Michel Giorgi

Calix[6]arene-BasedN3-Donors − A Versatile Supramolecular System with Tunable Electronic and Steric Properties − Study on the Formation of Tetrahedral Dicationic Zinc Complexes in a Biomimetic Environment

Novel tridentate N-ligands containing tertiary amines, pyrazoles, or benzimidazole groups were synthesized from tBu-calix[6]arene. Together with the previously described pyridine and imidazole-based ligands, they form a large family of biomimetic ligands (X6Me3N3) with different electronic and steric properties. Their capacity at stabilizing a tetrahedral Zn dicationic center in acetonitrile was investigated. Tertiary amines were too basic and sterically hindered, leading to precipitation of Zn(OH)2. The resulting protonated ligand was, in one case, structurally characterized by X-ray analysis. Ligands with pyrazole, benzimidazole and imidazole donors, all formed a stable Zn complex under stoichiometric conditions in acetonitrile. An 1H NMR spectroscopic study together with X-ray crystallography showed that the metal ion is coordinated to the three nitrogen arms with MeCN as a fourth ligand included in the calixarene conic pocket. These complexes provide new but rare examples of stable dicationic tetrahedral Zn species. The calixarene functionalized by three pyridine groups, on the other hand, did not appear to be a good ligand, which stands in contrast with its remarkable ability at stabilizing copper(I). Finally, these funnel complexes are chiral due to their helical shape. In solution, both enantiomers are in equilibrium. However, sterically hindered N-donors increased the enantiomerization barrier above 16 kcal/mol.

Supramolecular Assembly with Calix[6]arene and Copper Ions − Formation of a Novel Tetranuclear Core Exhibiting Unusual Redox Properties and Catecholase Activity

The supramolecular biomimetic chemistry based on calix[6]arene N-ligands has been further explored. A tris(imidazole)CuI complex was treated with 1 mol-equiv. of cuprous ion under dioxygen to produce a tetranuclear cupric species. X-ray structural determination of this novel Cu4 complex revealed that the self-inclusion of an imidazolyl coordinating arm into the hydrophobic calixarene cavity provides the base of coordination for a {ClImCu(OH)2CuIm2}2 assembly. The Cu4 core is maintained in solution and is stable even in a coordinating solvent such as acetonitrile. Magnetic susceptibility measurements evidenced a strong antiferromagnetic coupling in each Cu(OH)2Cu subunit with J = −408 cm−1. The complex displayed catecholase activity in the presence of 3,5-di-tert-butylcatechol behaving as a four-electron hole with, however, a sluggish CuI4 ⇄ CuII4 regeneration through O2 autooxidation. Finally, electrochemical studies revealed two oxidative reversible processes that successively gave rise to a {CuIICuIII}{CuII2} and a {CuIICuIII}2 mixed-valence species that could be characterized by UV/Vis and EPR spectroscopy. The overall structure and behavior of this tetranuclear complex is reminiscent of multicopper enzymes. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Substrate‐Binding Ligand Approach in Chemical Modeling of Copper‐Containing Monooxygenases, 1 Intramolecular Stereoselective Oxygen Atom Insertion into a Non‐Activated C–H Bond

We describe the reactivity of new copper AlkylPY2 type complexes which react with dioxygen and thus hydroxylate an aliphatic C–H bond of the ligand in the same manner as copper-containing monooxygenases.

Copper Complexes as Functional Models for Dopamine β-Hydroxylase – Stereospecific Oxygen Atom Transfer

The stereochemistry of oxygen atom transfer mediated by copper–oxygen species has been studied through a substrate binding ligand approach. Copper(II) [(IndPY2)Cu](CF3SO3)2 (2a) and copper(I) [(IndPY2)Cu]PF6 (5a) complexes were prepared and exposed to O2 in media of benzoin/NEt3/CH2Cl2 and CH2Cl2, respectively. In both cases, highly regio- and stereoselective oxygen atom transfer to the benzylic C–H bond of the indane ligand occurred. Using deuterium-labelled copper complexes 2b and 5b, we found that, in both cases, the oxygen atom transfer occurs with retention of configuration. The high deuterium kinetic isotope effects (7.6 and 11, respectively), determined by 13C-NMR spectroscopy, strongly suggest the intermediacy of two different copper–oxygen reactive species.

Bio-inspired Calix[6]Arene–Zinc Funnel Complexes

A bio-inspired supramolecular system is presented. A calix[6]arene possessing three imidazolyl arms on alternate phenolic positions binds a zinc ion. The resulting complex contains a hydrophobic pocket, which has a flattened conic shape. The system behaves as a selective molecular funnel for neutral guests that bind the metal centre. The exceptional stability of these tetrahedral dicationic complexes is exemplified by the acetaldehyde ternary adduct that was analysed by X-ray crystallography. The ligand is deeply buried in the heart of the calixarene cavity, pointing its methyl group selectively towards the centre of one of the aromatic walls, thereby establishing a stabilizing CH/π interaction. Protic guests undergo hydrogen bonding with the phenolic oxygens of the calixarene structure. The selectivity of the binding in the cavity is based on both the affinity of the donor atom of the guest ligand for the zinc ion and the relative host–guest geometries. The helical shape of the tris-imidazolyl groups binding the metal centre is the base of the chirality of the system. The twisted calix[6]arene structure of the zinc funnel complexes is shown to provide a new example of a cavity suitable for host–guest chiral induction. Formation of helical zinc complexes.

Supramolecular control of an organic radical coupled to a metal ion embedded at the entrance of a hydrophobic cavity

A novel N3ArO-calix[6]arene-based system is presented. It allows the formation of an aryloxy radical bound to a metal ion (CuII or ZnII) that presents a free coordination site in a concave cavity. Its oxidative activity appears highly controlled by the supramolecular system hence providing a good model for radical enzymes such as Galactose oxidase.

Copper(II)/H2O2-Mediated DNA cleavage: Involvement of a copper(III) species in H-atom abstraction of deoxyribose units

A new bis-amido-copper(II) complex 2 has been prepared. In the presence of reducing agents (ascorbate or DTT) under air atmosphere or hydrogen peroxide, complex 2 exhibited interesting nuclease activities in the 1-10 microM concentration range. For explaining the activity observed with hydrogen peroxide, we propose the occurrence of a bis-amido-copper(III) intermediate and an oxidation mechanism involving a H-atom abstraction of deoxyribose moieties of DNA.

Copper-containing monooxygenases: enzymatic and biomimetic studies of the O-atom transfer catalysis.

This review reports our recent studies or the mechanism of O-atom transfer to a benzylic C-H bond promoted by Dopamine beta-Hydroxylase (DBH) and its biomimetic models. We demonstrate that it is possible to carry out parallel and comparative studies on this enzyme (DBH) and its biomimetic models with the same substrate: 2-aminoindane (3). It was chosen because its two stereogenic centers, both in benzylic positions, make it very powerful for studying the stereochemistry of an O-atom transfer reaction. DBH-catalyzed hydroxylation of 3 produced exclusively 14% of trans-(1S,2S)-2-amino-1-indanol (4) (93% ee). Studies with stereospecifically deuterium-labeled 2-aminoindanes (1R,2S)-3b and (1S,2S)-3a showed that the formation of 4 was the rcsult of an overall process with retention of configuration where an O-atom is stereospecifically inserted in the trans pro-S position of the substrate. With copper(I) and (II) complexes of IndPY2 ligands we studied the reaction with dioxygen and observed an O-atom transfer to a benzylic C-H bond which was performed in the same manner as that of DBH. With the deuterium-labeled cis-2-d-IndPY2 ligand, we demonstrated that the reaction occurs by a stereospecific process with retention of configuration. In both cases (enzymatic vs. biomimetic) the O-atom transfers occur in a two-step process involving radical intermediates.

Hydrogen bonding and CH/π interactions for thestabilization of biomimetic zinc complexes: first examples of X-raycharacterized alcohol and amide adducts to a tetrahedral dicationic Zncenter

X-Ray analysis of two biomimetic n(N3ZnL)2+ complexes with L = nethanol and formamide revealed that hydrogen bonding and CH/π ninteractions between the guest ligand L and the calix[6]arene host nstructure play a key role in their stabilization.

Calix[6]arene-based models for mono-copper enzymes: a promising supramolecular system for oxidation catalysis

Abstract A novel supramolecular system that mimics the mono-copper site of enzymes is described. It is based on a calix[6]arene presenting either three pyridine (Py) or three imidazole (Im) groups that coordinate the copper center. Whereas Cu(I) is tetrahedral, Cu(II) is 5-coordinate. In both cases however, the Cu complexes possess a labile site located inside the calixarene cavity. A comparative study of the Py- and Im-based systems is presented in terms of chemical behaviour, electrochemistry and reactivity in the presence of hydrogen peroxide. Hence, the Py-based Cu(II) complex appears as the most interesting catalyst for the oxidation of aromatics and alcohols