Models for Extradiol Cleaving Catechol Dioxygenases:  Syntheses, Structures, and Reactivities of Iron(II)−Monoanionic Catecholate Complexes

Abstract

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-Me(3)-TPA (tris(6-methyl-2-pyridylmethyl)amine), catH = CatH (1,2-catecholate monoanion); 1b, L = 6-Me(3)-TPA, catH = DBCH (3,5-di-tert-butyl-1,2-catecholate monoanion); 1c, L = 6-Me(2)-bpmcn (N,N'-dimethyl-N,N'-bis(6-methyl-2-pyridylmethyl)-trans-1,2-diaminocyclohexane), catH = CatH; 1d, L = 6-Me(2)-bpmcn, catH = DBCH), that model such enzyme complexes. The crystal structure of [(6-Me(2)-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) A. Complexes 1 react with O(2) 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 O(2) 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-Me(3)-TPA)Fe(III)(cat)](+) (2a and 2b) and [(6-Me(3)-TPA)Fe(NO)(2)](+) (4) in comparable yield, while 3d converts to 2d in 90% yield. Complexes 2b and anti-2d react further with O(2) 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 alpha-methyl substituted pyridyl arm, generating a complex with a tridentate ligand. Surprisingly, syn-2d does not react with O(2) 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.

Crystallographic Comparison of Manganese- and Iron-Dependent Homoprotocatechuate 2,3-Dioxygenases

“…Despite a common peroxo intermediate structure, the two enzyme classes differ in the type of metal center to which the peroxo intermediate is co (34,36,43). It has also been suggested that the precise stereochemistry of the metal-peroxo-substrate unit determines the sites of cleavage (13).…”

Direct inhibition by nitric oxide of the transcriptional ferric uptake regulation protein via nitrosylation of the iron

“…UV-visible spectra (not shown) revealed three bands at 310, 365, and 400 nm, characteristic of charge-transfer bands observed with small NO-iron complexes (35)(36)(37)(38). The appearance of these bands grew in parallel with the increase of the EPR signal intensity.…”

“…The addition of NO gas to an anaerobic solution of FeFur resulted in immediate change from colorless to yellow-green, associated to the appearance of absorption bands in the UV-visible spectra as well as a g ϭ 2.03 EPR signal. Both features are characteristics of NO-iron complexes (34)(35)(36)(37)(38). The rate of NO complex formation was controlled by the decomposition of DEANO (t 1/2 ϭ 15 min at 20°C, pH 7.5).…”

The Coordination Chemistry of FeCl3 and FeCl2 to Bis[2‐(2,3‐dihydroxyphenyl)‐6‐pyridylmethyl](2‐pyridylmethyl)amine: Access to a Diiron(III) Compound with an Unusual Pentagonal‐Bipyramidal/Square‐Pyramidal Environment

“…This coordination mode is now well established in the chemistry of substituted TPA ligands and obviously reflects a gain in stability with respect to a more sterically hindered environment. [12,24,30] The 1 H NMR spectra of the FeCl 3 complexes generally display broad and unresolved signals in the paramagnetic region. [24,25] Complex 1, with an almost silent trace, is no exception to this rule.…”

“…[2,20,21,30] An iron(ii)-TPA complex in which a thiolate is coordinated to the metal has been found to react rapidly with dioxygen. [32] The redox potential for this complex is not available, but as it is a cationic species the value is likely to be positive.…”