Novel iron(III) complexes of sterically hindered 4N ligands: regioselectivity in biomimetic extradiol cleavage of catechols

Abstract

The iron(III) complexes of the 4N ligands 1,4-bis(2-pyridylmethyl)-1,4-diazepane (L1), 1,4-bis(6-methyl-2-pyridylmethyl)-1,4-diazepane (L2), and 1,4-bis(2-quinolylmethyl)-1,4-diazepane (L3) have been generated in situ in CH₃CN solution, characterized as [Fe(L1)Cl₂]⁺ 1, [Fe(L2)Cl₂]⁺ 2, and [Fe(L3)Cl₂]⁺ 3 by using ESI-MS, absorption and EPR spectral and electrochemical methods and studied as functional models for the extradiol cleaving catechol dioxygenase enzymes. The tetrachlorocatecholate (TCC^2-) adducts [Fe(L1)(TCC)](ClO₄) 1a, [Fe(L2)(TCC)](ClO₄) 2a, and [Fe(L3)(TCC)](ClO₄) 3a have been isolated and characterized by elemental analysis, absorption spectral and electrochemical methods. The molecular structure of [Fe(L1)(TCC)](ClO₄) 1a has been successfully determined by single crystal X-ray diffraction. The complex 1a possesses a distorted octahedral coordination geometry around iron(III). The two tertiary amine (Fe-N_amine, 2.245, 2.145 Å) and two pyridyl nitrogen (Fe-N_py, 2.104, 2.249 Å) atoms of the tetradentate 4N ligand are coordinated to iron(III) in a cis-β configuration, and the two catecholate oxygen atoms of TCC^2- occupy the remaining cis positions. The Fe-O_cat bond lengths (1.940, 1.967 Å) are slightly asymmetric and differ by 0.027 Å only. On adding catecholate anion to all the [Fe(L)Cl₂]⁺ complexes the linear tetradentate ligand rearranges itself to provide cis-coordination positions for bidentate coordination of the catechol. Upon adding 3,5-di-tert-butylcatechol (H₂DBC) pretreated with 1 equiv of Et₃N to 1-3, only one catecholate-to-iron(III) LMCT band (648-800 nm) is observed revealing the formation of [Fe(L)(HDBC)]²⁺ involving bidentate coordination of the monoanion HDBC^-. On the other hand, when H₂DBC pretreated with 2 equiv of Et₃N or 1 or 2 equiv of piperidine is added to 1-3, two intense catecholate-to-iron(III) LMCT bands appear suggesting the formation of [Fe(L)(DBC)]⁺ with bidentate coordination of DBC^2-. The appearance of the DBSQ/H₂DBC couple for [Fe(L)Cl₂]⁺ at positive potentials (-0.079 to 0.165 V) upon treatment with DBC^2- reveals that chelated DBC^2- in the former is stabilized toward oxidation more than the uncoordinated H₂DBC. It is remarkable that the [Fe(L)(HDBC)]²⁺ complexes elicit fast regioselective extradiol cleavage (34.6-85.5%) in the presence of O₂ unlike the iron(III) complexes of the analogous linear 4N ligands known so far to yield intradiol cleavage products exclusively. Also, the adduct [Fe(L2)(HDBC)]²⁺ shows a higher extradiol to intradiol cleavage product selectivity (E/I, 181:1) than the other adducts [Fe(L3)(HDBC)]²⁺ (E/I, 57:1) and [Fe(L1)(HDBC)]²⁺ (E/I, 9:1). It is proposed that the coordinated pyridyl nitrogen abstracts the proton from chelated HDBC^- in the substrate-bound complex and then gets displaced to facilitate O₂ attack on the iron(III) center to yield the extradiol cleavage product. In contrast, when the cleavage reaction is performed in the presence of a stronger base like piperidine or 2 equiv of Et₃N a faster intradiol cleavage is favored over extradiol cleavage suggesting the importance of bidentate coordination of DBC^2- in facilitating intradiol cleavage.