A novel class of glutathione peroxidase 1 (GPx1) inhibitors, namely tri‐ and tetracyclic pentathiepins, has been identified that is approximately 15 times more potent than the most active known GPx1 inhibitor, mercaptosuccinic acid. Enzyme kinetic studies with bovine erythrocyte GPx1 indicate that pentathiepins reversibly inhibit oxidation of the substrate glutathione (GSH). Moreover, no inhibition of superoxide dismutase, catalase, thioredoxin reductase or glutathione reductase was observed at concentrations that effectively inhibit GPx1. As well as potent enzyme inhibitory activity, the pentathiepins show strong anticancer activity in various human cancer cell lines, with IC₅₀ values in a low‐micromolar range. A representative tetracyclic pentathiepin causes the formation of reactive oxygen species in these cells, the fragmentation of nuclear DNA and induces apoptosis via the intrinsic pathway. Moreover, this pentathiepin leads to a rapid and strong loss of mitochondrial membrane potential in treated cancer cells. On the other hand, evidence for the induction of ferroptosis as a form of cell death was negative. These new findings show that pentathiepins possess interesting biological activities beyond those originally ascribed to these compounds.

Mo/W-containing formate dehydrogenases (FDH) catalyzed the reversible oxidation of formate to carbon dioxide at their molybdenum or tungsten active sites. While in the reaction of formate oxidation, the product is CO₂, which exits the active site via a hydrophobic channel; bicarbonate is formed as the first intermediate during the reaction at the active site. Other than what has been previously reported, bicarbonate is formed after an oxygen atom transfer reaction, transferring the oxygen from water to formate and a subsequent proton-coupled electron transfer or hydride transfer reaction involving the sulfido ligand as acceptor.

The synthesis and catalytic applications of the highly water‐soluble ligand 7‐phospha‐1,3,5‐triaza‐admantane butane sultonate (PTABS) has been described. The synthesized PTABS ligand along with palladium acetate exhibits excellent reactivity towards the amination reaction of 6‐chloro‐9‐(β‐D‐ribofuranosyl)‐9H‐purine at ambient temperature. This protocol offers an advantage over the previously published procedures for the amination of 6‐chloropurine nucleoside furnishing 6‐N‐substituted adenosine analogues. The validation of the present strategy has been demonstrated via synthesis of a uracil‐based, anti‐diabetic drug alogliptin. © 2018 by John Wiley & Sons, Inc.