RESUMEN
Gold(I) complexes of ClickPhos [2.2]paracyclophane ligands were synthesized in excellent yields and fully characterized by spectroscopic methods as well as X-ray crystallography. The complexes exhibit a rigid ligand backbone and a triazolyl moiety and were systematically studied with respect to their cytotoxic properties. In combination with the ionic complex [(GemPhos)Au(tht)][ClO4 ] (tht=tetrahydrothiophene), in which the gold(I) atom exhibits a distorted trigonal coordination sphere of two phosphines and a labile tht ligand, their efficiency in cytotoxicity was investigated in HeLa, MCF7, and HCT116 cells as well as in a zebrafish model. Their cytotoxicity and their mechanisms of action are different and involve apoptosis, necrosis, and DNA damage. The compounds presented herein are potent metal-based cytostatics displaying LD50 values from 3.5-38⠵m in different tumor cell lines and induce double-strand DNA breaks (DSB) as shown by H2AX phosphorylation (γH2AX) at foci of DSBs.
Asunto(s)
Complejos de Coordinación/química , Oro/química , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/toxicidad , Cristalografía por Rayos X , Roturas del ADN de Doble Cadena/efectos de los fármacos , Éteres Cíclicos/química , Células HCT116 , Células HeLa , Histonas/metabolismo , Humanos , Larva/efectos de los fármacos , Larva/fisiología , Ligandos , Células MCF-7 , Conformación Molecular , Fosfinas/química , Fosforilación/efectos de los fármacos , Pez Cebra/crecimiento & desarrolloRESUMEN
Using α-diazo-ß-ketoesters as reagents and combinations of CpRu fragments and diimine ligands as catalysts, a series of original transformations have been obtained that can be rationalized by the formation of metal carbenes and metal-bound ylide intermediates. Interesting 1,3-dioxole, enol-acetal and 1,4-dioxene motifs are obtained directly when the reactive mixture is reacted in presence of aldehydes or ketones, THF and epoxides.
RESUMEN
Reversible as well as stereo- and chemoselective: various proteases such as thermolysin and chymotrypsin catalyze amine acyl exchange in peptides. This acyl exchange can be used to modify amino-functionalized surfaces under physiological reaction conditions and provides an alternative mechanism for posttranslational transpeptidation reactions such as peptide-splicing reactions in the proteasome.
Asunto(s)
Quimotripsina/metabolismo , Oro/química , Péptidos/química , Termolisina/metabolismo , Acilación , Biocatálisis , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
The addition of a Lewis acidic metal triflate salt Mg(OTf)(2) as co-catalyst in the CpRu-catalyzed decarboxylative allylation of in situ-generated ketone enolates allows the reaction to proceed at lower temperature with higher regio- and enantioselectivity. Even so-far-unreactive substrates react.
RESUMEN
[CpRu(CH(3)CN)(3)][PF(6)] and diimine ligands catalyze together the decomposition of α-diazocarbonyl compounds leading to O-H insertion and condensation reactions. In comparison with Rh(II) and Cu(I) complexes, the CpRu catalysts produce rapid and often more selective reactions. Promising enantioselectivities are obtained in dioxole syntheses.