2D and 3D anticancer properties of C2-functionalised glucosamine-Pt (IV) prodrugs based on cisplatin scaffold.

A series of C2-functionalied Pt (IV) glycoconjugates based on glucosamine have been synthesised, characterised and tested as anticancer agents on a series of different 2D and 3D cancer cell lines. The carbohydrate will act as a targeted delivery system to improve the selectivity, exploiting the Warburg Effect and the GLUTs receptors that are overexpressed in most of the cancer cells. The hydroxyl at C2 of the carbohydrates does not participate in hydrogen bonding with the GLUTs receptors, making C2 an attractive position for drug conjugation as seen in literature.

Iridium(I) complexes with bidentate NHC ligands as catalysts for dehydrogenative directed C-H silylation.

A series of (NHC)(cod)Ir(I) complexes bearing NHC-carboxylate ligands were efficiently synthesized and fully characterized. Their solid-state structures confirmed the bidentate coordination mode of these LX-type NHC ligands. These unprecedented iridium(I) complexes demonstrated efficient catalytic activities in dehydrogenative directed C-H silylation of arenes, and allowed for excellent -selectivity control with aromatic silylating agents.

Alchemical Design of Pharmacological Chaperones with Higher Affinity for Phenylalanine Hydroxylase.

Phenylketonuria (PKU) is a rare metabolic disease caused by variations in a human gene, PAH, encoding phenylalanine hydroxylase (PAH), and the enzyme converting the essential amino acid phenylalanine into tyrosine. Many PKU-causing variations compromise the conformational stability of the encoded enzyme, decreasing or abolishing its catalytic activity, and leading to an elevated concentration of phenylalanine in the blood, which is neurotoxic. Several therapeutic approaches have been developed to treat the more severe manifestations of the disorder, but they are either not entirely effective or difficult to adhere to throughout life.

Rhodium-NHC-Catalyzed gem-Specific O-Selective Hydropyridonation of Terminal Alkynes.

The dinuclear complex [Rh(μ-Cl)(η -coe)(IPr)] is an efficient catalyst for the O-selective Markovnikov-type addition of 2-pyridones to terminal alkynes. DFT calculations support a hydride-free pathway entailing intramolecular oxidative protonation of a π-alkyne by a κ N-hydroxypyridine ligand. Subsequent O-nucleophilic attack on a metallacyclopropene species affords an O-alkenyl-2-oxypyridine chelate rhodium intermediate as the catalyst resting state.

Rhodium(I)-NHC Complexes Bearing Bidentate Bis-Heteroatomic Acidato Ligands as gem-Selective Catalysts for Alkyne Dimerization.

A series of Rh(κ -BHetA)(η -coe)(IPr) complexes bearing 1,3-bis-hetereoatomic acidato ligands (BHetA) including carboxylato (O,O), thioacetato (O,S), amidato (O,N), thioamidato (N,S), and amidinato (N,N), have been prepared by reaction of the dinuclear precursor [Rh(μ-Cl)(IPr)(η -coe)] with the corresponding anionic BHetA species. The Rh -NHC-BHetA compounds catalyze the dimerization of aryl alkynes, showing excellent selectivity for the head-to-tail enynes. Among them, the acetanilidato-based catalyst has shown an outstanding catalytic performance reaching unprecedented TOF levels of 2500 h with complete selectivity for the gem-isomer.