No abstract

Mono-copper enzymes play an important role in biology and their functionality is based on Cu(II)͞Cu(I) redox processes. Modeling a mono-nuclear site remains a challenge for a better understanding of its intrinsic reactivity. The first member of a third generation of calixarene-based mono-copper ''funnel'' complexes is described. The ligand is a calix[6]arene capped by a tren unit, hence presenting a N4 coordination site confined in a cavity. Its Cu(II) complexes were characterized by electronic and EPR spectroscopies. The x-ray structure of one of them shows a five-coordinated metal ion in a slightly distorted trigonal bipyramidal geometry thanks to its coordination to a guest ligand L (ethanol). The latter sits in the heart of the hydrophobic calixarene cone that mimics the active site chamber and the hydrophobic access channel of enzymes. bioinorganic ͉ supramolecular ͉ electrochemistry ͉ host-guest ͉ enzyme model C opper enzymes such as dopamine ␤-monooxygenase, peptidylglycine ␣-hydroxylating monooxygenase, and nitrate reductase present a mononuclear copper ion buried in their active pocket opened to the external medium through a selective substrate access channel. This organization is responsible for the efficiency and selectivity of their catalytic activity (1-6). A good chemical model for metalloenzymes is a key to the understanding of the fundamental mechanisms involved in the catalytic cycle and to the design of efficient and selective new tools for the synthetic chemist. Most classical models, however, irreversibly lead to dinuclear species because of the propensity of reactive cupric species to undergo dimerization (7-10). Trying to gain insights into the chemical and redox specificity (11-15) resulting from the proteic environment of mono-copper sites, we have developed a supramolecular system that mimics not only the polyhistidine binding core but also the hydrophobic pocket that controls the second coordination sphere of the metal and its binding to an exogenous molecule. The model is based on a calix[6]arene functionalized with a nitrogenous coordination core (16 -24). The first generation of such ligands (calix[6]N 3 , see Fig. 1) (16, 17) presents three amino arms that, upon binding to the copper ion, constrain the calix[6]arene into the cone conformation required to play the role of a host for a guest ligand L. The so-called funnel complexes best stabilize Cu(I) in a tetrahedral N 3 L environment (16, 18 -20), whereas the Cu(II) species adopt a square-based pyramidal geometry N 3 L(S) with the binding of a water molecule (S is H 2 O) as a fifth ligand that is added to the system by an upper access from the outside (21,22). Despite the coordination number change between both redox states, the calixarene cavity acts as a selective funnel for small neutral organic molecules (L) as a result of the innercavity coordination site. Interestingly, the guest ligand L was shown to play the role of a shoetree molecule (23, 24) that shapes the calixarene structure and fixes the global organization of the co...