John R. Hagadorn

A Bulky Benzoate Ligand for Modeling the Carboxylate-Rich Active Sites of Non-Heme Diiron Enzymes

John R. Hagadorn, Lawrence Que, Jr.,* and William B. Tolman* Department of Chemistry and Center for Metals in Biocatalysis, Uni Versity of Minnesota 207 Pleasant St. SE, Minneapolis, Minnesota 55455 Recei Ved September 18, 1998 A growing class of biologically important catalysts are the dioxygen-activating non-heme diiron enzymes, noteworthy members of which include methane monooxygenase (MMO), ribonucleotide reductase (RNR), and stearoyl-ACP ∆9-desaturase (∆9D).1 Carboxylate ligation to the diiron active site of these enzymes is a common feature that allows for tremendous structural flexibility during catalysis (via carboxylate shifts) 2 and helps stabilize the high oxidation states proposed for the intermediates involved in the various reaction cycles. Previous synthetic routes to diiron models of the biological centers have used polydentate N-donors with simple unhindered carboxylates 1b,f or semirigid linked derivatives (cf. the xylyl-bridged ligand derived from Kemp’s triacid). 3 We have begun to pursue an alternative strategy (albeit one with precedence in the organometallic chemistry literature)4 involving the use of extreme steric hindrance about the carboxylate ligand in order to control metal complex nuclearity, to stabilize biorelevant dioxygen adducts and derived intermediates, and to mimic the protein scaffold that encapsulates the metalloprotein active site. Here we report a new, very bulky benzoate ligand 5 that has enabled the preparation of coordinatively unsaturated monoand dinuclear iron(II) complexes, the latter of which accurately mimics the structural characteristics of the reduced forms of∆9D6 and RNR. 7 Additionally, studies of the reactivity of this complex with dioxygen have revealed the generation of a room-temperature stable purple species which spectroscopic data suggest is a ( μ-peroxo)diiron(III) complex. The bulky carboxylate 2,6-dimesitylbenzoate (Mes 2ArCO2, Scheme 1) was prepared from 2,6-Mes 2C6H3I (Mes ) 2,4,6trimethylphenyl) by lithiation9 with BuLi followed by reaction with dry CO2 in Et2O. The product was isolated in 82% yield as the Et2O adduct [(Mes 2ArCO2)Li(Et2O)]2 and characterized fully, including by X-ray crystallography (Figure S1 and S2). 10,11 The extreme steric bulk of the ligand derived from the enforcement of an orthogonal relationship between the Mes rings and the benzoate aryl unit results in a dimeric structure distinct from the polymeric topologies typically adopted by smaller carboxylates. 12

Complexation-mediated crystallization

Crown ether complexation solubilizes organic and inorganic salts in nonpolar media. Induction of crystallization from such solutions can result in crystallization of the free salt rather than the complex. This affords the opportunity to examine solvent effects on the crystallization of salts and other polar materials, leading to the modification of crystal shape and lattice. This approach, which we term complexation-mediated crystallization, has been applied to the crystallization of simple organic salts and to the formation of metal sulfides. The resulting crystal morphologies and structures are presented, as are the structures of an unusual potassium complex of 18-crown-6 and crown ether complexes of lead (11) acetate, hexaaquozinc(II), and aquo(trichloro)zinc(II).

Dicopper(I,I) and delocalized mixed-valent dicopper(I,II) complexes of a sterically hindered carboxylate ligand

Admixture of the lithium salt of the bulky ligand 2,6-dimesitylbenzoate [ArCO2]− with [Cu(CH3CN)4]O3SCF3 yielded the dicopper(I,I) complex [(ArCO2)2Cu2(THF)2)] (1), which upon oxidation with AgX (X = SbF6− or ClO4−) in THF afforded the mixed-valent complexes [(ArCO2)2Cu2(THF)2]SbF6 (2) and [(ArCO2)2Cu2(THF)3]ClO4 (3), respectively. Fully delocalized mixed-valent (Cu1.5Cu1.5) formulations for 2 and 3 were determined on the basis of X-ray crystallography and UV-vis, resonance Raman, 1H NMR, and EPR spectroscopy. Notably, solvent dependent UV-vis spectra suggest that THF and/or counter ion coordination influence the intermetal bonding interactions in the mixed-valent cores.