was purified further and characterized by nuclear magnetic resonance, mass spectral and X-ray crystallography analysis. A polyketide compound, 5-hydroxyramulosin, was identified as the constituent of the bioactive fungal extract fraction. This compound inhibited the fungal pathogen Aspergillus niger (IC50 1.56 μg/mL) and was cytotoxic against murine leukemia cells (IC50 2.10 μg/mL). 5-Hydroxyramulosin was the major compound produced by the endophytic fungus. This research suggests that fungal endophytes are a good source of bioactive metabolites which have potential applications in medicine.

Isolation and Characterization of a Bismuth(II) Radical

More than 80 years after Paneths report of dimethyl bismuth, the first monomeric Bi(II) radical that is stable in the solid state has been isolated and characterized. Reduction of the diamidobismuth(III) chloride Bi(NON(Ar))Cl (NON(Ar)=[O(SiMe2NAr)2](2-); Ar=2,6-iPr2C6H3) with magnesium affords the Bi(II) radical ˙Bi(NON(Ar)). X-ray crystallographic measurements are consistent with a two-coordinate bismuth in the +2 oxidation state with no short intermolecular contacts, and solid-state SQUID magnetic measurements indicate a paramagnetic compound with a single unpaired electron. EPR and density functional calculations show a metal-centered radical with >90% spin density in a p-type orbital on bismuth.

Transition metal complexes of 2-amino-3-chloro-5-trifluoromethylpyridine: syntheses, structures, and magnetic properties of [(TMCAPH)2CuBr4] and [(TMCAPH)2CuCl4]

The reaction of CuX2 (X = Br or Cl) with 2-amino-3-chloro-5-trifluoromethylpyridine in aqueous acids (HX; X = Br or Cl) yields bis(2-amino-3-chloro-5-trifluoromethylpyridinium)tetrabromocuprate(II) (1) and bis(2-amino-3-chloro-5-trifluoromethylpyridinium)tetrachlorocuprate(II) (2). These compounds have been characterized by IR, powder X-ray diffraction (XRD), single crystal XRD, combustion analysis, and temperature-dependent magnetic susceptibility. Compound 1 crystallizes in the monoclinic space group P21/c with three ions in the asymmetric unit, whereas 2 crystallizes in the triclinic space group P 1, and the asymmetric unit contains 18 ionic moieties. Both compounds exhibit antiferromagnetic exchange via the double halide exchange pathway and singlet ground states, with stronger exchange observed for 1. Both compounds exhibit multiple potential magnetic exchange pathways, but fitting of the data to available analytical models suggests that the magnetic exchange constants 2J/k B are ∼50 K in 1 and ∼6 K in 2, respectively.

Discrete Metal Complexes of Two Multiply Armed Ligands

The syntheses and metal complexes of 1,2,4,5-tetrakis(8-quinolyloxymethyl)benzene 1 and hexakis(8-quinolyloxymethyl)benzene 2 are described. X-Ray crystal structures are reported of the free ligand 1, a binuclear silver(i) and a tetranuclear copper(i) complex of 1, as well as a binuclear cobalt(ii) and trinuclear palladium(ii) and silver(i) complexes of 2. Within these discrete metal complexes the ligands are found to adopt a range of coordination modes, with considerable variation in the relative orientations of the ligand arms as a result of the flexibility imparted by the CH2O linker units.