Monocopper Center Embedded in a Biomimetic Cavity:  From Supramolecular Control of Copper Coordination to Redox Regulation

Abstract

The electrochemical behavior of diversely substituted Cu-N3-calix[6]arene, enzyme-like, "funnel" complexes is analyzed. The Cu(II)/Cu(I) redox process is regulated by the supramolecular organization of the Cu coordination. The presence of a "shoetree" alkyl nitrile guest molecule inside the host cavity is a prerequisite for a dynamic redox behavior. Combination of supramolecular CH-pi weak interactions with the calixarene cavity and electronic/steric effects from the N3 substituting groups (pyridine, imidazole, pyrrolidine) enforces the preferential geometrical pattern adopted by Cu. This dictates the pathway of the electron-transfer process and, thus, the thermodynamics and kinetics of the redox reaction in the framework of a square-scheme mechanism. The present observations recall strongly the redox control exerted by the protein matrix on copper proteins through biological concepts such as induced fit mechanism, protein foldings, and entatic and allosteric effects.

Collaborative routes to clarifying the murky waters of aqueous supramolecular chemistry

“…With a few important exceptions, 105 supramolecular chemists have paid less attention to enzyme mimicry. With respect to understanding and control, the focus has been exclusively on secondary structure.…”

Electrochemical and homogeneous electron transfers to the Alzheimer amyloid-β copper complex follow a preorganization mechanism

“…It involves classical stepwise pathways as already considered for copper complexes (26)(27)(28)(29). Two stepwise pathways may be envisaged.…”

Toward an Allosteric Metallated Container

“…Formation of a green 1:1 Cu 2+ complex with bidentate coordination of tris(5-methylpyrid-2-yl)amine was confirmed by X-ray structural analysis (see below) of the crystalline precipitate formed when the solution was treated with NaClO 4 and allowed to stand for several days at ambient temperature. In the noncompetitive solvent CH 2 Cl 2 , the Tris(pyrid-2-yl)methanol (4) is expected to form more stable tripodal transition-metal complexes due to better preorganization of the pyridyl groups linked to the central sp 3 carbon atom. In contrast, the coordination mode is am-biguous due to potential participation of the (deprotonated) OH group in metal binding.…”

“…The dihedral angles between the pyridyl rings and the (C) 3 plane were found to be 23.0, 40.2 and 40.9°( Figure 5). (2) [13] [CuL 2 -(NCCH 3 ) 2 ]·F 3 CSO 3 , [14] [CuL 2 (NO 3 ) 2 ] [15] and [CuL 2 -(ClO 4 ) 2 ].…”

“…[1] The design of such compounds has meanwhile developed into an important research line in bioinorganic and supramolecular chemistry, including "metallated containers" [2] and calixarene-based "funnel complexes". [3] In this context, complexes of tripodal ligands that mimic the tris(imidazole) donor sites in a number of zinc and copper proteins have attracted considerable attention; [4] open cavities around the metal site are generated by attachment of bulky substituents to the ligating groups. Substrate selectivity and shielding might be further optimized by complete encapsulation of the metal ion within a cage-like ligand framework without hindering access of the substrate to free metal sites, but synthesis of such compounds is expected to be more challenging and less versatile.…”