Aza‐ortho‐Quinone Methide and Its Conjugated Acid: Reactivity, Stability and Acidity

Abstract

Aza‐o‐quinone methides and their conjugated acids are reactive drug metabolites that might react with nucleophilic sites of DNAs and proteins to cause cancer or immune responses, and their reactivity with water is the key information to judge if these metabolites are harmful in living systems. For the first time, aza‐o‐quinone methide (1) and its conjugated acid (2) are observed by laser flash photolysis, and their reactivity, stability and acidity in water are determined.

High throughput selection of organic cathode materials

“…The highly reactive aza‐quinone methides 88 replace both carbonyl groups, one with a methide group and the other with an imine group. Aza quinone methide 18 yield reduction potentials 0.77 V lower than the quinone diimine 14 .…”

One-pot synthesis of dihydroquinolones by sequential reactions ofo-aminobenzyl alcohol derivatives with Meldrum's acids

“…Experiments to detect the key intermediate 19 with ESI-MS failed, most probably because the reaction is too fast. 22…”

“…Experiments to detect the key intermediate 19 with ESI-MS failed, most probably because the reaction is too fast. 22 Then to prove our hypothesis, we treated 4f with the ethoxyethene 20 (10 equiv.) in the presence of K 2 CO 3 (3 equiv.)…”

Asymmetric Catalytic Transformations of Aza‐ortho‐ and Aza‐para‐Quinone Methides

“…In the organism, cytochromes P450 and peroxidases catalyze the formation of these highly electrophilic species, which either tend to form covalent bonds with nucleophilic sites of the proteins and DNA in cells causing cytotoxicity, immunotoxicity, and carcinogenesis [1] or undergo its deactivation by hydration in water or reaction with glutathione. [2] Many efforts have been made in recent years in order to avoid the formation of these reactive molecules. Recently, a deep learning approach has been developed in order to predict its formation from different drugs, such as acetoamidophen or lumiracoxib.…”

“…Quinone species, such as quinone‐imines, quinone methides (QM), and aza‐quinone methides (aza‐QM), comprise over the 40 % of the reactive metabolites. In the organism, cytochromes P450 and peroxidases catalyze the formation of these highly electrophilic species, which either tend to form covalent bonds with nucleophilic sites of the proteins and DNA in cells causing cytotoxicity, immunotoxicity, and carcinogenesis [1] or undergo its deactivation by hydration in water or reaction with glutathione [2] . Many efforts have been made in recent years in order to avoid the formation of these reactive molecules.…”