Enhancing Phosphate Diester Cleavage by a Zinc Complex through Controlling Nucleophile Coordination. Issue 19 (18th March 2015)

• Record Type: Journal Article
• Authors: Tirel, Emmanuel Y.; Williams, Nicholas H.
• Is Part Of: Chemistry. Volume 21:Issue 19(2015)
• Page Start: 7053
• Page End: 7056
• Publication Date: 2015-03-18
• Subjects: bioinorganic chemistry -- DNA cleavage -- enzyme models -- kinetics -- zinc; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201500619
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Metal‐ion complexes are the most effective artificial catalysts capable of cleaving phosphate diesters under mild aqueous conditions. A central strategy for making these complexes highly reactive has been to use ligand‐based alcohols that are coordinated to the ion, providing an ionised nucleophile under neutral conditions but at the expense of deactivating it. We have created a highly reactive Zn complex that is 350‐fold more reactive than an alcohol analogue by preventing the nucleophile binding to the metal ion. This strategy successfully delivers the benefits of efficient nucleophile delivery without strongly deactivating the metal ion Lewis acidity nor the oxyanion nucleophilicity. Varying the leaving group reveals that the transition state of the reaction is much further advanced than the reaction with hydroxide. Abstract : How to activate a nucleophile : Using an oxime as a ligand‐based nucleophile generates a Zn complex, which is the most effective at cleaving DNA‐like phosphodiesters reported to date. This nucleophile is held in close proximity to the substrate‐binding site, but the geometry prevents the nucleophile binding to the Zn ion and so stops their mutual deactivation (see scheme).