Functional models for enzyme–substrate adducts of catechol dioxygenase enzymes: The Lewis basicity of facially coordinating tridentate phenolate ligands tunes the rate of dioxygenation and product selectivity

A few iron(III) 3,5-di-tert-butylcatecholate (DBC2−) adducts of the type [Fe(L)(DBC)(CH3OH)], where L is a tridentate substituted monophenolate ligand such as 2-((N-benzylpyrid-2-ylmethylamino)methyl)phenol (H(L1)), 2-((N-benzylpyrid-2-ylmethylamino)-methyl)-4,6-dimethylphenol (H(L2)), 2-((N-benzylpyrid-2-ylmethylamino)methyl)-4,6-di-tert-butylphenol (H(L3)) and 2-((N-benzylpyrid-2-ylmethylamino)methyl)-4-nitrophenol (H(L4)), have been isolated and characterized by elemental and ESI-MS analysis. The spectral and electrochemical properties and dioxygenase activities of the adducts have been studied in methanol solution. Upon varying the substituents on the phenolate ring from electron-releasing to electron-withdrawing, the redox potential of DBSQ/DBC2− couple is shifted to a more positive value indicating an increase in covalency of iron(III)–catecholate bonds. All the complexes elicit cleavage of DBC2− using molecular oxygen to afford both intra- (I) and extradiol (E) cleavage products with the product selectivity (E/I) varying in the range 0.3–1.9. Interestingly, the incorporation of electron-withdrawing substituents facilitates the regioselective extradiol cleavage of catechol while that of electron-releasing substituents facilitate the regioselective intradiol cleavage.

Graphical abstractIncorporation of the electron-withdrawing substituent –NO2 group on the phenolate ring of tridentate ligand in the iron(III)–catecholate adduct facilitates regioselective extradiol cleavage and enhances reaction rate. On the other hand, incorporation of electron-releasing substituents like t-butyl and methyl groups facilitates regioselective intradiol cleavage of catechol.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthetic models for enzyme-substrate adduct of protocatechuate 3,4-dioxygenase enzyme isolated. ► The incorporation of electron-withdrawing substituents facilitates extradiol cleavage pathway. ► The incorporation of electron-releasing substituents facilitate intradiol cleavage pathway.