Hydroxyl Radical Generation and DNA Nuclease Activity: A Mechanistic Study Based on a Surface‐Immobilized Copper Thioether Clip‐Phen Derivative

Abstract

Coordination compounds of copper have been invoked as major actors in processes involving the reduction of molecular oxygen, mostly with the generation of radical species the assignment for which has, so far, not been fully addressed. In the present work, we have carried out studies in solution and on surfaces to gain insights into the nature of the radical oxygen species (ROS) generated by a copper(II) coordination compound containing a thioether clip-phen derivative, 1,3-bis(1,10-phenanthrolin-2-yloxy)-N-(4-(methylthio)benzylidene)propan-2-amine (2CP-Bz-SMe), enabling its adsorption/immobilization to gold surfaces. Whereas surface plasmon resonance (SPR) and electrochemistry of the adsorbed complex indicated the formation of a dimeric Cu(I) intermediate containing molecular oxygen as a bridging ligand, scanning electrochemical microscopy (SECM) and nuclease assays pointed to the generation of a ROS species. Electron paramagnetic resonance (EPR) data reinforced such conclusions, indicating that radical production was dependent on the amount of oxygen and H2 O2 , thus pointing to a mechanism involving a Fenton-like reaction that results in the production of OH(.) .

Cu2+selective chelators relieve copper-induced oxidative stressin vivo

“…This is an important criterion for Cu chelation targeted toward assuaging Cu-induced oxidative stress since there are multiple examples of chelators that can bind to Cu 2+ and promote the production of hydroxyl radicals. 52 , 74 – 77 Hence, our chelators can be potentially useful for treating Cu ion overload associated disorders.…”

Is IQG-607 a Potential Metallodrug or Metallopro-Drug With a Defined Molecular Target in Mycobacterium tuberculosis?

“…The modulation of reactivity promoted by metals has also been explored in the design of donors of either nitric oxide or CO, where ruthenium-based compounds have stood out (Tfouni et al, 2012 ; Wright and Wright, 2016 ). Light and electron-transfer triggered processes have been used to generate cytotoxic metal-based compounds with production of reactive oxygen species (ROS), release of NO or CO, and hypoxia-responsive agents (Tfouni et al, 2010 ; Li et al, 2015 ; Pires et al, 2016 ; Romo et al, 2016 ; Sousa et al, 2016 ; Abreu et al, 2017 ; de Sousa et al, 2017 ). Cobalt(III) complexes, for example, have been used to release drugs or agents for imaging under hypoxia conditions, which enables reduction of Co(III) to Co(II).…”

“…The latter redox state is labile promoting the release of the active ligand that might be used to target tumors (Graf and Lippard, 2012 ; Pires et al, 2016 ). Catalytic-based metallodrugs have also been described, including intracellular reduction of copper(II) complexes that can generate ROS cytotoxic species (Romo et al, 2016 ; Yu and Cowan, 2017 ). These compounds have been reported to be active against bacteria and cancer cells (Yu and Cowan, 2017 ).…”

Neue Mitglieder und auswärtige Mitglieder der National Academy of Sciences

“…Abruña erforscht Hochleistungsmaterialien für Batterien und Brennstoffzellen, und er entwickelt Operando‐Untersuchungsmethoden für elektrochemische Grenzflächen. Er berichtete in der Angewandten Chemie über dünne poröse Polymerfilme für die elektrische Energiespeicherung und in Chemistry—A European Journal über die Bildung von Sauerstoffradikalen durch eine Kupfer(II)‐Koordinationsverbindung …”