Role of Fe(IV)-oxo intermediates in stoichiometric and catalytic oxidations mediated by iron pyridine-azamacrocycles.

An iron(II) complex with a pyridine-containing 14-membered macrocyclic (PyMAC) ligand L1 (L1 = 2,7,12-trimethyl-3,7,11,17-tetra-azabicyclo[11.3.1]heptadeca-1(17),13,15-triene), 1, was prepared and characterized. Complex 1 contains low-spin iron(II) in a pseudo-octahedral geometry as determined by X-ray crystallography. Magnetic susceptibility measurements (298 K, Evans method) and Mössbauer spectroscopy (90 K, δ = 0.50(2) mm/s, ΔE(Q) = 0.78(2) mm/s) confirmed that the low-spin configuration of Fe(II) is retained in liquid and frozen acetonitrile solutions. Cyclic voltammetry revealed a reversible one-electron oxidation/reduction of the iron center in 1, with E(1/2)(Fe(III)/Fe(II)) = 0.49 V vs Fc(+)/Fc, a value very similar to the half-wave potentials of related macrocyclic complexes. Complex 1 catalyzed the epoxidation of cyclooctene and other olefins with H(2)O(2). Low-temperature stopped-flow kinetic studies demonstrated the formation of an iron(IV)-oxo intermediate in the reaction of 1 with H(2)O(2) and concomitant partial ligand oxidation. A soluble iodine(V) oxidant, isopropyl 2-iodoxybenzoate, was found to be an excellent oxygen atom donor for generating Fe(IV)-oxo intermediates for additional spectroscopic (UV-vis in CH(3)CN: λ(max) = 705 nm, ε ≈ 240 M(-1) cm(-1); Mössbauer: δ = 0.03(2) mm/s, ΔE(Q) = 2.00(2) mm/s) and kinetic studies. The electrophilic character of the (L1)Fe(IV)═O intermediate was established in rapid (k(2) = 26.5 M(-1) s(-1) for oxidation of PPh(3) at 0 °C), associative (ΔH(‡) = 53 kJ/mol, ΔS(‡) = -25 J/K mol) oxidation of substituted triarylphosphines (electron-donating substituents increased the reaction rate, with a negative value of Hammet's parameter ρ = -1.05). Similar double-mixing kinetic experiments demonstrated somewhat slower (k(2) = 0.17 M(-1) s(-1) at 0 °C), clean, second-order oxidation of cyclooctene into epoxide with preformed (L1)Fe(IV)═O that could be generated from (L1)Fe(II) and H(2)O(2) or isopropyl 2-iodoxybenzoate. Independently determined rates of ferryl(IV) formation and its subsequent reaction with cyclooctene confirmed that the Fe(IV)-oxo species, (L1)Fe(IV)═O, is a kinetically competent intermediate for cyclooctene epoxidation with H(2)O(2) at room temperature. Partial ligand oxidation of (L1)Fe(IV)═O occurs over time in oxidative media, reducing the oxidizing ability of the ferryl species; the macrocyclic nature of the ligand is retained, resulting in ferryl(IV) complexes with Schiff base PyMACs. NH-groups of the PyMAC ligand assist the oxygen atom transfer from ferryl(IV) intermediates to olefin substrates.

Current challenges of modeling diiron enzyme active sites for dioxygen activation by biomimetic synthetic complexes.

This tutorial review describes recent progress in modeling the active sites of carboxylate-rich non-heme diiron enzymes that activate dioxygen to carry out several key reactions in Nature. The chemistry of soluble methane monooxygenase, which catalyzes the selective oxidation of methane to methanol, is of particular interest for (bio)technological applications. Novel synthetic diiron complexes that mimic structural, and, to a lesser extent, functional features of these diiron enzymes are discussed. The chemistry of the enzymes is also briefly summarized. A particular focus of this review is on models that mimic characteristics of the diiron systems that were previously not emphasized, including systems that contain (i) aqua ligands, (ii) different substrates tethered to the ligand framework, (iii) dendrimers attached to carboxylates to mimic the protein environment, (iv) two N-donors in a syn-orientation with respect to the iron-iron vector, and (v) a N-rich ligand environment capable of accessing oxygenated high-valent diiron intermediates.

Electronic structure of a paramagnetic {MNO}6 complex: MnNO 5,5-tropocoronand.

Using density functional theory (OLYP/STO-TZP) calculations, we have investigated the electronic structure of [Mn(5,5-tropocoronand)(NO)], a rare paramagnetic {MNO}(6) complex. Experimental methods, including magnetic susceptibility measurements and high-field electron paramagnetic resonance spectroscopy, have not provided an unambiguous spin state assignment for this complex. In other respects, however, the compound was fully characterized, including by means of single-crystal X-ray structure determination. The optimized S = 1 OLYP geometry reproduced all key aspects of the trigonal-bipyramidal molecular structure, including a short Mn-N(O) distance (approximately 1.7 A) and an essentially linear MnNO angle. In contrast, the S = 0 and S = 2 optimized structures disagreed with the crystal structure in critical respects. Moreover, three different exchange-correlation functionals (OLYP, B3LYP, and B3LYP*) indicated an S = 1 ground state by a clear margin of energy. An examination of the Kohn-Sham MOs of this state indicated a primarily d(xz)(2)d(yz)(2)d(xy)(1)d(x(2)-z(2))(1) electronic configuration, where the z axis is identified with the nearly linear MnNO axis. The d(y(2)) orbital is formally unoccupied in this state, interacting, as it does, head-on with two tropocoronand nitrogens lying along the y axis, the pseudo-3-fold axis of the trigonal bipyramid. The doubly occupied d(xz) and d(yz) orbitals are in actuality d(pi)(Fe)-pi*(NO)-based pi-bonding molecular orbitals, the alpha and beta "components" of which are significantly offset spatially. This offset results in excess minority spin density on the NO unit. Thus, the OLYP/TZP atomic spin populations are Mn, 2.85; N(O), -0.52; and O, -0.35.

Modeling the syn disposition of nitrogen donors in non-heme diiron enzymes. Synthesis, characterization, and hydrogen peroxide reactivity of diiron(III) complexes with the syn N-donor ligand H2BPG2DEV.

In order to model the syn disposition of histidine residues in carboxylate-bridged non-heme diiron enzymes, we prepared a new dinucleating ligand, H(2)BPG(2)DEV, that provides this geometric feature. The ligand incorporates biologically relevant carboxylate functionalities, which have not been explored as extensively as nitrogen-only analogues. Three novel oxo-bridged diiron(III) complexes, [Fe(2)(mu-O)(H(2)O)(2)(BPG(2)DEV)](ClO(4))(2) (6), [Fe(2)(mu-O)(mu-O(2)CAr(iPrO))(BPG(2)DEV)](ClO(4)) (7), and [Fe(2)(mu-O)(mu-CO(3))(BPG(2)DEV)] (8), were prepared. Single-crystal X-ray structural characterization confirms that two pyridyl groups are bound syn with respect to the Fe-Fe vector in these compounds. The carbonato-bridged complex 8 forms quantitatively from 6 in a rapid reaction with gaseous CO(2) in organic solvents. A common maroon-colored intermediate (lambda(max) = 490 nm; epsilon = 1500 M(-1) cm(-1)) forms in reactions of 6, 7, or 8 with H(2)O(2) and NEt(3) in CH(3)CN/H(2)O solutions. Mass spectrometric analyses of this species, formed using (18)O-labeled H(2)O(2), indicate the presence of a peroxide ligand bound to the oxo-bridged diiron(III) center. The Mossbauer spectrum at 90 K of the EPR-silent intermediate exhibits a quadrupole doublet with delta = 0.58 mm/s and DeltaE(Q) = 0.58 mm/s. The isomer shift is typical for a peroxodiiron(III) species, but the quadrupole splitting parameter is unusually small compared to those of related complexes. These Mossbauer parameters are comparable to those observed for a peroxo intermediate formed in the reaction of reduced toluene/o-xylene monooxygenase hydroxylase with dioxygen. Resonance Raman studies reveal an unusually low-energy O-O stretching mode in the peroxo intermediate that is consistent with a short diiron distance. Although peroxodiiron(III) intermediates generated from 6, 7, and 8 are poor O-atom-transfer catalysts, they display highly efficient catalase activity, with turnover numbers up to 10,000. In contrast to hydrogen peroxide reactions of diiron(III) complexes that lack a dinucleating ligand, the intermediates generated here could be re-formed in significant quantities after a second addition of H(2)O(2), as observed spectroscopically and by mass spectrometry.

Subtle modification of 2,2-dipicolylamine lowers the affinity and improves the turn-on of Zn(II)-selective fluorescent sensors.

The spectroscopic and proton- and Zn(II)-binding properties of two new members of the Zinpyr family of fluorescent sensors are reported. In ZP1B and ZP3B, a (2-picolyl)(4-picolyl)amine (2,4-DPA) moiety is installed in place of the di(2-picolyl)amine (2,2-DPA) ligand used in the parent sensors ZP1 and ZP3. This modification has the benefit of both lowering the proton-induced turn-on at physiological pH levels and altering the Zn(II) affinity so as to detect only the most concentrated stores of this ion in biological samples. Comparison of the proton affinities of all four probes, as determined by potentiometric titrations, contributes to our understanding of the solution properties of this family of sensors.

Solution and fluorescence properties of symmetric dipicolylamine-containing dichlorofluorescein-based Zn2+ sensors.

The mechanism by which dipicolylamine (DPA) chelate-appended fluorophores respond to zinc was investigated by the synthesis and study of five new analogues of the 2',7'-dichlorofluorescein-based Zn(2+) sensor Zinpyr-1 (ZP1). With the use of absorption and emission spectroscopy in combination with potentiometric titrations, a detailed molecular picture has emerged of the Zn(2+) and H(+) binding properties of the ZP1 family of sensors. The two separate N(3)O donor atom sets on ZP1 converge to form binding pockets in which all four heteroatoms participate in coordination to either Zn(2+) or protons. The position of the pyridyl group nitrogen atom, 2-pyridyl or 4-pyridyl, has a large impact on the fluorescence response of the dyes to protons despite relatively small changes in pK(a) values. The fluorescence quenching effects of such multifunctional electron-donating units are often taken as a whole. Despite the structural complexity of ZP1, however, we provide evidence that the pyridyl arms of the DPA appendages participate in the quenching process, in addition to the contribution from the tertiary nitrogen amine atom. Potentiometric titrations reveal ZP1 dissociation constants (K(d)) for Zn(2+) of 0.04 pM and 1.2 nM for binding to the first and second binding pockets of the ligand, respectively, the second of which correlates with the value observed by fluorescence titration. This result demonstrates that both binding pockets of this symmetric, ditopic sensor need to be occupied in order for full fluorescence turn-on to be achieved. These results have significant implications for the design and implementation of fluorescent sensors for studies of mobile zinc ions in biology.

Synthesis, Characterization, and Oxygenation Studies of Carboxylate-Bridged Diiron(II) Complexes with Aromatic Substrates Tethered to Pyridine Ligands and the Formation of a Unique Trinuclear Complex.

In this study, diiron(II) complexes were synthesized as small molecule mimics of the reduced active sites in the hydroxylase components of bacterial multicomponent monooxygenases (BMMs). Tethered aromatic substrates were introduced in the form of 2-phenoxypyridines, incorporating hydroxy and methoxy functionalities into windmill-type diiron(II) compounds [Fe(2)(µ-O(2)CAr(R))(2)-(O(2)CAr(R))(2)(L)(2)] (1-4), where (-)O(2)CAr(R) is a sterically encumbering carboxylate, 2,6-di(4-fluorophenyl)- or 2,6-di(p-tolyl)benzoate (R = 4-FPh or Tol, respectively). The inability of 1-4 to hydroxylate the aromatic substrates was ascertained. Upon reaction with dioxygen, compounds 2 and 3 (L = 2-(m-MeOPhO)Py, 2-(p-MeOPhO)Py, respectively) decompose by a known bimolecular pathway to form mixed-valent diiron(II,III) species at low temperature. Use of 2-(pyridin-2-yloxy)phenol as the ligand L resulted in a doubly-bridged diiron complex (4) and an unprecedented phenoxide-bridged triiron(II) complex (5) under slightly modified reaction conditions.

New strategy for quantifying biological zinc by a modified zinpyr fluorescence sensor.

Substitution of one pyridine by pyrazine in each DPA appendage of ZP1 leads to a new zinc sensor, ZPP1, with a modified background fluorescence and zinc affinity. ZPP1 exhibits a two-step zinc response during fluorescence titrations, which leads to a new method for zinc quantification. The ability of ZPP1 to image and quantify zinc was demonstrated in pancreatic Min6 cells.

Iron complexes of dendrimer-appended carboxylates for activating dioxygen and oxidizing hydrocarbons.

The active sites of metalloenzymes are often deeply buried inside a hydrophobic protein sheath, which protects them from undesirable hydrolysis and polymerization reactions, allowing them to achieve their normal functions. In order to mimic the hydrophobic environment of the active sites in bacterial monooxygenases, diiron(II) compounds of the general formula [Fe2([G-3]COO)4(4-RPy)2] were prepared, where [G-3]COO- is a third-generation dendrimer-appended terphenyl carboxylate ligand and 4-RPy is a pyridine derivative. The dendrimer environment provides excellent protection for the diiron center, reducing its reactivity toward dioxygen by about 300-fold compared with analogous complexes of terphenyl carboxylate ([G-1]COO-) ligands. An FeIIFeIII intermediate was characterized by electronic, electron paramagnetic resonance, Mössbauer, and X-ray absorption spectroscopic analyses following the oxygenation of [Fe2([G-3]COO)4(4-PPy)2], where 4-PPy is 4-pyrrolidinopyridine. The results are consistent with the formation of a superoxo species. This diiron compound, in the presence of dioxygen, can oxidize external substrates.

9-Triptycenecarboxylate-Bridged Diiron(II) Complexes: Capture of the Paddlewheel Geometric Isomer.

The synthesis and characterization of diiron(II) complexes supported by 9-triptycenecarboxylate ligands ((-)O(2)CTrp) is described. The interlocking nature of the triptycenecarboxylates facilitates formation of quadruply bridged diiron(II) complexes of the type [Fe(2)(µ-O(2)CTrp)(4)(L)(2)] (L = THF, pyridine or imidazole derivative) with a paddlewheel geometry. A systematic lengthening of the Fe-Fe distance occurs with the increase in steric bulk of the neutral donor L, resulting in values of up to 3 Å without disassembly of the paddlewheel structure. Reactions with an excess of water do not lead to decomposition of the diiron(II) core, indicating that these quadruply bridged complexes are of exceptional stability. The red-colored complexes [Fe(2)(µ-O(2)CTrp)(4)(4-AcPy)(2)] (10) and [Fe(2)(µ-O(2)CTrp)(4)(4-CNPy)(2)] (11) exhibit solvent-dependent thermochromism in coordinating solvents that was studied by variable temperature UV-vis spectroscopy. Reaction of [Fe(2)(µ-O(2)CTrp)(4)(THF)(2)] with N,N,N',N'-tetramethylethylenediamine (TMEDA), tetra-n-butyl ammonium thiocyanate, or excess 2-methylimidazole resulted in the formation of mononuclear complexes [Fe(O(2)CTrp)(2)(TMEDA)] (13), (n-Bu(4)N)(2)[Fe(O(2)CTrp)(2)(SCN)(2)] (14), and [Fe(O(2)CTrp)(2)(2-MeIm)(2)] (15) having an O(4)/N(2) coordination sphere composition.