Enantiocontrol in the intermolecular cyclopropanation reaction catalyzed by dirhodium(II) complexes with ortho-metalated aryl phosphine ligands

(P) and (M) dirhodium(II) complexes with ortho-metalated aryl phosphines are assessed as chiral catalysts in the enantioselective cyclopropanation of styrenes by ethyl diazoacetate; enantioselectivities up to 91% and up to 87%, respectively, for cis- and trans-2-arylcyclopropanecarboxylates are observed.Barberis, Mario, [email protected] ; Lahuerta Peña, Pascual, [email protected] ; Perez Prieto, Julia, [email protected] ; Sanau Torrecilla, Mercedes, [email protected]

Enantio- and diastereocontrol in intermolecular cyclopropanation reaction of styrene catalyzed by dirhodium(II) complexes with bulky ortho-metalated aryl phosphines

Enantiomerically pure dirhodium(II) complexes with ortho-metalated p-substituted aryl phosphines have been shown to be enantio- and diastereoselective in the cyclopropanation of styrene by ethyl diazoacetate. Enantioselectivities up to 91% and diastereoselectivities up to 90% are observed for ethyl cis-2-phenylcyclopropanecarboxylate.Estevan Estevan, Francisco, [email protected] ; Lahuerta Peña, Pascual, [email protected] ; Lloret Fillol, Julio, [email protected] ; Sanau Torrecilla, Mercedes, [email protected] ; Ubeda Picot, M Angeles, [email protected] ; Vila Gomez, Jaume Llorenc, [email protected]

Heterometallic titanium–gold complexes inhibit renal cancer cells in vitro and in vivo

Following recent work on heterometallic titanocene–gold complexes as potential chemotherapeutics for renal cancer, we report here on the synthesis, characterization and stability studies of new titanocene complexes containing a methyl group and a carboxylate ligand (mba ¼ S–C6H4–COO) bound to gold(I)-phosphane fragments through a thiolate group [(h-C5H5)2TiMe(m-mba)Au(PR3)]. The compounds are more stable in physiological media than those previously reported and are highly cytotoxic against human cancer renal cell lines. We describe here preliminary mechanistic data involving studies on the interaction of selected compounds with plasmid (pBR322) DNA used as a model nucleic acid, and with selected protein kinases from a panel of 35 protein kinases having oncological interest. Preliminary mechanistic studies in Caki-1 renal cells indicate that the cytotoxic and anti-migration effects of the most active compound 5 [(h-C5H5)2TiMe(m-mba)Au(PPh3)] involve inhibition of thioredoxin reductase and loss of expression of protein kinases that drive cell migration (AKT, p90-RSK, and MAPKAPK3). The co-localization of both titanium and gold metals (1 : 1 ratio) in Caki-1 renal cells was demonstrated for 5 indicating the robustness of the heterometallic compound in vitro. Two compounds were selected for further in vivo studies on mice based on their selectivity in vitro against renal cancer cell lines when compared to non-tumorigenic human kidney cell lines (HEK-293T and RPTC) and the favourable preliminary toxicity profile in C57BL/6 mice. Evaluation of Caki-1 xenografts in NOD.CB17-Prkdc SCID/J mice showed an impressive tumor reduction (67%) after treatment for 28 days (3 mg per kg per every other day) with heterometallic compound 5 as compared with the previously described [(h-C5H5)2Ti {OC(O)-4-C6H4-P(Ph2)AuCl}2] 3 which was non-inhibitory. These findings indicate that structural modifications on the ligand scaffold affect the in vivo efficacy of this class of compounds