Structural and functional models for the dinuclear copper active site in catechol oxidases: Synthesis, X-ray crystal structures, magnetic and spectroscopic properties of μ-methoxo-bridged dinuclear copper(II) complexes with N-substituted sulfonamide ligands

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Abstract

Two new μ-methoxo-bridged dinuclear copper(II) complexes with a N-substituted sulfonamide, [Cu(μ-OMe)(L)(NH3)]2 (1) and [Cu(μ-OMe)(L)(DMSO)]2 (2) [HL, N-2-(4-methylbenzothiazole)benzenesulfonamide], have been prepared and characterized by single-crystal X-ray difraction analyses. Compound 1 crystallizes in the monoclinic space group C2/c with a=22.0678(18), b=7.9134(7), c=21.1186(18)Å, β=113.788(4)° and Z=8. Compound 2 crystallizes in the monoclinic space group C2/c with a=18.0900(10), b=9.5720(10), c=24.2620(10) Å, β=98.7120(10)° and Z=8. In both complexes the copper atoms have square–planar environments bridged by two oxygen atoms from methoxide groups. Magnetic susceptibility measurements indicate a very strong antiferromagnetic coupling between the copper(II) ions in both complexes (2J<−1000 cm−1). Electronic Paramagnetic Resonance (EPR) spectra of the two complexes both in solid and in solution are silent. 13C NMR spectra of the complexes in solid state have been studied. The complexes have been evaluated as model systems for the catechol oxidase enzyme using 3,5-di-tert-butylcatechol as the test substrate. Complex 2 is slightly more active than complex 1.

Introduction

In the active site of numerous metalloenzymes, two adjacent metal ions work cooperatively in order to achieve the transformation of substrate molecules. Dicopper sites play a pivotal role in biological oxygen chemistry and, consequently, the understanding of structural and functional aspects of copper metalloenzymes is a subject of intensive research [1], [2], [3], [4], [5], [6], [7], [8], [9]. A prominent member of these copper proteins is catechol oxidase which features a type 3 centre with two proximate copper ions (Cu· · ·Cu distance, 2.9 Å) in N-donor (histidine) ligation and which catalyses the two-electron oxidation of ortho-diphenols to the corresponding quinones. Recently, structures of the oxidised and the reduced forms of catechol oxidase from sweet potato were determined by X-ray crystallography.

Quite a number of mono- and dinuclear copper coordination compounds have been investigated as biomimetic catalysis for catechol oxidation [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]. Copper dinuclear complexes are generally found to be more reactive than mononuclear compounds, and a steric match between the dicopper site and the substrate is assumed to be advantageous [10], [11], [18], [20].

For several years we have been interested in the coordination properties of N-substituted sulfonamides (i.e., sulfathiazole and sulfamethazine) [21], [22], [23], [24], [25]. In general, these ligands require deprotonation of the sulfonamido group in order to promote the bond with the metal ion. Although we have report numerous metal complexes with this type of ligands examples of polynuclear metal complexes have been rather scarce. They are limited to two antiferromagnetic dimers, [Cu2(sulfathiazolate)4] [Sulfathiazole, 4-amino-N-(thiazol-2-yl)benzenesulfonamide] [22] and [Cu2(CH3COO)2(sulfamethazinate)2] [Sulfamethazine, 4-amino-N-(4,6-dimethyl-2-pyrimidinyl)benzenesulfonamide] [23] and to three trinuclear compounds with [Cu3(L)2(CH3COO)2(OH)2] core where HL are aromatic sulfonamide ligands derived from 2-aminomethylpyridine that present strong ferromagnetic coupling [24], [25]. Besides their remarkable magnetic properties these polinuclear compounds exhibit interesting structural features. In both dinuclear complexes the copper ions are bridged by nonlinear NCN fragments of the ligands (a type of bridge also found in copper complexes with relevant biological molecules such as adenine). In the trinuclear compounds the three copper atoms form an exact linear arrangement and are connected by a hydroxo bridge and a bidentate synsyn carboxylato group.

The interesting structural and magnetic properties of these dinuclear and trinuclear copper compounds has lead us to develop a new series of N-benzothiazole sulfonamides and to study their coordination properties to copper(II). Here, on the basis of the proposed catalytic mechanism and the X-ray information available for catechol oxidase, we have planned the synthesis of model compounds having as a main requirement the presence of two copper centres.

In this work, the synthesis, crystal structures and magnetic properties of two new dicopper complexes with the N-2-(4-methylbenzothiazole)benzenesulfonamide ligand are described and their catecholase activity is studied using 3,5-di-tert-butylcatechol as a convenient model substrate for the identification of functional models for the metalloenzymes, in a biomimetic approach.

Section snippets

General

Reagents and solvents were commercially available and used without further purification

Elemental analyses were performed on a Carlo Erba AAS instrument. IR spectra were recorded as KBr pellets on a Mattson satellite FT-IR in the range 4000–400 cm−1. Diffuse reflectance spectra of the Nujol mulls of the complexes were carried out on a Shimadzu UV-2101 PC spectrophotometer. Electrochemical measurements were made using a Princenton Applied Research Model 273A potentiostat/galvanostat. Cyclic

[Cu(μ-OMe)(L)(NH3)]2 (1) and [Cu(μ-OMe)(L)(DMSO)]2 (2)

A blue crystal, crystal size 0.17×0.15×0.12 mm, monoclinic, space group C2/c (determined from the systematic absences) was used for the data collection of compound 1. A dark green crystal, crystal size 0.40×0.27×0.25 mm, monoclinic, space group C2/c (determined from the systematic absences and structure determination) was used for the data collection of compound 2. For both complexes data collection was performed at 200(2) K on a Nonius KappaCCD single-crystal diffractometer, using Cu-Kα

Catalytic activity for the oxidation of 3,5-di-tert-butylcatechol

The catalytic activity of the complexes for the oxidation of 3,5-di-tert-butylcatechol with O2 was studied at 25 °C by adding 1 ml of 3,5-di-tert-butylcatechol (5 mM) in methanol to 1 ml of solutions (5×10−5 M) of the complexes 1 and 2 and recording the electronic spectra in the range between 300 and 550 nm at different time intervals (10, 20, 30, 50, 70 and 90 min). The quinone formed in the oxidation in methanol was determined from the measured absorbances at 400 nm of the resulting solutions

Description of the crystal structures

The crystal structures of the complexes 1 and 2 are illustrated in Fig. 1, Fig. 2, respectively. Bond distances and angles relevant to the copper co-ordination sphere of both compounds are listed in Table 2.

The copper coordination structures of 1 and 2 are similar to each other. Bond lengths and angles differ only slightly. In the two complexes the geometry around each copper atom is distorted square planar. For 1, it is formed by two μ-methoxo oxygen atoms, an ammonia nitrogen atom and a

Acknowledgements

The authors thank Prof. J.A. Real (University of Valencia) for magnetic measurements and E. Monzani (University of Pavia) for his helpful comments and suggestions. J.B. and G.A. acknowledge financial support from the Spanish CICYT (BQU2001-3173-C02-01). M. G.-A. wishes to thank the Spanish Ministerio de Ciencia y Tecnologı́a for a doctoral fellowship. J.-M. M.-B. and S. G.-G. are grateful for financial support from CICYT (BQU2000-0219) and FICYT (PR-01-GE-4).

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