Iron(III) complexes of sterically hindered tetradentate monophenolate ligands as functional models for catechol 1,2-dioxygenases: the role of ligand stereoelectronic properties

Abstract

The iron(III) complexes of the monophenolate ligands 2-(bis(pyrid-2-ylmethyl)aminomethyl)-4-nitrophenol [H(L1)], N,N-dimethyl-N'-(pyrid-2-ylmethyl)-N'-(2-hydroxy-4-nitrobenzyl)ethylenediamine [H(L2)], N,N-dimethyl-N'-(6-methyl-pyrid-2-ylmethyl)-N'-(2-hydroxy-4-nitrobenzyl)ethylenediamine [H(L3)], and N,N-dimethyl-N'-(1-methylimidazole-2-ylmethyl)-N'-(2-hydroxy-4-nitrobenzyl)ethylenediamine [H(L4)] have been obtained and studied as structural and functional models for the intradiol-cleaving catechol dioxygenase enzymes. The complexes [Fe(L1)Cl₂]·CH₃CN (1), [Fe(L2)Cl₂] (2), [Fe(L3)Cl₂] (3), and [Fe(L4)Cl₂] (4) have been characterized using absorption spectral and electrochemical methods. The single crystal X-ray crystal structures of 1 and 2 have been successfully determined. Both the complexes possess a rhombically distorted octahedral coordination geometry for the FeN₃OCl₂ chromophore. In 2, the phenolate oxygen, the pyridine nitrogen, an amine nitrogen, and a chloride ion are located on the corners of a square plane with the nitrogen atom of a -NMe₂ group and the other chloride ion occupying the axial positions. In 1, also the equatorial plane is constituted by the phenolate oxygen, the pyridine nitrogen, an amine nitrogen atom, and a chloride ion; however, the axial positions are occupied by the second pyridine nitrogen and the second chloride ion. Interestingly, the Fe-O-C angle of 136.1° observed for 2 is higher than that (128.5° ) in 1; however, the Fe-O(phenolate) bond distances in both the complexes are the same (1.929 Å). This illustrates the importance of the nearby sterically demanding coordinated -NMe₂ group and implies similar stereochemical constraints from the other ligated amino acid moieties in the 3,4-PCD enzymes, the enzyme activity of which is traced to the difference in the equatorial and axial Fe-O(tyrosinate) bonds (Fe-O-C, 133° , 148° ). The nature of heterocyclic rings of the ligands and the methyl substituents on them regulates the electronic spectral features, Fe^III/Fe^II redox potentials, and catechol cleavage activity of the complexes. Upon interacting the complexes with catecholate anions, two catecholate to iron(III) charge transfer bands appear, and the low energy band is similar to that of catechol dioxygenase-substrate complex. Complexes 1 and 3 fail to catalyze the oxidative intradiol cleavage of 3,5-di-tert-butylcatechol (H₂DBC). However, interestingly, the replacement of pyridine pendant in 1 by the -NMe₂ group to obtain 2 restores the dioxygenase activity, which is consistent with its higher Fe-O-C bond angle. Remarkably, the more basic N-methylimidazole ring in 4 facilitates the rate-determining product releasing phase of the catalytic reaction, leading to enhancement in reaction rate and efficient conversion (77.1%) of the substrate to intradiol cleavage products as well. All these observations provide support to the novel substrate activation mechanism proposed for the intradiol-cleavage pathway.