RESUMEN
Three pairs of asymmetric dicarboxylato derivatives based on the cisplatin and oxaliplatin-like skeletons have been synthesized de novo or re-synthesized. The axial ligands consist of one medium-chain fatty acid (MCFA), namely clofibrate (i.e. 2-(p-chlorophenoxy)-2-methylpropionic acid, CA), heptanoate (HA) or octanoate (OA), respectively, and an inactive acetato ligand that imparts acceptable water solubility to such conjugates. Stability tests provided evidence for the partial formation of two hydrolyzed products, corresponding to two monoaqua diastereomers derived from the substitution of an equatorial chlorido ligand with a water molecule. The complexes have been tested on three different colon cancer cell lines having different histological history, and also on the cisplatin-sensitive A2780 ovarian cancer cell line for comparison. This allowed the evaluation not only of the increase in activity on passing from Pt(ii) to Pt(iv) derivatives, but also the selectivity towards colon cancer cells brought about by the cyclohexane-1R,2R-diamine carrier ligand.
Asunto(s)
Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Compuestos Organoplatinos/síntesis química , Profármacos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Neoplasias del Colon/patología , Estabilidad de Medicamentos , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Compuestos Organoplatinos/química , Compuestos Organoplatinos/farmacología , Profármacos/química , Profármacos/farmacología , SolubilidadRESUMEN
Treatment of 1-[axial]-(trimethylsilylethynyl)cyclohexan-1-ol with dicobalt octacarbonyl results in a conformational ring flip such that the bulky dicobalt-alkyne cluster moiety now occupies the favored equatorial site. However, when a 4-tert-butyl substituent is present, the coordinated alkynyl group retains its original axial or equatorial position. Complexation of trans-[diaxial]-1,4-bis(triphenylsilylethynyl)cyclohexane-1,4-diol brings about a chair-to-chair conformational inversion such that both cluster fragments now occupy equatorial sites. In contrast, cis-1,4-bis(triphenylsilylethynyl)cyclohexane-1,4-diol reacts with Co(2)(CO)(8) to yield the twist-boat conformer in which the two axial hydroxy substituents exhibit intra-molecular hydrogen bonding. Likewise, the corresponding reaction of cis-1,4-bis(trimethylsilylethynyl)cyclohexane-1,4-diol with Co(2)(CO)(8) leads to a twist-boat, but in this case, the molecules are linked through inter-molecular hydrogen bonds. Eight of these cobalt clusters have been characterized by X-ray crystallography, and the potential use of twist-boats in synthesis is discussed.
RESUMEN
The coordination of an additional [Cp(CO)2Mn] fragment to the alkyne linkage of an alkynylcarbene complex of the type Cp(CO)2Mn=C(R')C identical to CR" yields a highly fluxional molecule, in which the [eta 1-carbene] and [eta 2-alkyne] moieties are seen to exchange rapidly on the NMR time scale.