Synthesis and Characterization of Imidazolate-Bridged Dinuclear Complexes as Active Site Models of Cu,Zn-SOD

New dinucleating ligands having two metal-binding sites bridged by an imidazolate moiety, Hbdpi and HMe 4 bdpi (Hbdpi = 4,5-bis(di(2-pyridylmethyl)aminomethyl)imidazole, HMe 4 bdpi = 4,5-bis(di(6-methyl-2-pyridylmethyl)aminomethyl)imidazole), have been designed and synthesized as model ligands for copper−zinc superoxide dismutase (Cu,Zn-SOD). The corresponding mononucleating ligand, MeIm(Py) 2 (MeIm(Py) 2 = ((1-methyl-4-imidazolyl)methyl)bis(2-pyridylmethyl)amine), has also been synthesized for comparison. The imidazolate-bridged Cu(II)−Cu(II) homodinuclear complexes represented as [Cu 2 (bdpi)(CH 3 CN) 2 ](ClO 4 ) 3 ·CH 3 CN·3H 2 O ( 1 ), [Cu 2 (Me 4 bdpi)(H 2 O) 2 ](ClO 4 ) 3 ·4H 2 O ( 2 ), a Cu(II)−Zn(II) heterodinuclear complex of the type of [CuZn(bdpi)(CH 3 CN) 2 ](ClO 4 ) 3 ·2CH 3 CN ( 3 ), and a Cu(II) mononuclear complex of [Cu(MeIm(Py) 2 (CH 3 CN)](ClO 4 ) 2 ·CH 3 CN ( 4 ) have been synthesized, and the structures of complexes 1 − 4 were determined by X-ray crystallography. The Cu(II)−Zn(II) distance of 6.197(2) Å in 3 agrees well with that of native Cu,Zn-SOD (6.2 Å). All the metals in 1 − 4 have pentacoordinate geometries with the imidazolate or 1-methylimidazole nitrogen, two pyridine nitrogens, the tertiary amine nitrogen, and a solvent (CH 3 CN or H 2 O). The coordination site occupied by a solvent can be susceptible to ligand substitution, providing a binding site for substrate superoxide. Magnetic measurements of the Cu(II)−Cu(II) homodinuclear complexes 1 and 2 have shown an antiferromagnetic exchange interaction with a coupling constant of −2 J = 73.4 and 145.9 cm - 1, respectively. The ESR spectra of 1 and 2 exhibited broad signals centered at g ≅ 2.13 due to the spin−spin interaction between two copper ions, while the ESR spectrum of the Cu(II)−Zn(II) heterodinuclear complex 3 showed a signal which is characteristic of mononuclear trigonal-bipyramidal Cu(II) complexes ( g ∥ = 2.10, g ⊥ = 2.24, | A ∥ | = 11.7 mT, and | A ⊥ | = 12.4 mT). The cyclic voltammograms of homodinuclear complexes ( 1 and 2 ) in CH 3 CN gave two reversible waves which correspond to the Cu(I,I)/Cu(I,II) and Cu(I,II)/Cu(II,II) redox processes: E 1/2 = −0.31 and −0.03 V vs Ag/AgCl for 1 and E 1/2 = −0.29 and +0.12 V vs Ag/AgCl for 2, respectively. On the other hand, the Cu(II)−Zn(II) heterodinuclear complex 3 exhibited one Cu(I)/(II) reversible wave, E 1/2 = −0.03 V vs Ag/AgCl, which is shifted in a positive direction (0.21 and 0.19 V) as compared to those of the corresponding Cu(II) mononuclear complexes. All the examined complexes catalyzed the dismutation of superoxide at biological pH; the SOD activity increased in the order 2 < 1 < 3 .