Detoxifying Polyhalogenated Catechols through a Copper‐Chelating Agent by Forming Stable and Redox‐Inactive Hydrogen‐Bonded Complexes with an Unusual Perpendicular Structure

Abstract

The use of selective metal chelating agents with preference for binding of a specific metal ion to investigate its biological role is becoming increasingly common. We found recently that a well-known copper-specific chelator 2,9-dimethyl-1,10-phenanthroline (2,9-Me 2 OP) could completely inhibit the synergistic toxicity induced by tetrachlorocatechol (TCC) and sodium azide (NaN 3 ). However, its underlying molecular mechanism is still not clear. Here, we show that the protection by 2,9-Me 2 OP is not due to its classic copper-chelating property, but rather due to formation of a multiple hydrogen-bonded complex between 2,9-Me 2 OP and TCC, featuring an unusual perpendicular arrangement of the two binding partners. The two methyl groups at the 2,9 positions in 2,9-Me 2 OP were found to be critical to stabilize the 2,9-Me 2 OP/TCC complex due to steric hindrance, and therefore completely prevents the generation of the reactive and toxic semiquinone radicals by TCC/NaN 3 . This represents the first report showing that an unexpected new protective mode of action for the copper "specific" chelating agent 2,9-Me 2 OP by using its steric hindrance effect of the two CH 3 groups not only to chelate copper, but also to "chelate" a catechol through multiple H-bonding. These findings may have broad biological implications for future research of this widely used copper-chelating agent and the ubiquitous catecholic compounds.

Binary Co‐Crystals of Quercetin: Synthesis, Structure, and Spectroscopic Characterization

“…The crystal network of some molecular complexes contains solvent molecules. As follows from the literature review 49 co‐crystals or solvated QUE co‐crystals have been studied so far [11,12,19–34] . In the described co‐crystal structures, quercetin and co‐former are linked by the hydrogen bonds of different types: O−H…N, O−H…O, N−H…O, O−H…S, N−H + …O − (Table S1).…”

“…[18] Intensive research on co-crystallization of QUE with various organic co-formers has been carried out to improve its physicochemical properties and pharmacokinetic profiles. [11,12,[19][20][21][22][23][24][25][26][27][28][29][30][31] The molecules of the co-formers contained amino, carbonyl, carboxyl, amide or heterocyclic groups (with nitrogen or sulphur atoms). The crystal network of some molecular complexes contains solvent molecules.…”

“…As follows from the literature review 49 co-crystals or solvated QUE cocrystals have been studied so far. [11,12,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] In the described cocrystal structures, quercetin and co-former are linked by the hydrogen bonds of different types: OÀ H…N, OÀ H…O, NÀ H…O, OÀ H…S, NÀ H + …O À (Table S1). Moreover, common motifs for the intramolecular interactions of QUE are observed.…”

Mechanistic Study on Oxidative DNA Damage and Modifications by Haloquinoid Carcinogenic Intermediates and Disinfection Byproducts

“…During our systematic studies on synergism of biochemical and toxicological interactions between organic environmetal pollutants (especially chlorophenols and their quinoid metabolites) and inorganic compounds (especially redox-active transition metals such as copper and iron, and H 2 O 2 ), − we found that reactive hydroxyl/alkoxyl radicals can be produced by XQs and hydroperoxides through the novel pathway independent of transition-metal ions, which was proposed through a new-type nucleophilic substitution followed by homolytical decomposition reaction mechanism ,− (Scheme ). Intriguingly, except for the traditional hydroxyl/alkoxyl radicals, several unprecedented carbon-centered quinone ketoxy radicals and oxygen-centered quinone-enoxy radicals were also measured and identified from the XQs/hydropeoxide system. , …”