Tuning the Activity of Catechol Oxidase Model Complexes by Geometric Changes of the Dicopper Core

• Published in: Chemistry : a European journal 2002-01, Vol.8 (1), p.247-258
• Main Authors: Ackermann, Jens, Meyer, Franc, Kaifer, Elisabeth, Pritzkow, Hans
• Format: Article
• Language: English
• Subjects: bimetallic complexes; bioinorganic chemistry; Catalysis; Catalytic Domain; Catechol Oxidase - chemistry; Catechol Oxidase - metabolism; Catechols - chemistry; Catechols - metabolism; Chemical Phenomena; Chemistry, Physical; Chlorates - chemistry; cooperative phenomena; copper; Copper - chemistry; Copper - metabolism; Crystallography, X-Ray; Hydrogen Bonding; Hydrogen Peroxide - chemistry; Ligands; Models, Molecular; Molecular Conformation; Molecular Mimicry; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Organometallic Compounds - metabolism; oxidation; Oxidation-Reduction; Pyrazoles - chemistry; Pyrazoles - metabolism; Quinones - chemistry; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/1521-3765(20020104)8:1<247::AID-CHEM247>3.0.CO;2-P

Dicopper(II) complexes of a series of different pyrazolate‐based dinucleating ligands [L1]−–[L4]− have been synthesized and characterized structurally and spectroscopically. A major difference between the four complexes is the individual metal–metal separation that is enforced by the chelating side arms of the pyrazolate ligand scaffold: it varies from 3.45 Å in 2⋅(BF4)4 to 4.53 Å in 4⋅(ClO4)2. All complexes have been evaluated as model systems for the catechol oxidase enzyme by using 3,5‐di‐tert‐butylcatechole (DTBC) as the test substrate. They were shown to exhibit very different catecholase activities ranging from very efficient to poor catalysts (kobs between 2430±202 and 22.8±1.2 h−1), with an order of decreasing activity 2⋅(ClO4)4> 1⋅(ClO4)2>3⋅(ClO4)2≫4⋅(ClO4)2. A correlation of the catecholase activities with the variation in Cu⋅⋅⋅Cu distances, as well as other effects resulting from the distinct redox potentials, neighboring groups, and the individual coordination spheres are discussed. Saturation behavior for the rate dependence on substrate concentration was observed in only two cases, that is, for the most active 2⋅(ClO4)4 and for the least active 4⋅(ClO4)2, whereas a catalytic rate that is almost independent of substrate concentration (within the range studied) was observed for 1⋅(ClO4)2 and 3⋅(ClO4)2. H2O2 was detected as the product of O2 reduction in the catecholase reaction of the three most active systems. The structures of the adducts of “L3Cu2” and “L4Cu2” with a substrate analogue (tetrachlorocatecholate, TCC) suggest a bidentate substrate coordination to only one of the copper ions for those catalysts that feature short ligand side arms and correspondingly exhibit larger metal–metal separations; this possibly contributes to the lower activity of these systems. TCC binding is supported by several H‐bonding interactions to water molecules at the adjacent copper or to ligand‐side‐arm N‐donors; this emphasizes the importance of functional groups in proximity to the bimetallic active site. The effect of the ligand side arm. Dicopper(II) complexes of a series of pyrazolate‐based dinucleating ligands have been synthesized, characterized, and evaluated as model systems for catechol oxidase, as shown in the scheme. The length of the ligand side arms determines the Cu⋅⋅⋅Cu separation in the individual complexes. Correlation of the very different catecholase activities of the four complexes with this variation, as well as other effects resulting