title: Spin exchange monitoring of the strong positive homotropic allosteric binding of a tetraradical by a synthetic receptor in water.
abstract: The flexible tetranitroxide 4T has been prepared and was shown to exhibit a nine line EPR spectrum in water, characteristic of significant through space spin exchange (J(ij)) between four electron spins interacting with four nitrogen nuclei (J(ij) ≫ a(N)). Addition of CB[8] to 4T decreases dramatically all the Jij couplings, and the nine line spectrum is replaced by the characteristic three line spectrum of a mononitroxide. The supramolecular association between 4T and CB[8] involves a highly cooperative asymmetric complexation by two CB[8] (K1 = 4027 M(-1); K2 = 202,800 M(-1); α = 201) leading to a rigid complex with remote nitroxide moieties. The remarkable enhancement for the affinity of the second CB[8] corresponds to an allosteric interaction energy of ≈13 kJ mol(-1), which is comparable to that of the binding of oxygen by hemoglobin. These results are confirmed by competition and reduction experiments, DFT and molecular dynamics calculations, mass spectrometry, and liquid state NMR of the corresponding reduced complex bearing hydroxylamine moieties. This study shows that suitably designed molecules can generate allosteric complexation with CB[8]. The molecule must (i) carry several recognizable groups for CB[8] and (ii) be folded so that the first binding event reorganizes the molecule (unfold) for a better subsequent recognition. The presence of accessible protonable amines and H-bond donors to fit with the second point are also further stabilizing groups of CB[8] complexation. In these conditions, the spin exchange coupling between four radicals has been efficiently and finely tuned and the resulting allosteric complexation induced a dramatic stabilization enhancement of the included paramagnetic moieties in highly reducing conditions through the formation of the supramolecular 4T@CB[8]2 complex.
authors.affiliation: Aix-Marseille Université, CNRS, Institut de Chimie Radicalaire, UMR 7273 , 13397 Marseille, France.
authors.forename: David
authors.initials: D
authors.lastname: Bardelang
authors.forename: Gilles
authors.initials: G
authors.lastname: Casano
authors.forename: Florent
authors.initials: F
authors.lastname: Poulhès
authors.forename: Hakim
authors.initials: H
authors.lastname: Karoui
authors.forename: Jessica
authors.initials: J
authors.lastname: Filippini
authors.forename: Antal
authors.initials: A
authors.lastname: Rockenbauer
authors.forename: Roselyne
authors.initials: R
authors.lastname: Rosas
authors.forename: Valérie
authors.initials: V
authors.lastname: Monnier
authors.forename: Didier
authors.initials: D
authors.lastname: Siri
authors.forename: Anouk
authors.initials: A
authors.lastname: Gaudel-Siri
authors.forename: Olivier
authors.initials: O
authors.lastname: Ouari
authors.forename: Paul
authors.initials: P
authors.lastname: Tordo
mesh_terms: D000495:Allosteric Site; D001665:Binding Sites; D003497:Cyclic N-Oxides / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D008958:Models, Molecular; D009569:Nitric Oxide / Q000737:chemistry*; D062165:Receptors, Artificial / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D003497:Cyclic N-Oxides; D062165:Receptors, Artificial; C000603552:tetranitroxide 4T; D014867:Water; D009569:Nitric Oxide