π-π Stacking Interaction of Metal Phenoxyl Radical Complexes.

π-π stacking interaction is well-known to be one of the weak interactions. Its importance in the stabilization of protein structures and functionalization has been reported for various systems. We have focused on a single copper oxidase, galactose oxidase, which has the π-π stacking interaction of the alkylthio-substituted phenoxyl radical with the indole ring of the proximal tryptophan residue and catalyzes primary alcohol oxidation to give the corresponding aldehyde. This stacking interaction has been considered to stabilize the alkylthio-phenoxyl radical, but further details of the interaction are still unclear. In this review, we discuss the effect of the π-π stacking interaction of the alkylthio-substituted phenoxyl radical with an indole ring.

Formation of Ni(II)-phenoxyl radical complexes by O2: a mechanistic insight into the reaction of Ni(II)-phenol complexes with O2.

A reaction of Ni(ClO4)2·6H2O with a tripodal ligand having two di(tert-butyl)phenol moieties, H2tbuL, and 1 equivalent of triethylamine in CH2Cl2/CH3OH (1 : 1, v/v) under N2 gave a NiII-(phenol)(phenolate) complex, [Ni(HtbuL)(CH3OH)2]ClO4. The formation of the NiII-phenoxyl radical complex by O2 was observed in the reaction of this complex in the solid state. On the other hand, the NiII-phenoxyl radical complex [Ni(Me2NL)(CH3OH)2]ClO4 was obtained by the reaction of H2Me2NL having a p-(dimethylamino)phenol moiety with Ni(ClO4)2·6H2O in a similar procedure under O2, through the oxidation of the NiII-(phenol)(phenolate) complex. However, a direct redox reaction of the NiII ion could not be detected in the phenoxyl radical formation. The results of the reaction kinetics, XAS and X-ray structure analyses suggested that the O2 oxidation from the NiII-(phenol)(phenolate) complex to the NiII-phenoxyl radical complex occurs via the proton transfer-electron transfer (PT-ET) type mechanism of the phenol moiety weakly coordinated to the nickel ion.

Recent Advances in One-Electron-Oxidized CuII -Diphenoxide Complexes as Models of Galactose Oxidase: Importance of the Structural Flexibility in the Active Site.

The phenoxyl radical plays important roles in biological systems as cofactors in some metalloenzymes, such as galactose oxidase (GO) catalyzing oxidation of primary alcohols to give the corresponding aldehydes. Many metal(II)-phenoxyl radical complexes have hitherto been studied for understanding the detailed properties and reactivities of GO, and thus the nature of GO has gradually become clearer. However, the effects of the subtle geometric and electronic structural changes at the active site of GO, especially the structural change in the catalytic cycle and the effect of the second coordination sphere, have not been fully discussed yet. In this Review, we focus on further details of the model studies of GO and discuss the importance of the structural change at the active site of GO.

Formation of the CuII -Phenoxyl Radical by Reaction of O2 with a CuII -Phenolate Complex via the CuI -Phenoxyl Radical.

Reaction of Cu(ClO4 )2 ⋅6 H2 O with a tripodal 2N2O ligand, H2 Me2 NL, having a p-(dimethylamino)phenol moiety, in CH2 Cl2 /MeOH (1:1 v/v) under basic conditions under an inert gas atmosphere gave [Cu(Me2 NL)(H2 O)] (1). The same reaction carried out under aerobic conditions gave [Cu(Me2 NL)(MeOH)]ClO4 (2), which could be obtained also from the isolated complex 1 by reaction with O2 in CH2 Cl2 /MeOH. The X-ray crystal structures of 1 and 2 revealed similar square-pyramidal structures, but 2 showed the (dimethylamino)phenoxyl radical features. Complex 1 exhibits characteristic CuII EPR signals of the d x 2 - y 2 ground state in CH2 Cl2 /MeOH at 77 K, whereas 2 is EPR-silent. The EPR and X-ray absorption fine structure (XAFS) results suggest that 2 is assigned to the CuII -(dimethylamino)phenoxyl radical. However, complex 1 showed different features in the absence of MeOH. The EPR spectrum of the CH2 Cl2 solution of 1 exhibits distortion from the d x 2 - y 2 ground state and a temperature-dependent equilibrium between the CuII -(dimethylamino)phenolate and the CuI -(dimethylamino)phenoxyl radical. From these results, CuII -phenoxyl radical complex 2 is concluded to be formed by the reaction of 1 with O2 via the CuI -phenoxyl radical species.

The effect of π-π stacking interaction of the indole ring with the coordinated phenoxyl radical in a nickel(ii)-salen type complex. Comparison with the corresponding Cu(ii) complex.

In order to gain new insights into the effect of the π-π stacking interaction of the indole ring with the phenoxyl radical moiety as seen in the active form of galactose oxidase, we have prepared Ni(ii) complexes of a methoxy substituted salen-type ligand containing a pendent indole ring on the dinitrogen chelate backbone and characterized their one-electron oxidized forms. The X-ray crystal structure analysis and the other physicochemical experiments of the Ni(ii) complex revealed no significant intramolecular interaction of the indole ring with the coordination plane. On the other hand, the X-ray crystal structures of the oxidized Ni(ii) complex exhibited the π-π stacking interaction of the indole ring mainly with one of the two phenolate moieties. While the phenoxyl radical electron was delocalized on the two phenolate moieties in the Ni(ii)-salen coordination plane, the phenolate moiety in close contact with the indole moiety was considered to be the initial oxidation locus, indicating that the indole ring interacted with the phenoxyl radical by π-π stacking. The UV-vis-NIR spectrum of the oxidized Ni(ii) complex with the pendent indole ring was different from that of the complex without the side chain indole ring, but the differences were rather small in comparison with the oxidized Cu(ii)-salen complexes with the π-π stacking interaction of the indole ring. Such differences are due to the electronic structure difference, the localized radical electron on one of the phenolate moieties in the oxidized Cu(ii) complexes being more favorable for the π-π stacking interaction.

π-π Stacking Interaction in an Oxidized CuII -Salen Complex with a Side-Chain Indole Ring: An Approach to the Function of the Tryptophan in the Active Site of Galactose Oxidase.

In order to gain new insights into the effect of the π-π stacking interaction of the indole ring with the CuII -phenoxyl radical as seen in the active form of galactose oxidase, we have prepared a CuII complex of a methoxy-substituted salen-type ligand, containing a pendent indole ring on the dinitrogen chelate backbone, and characterized its one-electron-oxidized forms. The X-ray crystal structures of the oxidized CuII complex exhibited the π-π stacking interaction of the indole ring mainly with one of the two phenolate moieties. The phenolate moiety in close contact with the indole moiety showed the characteristic phenoxyl radical structural features, indicating that the indole ring favors the π-π stacking interaction with the phenoxyl radical. The UV/Vis/NIR spectra of the oxidized CuII complex with the pendent indole ring was significantly different from those of the complex without the side-chain indole ring, and the absorption and CD spectra exhibited a solvent dependence, which is in line with the phenoxyl radical-indole stacking interaction in solution. The other physicochemical results and theoretical calculations strongly support that the indole ring, as an electron donor, stabilizes the phenoxyl radical by the π-π stacking interaction.

Characterization of the one-electron oxidized Cu(II)-salen complexes with a side chain aromatic ring: the effect of the indole ring on the Cu(II)-phenoxyl radical species.

To gain insights into the role of the proximal indole ring in the redox-active metal center as seen in galactose oxidase, we prepared the Cu(II)-salen-type complexes having a pendent indol-3-ylmethyl (1), methyl (2) or benzyl (3) group substituted on the ethylenediamine moiety and investigated the structures and redox properties by various physicochemical methods and theoretical calculations. Neutral complexes 1, 2, and 3 showed no significant difference in the UV-Vis-NIR and EPR spectra. One-electron oxidation of 1, 2, and 3 by addition of 1 equiv. of thianthrenyl radical gave [1]SbCl 6 , [2]SbCl 6 , and [3]SbCl 6 , respectively, which could be assigned to relatively localized phenoxyl radical species. The cyclic and differential pulse voltammograms of [1]SbCl 6 showed two redox waves with a large separation between the first and second redox potentials compared with the separations observed for [2]SbCl 6 and [3]SbCl 6 . This suggests that [1]SbCl 6 is more stabilized than [2]SbCl 6 and [3]SbCl 6 . The NIR band of [1]SbCl 6 showed a larger blue shift than that of [2]SbCl 6 and [3]SbCl 6 . The EPR spectrum of [2]SbCl 6 exhibited an intense signal at the g value of 2 due to partial disproportionation to form the EPR active two-electron oxidized complex [2] 2+ , while the EPR intensity of [1]SbCl 6 was much weaker than that of [2]SbCl 6 . These results indicate that the pendent indole moiety stabilizes the Cu(II)-phenoxyl radical in [1]SbCl 6 most probably by stacking with the phenoxyl moiety, which is further supported by DFT calculations.