The Mechanism of Formation of Active Fe-TAMLs Using HClO Enlightens Design for Maximizing Catalytic Activity at Environmentally Optimal, Circumneutral pH.

Fe-TAML/peroxide catalysis provides simple, powerful, ultradilute approaches for removing micropollutants from water. The typically rate-determining interactions of H2O2 with Fe-TAMLs (rate constant kI) are sharply pH-sensitive with rate maxima in the pH 9-10 window. Fe-TAML design or process design that shifts the maximum rates to the pH 6-8 window of most wastewaters would make micropollutant eliminations even more powerful. Here, we show how the different pH dependencies of the interactions of Fe-TAMLs with peroxide or hypochlorite to form active Fe-TAMLs (kI step) illuminate why moving from H2O2 (pKa, ca. 11.6) to hypochlorite (pKa, 7.5) shifts the pH of the fastest catalysis to as low as 8.2. At pH 7, hypochlorite catalysis is 100-1000 times faster than H2O2 catalysis. The pH of maximum catalytic activity is also moderated by the pKa's of the Fe-TAML axial water ligands, 8.8, 9.3, and 10.3, respectively, for [Fe{4-NO2C6H3-1,2-(NCOCMe2NSO2)2CHMe}(H2O)n]- (2) [n = 1-2], [Fe{4-NO2C6H3-1,2-(NCOCMe2NCO)2CF2}(H2O)n]- (1b), and [Fe{C6H4-1,2-(NCOCMe2NCO)2CMe2}(H2O)n]- (1a). The new bis(sulfonamido)-bis(carbonamido)-ligated 2 exhibits the lowest pKa and delivers the largest hypochlorite over peroxide catalytic rate advantage. The fast Fe-TAML/hypochlorite catalysis is accompanied by slow noncatalytic oxidations of Orange II.

On TAML Catalyst Resting State Lifetimes: Kinetic, Mechanistic, and Theoretical Insight into Phosphate-Induced Demetalation of an Iron(III) Bis(sulfonamido)bis(amido)-TAML Catalyst.

At ambient temperatures, neutral pH and ultralow concentrations (low nM), the bis(sulfonamido)bis(amido) oxidation catalyst [Fe{4-NO2C6H3-1,2-(NCOCMe2NSO2)2CHMe}(OH2)]- (1) has been shown to catalyze the addition of an oxygen atom to microcystin-LR. This persistent bacterial toxin can contaminate surface waters and render drinking water sources unusable when nutrient concentrations favor cyanobacterial blooms. In mechanistic studies of this oxidation, while the pH was controlled with phosphate buffers, it became apparent that iron ejection from 1 becomes increasingly problematic with increasing [phosphate] (0.3-1.0 M); 1 is not noticeably impacted at low concentrations (0.01 M). At pH < 6.5 and [phosphate] ≥ 1.0 M, 1 decays quickly, losing iron from the macrocycle. Iron ejection is surprisingly mechanistically complex; the pseudo-first-order rate constant kobs has an unusual dependence on the total phosphate concentration ([Pt]), kobs = k1[Pt] + k2[Pt]2, indicating two parallel pathways that are first and second order in [phosphate], respectively. The pH profiles in the 5.5-8.3 range for k1 and k2 are different: bell-shaped with a maximum of around pH 7 for k1 and sigmoidal for k2 with higher values at lower pH. Mechanistic proposals for the k1 and k2 pathways are detailed based on both the kinetic data and density functional theory analysis. The major difference between k1 and k2 is the involvement of different phosphate species, i.e., HPO42- (k1) and H2PO4- (k2); HPO42- is less acidic but more nucleophilic, which favors intramolecular rate-limiting Fe-N bond cleavage. Instead, H2PO4- acts intermolecularly, where the kinetics suggest that [H4P2O8]2- drives degradation.

Cyclometalated Osmium Compounds and beyond: Synthesis, Properties, Applications.

The synthesis of cyclometalated osmium complexes is usually more complicated than of other transition metals such as Ni, Pd, Pt, Rh, where cyclometalation reactions readily occur via direct activation of C-H bonds. It differs also from their ruthenium analogs. Cyclometalation for osmium usually occurs under more severe conditions, in polar solvents, using specific precursors, stronger acids, or bases. Such requirements expand reaction mechanisms to electrophilic activation, transmetalation, and oxidative addition, often involving C-H bond activations. Osmacycles exhibit specific applications in homogeneous catalysis, photophysics, bioelectrocatalysis and are studied as anticancer agents. This review describes major synthetic pathways to osmacycles and related compounds and discusses their practical applications.

The Exchange of Cyclometalated Ligands.

Reactions of cyclometalated compounds are numerous. This account is focused on one of such reactions, the exchange of cyclometalated ligands, a reaction between a cyclometalated compound and an incoming ligand that replaces a previously cyclometalated ligand to form a new metalacycle: + H-C*~Z ⇄ + H-C~Y. Originally discovered for PdII complexes with Y/Z = N, P, S, the exchange appeared to be a mechanistically challenging, simple, and convenient routine for the synthesis of cyclopalladated complexes. Over four decades it was expanded to cyclometalated derivatives of platinum, ruthenium, manganese, rhodium, and iridium. The exchange, which is also questionably referred to as transcyclometalation, offers attractive synthetic possibilities and assists in disclosing key mechanistic pathways associated with the C-H bond activation by transition metal complexes and C-M bond cleavage. Both synthetic and mechanistic aspects of the exchange are reviewed and discussed.

Quantifying evolving toxicity in the TAML/peroxide mineralization of propranolol.

Oxidative water purification of micropollutants (MPs) can proceed via toxic intermediates calling for procedures for connecting degrading chemical mixtures to evolving toxicity. Herein, we introduce a method for projecting evolving toxicity onto composite changing pollutant and intermediate concentrations illustrated through the TAML/H2O2 mineralization of the common drug and MP, propranolol. The approach consists of identifying the key intermediates along the decomposition pathway (UPLC/GCMS/NMR/UV-Vis), determining for each by simulation and experiment the rate constants for both catalytic and noncatalytic oxidations and converting the resulting predicted concentration versus time profiles to evolving composite toxicity exemplified using zebrafish lethality data. For propranolol, toxicity grows substantially from the outset, even after propranolol is undetectable, echoing that intermediate chemical and toxicity behaviors are key elements of the environmental safety of MP degradation processes. As TAML/H2O2 mimics mechanistically the main steps of peroxidase catalytic cycles, the findings may be relevant to propranolol degradation in environmental waters.

TAML- and Buffer-Catalyzed Oxidation of Picric Acid by H2O2: Products, Kinetics, DFT, and the Mechanism of Dual Catalysis.

Studies of the oxidative degradation of picric acid (2,4,6-trinitrophenol) by H2O2 catalyzed by a fluorine-tailed tetraamido macrocyclic ligand (TAML) activator of peroxides [FeIII{4,5-Cl2C6H2-1,2-(NCOCMe2NCO)2CF2}(OH2)]- (2) in neutral and mildly basic solutions revealed that oxidative degradation of this explosive demands components of phosphate or carbonate buffers and is not oxidized in their absence. The TAML- and buffer-catalyzed oxidation is subject to severe substrate inhibition, which results in at least 1000-fold retardation of the interaction between the iron(III) resting state of 2 and H2O2. The inhibition accounts for a unique pH profile for the TAML catalysis with the highest activity at pH 7. Less aggressive TAMLs such as [FeIII{C6H4-1,2-(NCOCMe2NCO)2CMe2}(OH2)]- are catalytically inactive. The roles of buffer components in modulating catalysis have been clarified through detailed kinetic investigations of the degradation process, which is first order in the concentration of 2 and shows ascending hyperbolic dependencies in the concentrations of all three participants, i.e., H2O2, picrate, and phosphate/carbonate. The reactivity trends are consistent with a mechanism involving the formation of double ([LFeIII-Q]2-) and triple ([LFeIII-{Q-H2PO4}]3-) associates, which are unreactive and reactive toward H2O2, respectively. The binding of phosphate converts [LFeIII-Q]2- to the reactive triple associate. Density functional theory suggests that the stability of the double associate is achieved via both Fe-Ophenol binding and π-π stacking. The triple associate is an outer-sphere complex where phosphate binding occurs noncovalently through hydrogen bonds. A linear free energy relationship analysis of the reactivity of the mono-, di-, and trinitro phenols suggests that the rate-limiting step involves an electron transfer from phenolate to an oxidized ironoxo intermediate, giving phenoxy radicals that undergo further rapid oxidation that lead to eventual mineralization.

Predicting Properties of Iron(III) TAML Activators of Peroxides from Their III/IV and IV/V Reduction Potentials or a Lost Battle to Peroxidase.

A cyclic voltammetry study of a series of iron(III) TAML activators of peroxides of several generations in acetonitrile as solvent reveals reversible or quasireversible FeIII/IV and FeIV/V anodic transitions, the formal reduction potentials (E°') for which are observed in the ranges 0.4-1.2 and 1.4-1.6 V, respectively, versus Ag/AgCl. The slope of 0.33 for a linear E°'(IV/V) against E°'(III/IV) plot suggests that the TAML ligand system plays a bigger role in the FeIII/IV transition, whereas the second electron transfer is to a larger extent an iron-centered phenomenon. The reduction potentials appear to be a convenient tool for analysis of various properties of iron TAML activators in terms of linear free energy relationships (LFERs). The values of E°'(III/IV) and E°'(IV V-1 ) correlate 1) with the pKa values of the axial aqua ligand of iron(III) TAMLs with slopes of 0.28 and 0.06 V, respectively; 2) with the Stern-Volmer constants KSV for the quenching of fluorescence of propranolol, a micropollutant of broad concern; 3) with the calculated ionization potentials of FeIII and FeIV TAMLs; and 4) with rate constants kI and kII for the oxidation of the resting iron(III) TAML state by H2 O2 and reactions of the active forms of TAMLs formed with donors of electrons S, respectively. Interestingly, slopes of log kII versus E°'(III/IV) plots are lower for fast-to-oxidize S than for slow-to-oxidize S. The log kI versus E°'(III/IV) plot suggests that the manmade TAML catalyst can never be as reactive toward H2 O2 as a horseradish peroxidase enzyme.

Oxidative Catalysis by TAMLs: Obtaining Rate Constants for Non-Absorbing Targets by UV-Vis Spectroscopy.

Understanding the catalysis of oxidative reactions by TAML activators of peroxides, i. e. iron(III) complexes of tetraamide macrocyclic ligands, advocated a spectrophotometric procedure for quantifying the catalytic activity of TAMLs for colorless targets (kII ', M-1 s-1 ), which is incomparably more advantageous in terms of time, cost, energy, and ecology than NMR, HPLC, UPLC, GC-MS and other similar techniques. Dyes Orange II or Safranin O (S) are catalytically bleached by non-excessive amount of H2 O2 in the presence of colorless substrates (S1 ) according to the rate law: -d[S]/dt=kI kII [H2 O2 ][S][TAML]/(kI [H2 O2 ]+kII [S]+kII '[S1 ]). The bleaching rate is thus a descending hyperbolic function of S1 : v=ab/(b+[S1 ]). Values of kII ' found from a and b for phenol and propranolol with commonly used TAML [FeIII {o,o'-C6 H4 (NCONMe2 CO)2 CMe2 }2 (OH2 )]+ are consistent with those for S1 (phenol, propranolol) obtained directly by UPLC. The study sends vital messages to enzymologists and environmentalists.

Zero-Order Catalysis in TAML-Catalyzed Oxidation of Imidacloprid, a Neonicotinoid Pesticide.

Bis-sulfonamide bis-amide TAML activator [Fe{4-NO2 C6 H3 -1,2-(NCOCMe2 NSO2 )2 CHMe}]- (2) catalyzes oxidative degradation of the oxidation-resistant neonicotinoid insecticide, imidacloprid (IMI), by H2 O2 at pH 7 and 25 °C, whereas the tetrakis-amide TAML [Fe{4-NO2 C6 H3 -1,2-(NCOCMe2 NCO)2 CF2 }]- (1), previously regarded as the most catalytically active TAML, is inactive under the same conditions. At ultra-low concentrations of both imidacloprid and 2, 62 % of the insecticide was oxidized in 2 h, at which time the catalyst is inactivated; oxidation resumes on addition of a succeeding aliquot of 2. Acetate and oxamate were detected by ion chromatography, suggesting deep oxidation of imidacloprid. Explored at concentrations [2]≥[IMI], the reaction kinetics revealed unusually low kinetic order in 2 (0.164±0.006), which is observed alongside the first order in imidacloprid and an ascending hyperbolic dependence in [H2 O2 ]. Actual independence of the reaction rate on the catalyst concentration is accounted for in terms of a reversible noncovalent binding between a substrate and a catalyst, which usually results in substrate inhibition when [catalyst]≪[substrate] but explains the zero order in the catalyst when [2]>[IMI]. A plausible mechanism of the TAML-catalyzed oxidations of imidacloprid is briefly discussed. Similar zero-order catalysis is presented for the oxidation of 3-methyl-4-nitrophenol by H2 O2 , catalyzed by the TAML analogue of 1 without a NO2 -group in the aromatic ring.

A Synthetically Generated LFeIVOH n Complex.

High-valent Fe-OH species are important intermediates in hydroxylation chemistry. Such complexes have been implicated in mechanisms of oxygen-activating enzymes and have thus far been observed in Compound II of sulfur-ligated heme enzymes like cytochrome P450. Attempts to synthetically model such species have thus far seen relatively little success. Here, the first synthetic FeIVOH n complex has been generated and spectroscopically characterized as either [LFeIVOH]- or [LFeIVOH2]0, where H4L = Me4C2(NHCOCMe2NHCO)2CMe2 is a variant of a tetra-amido macrocyclic ligand (TAML). The steric bulk provided by the replacement of the aryl group with the -CMe2CMe2- unit in this TAML variant prevents dimerization in all oxidation states over a wide pH range, thus allowing the generation of FeIVOH n in near quantitative yield from oxidation of the [LFeIIIOH2]- precursor.

Structural, Mechanistic, and Ultradilute Catalysis Portrayal of Substrate Inhibition in the TAML-Hydrogen Peroxide Catalytic Oxidation of the Persistent Drug and Micropollutant, Propranolol.

TAML activators enable unprecedented, rapid, ultradilute oxidation catalysis where substrate inhibitions might seem improbable. Nevertheless, while TAML/H2O2 rapidly degrades the drug propranolol, a micropollutant (MP) of broad concern, propranolol is shown to inhibit its own destruction under concentration conditions amenable to kinetics studies ([propranolol] = 50 µM). Substrate inhibition manifests as a decrease in the second-order rate constant kI for H2O2 oxidation of the resting FeIII-TAML (RC) to the activated catalyst (AC), while the second-order rate constant kII for attack of AC on propranolol is unaffected. This kinetics signature has been utilized to develop a general approach for quantifying substrate inhibitions. Fragile adducts [propranolol, TAML] have been isolated and subjected to ESI-MS, florescence, UV-vis, FTIR, 1H NMR, and IC examination and DFT calculations. Propranolol binds to FeIII-TAMLs via combinations of noncovalent hydrophobic, coordinative, hydrogen bonding, and Coulombic interactions. Across four studied TAMLs under like conditions, propranolol reduced kI 4-32-fold (pH 7, 25 °C) indicating that substrate inhibition is controllable by TAML design. However, based on the measured kI and calculated equilibrium constant K for propranolol-TAML binding, it is possible to project the impact on kI of reducing [propranolol] from 50 µM to the ultradilute regime typical of MP contaminated waters (≤2 ppb, ≤7 nM for propranolol) where inhibition nearly vanishes. Projecting from 50 µM to higher concentrations, propranolol completely inhibits its own oxidation before reaching mM concentrations. This study is consistent with prior experimental findings that substrate inhibition does not impede TAML/H2O2 destruction of propranolol in London wastewater while giving a substrate inhibition assessment tool for use in the new field of ultradilute oxidation catalysis.

Bis phenylene flattened 13-membered tetraamide macrocyclic ligand (TAML) for square planar cobalt(III).

The preparation, characterization, and evaluation of a cobalt(III) complex with 13-membered tetraamide macrocyclic ligand (TAML) is described. This is a square-planar (X-ray) S = 1 paramagnetic (1H NMR) compound, which becomes an S = 0 diamagnetic octahedral species in excess d5-pyridine. Its one-electron oxidation at an electrode is fully reversible with the lowest E 1/2 value (0.66 V vs SCE) among all investigated CoIII TAML complexes. The oxidation results in a neutral blue species which is consistent with a CoIII/radical-cation ligand. The ease of oxidation is likely due to the two benzene rings incorporated in the ligand structure (whereas there is just one in many other CoIII TAMLs). The oxidized neutral species are unexpectedly EPR silent, presumably due to the π-stacking aggregation. However, they display eight-line hyperfine patterns in the presence of excess of 4-tert-butylpyridine or 4-tert-butyl isonitrile. The EPR spectra are more consistent with the CoIII/radical-cation ligand formulation rather than with a CoIV complex. Attempts to synthesize a similar vanadium complex under the same conditions as for cobalt using [VVO(OCHMe2)3] were not successful. TAML-free decavanadate was isolated instead.

Iron(III) Ejection from a "Beheaded" TAML Activator: Catalytically Relevant Mechanistic Insight into the Deceleration of Electrophilic Processes by Electron Donors.

Kinetic studies of the acid-induced ejection of iron(III) show that the more electron-rich tetra-amido-N macrocyclic ligand (TAML) activator [FeIII{(Me2CNCOCMe2NCO)2CMe2}OH2]- (4), which does not have a benzene ring in its head component ("beheaded" TAML), is up to 1 × 104 times more resistant than much less electron-rich [FeIII{1,2-C6H4(NCOCMe2NCO)2CMe2}OH2]- (1a) to the electrophilic attack. This counterintuitive increased resistance is seen in both the specific acid (kobs = k1[H+]/(K + [H+])) and phosphate general acid (kII = (kdiKa1 + ktri[H+])/(Ka1+[H+])) demetalation pathways. Insight into this reactivity puzzle was obtained from coupling kinetic data with theoretical density functional theory modeling. First, although 1a and related complexes are six-coordinate in water, 4 has a strong tendency to repel the second aqua ligand favoring [LFe(OH2)]- and making appropriate the comparison of monoaqua-4 with diaqua-1a in the demetalation process. Second, dearomatization exerts a strong effect on the highest occupied molecular orbital (HOMO) energy of five-coordinate monoaqua-4, the presumed target in proton-induced demetalation, stabilizing it by ca. 51 kJ mol-1 compared with monoaqua-1a. Third, the monoaqua-4 HOMO is localized over the N-pπ system of all four N donors in contrast with monoaqua-1a, where N-pπ contributions from the head amides only mix with the aromatic ring π system. Fourth, addition of a second water ligand to monoaqua-1a giving [LFe(OH2)2]- reshapes the monoaqua-1a HOMO by shifting its entire locus from the head to the tail diamido-N section-this HOMO is by 54 kJ mol-1 less stable than the monoaqua-4 HOMO. These features provide the foundations for mechanistic conclusions concerning demetalation that (i) axial water ligands enable a favored path in the six-coordinate case of 1a, where a proton "slides" toward the Fe-N bond and (ii) early and late transition states are realized for 4 and 1a, respectively, with a larger free energy of activation for the beheaded TAML activator 4.

Targeting of High-Valent Iron-TAML Activators at Hydrocarbons and Beyond.

TAML activators of peroxides are iron(III) complexes. The ligation by four deprotonated amide nitrogens in macrocyclic motifs is the signature of TAMLs where the macrocyclic structures vary considerably. TAML activators are exceptional functional replicas of the peroxidases and cytochrome P450 oxidizing enzymes. In water, they catalyze peroxide oxidation of a broad spectrum of compounds, many of which are micropollutants, compounds that produce undesired effects at low concentrations-as with the enzymes, peroxide is typically activated with near-quantitative efficiency. In nonaqueous solvents such as organic nitriles, the prototype TAML activator gave the structurally authenticated reactive iron(V)oxo units (FeVO), wherein the iron atom is two oxidation equivalents above the FeIII resting state. The iron(V) state can be achieved through the intermediacy of iron(IV) species, which are usually µ-oxo-bridged dimers (FeIVFeIV), and this allows for the reactivity of this potent reactive intermediate to be studied in stoichiometric processes. The present review is primarily focused at the mechanistic features of the oxidation by FeVO of hydrocarbons including cyclohexane. The main topic is preceded by a description of mechanisms of oxidation of thioanisoles by FeVO, because the associated studies provide valuable insight into the ability of FeVO to oxidize organic molecules. The review is opened by a summary of the interconversions between FeIII, FeIVFeIV, and FeVO species, since this information is crucial for interpreting the kinetic data. The highest reactivity in both reaction classes described belongs to FeVO. The resting state FeIII is unreactive oxidatively. Intermediate reactivity is typically found for FeIVFeIV; therefore, kinetic features for these species in interchange and oxidation processes are also reviewed. Examples of using TAML activators for C-H bond cleavage applied to fine organic synthesis conclude the review.

A "Beheaded" TAML Activator: A Compromised Catalyst that Emphasizes the Linearity between Catalytic Activity and pKa.

Studies of the new tetra-amido macrocyclic ligand (TAML) activator [FeIII{(Me2CNCOCMe2NCO)2CMe2}OH2]- (4) in water in the pH range of 2-13 suggest its pseudo-octahedral geometry with two nonequivalent axial H2O ligands and revealed (i) the anticipated basic drift of the first pKa of water to 11.38 due to four electron-donating methyl groups alongside (ii) its counterintuitive enhanced resistance to acid-induced iron(III) ejection from the macrocycle. The catalytic activity of 4 in the oxidation of Orange II (S) by H2O2 in the pH range of 7-12 is significantly lower than that of previously reported TAML activators, though it follows the common rate law (v/[FeIII] = kIkII[H2O2][S]/(kI[H2O2] + kII[S]) and typical pH profiles for kI and kII. At pH 7 and 25 °C the rate constants kI and kII equal 0.63 ± 0.02 and 1.19 ± 0.03 M-1 s-1, respectively. With these new values for pKa, kI and kII establishing new high and low limits, respectively, the rate constants kI and kII were correlated with pKa values of all TAML activators. The relations log k = log k0 + α × pKa were established with log k0 = 13 ± 2 and 20 ± 4 and α = -1.1 ± 0.2 and -1.8 ± 0.4 for kI and kII, respectively. Thus, the reactivity of TAML activators across four generations of catalysts is predictable through their pKa values.

NaClO-Generated Iron(IV)oxo and Iron(V)oxo TAMLs in Pure Water.

The unique properties of entirely aliphatic TAML activator [FeIII{(Me2CNCOCMe2NCO)2CMe2}OH2]- (3), namely the increased steric bulk of the ligand and the unmatched resistance to the acid-induced demetalation, enables the generation of high-valent iron derivatives in pure water at any pH. An iron(V)oxo species is readily produced with NaClO at pH values from 2 to 10.6 without any observable intermediate. This is the first reported example of iron(V)oxo formed in pure water. At pH 13, iron(V)oxo is not formed and NaClO oxidizes 3 to an iron(IV)oxo derivative.

Impact of cyclometalated ruthenium(II) complexes on lactate dehydrogenase activity and cytotoxicity in gastric and colon cancer cells.

Lactate dehydrogenase (LDH) is a redox enzyme often overexpressed in cancer cells allowing their survival in stressful metabolic tumor environment. Ruthenium(II) complexes have been shown to impact on the activity of purified horseradish peroxidase and glucose oxidase but the physiological relevance remains unclear. In this study we investigated how ruthenium complexes impact on the activity of LDH in vitro and in cancer cells and performed a comparative study using polypyridine ruthenium(II) complex [Ru(bpy)3]2+ (1) and its structurally related cyclometalated 2-phenylpyridinato counterpart [Ru(phpy)(bpy)2]+ (2) (bpy=2,2'-bipyridine, phpyH=2-phenylpyridine). We show that the cytotoxicity in gastric and colon cancer cells induced by 2 is significantly higher compared to 1. The kinetic inhibition mechanisms on purified LDH and the corresponding inhibition constants Ki or i0.5 values were calculated. Though complexes 1 and 2 are structurally very similar (one Ru-C bond in 2 replaces one Ru-N bond in 1), their inhibition modes are different. Cyclometalated complex 2 behaves exclusively as a non-competitive inhibitor of LDH from rabbit muscle (LDHrm), strongly suggesting that 2 does not interact with LDH in the vicinities of either lactate/pyruvate or NAD+/NADH binding sites. Sites of interaction of 1 and 2 with LDHrm were revealed theoretically through computational molecular docking. Inhibition of LDH activity by 2 was confirmed in cancer cells. Altogether, these results revealed an inhibition of LDH activity by ruthenium complex through a direct interaction structurally tuned by a Ru-C bond.

Unifying Evaluation of the Technical Performances of Iron-Tetra-amido Macrocyclic Ligand Oxidation Catalysts.

The main features of iron-tetra-amido macrocyclic ligand complex (a sub-branch of TAML) catalysis of peroxide oxidations are rationalized by a two-step mechanism: Fe(III) + H2O2 → Active catalyst (Ac) (kI), and Ac + Substrate (S) → Fe(III) + Product (kII). TAML activators also undergo inactivation under catalytic conditions: Ac → Inactive catalyst (ki). The recently developed relationship, ln(S0/S∞) = (kII/ki)[Fe(III)]tot, where S0 and S∞ are [S] at time t = 0 and ∞, respectively, gives access to ki under any conditions. Analysis of the rate constants kI, kII, and ki at the environmentally significant pH of 7 for a broad series of TAML activators has revealed a 6 orders of magnitude reactivity differential in both kII and ki and 3 orders differential in kI. Linear free energy relationships linking kII with ki and kI reveal that the reactivity toward substrates is related to the instability of the active TAML intermediates and suggest that the reactivity in all three processes derives from a common electronic origin. The reactivities of TAML activators and the horseradish peroxidase enzyme are critically compared.

Activation of Dioxygen by a TAML Activator in Reverse Micelles: Characterization of an Fe(III)Fe(IV) Dimer and Associated Catalytic Chemistry.

Iron TAML activators of peroxides are functional catalase-peroxidase mimics. Switching from hydrogen peroxide (H2O2) to dioxygen (O2) as the primary oxidant was achieved by using a system of reverse micelles of Aerosol OT (AOT) in n-octane. Hydrophilic TAML activators are localized in the aqueous microreactors of reverse micelles where water is present in much lower abundance than in bulk water. n-Octane serves as a proximate reservoir supplying O2 to result in partial oxidation of Fe(III) to Fe(IV)-containing species, mostly the Fe(III)Fe(IV) (major) and Fe(IV)Fe(IV) (minor) dimers which coexist with the Fe(III) TAML monomeric species. The speciation depends on the pH and the degree of hydration w0, viz., the amount of water in the reverse micelles. The previously unknown Fe(III)Fe(IV) dimer has been characterized by UV-vis, EPR, and Mössbauer spectroscopies. Reactive electron donors such as NADH, pinacyanol chloride, and hydroquinone undergo the TAML-catalyzed oxidation by O2. The oxidation of NADH, studied in most detail, is much faster at the lowest degree of hydration w0 (in "drier micelles") and is accelerated by light through NADH photochemistry. Dyes that are more resistant to oxidation than pinacyanol chloride (Orange II, Safranine O) are not oxidized in the reverse micellar media. Despite the limitation of low reactivity, the new systems highlight an encouraging step in replacing TAML peroxidase-like chemistry with more attractive dioxygen-activation chemistry.

Reactivity and operational stability of N-Tailed TAMLs through kinetic studies of the catalyzed oxidation of orange†II by H2 O2 : synthesis and X-ray structure of an N-phenyl TAML.

Invited for the cover of this issue are Terrence J. Collins and co-workers at Carnegie Mellon University (USA) and the National Chemical Laboratory (India). The image depicts five generations of tetraamido macrocyclic ligand (TAML) activators, which are small molecule, full-functional mimics of oxidizing enzymes that arguably outperform the peroxidase enzymes they mimic. Read the full text of the article at 10.1002/chem.201406061.