Yves Le Mest

Calixarene‐Based Copper(I) Complexes as Models for Monocopper Sites in Enzymes

A cavity that acts as a molecular funnel is formed from calix[6]arene 1 and [CuI (NCCH3 )4 ]PF6 [Eq. (a)]. An exchange of the well-protected acetonitrile ligand for other nitriles RCN is only possible with small R groups. The protection of the copper ions precludes oxidative dimerization; thus, the complexes mimic the mononuclear site of copper enzymes.

Dioxygen activation at a mononuclear Cu(I) center embedded in the calix[6]arene-tren core.

The reaction of a cuprous center coordinated to a calix[6]arene-based aza-cryptand with dioxygen has been studied. In this system, Cu(I) is bound to a tren unit that caps the calixarene core at the level of the small rim. As a result, although protected from the reaction medium by the macrocycle, the metal center presents a labile site accessible to small guest ligands. Indeed, in the presence of O2, it reacts in a very fast and irreversible redox process, leading, ultimately, to Cu(II) species. In the coordinating solvent MeCN, a one electron exchange occurs, yielding the corresponding [CalixtrenCu-MeCN](2+) complex with concomitant release of superoxide in the reaction medium. In a noncoordinating solvent such as CH2Cl2, the dioxygen reaction leads to oxygen insertions into the ligand itself. Both reactions are proposed to proceed through the formation of a superoxide-Cu(II) intermediate that is unstable in the Calixtren environment due to second sphere effects. The transiently formed superoxide ligand either undergoes fast substitution for a guest ligand (in MeCN) or intramolecular redox evolutions toward oxygenation of Calixtren. Interestingly, the latter process was shown to occur twice on the same ligand, thus demonstrating a possible catalytic activation of O2 at a single cuprous center. Altogether, this study illustrates the oxidizing power of a [CuO2](+) adduct and substantiates a mechanism by which copper mono-oxygenases such as DbetaH and PHM activate O2 at the Cu(M) center to produce such an intermediate capable of C-H breaking before the electron input provided by the noncoupled Cu(H) center.

Electrochemically Triggered Double Translocation of Two Different Metal Ions with a Ditopic Calix(6)arene Ligand

A ditopic ligand based on a calix[6]arene with three imidazoles (Im) appended at the small rim and three triazoles (Tria) at the large one is able to form selectively two stable heterodinuclear complexes with Zn(II)(Im)/Cu(I)(Tria) and Cu(II)(Im)/Zn(II)(Tria). In the Cu(I) case, the zinc cation is preferentially coordinated at the Im site while the copper is bound at the Tria site. The situation is the opposite when Cu(II) is used. The position of the two cations within the complex can be electrochemically switched via the oxidation-reduction of the copper cation between oxidation states +I and +II. The presence of the zinc cation is crucial (i) to control the bistability of the system by an allosteric structuring role and (ii) to promote the metal switch since the monocopper complex exhibits reversible behavior with Cu located at the imidazole site in both oxidation states. This represents the first example of a double translocation of two different metal cations.

Mimicking the protein access channel to a metal center: effect of a funnel complex on dissociative versus associative copper redox chemistry.

The control of metal-ligand exchange in a confined environment is of primary importance for understanding thermodynamics and kinetics of the electron transfer process governing the reactivity of enzymes. This study reveals an unprecedented change of the Cu(II)/Cu(I) binding and redox properties through a subtle control of the access to the labile site by a protein channel mimic. The cavity effect was estimated from cyclic voltammetry investigations by comparison of two complexes displaying the same coordination sphere (tmpa) and differing by the presence or absence of a calix[6]arene cone surrounding the metal labile site L. Effects on thermodynamics are illustrated by important shifts of E(1/2) toward higher values for the calix complexes. This is ascribable to the protection of the labile site of the open-shell system from the polar medium. Such a cavity control also generates specific stabilizations. This is exemplified by an impressively exalted affinity of the calixarene system for MeCN, and by the detection of a kinetic intermediate, a noncoordinated DMF guest molecule floating inside the cone. Kinetically, a unique dissymmetry between the Cu(I) and Cu(II) ligand exchange capacity is highlighted. At the CV time scale, the guest interconversion is only feasible after reduction of Cu(II) to Cu(I). Such a redox-switch mechanism results from the blocking of the associative process at the Cu(II) state, imposed by the calixarene funnel. All of this suggests that the embedment of a reactive redox metal ion in a funnel-like cavity can play a crucial role in catalysis, particularly for metallo-enzymes associating electron transfer and ligand exchange.

Electrooxidation of porphyrin free bases: fate of the π-cation radical

In contrast to metalloporphyrins with non-electroactive metal centres, the π-cation radicals of porphyrin free bases (H2OEP, H2TPP, H2CdiE) electrogenerated in strictly anhydrous solvents are not stable and give rise to a quantitative chemical reaction. Conjunction of electrochemical and spectroscopic data (UV/VIS, EPR and NMR) demonstrates unambiguously that the porphyrin skeleton is not modified during the chemical reaction. The reaction product is the protonated free base, and thus the free base can be regenerated by reduction of the protons.

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)

Comparison of the properties of the 1,1,2,4,5,5-hexacyano-3-aza-penta-1,4-dienide[(NC)2CC(CN)NC(CN)C(CN)2] unit as anion and as ligand. Crystal structures of (Et4N)(C10N7) and [{Ag(C10N7)}∞]

Abstract The previously reported compounds, Et 4 N(C 10 N 7 ), 1 , and [{Ag(C 10 N 7 )} ∞ ], 2 , have been structurally characterized by X-ray diffraction. The C 10 N 7 unit acts in 1 as a monoanion and in 2 as a sophisticated bridging ligand (via the nitrogen atoms of its four external cyanogroups) leading to a structure with two crystallographically distinct silver cations. The first one has an usual pseudo-tetrahedral coordination, the second one presents an unexpected square planar coordination which is discussed. The geometry of the organic fragment is only slightly modified upon coordination: in both cases, the C 10 N 7 unit is essentially planar with central CN bond lengths of 1.317(4) and 1.334(4) A in 1 , 1.33(1) and 1.34(1) A in 2 and CNC angles of 128.3(3) in 1 and 129.2(9)° in 2 . In benzonitrile solutions, the C 10 N 7 anion shows two one electron diffusion-controlled reversible reduction rocesses, the first one leading to the radical species [(C 10 N 7 )] 2− characterized by ESR.

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.

Redox behaviour of the dicobalt cofacial porphyrin Co2FTF4 and related complexes adsorbed on graphite electrodes

Abstract Adsorbed on graphite electrodes, Co 2 FTF4 in a potent catalyst for O 2 reduction by a four-electron mechanism. The two observable redox surface waves have been previously assigned to the two cobalt centres. Using differential pulse polarography (DPP), the behaviour of this dicobalt cofacial dimer was re-examined at different pH values in aqueous solutions and in the presence of potential axial ligands for cobalt. From these observations and from a comparison with other adsorbed porphyrins it can be concluded that (a) the porphyrins are probably adsorbed by strong interactions between graphite and the aromatic rings, and (b) the more negative surface wave is cobalt-based but the more positive one is instead a porphyrin ring oxidation. This implies that the catalyst is in the Co II Co III FTF4 state when catalytic oxygen reduction begins.

Tris(triazolyl) calix[6]arene-based zinc and copper funnel complexes: imidazole-like or pyridine-like? A comparative study.

Huisgen dipolar cycloaddition leads straightforwardly to new funnel complexes based on the calix[6]arene macrocycle bearing three functionalized triazoles as coordinating units at the small rim. Coordination to Zn(II) and Cu(I) cations was studied using (1)H NMR and IR spectroscopies and cyclic voltammetry. The nature of the substituents on the triazole ring affects the behavior of the ligands and their coordinating ability and controls the host-guest properties of the metal receptors for exogenous substrates. Depending on their substitution pattern but also on the metal ion and the guest ligand, the triazole-based systems behave either imidazole-like or pyridine-like. The ease of preparation and the versatility of 1,4-disubstituted-1,2,3-triazoles with tunable steric and electronic properties make them promising candidates for further applications from biology to materials.