Models for extradiol cleaving catechol dioxygenases: Syntheses, structures, and reactivities of iron(II)-monoanionic catecholate complexes

Crystallographic and spectroscopic studies of extradiol cleaving catechol dioxygenases indicate that the enzyme-substrate complexes have both an iron(II) center and a monoanionic catecholate. Herein we report a series of iron(II)-monoanionic catecholate complexes, [(L)Fe^II(catH)](X) (1a, L = 6-Me₃-TPA (tris(6-methyl-2-pyridyl-methyl)amine), catH = CatH (1,2-catecholate monoanion); 1b, L = 6-Me₃-TPA, catH = DBCH (3,5-di-tert-butyl-1,2-catecholate monoanion); 1c, L = 6-Me₂-bpmcn (N, N′-dimethyl-N, N′-M-bis(6-methyl-2-pyridylmethyl)-trans-1,2-diaminocyclohexane), catH = CatH; 1d, L = 6-Me₂-bpmcn, catH = DBCH), that model such enzyme complexes. The crystal structure of [(6-Me₂-bpmcn)Fe^II(DBCH)]⁺ (1d) shows that the DBCH ligand binds to the iron asymmetrically as previously reported for 1b, with two distinct Fe-O bonds of 1.943(1) and 2.344(1) Å. Complexes 1 react with O₂ or NO to afford blue-purple iron(III)-catecholate dianion complexes, [(L)Fe^III(cat)⁺ (2). Interestingly, crystallographically characterized 2d, isolated from either reaction, has the N-methyl groups in a syn configuration, in contrast to the anti configuration of the precursor complex, so epimerization of the bound ligand must occur in the course of isolating 2d. This notion is supported by the fact that the UV-vis and EPR properties of in situ generated 2d(anti) differ from those of isolated 2d(syn). While the conversion of 1 to 2 in the presence of O₂ occurs without an obvious intermediate, that in the presence of NO proceeds via a metastable S = 3/2 [(L)Fe(catH)(NO)]⁺ adduct 3, which can only be observed spectroscopically but not isolated. Intermediates 3a and 3b subsequently disproportionate to afford two distinct complexes, [(6-Me₃-TPA)Fe^III(cat)]⁺ (2a and 2b) and [(6-Me₃-TPA)Fe(NO)₂]⁺ (4) in comparable yield, while 3d converts to 2d in 90% yield. Complexes 2b and anti-2d react further with O₂ over a 24 h period and afford a high yield of cleavage products. Product analysis shows that the products mainly derive from intradiol cleavage but with a small extent of extradiol cleavage (89:3% for 2b and 78:12% for anti-2d). The small amounts of the extradiol cleavage products observed may be due to the dissociation of an α-methyl substituted pyridyl arm, generating a complex with a tridentate ligand. Surprisingly, syn-2d does not react with O₂ over the course of 4 days. These results suggest that there are a number of factors that influence the mode and rate of cleavage of catechols coordinated to iron centers.