Novel Iron(III) Complexes of Tripodal and Linear Tetradentate Bis(phenolate) Ligands:  Close Relevance to Intradiol-Cleaving Catechol Dioxygenases

Abstract

Four new iron(III) complexes of the bis(phenolate) ligands N,N-dimethyl-N',N'-bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine [H2(L1)], N,N-dimethyl-N',N'-bis(2-hydroxy-4-nitrobenzyl)ethylenediamine [H2(L2)], N,N'-dimethyl-N,N'-bis(2-hydroxy-3,5-dimethylbenzyl)ethylenediamine [H2(L3)], and N,N'-dimethyl-N,N'-bis(2-hydroxy-4-nitrobenzyl)ethylenediamine [H2(L4)] have been isolated and studied as structural and functional models for the intradiol-cleaving catechol 1,2-dioxygenases (CTD). The complexes [Fe(L1)Cl] (1), [Fe(L2)(H2O)Cl] (2), [Fe(L3)Cl] (3), and [Fe(L4)(H2O)Cl] (4) have been characterized using absorption spectral and electrochemical techniques. The single-crystal X-ray structures of the ligand H2(L1) and the complexes 1 and 2 have been successfully determined. The tripodal ligand H2(L1) containing a N2O2 donor set represents the metal-binding region of the iron proteins. Complex 1 contains an FeN2O2Cl chromophore with a novel trigonal bipyramidal coordination geometry. While two phenolate oxygens and an amine nitrogen constitute the trigonal plane, the other amine nitrogen and chloride ion are located in the axial positions. In contrast, 2 exhibits a rhombically distorted octahedral coordination geometry for the FeN2O3Cl chromophore. Two phenolate oxygen atoms, an amine nitrogen atom, and a water molecule are located on the corners of a square plane with the axial positions being occupied by the other nitrogen atom and chloride ion. The interaction of the complexes with a few monodentate bases and phenolates and differently substituted catechols have been investigated using absorption spectral and electrochemical methods. The effect of substituents on the phenolate rings on the electronic spectral features and FeIII/FeII redox potentials of the complexes are discussed. The interaction of the complexes with catecholate anions reveals changes in the phenolate to iron(III) charge-transfer band and also the appearance of a low-energy catecholate to iron(III) charge-transfer band similar to catechol dioxygenase-substrate complexes. The redox behavior of the 1:1 adducts of the complexes with 3,5-di-tert-butylcatechol (H2DBC) has been also studied. The reactivities of the present complexes with H2DBC have been studied and illustrated. Interestingly, only 2 and 4 catalyze the intradiol-cleavage of H2DBC, the rate of oxygenation being much faster for 4. Also 2, but not 4, yields an extradiol cleavage product. The reactivity of the complexes could be illustrated not on the basis of the Lewis acidity of the complexes alone but by assuming that the product release is the rate-determining phase of the catalytic reaction.

Fine‐Tuning of Catalytic Properties of Catechol 1,2‐Dioxygenase by Active Site Tailoring

“…[44] Also several works were published on functional mimics of both intradiol and extradiol-cleaving enzymes. [45][46][47] These structure-function studies highlight the great plasticity of the enzyme active site and make these enzymes particularly promising for protein-engineering studies that aim both at a more precise characterisation of the catalytic properties and at reshaping for technological applicative purposes. To date, to our knowledge, no protein-engineering approach has been performed on catechol 1,2-dioxygenases.…”

Iron(III) Contrast Agent Candidates for MRI: a Survey of the Structure–Effect Relationship in the Last 15 ­Years of Studies

“…The most threatening consequence of such iron behavior is the possibility of generating radicals: for example, · OH [generated directly by Fe II species: Equation (6)] has a lifetime of 10 -9 s; therefore its tremendous activity is directly associated with the potential for serious deleterious effects. The assumption of the high redox activity of Fe 3+ complexes leading to the formation of radicals was based (as supposed) on the following well-established hypotheses: (1) Haber-Weiss process [see Equations (5) and (6)] found for iron ions [38] and also shown for the [Fe(EDTA)] -complex in vitro, [39,40] (2) direct coordination of water molecules even in polydentate but rigid Fe 3+ chelates (e.g., the above-mentioned EDTA, and also other N,O-chelates), [41] and (3) efficient redox activity of many iron enzymes leading to the transformation of radicals, including potentially dangerous reactive oxygen species (ROS). [42] However, these issues have been elaborated and several studies have shown that the direct coordination of oxygen does not necessarily have to lead to serious deleterious effects.…”

The Synthesis, Structures and Characterisation of New Mixed‐Ligand Manganese and Iron Complexes with Tripodal, Tetradentate Ligands

“…In the complexes 3 and 10 this absorption is obscured by very intense π-π* charge-transfer transitions, due to the phenyl rings of the dbm ligand for 3 and the nitro groups on the dnpppy ligand for 10. [7,39] All manganese complexes show an absorption at around 230-260 nm, which is attributed to a π-π* transition originating from the (substituted) pppy ligand.…”