RESUMEN
The synthesis and characterization of a novel class of highly-metallized, redox-active polyelectrolytes that employ phosphorus as a scaffold for the installation of transition metals is described. Pyrolysis of thin films of the title polyelectrolytes resulted in the production of magnetite crystallites and ill-defined carbon-, phosphorus- and oxygen-rich phases in char yields of nearly 50%.
RESUMEN
We report the discovery of nontoxic fungicide fenarimol (1) as an inhibitor of Trypanosoma cruzi ( T. cruzi ), the causative agent of Chagas disease, and the results of structure-activity investigations leading to potent analogues with low nM IC(50)s in a T. cruzi whole cell in vitro assay. Lead compounds suppressed blood parasitemia to virtually undetectable levels after once daily oral dosing in mouse models of T. cruzi infection. Compounds are chemically tractable, allowing rapid optimization of target biological activity and drug characteristics. Chemical and biological studies undertaken in the development of the fenarimol series toward the goal of delivering a new drug candidate for Chagas disease are reported.
Asunto(s)
Enfermedad de Chagas/tratamiento farmacológico , Pirimidinas/química , Pirimidinas/farmacología , Tripanocidas/química , Tripanocidas/farmacología , Trypanosoma cruzi/efectos de los fármacos , Animales , Línea Celular , Enfermedad de Chagas/metabolismo , Enfermedad de Chagas/parasitología , Modelos Animales de Enfermedad , Cromatografía de Gases y Espectrometría de Masas , Concentración 50 Inhibidora , Masculino , Ratones , Resonancia Magnética Nuclear Biomolecular , Pirimidinas/síntesis química , Pirimidinas/farmacocinética , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad , Tripanocidas/síntesis química , Tripanocidas/farmacocinéticaRESUMEN
A variety of Group 10 metal complexes [MXY(dfppp)], M = Ni, X, Y = Cl, Br, M = Pd, Pt, X, Y = Cl or CH(3), containing the recently reported highly fluorous diphosphine ligand, dfppp, 1,3-bis[di(fluoroponytail)phosphino]propane, {(p-F(13)C(6)C(6)H(4))(2)P}(2)(CH(2))(3) have been synthesised. They have been characterised by NMR, mass spectrometry and microanalysis, with two platinum complexes, [PtCl(2)(dfppp)] and [PtClMe(dfppp)], structurally characterised by single crystal X-ray diffraction studies. The highly fluorous nature of the ligands affords the complexes good supercritical CO(2) solubility as measured by supercritical fluid extraction (SFE), and has allowed for the copolymerisation of CO and ethylene using [PdClMe(dfppp)] as the catalyst precursor and CO(2) as the solvent. Additionally, PtCl(2) complexes of the new ligands dfppb, {(p-F(13)C(6)C(6)H(4))(2)P}(2)(CH(2))(4), and dfpop, {(p-F(13)C(6)C(6)H(4)O)(2)P}(2)(CH(2))(3), have also been prepared and characterised.
Asunto(s)
Dióxido de Carbono/química , Metales Pesados/química , Compuestos Organometálicos/química , Presión , Catálisis , Modelos Moleculares , Conformación Molecular , Níquel/química , Paladio/química , Fosfinas/química , Platino (Metal)/química , Polimerizacion , SolubilidadRESUMEN
A series of ruthenium and osmium complexes containing highly fluorous diphosphine ligands (F)P(wedge)P(F) = (F(13)C(6)C(6)H(4)-p)(2)P(CH(2))(2)P(p-C(6)H(4)C(6)F(13))(2) (dfppe) and (F(13)C(6)C(6)H(4)-p)(2)P(CH(2))(3)P(p-C(6)H(4)C(6)F(13))(2) (dfppp) has been prepared. The fluorous diphosphine ligands incorporate four C(6)F(13) "fluoro-ponytails", and these have been effective in solubilizing the complexes in supercritical carbon dioxide (scCO(2)). Precise solubility measurements in scCO(2) were performed for some of the complexes. The new complexes [MX(2)((F)P(wedge)P(F))(2)] and [MX((F)P(wedge)P(F))(eta-C(5)H(5))], M = Ru, Os, X = Cl, Br, have been characterized by a number of spectroscopic techniques and their electrochemical properties measured, three of the ruthenium complexes also being characterized by single-crystal X-ray studies. The noncovalent interactions observed in the X-ray structures have been analyzed by the Hirshfeld surface approach, putting them on a more solid footing. The fluorinated complexes show significantly different solvation properties from those of the analogous unfluorinated compounds, particularly with respect to their behavior in common organic solvents and their good scCO(2) solubility.