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 CH 3CN solution, characterized as [Fe(L1)Cl 2] (+) 1, [Fe(L2)Cl 2] (+) 2, and [Fe(L3)Cl 2] (+) 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)](ClO 4) 1a, [Fe(L2)(TCC)](ClO 4) 2a, and [Fe(L3)(TCC)](ClO 4) 3a have been isolated and characterized by elemental analysis, absorption spectral and electrochemical methods. The molecular structure of [Fe(L1)(TCC)](ClO 4) 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 A) and two pyridyl nitrogen (Fe-N py, 2.104, 2.249 A) atoms of the tetradentate 4N ligand are coordinated to iron(III) in a cis-beta 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 A) are slightly asymmetric and differ by 0.027 A only. On adding catecholate anion to all the [Fe(L)Cl 2] (+) 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 (H 2DBC) pretreated with 1 equiv of Et 3N 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 H 2DBC pretreated with 2 equiv of Et 3N 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/H 2DBC couple for [Fe(L)Cl 2] (+) 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 H 2DBC. It is remarkable that the [Fe(L)(HDBC)] (2+) complexes elicit fast regioselective extradiol cleavage (34.6-85.5%) in the presence of O 2 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 O 2 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 Et 3N a faster intradiol cleavage is favored over extradiol cleavage suggesting the importance of bidentate coordination of DBC (2-) in facilitating intradiol cleavage.