Tetraazamacrocyclic Ligand Research Articles

Pharmacologically important tetraaza macrocyclic Schiff base complexes of Zn(II), Cu(II) and Co(II): Synthesis, characterization, DFT studies, molecular docking and in vitro anti-bacterial and anti-cancer studies

A novel tetraaza macrocyclic Schiff base ligand and its metal complexes [Zn(II), Cu(II), and Co(II)] were successfully synthesized and characterized using various analytical techniques including FT-IR, NMR, ESI-MS, UV-Vis, PXRD, ESR, and TGA. The chemical reactivity and molecular geometry of the compounds were further elucidated through DFT calculations. The synthesized compounds were evaluated for their anti-bacterial activity against both Gram +ve and Gram -ve bacteria. Remarkably, the metal complexes exhibited enhanced anti-bacterial activity compared to the ligand. All compounds displayed moderate antibacterial activity against various strains, with complexes 4a and 4b demonstrating the highest inhibition against Gram +ve bacteria at 0.1 µM concentration. Furthermore, the cytotoxicity of these compounds against a human liver cancer cell line (HepG2) was assessed, revealing substantial anti-proliferative activity. Notably, the Zn(II) complex demonstrated an IC50 value comparable to the standard drug Doxorubicin. Importantly, the ligand and Zn(II) and Co(II) complexes exhibited minimal (< 5%) hemolysis at their IC50 values, suggesting their non-toxic nature. Molecular docking studies were conducted to investigate the binding interactions of the synthesized compounds with the active site of the topoisomerase IIβ enzyme (PDB ID: 4G0V), a crucial target for anti-bacterial and anti-cancer medications. Complex 4a displayed the strongest binding affinity (-8.2 kcal/mol) and the most favourable docked conformation, with multiple hydrogen bonds to the protein's active site. These results suggest its potential for further development as a therapeutic agent.

Synthetic Advances for Mechanistic Insights: Metal-Oxygen Intermediates with a Macrocyclic Pyridinophane System.

ConspectusMetalloenzymes, which are proteins containing earth-abundant transition-metal ions as cofactors in the active site, generate various metal-oxygen intermediates via activating a dioxygen molecule (O2) to mediate vital metabolic functions, such as the oxidative metabolism of xenobiotics and the biotransformation of naturally occurring molecules. By replicating the active sites of metalloenzymes, many bioinorganic chemists have studied the geometric and electronic properties and reactivities of model complexes to understand the nature of enzymatic intermediates and develop bioinspired metal catalysts. Among the reported model complexes, nonporphyrinic macrocyclic ligands are the predominant coordination system widely used in stabilizing and isolating diverse metal-oxygen intermediates, which allows us to extensively investigate the physicochemical characteristics of the analogs of reactive intermediates of metalloenzymes. In particular, it has been reported that the ring size of the macrocyclic ligands, defined by the number of atoms in the macrocyclic ring, drastically affects the identity of the metal-oxygen intermediate. Thus, systematic modification of the macrocyclic ligands has been a great subject being examined in various inorganic fields.In this Account, we describe synthetic advances of a macrocyclic ligand system by introducing pyridine donors into a 12-membered tetraazamacrocyclic ligand (12-TMC) that initially has 4 amine donors. Interestingly, the backbone of the pyridinophane ligand with 2 pyridine and 2 amine donors in a 12-membered ring is shown to be much more folded than in other macrocyclic ligands, thereby allowing the axial and equatorial donors to separately control the electronic structure of metal complexes. Then, we looked over independent electronic and steric effects on metal-oxygen species with thorough physicochemical analysis. The NiIII-peroxo complexes exhibit nucleophilic reactivity dependent on the steric hindrance of the second coordination sphere. Furthermore, the C-H bond strength of the second coordination sphere has also been an important factor in determining the stability of MnIV-bis(hydroxo) intermediates. Electronic tuning on CoIII-hydroperoxo intermediates results in a trend between the electron-donating abilities of para-substituents on pyridine in the pyridinophane ligand and electrophilic reactivities, from which mechanistic insights into the metal-hydroperoxo species have been gained. Importantly, the metal-oxygen intermediates supported by the pyridinophane ligand system have revealed quite challenging chemical reactions, including dioxygenase-like nitrile activation by CoIII-peroxo intermediates and the oxidation of aldehyde and aromatic compounds by manganese-oxygen intermediates. Based on the fine substitution of donors, we have addressed that those novel reactions originated from the unique framework of the pyridinophane system incorporating spin-crossover behavior and high redox potentials of the metal-oxygen intermediates. These results will be valuable for the structure-activity relationship of metal-oxygen intermediates, giving a better understanding on the enzymatic coordination system where amino acid ligands vary for specific chemical reactions.

Unexpected Reduction of a Coordinated Diazapyridinophane Ligand Bound to Chromium(III) Ion Leading to Delocalization of the Unpaired Electron across Two Isolated Pyridine Units.

In the tetraazamacrocyclic ligand N,N'-dimethyl-2,11-diaza-[3.3](2,6)pyridinophane (L-N4 Me2 ), the two pyridine units are separated from each other by sp3 -hybridized triatomic bridges. Such electronically isolated pyridine moieties are considerably less prone to reductions than di- or triimines. A detailed structural, magnetic, and spectroscopic investigation of the complexes [Cr(L-N4 Me2 )(OAc)2 ] and [Cr(L-N4 Me2 )(OAc)2 ](PF6 ), in combination with theoretical calculations, reveals that the reduced complex must be described as a chromium(III) ion coordinated to the anionic radical ligand (L-N4 Me2 )⋅- rather than a low-spin chromium(II) ion bound to closed-shell ligands. Thus, it is, to the best of our knowledge, only the second example of a stable and structurally characterized metal complex containing a reduced isolated pyridine unit. The stability is attributed to the delocalization of the unpaired electron across the two pyridine units, mediated by their interaction to the metal ion.

Zinc(II) Complexes with One Isomer of Tetraazamacrocyclic Ligand and its N-Pendent Bis-cyanoethyl Derivative: Synthesis, Characterization and Antibacterial Studies

Zinc(II) Complexes with One Isomer of Tetraazamacrocyclic Ligand and its N-Pendent Bis-cyanoethyl Derivative: Synthesis, Characterization and Antibacterial Studies

Magnetic Exchange Coupling in Macrocyclic Cobalt (II) Complexes: The Influence of Bridging Ligands and Choice of the Computational Methodologies

AbstractExchange‐coupled spin states of cobalt complexes represent the key to understanding the challenging nature of the magnetism of cobalt dimer. In this study, we introduce a comprehensive investigation of the nature of magnetic super‐exchange coupling interactions between two metallic centers in a macro ligand cobalt dimer. More importantly, we provide a detailed comparison between a series of bridging ligands and study their role in the magnetic exchange coupling constant in cobalt dimer with tetraaza macrocycle ligand scaffold. By varying the types of bridging and terminal ligands, we explored the nature of magnetic coupling in 24 species of cobalt dimers, which allowed us to draw a magneto‐structure relationship and monitor the effect of bridging/terminal ligands on the overall magnetism. We employed different density functional theory (DFT) methodologies and complete active space self‐consistent field (CASSCF) in our investigation. The results show that there are comprehensible functional dependencies, and the choice of exchange‐correlation functional is critical for calculating the magnetic properties. Using the experimental values of the exchange coupling, we found that hybrid functionals with 10–20 % Hartree‐Fock exchange integrals give acceptable accuracy. Furthermore, we adjusted the percentage of HF integrals to estimate the optimum value required to be included in the hybrid functionals. Finally, we used CASSCF to gain deeper understanding of the magnetic coupling for the valence magnetic electrons and to achieve the true ground state wavefunction, which is not feasible with conventional DFT calculations. However, the CASSCF calculations poorly underestimate the magnetic coupling, which can be significantly improved by including the dynamic correlations, as implemented in the NEVPT2 methodology.

Hydrogen Peroxide Disproportionation Activity Is Sensitive to Pyridine Substitutions on Manganese Catalysts Derived from 12-Membered Tetra-Aza Macrocyclic Ligands.

The abundance of manganese in nature and versatility to access different oxidation states have made manganese complexes attractive as catalysts for oxidation reactions in both biology and industry. Macrocyclic ligands offer the advantage of substantially controlling the reactivity of the manganese center through electronic tuning and steric constraint. Inspired by the manganese catalase enzyme, a biological catalyst for the disproportionation of H2O2 into water and O2, the work herein employs 12-membered tetra-aza macrocyclic ligands to study how the inclusion of and substitution to the pyridine ring on the macrocyclic ligand scaffold impacts the reactivity of the manganese complex as a H2O2 disproportionation catalyst. Synthesis and isolation of the manganese complexes was validated by characterization using UV-vis spectroscopy, SC-XRD, and cyclic voltammetry. Potentiometric titrations were used to study the ligand basicity as well as the thermodynamic equilibrium with Mn(II). Manganese complexes were also produced in situ and characterized using electrochemistry for comparison to the isolated species. Results from these studies and H2O2 reactivity showed a remarkable difference among the ligands studied, revealing instead a distinction in the reactivity regarding the number of pyridine rings within the scaffold. Moreover, electron-donating groups on the 4-position of the pyridine ring enhanced the reactivity of the manganese center for H2O2 disproportionation, demonstrating a handle for control of oxidation reactions using the pyridinophane macrocycle.

Systematic Electronic Tuning on the Property and Reactivity of Cobalt–(Hydro)peroxo Intermediates

A series of cobalt(III)-peroxo complexes, [CoIII(R2-TBDAP)(O2)]+ (1R2; R2 = Cl, H, and OMe), and cobalt(III)-hydroperoxo complexes, [CoIII(R2-TBDAP)(O2H)(CH3CN)]2+ (2R2), bearing electronically tuned tetraazamacrocyclic ligands (R2-TBDAP = N,N'-di-tert-butyl-2,11-diaza[3.3](2,6)-p-R2-pyridinophane) were prepared from their cobalt(II) precursors and characterized by various physicochemical methods. The X-ray diffraction and spectroscopic analyses unambiguously showed that all 1R2 compounds have similar octahedral geometry with a side-on peroxocobalt(III) moiety, but the O-O bond lengths of 1Cl [1.398(3) Å] and 1OMe [1.401(4) Å] were shorter than that of 1H [1.456(3) Å] due to the different spin states. For 2R2, the O-O bond vibration energies of 2Cl and 2OMe were identical at 853 cm-1 (856 cm-1 for 2H), but their Co-O bond vibration frequencies were observed at 572 cm-1 for 2Cl and 550 cm-1 for 2OMe, respectively, by resonance Raman spectroscopy (560 cm-1 for 2H). Interestingly, the redox potentials (E1/2) of 2R2 increased in the order of 2OMe (0.19 V) < 2H (0.24 V) < 2Cl (0.34 V) according to the electron richness of the R2-TBDAP ligands, but the oxygen-atom-transfer reactivities of 2R2 showed a reverse trend (k2: 2Cl < 2H < 2OMe) with a 13-fold rate enhancement at 2OMe over 2Cl in a sulfoxidation reaction with thioanisole. Although the reactivity trend contradicts the general consideration that electron-rich metal-oxygen species with low E1/2 values have sluggish electrophilic reactivity, this could be explained by a weak Co-O bond vibration of 2OMe in the unusual reaction pathway. These results provide considerable insight into the electronic nature-reactivity relationship of metal-oxygen species.

Alkali Metal Complexes of an Octamethyl Isomeric Macrocycle: Synthesis, Characterization and Antimicrobial Studies

Fourteen membered octamethyl tetraazamacrocyclic ligand salt, Me8[14]diene·2HClO4 and three isomeric ligands (LA, LB and LC) of its saturated analog have been synthesized as per literature. Interaction between the isomeric ligand LB and KX (X = SCN, NO3, Cl, Br and I) afforded white-coloured five coordinated square pyramidal potassium complexes [KLBX]. Moreover, the reaction between RbCl and LB produced five coordinated [RbLBCl] having square pyramidal geometry. Then, the axial substitution reaction on [RbLBCl] furnished a substituted rubidium complex with the same geometry of the mother complex. All the alkali metal complexes have been characterized by using modern analytical techniques. Furthermore, antibacterial and antifungal activities of ligand LB and its alkali metal (K and Rb) complexes have been investigated against different bacteria and fungi.

Nickel(II) Complexes of Octamethyl Tetraazamacrocycle and its N-Pendent Derivative: Syntheses, Characterization, Electrolytic Behaviour and Antimicrobial Activities

Octamethyl tetraazamacrocycle, Me8[14]diene·2HClO4 and its three isomeric ligands (LA, LB and LC) were synthesized and characterized using analytical and spectroscopic data, and the antibacterial activities were evaluated against selected bacteria and yeast. Interaction of LC with excess acrylonitrile resulted in an N-pendent derivative (LCX). Square planar nickel(II) diperchlorate complex of LC, [NiLCα](ClO4)2, underwent axial addition reactions with KI and NaNO2 to yield six coordinated octahedral species, [NiLCαI2]·2H2O and [NiLCα(NO2)(ClO4)]. Five coordinated square pyramidal Ni(II) complexes, [NiLCXCl](ClO4), [NiLCX(NCS)](NO3) and [NiLCXI](NO3), were synthesized from Ni(II) salts and tetraazamacrocyclic ligand LCX. Among the complexes, [NiLCXCl](ClO4) was synthesized through the direct interaction of NiCl2 with LCX, followed by the subsequent addition of NaClO4·6H2O. On the other hand, [NiLCX(NCS)](NO3) and [NiLCXI](NO3) as well as octahedral [NiLCXBr2] and [NiLCX(NO2)(NO3)] were synthesized by the interaction of LCX with different Ni(II) salts.

Nickel-Catalyzed Sustainable and Selective Alkylation of Alcohols to α-Alkylated Ketones via Borrowing Hydrogen Approach

AbstractHerein, we report a nickel-catalyzed sustainable, environment­-friendly, and economically affordable borrowing hydrogen approach (BHA) for synthesizing various α-alkylated ketones via dehydro­genative coupling of primary and secondary alcohols. Using a well-­defined, air-stable, inexpensive, and easy-to-prepare four-coordinate macrocyclic Ni(II)-catalyst [Ni(MeTAA)] of a tetra-aza macrocyclic ligand (tetramethyltetraaza[14]annulene (H2MeTAA)), a series of α-alkylated ketones were prepared in good yields. A few control reactions, including deuterium-labelling experiments, were performed to unveil the reaction mechanism.

High incorporation of magnetite nanoparticles inside tetraaza macrocyclic Schiff base cavity: spectroscopic characterization and modeling by DFT calculation

This work presents a simple synthesis of tetraaza macrocyclic Schiff base ligand (C40H28N4), its complex [(C40H28N4)@Fe(II)], and a novel complex of magnetite Fe3O4NPs incorporated inside tetraaza macrocyclic cavity [(C40H28N4)@Fe3O4NPs] by the co-precipitation method in order to obtain well-dispersed nanoparticles, controlled size and prevent the aggregation of Fe3O4 NPs due to strong dipole–dipole magnetic attractions and interactions between particles. The characterization and structural identification were carried out by X-ray spectroscopy as well by 1H NMR, 13C and DEPT 135 NMR spectroscopy, FT-IR, UV–visible, EDX, TGA, and finally by VSM using both experimental and theoretical methods. XRD measurements indicate that the presence of Schiff's bases does not modify the crystal structure of the nanoparticles (11.05 nm). All the NMR spectra suggested the success of the synthesis of all structures with high purity. FTIR was used to illuminate the presence of Fe3O4NPs in tetrahedral and octahedral sites as well as their coordination with imine (C = N) of tetraaza macrocyclic. The UV–visible spectra and frontier molecular orbitals (FMOs) of the title compounds were calculated at TD-DFT/CAM-B3LYP-D3/6–311 G (d, p) level of theory. The corresponding calculated result yield shows a good agreement with the experimental data. The morphological characterization of the nanoparticles was carried out by SEM, which revealed that the shape of the NPs was generally spherical. The SEM images also show that the nanoparticles prepared by in situ with co-precipitation method were able to form stable complexes. Thermal characterization by TGA shows that there are 64% of the magnetite nanoparticles formed in situ, which corresponds to a grafting density of 25 mmol.g−1. The VSM analysis displays a similar magnetic hysteresis loop shape compared to free Fe3O4 NPs, which confirmed a ferromagnetic character due to the significant decrease in saturated magnetization.Graphical abstract

Noncovalent Assembly and Catalytic Activity of Hybrid Materials Based on Pd Complexes Adsorbed on Multiwalled Carbon Nanotubes, Graphene, and Graphene Nanoplatelets.

Green catalysts with excellent performance in Cu-free Sonogashira coupling reactions can be prepared by the supramolecular decoration of graphene surfaces with Pd(II) complexes. Here we report the synthesis, characterization, and catalytic properties of new catalysts obtained by the surface decoration of multiwalled carbon nanotubes (MWCNTs), graphene (G), and graphene nanoplatelets (GNPTs) with Pd(II) complexes of tetraaza-macrocyclic ligands bearing one or two anchor functionalities. The decoration of these carbon surfaces takes place under environmentally friendly conditions (water, room temperature, aerobic) in two steps: (i) π–π stacking attachment of the ligand via electron-poor anchor group 6-amino-3,4-dihydro-3-methyl-5-nitroso-4-oxo-pyrimidine and (ii) Pd(II) coordination from PdCl42–. Ligands are more efficiently adsorbed on the flat surfaces of G and GNPTs than on the curved surfaces of MWCNTs. All catalysts work very efficiently under mild conditions (50 °C, aerobic, 7 h), giving a similar high yield (90% or greater) in the coupling of iodobenzene with phenylacetylene to form diphenylacetylene in one catalytic cycle, but catalysts based on G and GNPTs (especially on GNPTs) provide greater catalytic efficiency in reuse (four cycles). The study also revealed that the active centers of the ligand-Pd type decorating the support surfaces are much more efficient than the Pd(0) and PdCl42– centers sharing the same surfaces. All of the results allow a better understanding of the structural factors to be controlled in order to obtain an optimal efficiency from similar catalysts based on graphene supports.

Analysis of Anion Binding Effects on the Sensitized Luminescence of Macrocyclic Europium(III) Complexes

AbstractFour triazamacrocyclic and two tetraazamacrocyclic ligands carrying two and three coordinating donor groups, respectively, and a carbostyril light‐harvesting antenna were synthesized. The antenna was linked to a macrocycle either via secondary or tertiary amide. Complexation with europium (Eu), gadolinium (Gd), terbium (Tb), and ytterbium (Yb) yielded overall +1 or +2 charged species. Paramagnetic 1H NMR, and steady‐state and time‐resolved luminescence spectroscopies showed that the complexes had 1–3 inner‐sphere water molecules and displayed a variety of coordination geometries in solution. The antennae sensitized Eu(III) and Tb(III) emission with quantum yields of 0.3–4.3 % and 9.9–24.5 %, respectively. The addition of excess fluoride or cyanide to buffered Eu(III) complex solutions resulted in anion‐dependent changes. Fluoride addition increased the Eu(III) luminescence intensity by displacing all inner‐sphere water molecules and stabilizing the +3 oxidation state of Eu. Eu(III) luminescence increased up to 25‐fold for one emitter. Cyanide quenched Eu(III) luminescence in all cases despite partial water ligand displacement.

Front Cover: Manganese (III/IV) μ‐Oxo Dimers and Manganese (III) Monomers with Tetraaza Macrocyclic Ligands and Historically Relevant Open‐Chain Ligands (Eur. J. Inorg. Chem. 19/2022)

The Front Cover shows how the discovery of manganese containing enzymes has prompted a range of synthetic small-molecule complexes to be used as structural and functional mimics of the metalloenzyme chemistries. On the basis of this work, aza-macrocyclic ligands have resulted in a small library of Mn(III) and bis μ-oxo Mn(III)/Mn(IV) complexes, which built on the earlier work established with open-chain ligand scaffolds. The characterization and structural information from these studies has now allowed studies to be expanded to applications beyond mimicking the metalloenzymes that inspired their synthesis, making the transit between monomeric Mn(III) and Mn(III)/Mn(IV) μ-oxo dimer complexes of great interest. More information can be found in the Review by K. N. Green and co-workers.

Manganese (III/IV) μ-Oxo Dimers and Manganese (III) Monomers with Tetraaza Macrocyclic Ligands and Historically Relevant Open-Chain Ligands.

The oxygen-evolving complex (OEC) located in photosystem II (PSII) of green plants is one of the best-known examples of a manganese-containing enzyme in nature, but it is also used in a range of other biological processes. OEC models incorporate two multi-dentate nitrogen-containing ligands coordinated to a bis-μ-oxo Mn(III,IV) core. Open-chain ligands were the initial scaffold used for biomimetic studies, but their macrocyclic counterparts have proven to be particularly appropriate due to their enhanced stability. Dimer and monomer complexes with such ligands have shown to be useful for a wide range of applications, which will be reviewed herein. The purpose of this review is to state with some clarity the different spectroscopic and structural characteristics of the Mn complexes formed with tetraaza macrocyclic ligands both in solution and solid-state that allow the reader to successfully identified the species involved when dealing with similar complexes of Mn.

Studies of the hydrophobic interaction between a pyrene-containing dye and a tetra-aza macrocyclic gadolinium complex

An in vivo and an in vitro investigation of the hydrophobic interaction between HPTS and the gadolinium(iii)-complex of tetra-aza macrocyclic ligand HP-DO3A (Gd(HP-DO3A)) are reported.

Electrocatalytic reduction of protons to dihydrogen by the cobalt tetraazamacrocyclic complex [Co(N4H)Cl2]+: mechanism and benchmarking of performances.

The cobalt tetraazamacrocyclic [Co(N4H)Cl2]+ complex is becoming a popular and versatile catalyst for the electrocatalytic evolution of hydrogen, because of its stability and superior activity in aqueous conditions. We present here a benchmarking of its performances based on the thorough analysis of cyclic voltammograms recorded under various catalytic regimes in non-aqueous conditions allowing control of the proton concentration. This allowed a detailed mechanism to be proposed with quantitative determination of the rate-constants for the various protonation steps, as well as identification of the amine function of the tetraazamacrocyclic ligand to act as a proton relay during H2 evolution.

Sequestration of Am3+ and Eu3+ into ionic liquid containing Aza-macrocycle based multiple-diglycolamide ligands: Extraction, complexation, luminescence and DFT studies

Extraction of Am3+ and Eu3+ was carried out into a room temperature ionic liquid, C8mim⋅Tf2N, using two multiple-diglycolamide extractants with three or four diglycolamide arms tethered to either a triaza- or tetraazamacrocyclic ligand termed as TAM-3-DGA and TAM-4-DGA, respectively. The metal ion extraction was highly efficient as only 5 × 10-4 M solutions of TAM-3-DGA resulted in D values of 680 and 845 for Am3+ and Eu3+, respectively, at pH 2.0, while the respective values with a five times lower concentration of TAM-4-DGA were 142 and 296, which is probably the best reported thus far. Though Eu3+ ion was preferentially extracted over Am3+, the selectivity was not as good as reported in molecular diluent-based extraction systems. The extracted species contained two units of the extractant and did not contain any nitrate ion suggesting a cation-exchange mechanism. Studies on the temperature effect on metal ion extraction were carried out to determine the thermodynamic parameters. Luminescence studies of the extracts were also performed which suggested strong complex formation with no inner-sphere water molecules. To understand the ligand coordination to Eu3+ and Am3+ and other bonding parameters, DFT studies were carried out.

PH-dependent concatenation of an inorganic complex results in solid state helix formation

Growth of the library of tetraaza macrocyclic pyridinophane ligands is a result of the potential to treat neurodegenerative diseases by binding unregulated redox active metal-ions, scavenging radicals, and reducing oxidative stress. As part of this work, the copper complex of OHPyN3Cu (3,6,9,15-tetraazabicyclo[9.3.1]penta-deca-1(15),11,13-trien-13-ol) was previously identified as a discrete molecule in the solid state when isolated at lower pH values. However, here we report that OHPyN3Cu forms a helical structure upon crystallization around pH 6.5. Several properties of the ligand and complex were evaluated to understand the driving forces that led to the concatenation and formation of this solid-state helix. DFT studies along with a comparison of keto/enol tautomerization stability and bond lengths were used to determine the keto-character of the CO within each subunit. This pH-dependent keto-enol tautomerization is responsible for the solid state intermolecular CO···Cu bonds observed in this metallohelix (Cu1H) when produced around pH 6.5. Perchlorate templating that occurs through hydrogen bonding between perchlorate counter ions and each Cu1H unit is the primary driving factor for the twist that leads to the helix structure. Cu1H does not exhibit the typical factors that stabilize the formation of helices, such as intra-strand hydrogen bonding or π-stacking. The helix structure further highlights the diversity of inorganic metallohelices and demonstrates the importance of tautomerization and pH that occurs with the pyridinophane ligand used in this study. To our knowledge and although these phenomena have been observed individually, this is the first example of a pH-dependent keto-enol tautomerization in an azamacrocycle being the driving force for the formation of a metallohelix solid state structure and is a particularly unique observation for pyridinophane complexes.

Combining Structural with Functional Model Properties in Iron Synthetic Analogue Complexes for the Active Site in Rabbit Lipoxygenase.

Iron complexes that model the structural and functional properties of the active iron site in rabbit lipoxygenase are described. The ligand sphere of the mononuclear pseudo-octahedral cis-(carboxylato)(hydroxo)iron(III) complex, which is completed by a tetraazamacrocyclic ligand, reproduces the first coordination shell of the active site in the enzyme. In addition, two corresponding iron(II) complexes are presented that differ in the coordination of a water molecule. In their structural and electronic properties, both the (hydroxo)iron(III) and the (aqua)iron(II) complex reflect well the only two essential states found in the enzymatic mechanism of peroxidation of polyunsaturated fatty acids. Furthermore, the ferric complex is shown to undergo hydrogen atom abstraction reactions with O-H and C-H bonds of suitable substrates, and the bond dissociation free energy of the coordinated water ligand of the ferrous complex is determined to be 72.4 kcal·mol-1. Theoretical investigations of the reactivity support a concerted proton-coupled electron transfer mechanism in close analogy to the initial step in the enzymatic mechanism. The propensity of the (hydroxo)iron(III) complex to undergo H atom abstraction reactions is the basis for its catalytic function in the aerobic peroxidation of 2,4,6-tri(tert-butyl)phenol and its role as a radical initiator in the reaction of dihydroanthracene with oxygen.