J. CHEM. SOC. DALTON TRANS. 1995 31 Comparative Study of the Catalytic Oxidation of Catechols by Copper(ii) Complexes of Tripodal Ligands Mitchell R. Malachowski,*-e Hong B. Huynh,B Laura J. Tomlinson,a Richard S. Kellyb and James W. Furbee jun? a Department of Chemistry, University of San Diego, Alcala Park, San Diego, CA 921 10, USA Illinois 60045, USA Department of Chemistry, Lake Forest College, 555 North Sheridan Road, Lake Forest, Copper( 11) complexes of the ligands tris( 2-pyridylmethy1)amine (tpyma), tris( 2- pyridylet hyl) amine (tpyea), tris( 3,5-dimethylpyrazol- 1 - ylmethy1)amine (tpzma) and tris( 3.5-dimethylpyrazol- 1 -ylethyl) - amine (tpzea) were prepared. The complexes, [Cu(ligand)CI]CI or [Cu(ligand)(H,O)] [BF,],, were characterized by a combination of absorption and EPR spectroscopies and chemical analysis.The ability of the complexes to oxidize 3.5-di-tert-butylcatechol to 3,5-di-tert-butyl-o-benzoquinone has been studied and the results show that the rate of reaction is dependent on the nature of the heterocyclic donor, its basicity, steric considerations, the chelate ring size and the type of exogenous donor present. Large variations in the rate were observed with the most effective catalysts being those with pyridine donors which formed six-membered chelate rings; the complex [Cu(tpyea) (H,O)] [BF,], was the most active while [Cu(tpzea) (H,O)] [BF,], and [Cu(tpzea)CI]CI were inactive. Electrochemical data for the series of compounds show that there is a non-linear relationship between their ability to oxidize catechols and their reduction potentials.The most effective catalysts were those complexes which exhibited reduction potentials close to 0.00 V, while those that deviated from that potential by 200-300 mV in either direction were largely inactive. Within the range of complexes which were active, a steric match between the substrate and the complex also largely defined their reactivity. Comparisons to the biological system tyrosinase are drawn. Tripodal ligands continue to find extensive use in the synthesis of metal complexes because of their ease of preparation, the wealth of spectroscopic and X-ray crystallographic data which has been generated for their metal complexes, and the predictable changes in the physical properties of the metal complexes as the ligand sets are varied.We are particularly interested in using nitrogen-containing tripodal ligands as models for the protein backbone of the enzyme tyrosinase. Spectroscopic and physical studies indicate that this metal- loenzyme has two copper atoms at the active site, each bound to three nitrogens of histidine residues from the protein back- bone.14 Tyrosinase is a monooxygenase and, as is shown in Fig. 1, it is responsible for the air oxidation of phenol to catechol (benzene- 1,2-diol) (cresolase activity) and the subse- quent oxidation of catechol to o-benzoquinone (catecholase activity) . Models for biological systems can be designed to reproduce the structural, spectroscopic or reactivity properties of the protein of interest. In this study we are particularly interested in developing a better understanding of the parameters which lead to effective catalysis for synthetic copper(@ complexes.Synthetic model studies of the reactivity of copper(I1) complexes towards catechols implicate the geometry around the copper ions as the most dominant feature in determining the catalytic activity of the complexes. Non-planar mononuclear complexes and binuclear complexes with the two coppers separated by ca. 3-4 A catalyse the oxidatiori process, while square-planar mononuclear complexes and dinuclear complexes with a large Cu-Cu distance ( > 5 A) are generally unreactive towards catechol.6-17 No correlation between the redox potential of the copper complexes and the rate of the oxidation has been uncovered; instead, the determining factor is thought to be a steric match between the substrate and the copper ion.Systematic studies which selectively change the structural and electronic features of copper complexes and assess the effect on aoH - aoH OH aO"- OH Fig. 1 Reactions catalysed by tyrosinase their catalytic properties should help explain which features of tyrosinase are primarily responsible for its activity. In addition, studies of this type would allow for the rational design and synthesis of more efficient catalysts. There is a rich chemistry associated with the reactivity of copper complexes of tripodal ligands. Germane to this work are the reactivity studies on copper(1) complexes of quinoline and pyridine tripodal ligands which have been shown to form copper-oxygen complexes of varying stoichiometry depending on the nature of the ligand.18*19 Kinetic and thermodynamic properties have been determined for the reactions between 0, and the copper(1) tripodal complexes which show that ligand modifications dramatically effect the rate of formation and dissociation of the Cu-0, adducts.20,21 Copper-oxygen adducts have been shown to be important intermediates in a number of protein active sites including tyrosinase,22 haemo- cyan in^,^^.^^ amine oxidases,, phenylalanine hydroxylase 26 and dopamine B-hydroxylase.' ' As part of our studies on the electron-transfer properties of copper(I1) complexes, we have shown that the tripodal ligand tri~(3~5-dimethylpyrazol- 1 -ylmethyl)amine (tpzma) forms copper(n) complexes which are capable of mediating electron transfer to both negative and positively charged32 J.CHEM. SOC. DALTON TRANS. 1995 proteins. ' Nafion-coated glassy carbon electrodes containing the copper(I1) complex show electron transfer to cytochrome c or to tyrosinase, a result which is unobtainable with the untreated electrode. A second-order EC (electrochemical- chemical) catalytic reaction mechanism is operative at the reduction potential of the copper complex for both the reduction of cytochrome c and tyrosinase. Along with their electron-transfer properties, we have also been probing the catalytic properties of copper(rr) com- plexes.6-8 The kinetic results for the oxidation of catechol to benzoquinone using the copper(I1) complexes of the tripodal ligands tpzma and tris(3,5-dimethylpyrazol- 1 -ylethyl)amine (tpzea) have recently been reported.' The trigonal-bipyramidal tpzma complexes were found to act as efficient catalysts towards the oxidation of catechol, while the square-pyramidal complexes formed from tpzea did not catalyse this oxidation. Regardless of the various permutations present (monomeric or dimeric, the nature of the fifth ligand, or the counter ion), the copper(@ complexes of tpzma catalysed the oxidation of catechol and substituted catechols, while those of tpzea did not. The lack of reactivity exhibited by the square-pyramidal tpzea complexes is striking since simple copper(I1) salts such as CuC1, will catalyse the reaction. In order to determine whether the results obtained using the pyrazole-containing ligands are a general feature of the reactivity for trigonal-bipyramidal and square-pyramidal copper(I1) complexes, the pyridine analogues of these two ligands, tris(2-pyridylmethy1)amine (tpyma) and tris(2-pyridylethy1)amine (tpyea) and a variety of their copper- (11) complexes have been prepared. The reactivity of the complexes towards 3,5-di-tert-butylcatechol was studied using UV/VIS spectroscopy and the results compared to those previously found for the tpzma and tpzea complexes.In addition, electrochemical data were obtained in order to attempt to correlate the reduction potentials to the reactivity of the complexes. Experimental General.-All reagents and solvents were purchased from commercial sources and used as received unless noted otherwise. 1 -(Hydroxymethyl)-3,5-dimethylpyrazole, tris( 3,5- dimethylpyrazol-1 -ylethyl)amine (tpzea),,' tris(3,5-dimethyl- pyrazol- 1 -ylmethyl)amine (tpzma),' and [Cu(tpzea)(H,O)]- [BF,], 30 were prepared by the literature methods.Melting points were obtained with the use of a Fisher-Johns apparatus and are uncorrected. The C, H and N elemental analyses were performed at Desert Analytical, Tucson, AZ. Metal contents were determined complexometrically by indirect titration with Na,(H,edta) (H,edta = ethylenediaminetetraacetic acid) and zinc acetate after destruction of the sample with concentrated nitric acid. Electronic spectroscopy was performed on a Uvikon 860 spectrophotometer using methanol as the solvent, while IR spectra were recorded on a Nicolet 5ZDX instrument. Proton NMR spectra were recorded on a Bruker WM 250 instrument using CDCI, as the solvent. All chemical shifts are reported in ppm relative to an internal standard of SiMe,.X-Band EPR spectra were recorded on a Varian E-3 spectrophotometer at 77 K in methanol solution using diphenylpicrylhydrazyl (dpph) as the calibrating field marker. Kinetics were followed '@)3 N W )3 tpzma tpzea spectrophotometrically on a Uvikon 860 spectrophotometer by following the appearance of 3,5-di-tert-butyl-o-benzoquinone over time using the 390 nm peak. The metal complex (0.3 cm3 of a 1 x mol dm-3 methanol solution) and a 2.0 cm3 solution (1 x lo-' mol dm-, methanol solution) of 3,5-di-tert-butyl- catechol were added together in the spectrophotometric cell at 25 "C. Electrochemistry was performed in an aqueous solution that was 0.1 mol dm-, in Tris [tris(hydroxymethyl)methylamine] buffer.The concentration of metal complex was 1 x lo-, mol drn-,. All complexes undergo chemically reversible oxidation- reduction reactions at a glassy carbon electrode with an Ag-AgC1 reference electrode and a platinum wire as the auxiliary electrode. CAUTlO N : perchlorates may explode violently. Syntheses of Ligands.-Tris(2-pyridylmethyl)amine (tpyma). To a solution of tris(2-pyridylmethy1)ammonium perchlorate 32 (6.0 g, 0.015 mol) in H 2 0 (200 cm3) was added 5 mol dm-3 NaOH (40 cm3). The solution was stirred at room temperature for 3 h and extracted with CHCl, (3 x 50 cm3). The CHCl, solu- tion was dried over Na2S04, filtered, and evaporated to 10 cm3. After cooling overnight to - 20 "C, white crystals formed (2.66 g, 61%), m.p.84-86 "C (lit.,32 84.5-86.5 "c); GH(CDC13) 4.05 (6 H, s, CH,), 7.1 1-7.65 (9 H, m, py), 8.40-8.52 (3 H, d, py). Tris(2-pyridylethy1)amine (tpyea). A solution of 2-vinyl- pyridine (25.0 cm3, 0.238 mol) (purified by passage through an alumina column) and ammonium acetate (3.0 g, 0.039 mol) in MeOH-H,O (2: 1, 300 cm3) was refluxed for 5 d. The solvent was evaporated, the residue dissolved in 20% NaOH (1 00 cm3) and then extracted with CH,Cl, (4 x 100 cm3). The combined organic solvents were dried over Na,SO,, filtered and evaporated. The product was purified using flash chromato- graphy on silica using MeOH as the eluent. A colourless oil (5.6 g, 43%) was obtained; GH(CDCI,) 2.53 (6 H, t, CH,), 3.02 (6 H, t, CH,), 7.09-7.84 (9 H, m, py), 8.63-8.82 (3 H, d, py).Syntheses of Metal Complexes.-[Cu(tpyma)( H,O)] [ BF,] 1. A solution of Cu(BF,),.6H2O (0.46 g, 1.3 mmol) in MeOH (25 cm3) was filtered into a solution of tpyma (0.39 g, 1.3 mmol) in MeOH (10 cm3). The solvent was reduced in volume to 5 cm3 and diethyl ether was slowly added. Blue crystals (0.30 g, 43%) formed on standing at -20 "C (Found: C, 39.30; H, 4.05; Cu, 11.90; N, 10.40. C,,H,oB,CuF,N,O requires C, 39.65; H, 3.70; Cu, 11.65; N, 10.25%). [Cu(tpyma)Cl]C12. A solution of CuC1,=2H2O (1.17 g, 6.88 mmol) in MeOH (50 cm3) was filtered into a solution of tpyma (2.00 g, 6.88 mmol) in MeOH (25 cm3). The solution was filtered and green-blue crystals (1.52 g, 52%) formed on standing at -20 "C(Found: C, 50.55; H, 4.70; Cu, 15.25; N, 12.95.C18H,,- Cl,CuN, requires C, 50.90; H, 4.30; Cu, 14.95; N, 13.20%). [Cu(tpyea)(H,O)][BF,], 3. A solution of Cu(BF,),*6H2O (2.08 g, 6.02 mmol) in MeOH (50 cm3) was filtered into a solution of tpyea (2.00 g, 6.02 mmol) in MeOH (25 cm3). Slow evaporation of the solvent in air led to the isolation of blue crystals (1.95 g, 55%) (Found: C, 43.20; H, 4.50; Cu, 10.85; N, 9.60. C2,H26B,CuF,N40 requires C, 42.90; H, 4.45; Cu, 10.80; N, 9.55%). [Cu(tpyea)CI]CI 4. A solution of CuC1,.2H20 (1.03 g, 6.02 mmol) in MeOH (50 cm3) was filtered into a solution of tpyea (2.00 g, 6.02 mmol) in MeOH (25 cm3). Green crystals (2.05 g, 73%) formed on standing at -20°C (Found: C, 54.35; H, 5.30; Cu, 13.70; N, 11.75. C2,H,,Cl,CuN, requires C, 54.00; H, 5.20; Cu, 13.60; N, 12.00%).[Cu(tpnna)(H,O)][BF,],-H,O 5. A solution of Cu(BF,),- 6H,O (2.04 g, 5.90 mmol) in MeOH (50 cm3) was filtered into a solution of tpzma (2.00 g, 5.90 mmol) in MeOH (25 cm3). On allowing the solution to stand overnight at -20 "C, blue crystals (1.67 g, 46%) were formed (Found: C, 35.55; H, 5.25; Cu, 10.40; N, 16.45. Cl8H3,B,CuF,N,0, requires C, 35.15; H, 5.10; Cu, 10.40; N, 15.95%).J. CHEM. SOC. DALTON TRANS. 1995 33 [Cu(tpzma)Cl]C16. A solution of CuC12.2H20 (1.01 g, 5.90 mmol) in MeOH (50 cm3) was filtered into a solution of tpzma (2.00 g, 5.90 mmol) in MeOH (25 cm3). The solution was filtered, reduced in volume to 25 an3, and cooled to -20 "C from which small green crystals (1.71 g, 61%) formed (Found: C, 45.00; H, 6.00; Cu, 13.20; N, 20.55.C18H2,C12CuN, requires C, 45.45; H, 5.75; Cu, 13.35; N, 20.60%). [Cu(tpzea)Cl)C18. To a solution of CuC12*2H20 (1.13 g, 6.60 mmol) in MeOH (50 cm3) was added tpzea (2.53 g, 6.60 mmol) in MeOH (25 cm3). After filtration, the green solution was slowly treated with diethyl ether. It was cooled to -20 "C from yielding green crystals (1.23 g, 36%) (Found: C, 48.20; H, 6.30; Cu, 12.30; N, 18.75. C2,H3,C12CuN, requires C, 48.70; H, 6.45; Cu, 12.25; N, 18.90%). Results Synthesis.-Pyrazole- and pyridine-containing ligands have found extensive use in a variety of multidentate ligands complexed to metal ions which serve as models for metal lop rote in^.^^ The donor ligands in this study were chosen because of their demonstrated similarity to the biological donor imidazole.34 Tripodal compounds are attractive candidates for ligands because of the variety and predictability of geometries which are possible for their subsequent metal complexes. Tris(2-pyridylmethy1)amine (tpyma) was synthesized using a modification of the method of Anderegg and Wenk32 via the condensation of 2-(chloromethy1)pyridine and 2-(aminomethy1)- pyridine through the isolation of the intermediate perchlorate salt of the amine. Tris(3,5-dimethylpyrazol-l-ylmethyl)amine (tpzma) was synthesized from ammonium chloride and 1 -(hydroxymethyl)-3,5-dimethylpyrazole using the method of Driessen 29 for the pyrazolylmethylation of amines, while tris(2-pyridylethy1)amine (tpyea) was prepared from ammonium acetate and 2-vinylpyridine using an adaptation of Reich and Levine for the pyridylethylation of amines.Tris(3,Sdimethyl- pyrazol- 1 -ylethyl)amine (tpzea) was prepared from tris(2- chloroethy1)amine and the 3,5-dimethylpyrazolate anion as described by Sorrel1 and Jame~on.~' A variety of copper(I1) complexes formed from these ligands were isolated in crystalline form. A methanolic solution of the ligand was added to either Cu(BF4),*6H20 or CuCl,*2H20 in methanol from which the complexes were isolated directly. Spectroscopy.-Elemental analyses, EPR spectroscopy and electronic spectroscopy show the complexes to exist as five-co- ordinate species of the form [Cu(ligand)(H,O)][BF41, or [Cu(ligand)Cl]Cl. In the case of tpzma with Cu(BF4),.6H2O two different complexes can be isolated, a blue form and a green one. The blue compound has been identified as a dimer of formula [Cu,(tpzma),F(H,O),] [BF,] in the solid state.36 Evidence for its formulation as a dimer came from elemental analysis, solid-state EPR spectroscopy and the crystal structure of the analogous cobalt complex. However, it was shown by conductivity studies that even in nitromethane, the dimer breaks down to monomeric cations. In our work, we have isolated the green complex and studied its solution properties by EPR spectroscopy and electrochemistry (see later); neither technique shows evidence of a dimer in solution and the elemental analysis is consistent with the formulation [Cu- Copper(@ complexes formed from tripodal ligands typically exist as five-co-ordinate species of either trigonal-bipyramidal or square-pyramidal geometry, depending on the length of the arms connecting the donor atoms.It has previously been shown using a combination of X-ray crystallography, electronic spectroscopy and EPR spectroscopy that numerous copper@) complexes formed from tpzea and tpyea (which have three atoms separating the donor atoms) exist both in solution and in the solid state as five-co-ordinate mononuclear species with square-pyramidal geometry. 30*3 ' In comparison, complexes of (tpzma)(H,O)I CBF4I 2-20. tpzma and tpyma (which have two atoms separating the donors) generally form copper(r1) complexes with trigonal- bipyramidal geometry. 36*38 Chemical and spectroscopic analyses of the copper(I1) complexes prepared here are in accord with those assignments. Electronic and EPR spectroscopic data for the complexes are given in Table 1.The EPR spectra for complexes of tpyea and tpzea display gll > g , > 2.00 and A l l = (120-150) x lo4 cm-', typical of a square-pyramidal geometry. 39 An illustration of this is the frozen solution spectrum of [Cu(tpzea)- (H20)][BF4I2 7 which has gll = 2.23, g, = 2.09 and All = 156 x lo4 cm-'. This is in contrast to complexes formed from tpyma and tpzma which give EPR spectra consistent with a trigonal-bipyramidal geometry (8, > gll > 2.00, A l l = (60- 100) x lo4 cm-I). For example, for [Cu(tpyma)Cl]C12 gll = 1.98, g , = 2.26 and A l l = 80 x lo4 cm-'. Unlike the results from the solid-state analysis of [Cu2- (tpzn1a)~F(H~O),][BF~3,,~~ in the frozen solution EPR spectrum of the green complex formed from tpzma and CU(BF,)~-~H~O a half-field signal is not observed.Along with the electrochemical results described below, we believe that the complex exists as [Cu(tpzma)(H,O)][BF,], in the solid state and in solution. The electronic absorption spectra of five-co-ordinate copper(rr) complexes also fall into two general categories.,' Square-pyramidal complexes typically show a high-energy absorption band in the visible region with a low-energy shoulder. In contrast, trigonal-bipyramidal complexes have a low-energy absorption band with a high-energy shoulder in the visible region. As shown in Table 1, the results for complexes 1- 8 are consistent with these criteria. For example, the electronic spectrum of [Cu(tpyea)Cl]C14 shows a visible absorption band maximum at 660 nm (E 185 dm3 mol-' cm-') with a low-energy shoulder at 950 nm (E 54 dm3 mol-' cm-'). In contrast, the electronic spectrum of [Cu(tpzma)Cl]C16 shows a maximum at 855 nm (E 225 dm3 mol-' cm-') with a high-energy shoulder at 708 nm (E 77 dm3 mol-' cm-I).Electrochemistry.-The cyclic voltammetric data for com- plexes 1-8 are shown in Table 2, and cyclic voltammograms of the representative complexes [Cu(tpyea)(H,O)][BF,], 3 and [Cu(tpyma)Cl]Cl 2 are shown in Fig. 2. In all cases, a one-electron reduction is observed. This is of particular 10 Y -51 -10 I W I I L 0.25 0.00 -0.25 -0.50 -0.75 E N vs As-AgCI Fig. 2 Cyclic voltammograms for: (a) [Cu(tpyea)(H,O)][BF,], 3 (0.5 mmol dm-3 solution, E, = -0.032 V, AE, = 0.15 V) and (b) [Cu(tpyma)Cl]C12 (1 -0 mmol dm-3 aqueous solution, E+ = - 0.32 V, AE, = 0.073 V).Both scans recorded in 0.1 mol dm-3 Tris buffer (pH 7.0) at a scan rate of 0.050 V s-' against a Ag-AgCI reference electrode34 J. CHEM. soc. DALTON TRANS. 1995 Table 1 UV/VIS absorption data and EPR spectral data for copper complexes 1-8 UV/VIS h,,,/nm (&/drn3 mol-' cm-') 930 (205), 640 (85) 855 (225), 708 (77) 890 (70), 680 (240) 950 (54), 660 (1 85) 847 (210) 708 (77), 855 (225) 800 (63), 660 (61) 760 (70), 630 (60) EPR 811 1.99 1.98 2.27 2.21 2.03 1.98 2.23 2.19 g, 2.22 2.26 2.01 2.02 2.26 2.26 2.09 2.06 1 04,4 ,I /cm-' 90 80 160 154 85 80 156 150 Table 2 Catalytic activities and cyclic electrochemical * data for copper complexes 1-8 Activity (pmol substrate per mg catalyst per min) 0.000 471 0.001 34 84.9 63.2 0.523 0.238 No reaction No reaction E+IV -0.31 -0.32 - 0.03 - 0.04 + 0.06 -0.01 + 0.21 + 0.32 * Electrochemistry was performed in a solution that was 0.1 mol dm-3 in Tris buffer. The concentration of metal complex was 1 x rnol dm-3.All complexes undergo chemically reversible oxidation-reduction reactions at a glassy carbon electrode with an Ag-AgCI reference electrode and a platinum wire as the auxiliary electrode. importance in the case of [Cu(tpzma)(H20)][BF4], 5 since the blue form was formulated as a dimer in the solid state.36 The electrochemical data, along with the EPR results previously described, establish that the complex exists as a monomer in solution. The reduced forms of complexes 1-8 all display reasonable chemical stability on the time-scale of the cyclic voltammetry experiment; ratios of reverse to forward currents ( i J Q range between 0.72 and 1 .OO at a scan rate of 0.050 V s-'.The electrochemical data show that the reduction potentials of the bound copper(I1) species depend more on the nature of the resulting chelate ring than on the fifth donor or counter ion. In general, the E3 values for the complexes which form six- membered chelate rings (tpzea and tpyea) are more positive than the corresponding complexes which form five-membered rings (tpzma and tpyma). These values are in accord with what is expected as the size of the chelate ring is ~hanged.~' Significant (and predictable) electronic differences can be built into metal complexes by changing the length of the tripodal arms connecting the donor atoms.When the fifth donor is changed from chloride to H,O, and the counter ion from C1 to BF,, the reduction potentials of complexes formed with the same tetradentate ligand change very little. It can also be gleaned from the E+ values that pyrazole-containing complexes have more positive reduction potentials than the corresponding pyridine complexes. This is illustrated by comparing complex 7 (E+ = 0.21 V) with 3 (E+. = - 0.03 V). These results suggest that the pyrazole-containing ligands are weaker ligands than the pyridine ones and that the co-ordination environment of the complexes is softer for the pyrazole c~mplexes.~' Similar results have been found for other pyrazole and pyridine systems.42 Consequently, differences in the chelate ring size and the nature of the heterocyclic donor largely determine the electrochemical properties of the complexes.Reactivity with 3,5-Di-tert-butylcatechol.-The reactivity of the copper(I1) complexes 1-8 towards 3,5-di-tert-butylcatechol under catalytic conditions (0.3 cm3 of a 1.0 x mol dm-3 methanol solution of catalyst and 2.0 cm3 of a 0.1 mol dm-3 methanolic solution of 3,5-di-tert-butylcatechol) in the presence of atmospheric O2 was studied using electronic spectroscopy by following the appearance of the absorption maximum of the quinone at 390 nm over time. The results of the oxidations are presented in Table 2 and it is clear that there are profound differences in the ability of the complexes to catalyse the oxidation reaction. Discussion The two-electron oxidation of substituted o-catechols to quinones was investigated because this is one of the reactions that the copper-containing enzyme tyrosinase catalyses.There are a number of factors which need to be considered in explaining the differences in the catalytic properties of complexes 1-8. These include (a) the electrochemical properties of the complexes, (b) the geometry imposed by the ligands on the metal ion, (c) the nature of any exogenous donors, ( d ) the basicity of the donor atoms and (e) the steric features of the ligands. Of these factors, (b), (c), ( d ) and (e) are inherent features of the molecules while factor (a) is a secondary effect derived from those. All of these factors will be considered sequentially. Electrochemical Considerations.-Upon oxidizing catechol, both tyrosinase and the synthetic copper(I1) complexes studied here are reduced to Cut.Therefore, electrochemistry was used to establish whether there is a correlation between the redox potential and catalytic capabilities of the copper complexes and to assess the ease of reduction of the complexes. A comparison of the E+ values for the eight complexes studied with the observed catalytic properties yields a number of interesting results. First, the four complexes with appreciable activity in the oxidation of 3,5-di-tert-butylcatechol (3-6) have reduction potentials intermediate between the most positive and negative potentials in the group. Thus, complexes exhibiting reduction potentials close to 0.00 V demonstrate activity, while those that deviate from that potential by 200-300 mV in either direction lead to significant or complete loss of activity.Complexes 7 and 8 have the most positive reduction potentials and, as a result, are catalytically inactive since the pyrazole donors stabilize the Cu' site at the expense of the Cu" form; at the other extreme, complexes 1 and 2 have the most negative potentials and are difficult to reduce from the Cu" state. Other attempts to compare the redox properties of copper(1r) complexes with catalytic activity have failed to show a direct correlation. ' While our data do suggest an interdependency between the catalytic properties of the complexes and their redox potentials, it is clear that electronic effects do not totally control the reactivity and that other factors are also at work in the catalytic cycle.This is best illustrated by examining the reactivity of complexes 4 (63.2 pmol substrate per mg catalystJ. CHEM. soc. DALTON TRANS. 1995 35 per min) and 6 (0.238 pmol substrate per mg catalyst per min) which have virtually identical reduction potentials but enormously different rates of reaction. There are other examples of copper(I1) complexes which have essentially identical reduction potentials but drastically different catalytic properties." The origin of these differences in reactivity will be discussed below. Regardless of these other factors though, one can assume that a balance between ease of reduction (more positive reduction potential) and subsequent reoxidation (more negative reduction potential) by molecular oxygen must be maintained for efficient catalysis to occur; this would imply that a window of E+ values exists wherein effective catalysis can take place. If the reduction potential is too negative, reduction to Cu' would be unattainable; on the other hand, if the reduction potential is too positive, the catalytic cycle would be short- circuited because once reduced to Cu', the complexes would be unable to be easily reoxidized to Cu" by 0,.Within a certain range of E+ values catalysis is possible, while outside that range the drop off in rate is quite significant. It should be noted that the enzyme tyrosinase isolated from mushroom (Agaricus bisporus) has a reported value for E, of 0.36 V us. the standard calomel reference; 43 this value lies at the positive end of the series of our complexes.It is obvious however, that the enzyme has been able to balance successfully the requirements of the different oxidation states of the metal in performing its catalytic tasks. Geometrical Effects.-The geometry of the pyrazole-contain- ing complexes was probed in our earlier work.8 The data for complexes 1-8 show that first, and most importantly, the square-pyramidal complexes [Cu(tpzea)(H20)][BF4], 7 and [Cu(tpzea)Cl]Cl 8 are unique in their inability to catalyse the oxidation of 3,5-di-tert-butylcatechol. As shown in Table 2, the square-pyramidal complexes [Cu(tpyea)(H,O)][BF,], 3 and [Cu(tpyea)Cl]Cl 4 do catalyse the oxidation reaction. Our original premise that a geometrical effect may be responsible for the lack of reactivity of the square-pyramidal tpzea complexes is clearly inoperative since complexes of tpyea catalyse the reaction, as do the trigonal-bipyramidal tpzma and tpyma complexes. Therefore, in considering five-co-ordinate copper(1r) complexes, either square-pyramidal or trigonal- bipyramidal complexes are capable of serving as catalysts for oxidation reactions so other factors must be responsible for the differences in rate.Exogenous Donors.-We have previously shown that changing the nature of the fifth donor atom, the counter ion, or any bridging group bound to the copper ions has an effect on the rate of In addition, it has been shown that electron transfer from catechol to Cu" can begin only after catechol and the Cu" species form a Cu" catecholate intermediate; 44 this situation would require a vacant co- ordination site on the metal so that complexation of the catechol can occur.The results for the complexes described here affirm that the reaction is dependent on either the rate of dissociation of the fifth donor, or the differences in the dissociation constants for the loss of the fifth donor. This is evident when one compares the reactivity of the systems having the same tetradentate ligand but different fifth donors, such as [Cu(tpyma)(H,O)][BF,], 1 and [Cu(tpyma)Cl]C12. In these cases, the activities are 4.71 x lo4 and 1.34 x lo-' pmol substrate per mg of catalyst per min respectively. However, when comparing different ligand sets with identical fifth donors, no trend which would correlate the nature of the fifth donor with the reactivity of the complex is apparent.The differences in rate as a result of changes in the fifth donor are relatively minor compared to other effects described below. Since the catalysis is performed in methanol, the relatively small differences may be a result of the formation of [Cu(ligand)(CH3OH)l2+ oiu a solvolysis reaction which occurs after dissociation of the fifth donor. Basicity.-The fourth consideration in assessing the reactivity of these complexes is the basicity of the donor atoms. Pyrazole has a p& value of I 1 .5 while pyridine has p& = 8.7.45 Since the biological donor imidazole has a p&, value of 7.0, this suggests that if basicity alone is considered, pyridine is a better mimic for imidazole. Analogous to results found for the tpyma ligand and its quinoline (p& = 9.1) derivatives," replacing pyridine by pyrazole should result in a more stable Cu' form for the pyrazole complexes because of its higher pK,. This feature will affect the reduction potentials of the complexes by shifting the pyrazole E+ values to more positive values compared to their pyridine counterparts. In contrasting complexes 1 with 5 or 2 with 6, it can be seen that this is the case.The data are consistent with the premise that the basicity of the donor atoms is one of the primary factors in modulating the resultant electrochemical properties of the complexes. Steric Considerations.-There are a number of stud- ies 19.30*41 9 4 6 on complexes of tripodal ligands which have considered the impact of changing the steric features of the ligands on the stability of the oxidized and reduced forms of the Cu'-Cu" couple; two are pertinent to the work described here.Sorrel1 and Jameson'O have shown that as the steric bulk on a series of pyrazole ligands (one of which was tpzea) is increased, the Cu' form is stabilized resulting in more positive reduction potentials for the sterically hindered complexes. Karlin and co- workers l9 reported similar effects when pyridine donors are replaced by the bulkier quinoline, suggesting that the change to non-polar quinolyl substituents leads to increased hydrophob- icity which stabilizes the lower charged species (Cu' over Cu"). Karlin et aL2' have also generated oxygen complexes from their tripodal species where the differences in the relative stabilities of the oxygen complexes are attributed to steric factors.When exposed to the atmosphere at -8O"C, the copper(r) complex [Cu(tpyma)(MeCN)] + was shown to react o h the initial reversible formation of the 1 : 1 Cu : 0, complex [Cu(tpyma)(O,)] + which reacts reversibly with the starting Cu' species to form the 2: 1 complex [(C~(tpyma)),(O,)]~+.~' In contrast, the complex with three quinoline donors is much bulkier than the pyridine-containing complex and as a result is unreactive towards 0,. A similar result was found as the size of the alkyl substituents was increased on the pyrazole arms of tpzea." It is possible that similar copper-oxygen species exist during the reaction of the tripodal-containing complexes with 3,5-di-tert-butylcatechol prepared here; however, we have not probed the detailed mechanism of the reactions.Differences in the steric features of the ligands can be manifested in a variety of ways. These include differences in the hydrophobicity of the complexes, accessibility of the substrate to the metal ion due to the steric bulk of the ligand, and the extent of the steric match between the substrate and the complex. If any of these steric considerations are important, the reactivity properties of the copper(@ complexes should be affected. An examination of Table 2 shows that the pyridine- containing complexes [Cu(tpyea)(H,O)][BF,], 3 and [Cu- (tpyea)Cl]Cl 4 are significantly more reactive than the corresponding pyrazole complexes [Cu(tpzma)(H,O)] [BF,] , 5 and [Cu(tpzma)Cl]C16, even though their redox potentials are very similar.Activity values for the oxidation of 3,s-di-tert- butylcatechol by mononuclear copper(r1) complexes typically fall in the range (0.5-1) x lo-' pmol substrate per mg of catalyst per min.6-8 However, complexes formed from the pyridine-containing tpyea have significantly higher rates of reaction, and indeed are the most active catalysts that we have studied. There are other examples of enhanced reactivity for pyridine over pyrazole containing copper complexes. The most striking example is the hydroxylation of aromatic moieties by N, pyridine complexes while the analogous N, pyrazole systems do not activate 0, for this r e a ~ t i o n . ~ ~ , ~ ' . ~ ~ It has been hypothesized that the geometry needs to be optimized for36 J.CHEM. soc. DALTON TRANS. 1995 correct orientation of the bound peroxo group and the arene ring in order for hydroxylation to A more optimal steric match between complexes 3 and 4 and catechol or O2 compared to that found for complexes 5 and 6 may be partly responsible for the differences in their reactivity towards catechols. However, if steric factors were exclusively responsible for controlling the rates of reaction, then the pyrazole-based complexes should have slower rates than the corresponding pyridine-based complexes. As shown in Table 2, this is not always the case. Although complexes 3 and 4 are appreciably more reactive than 7 and 8, the pyrazole-containing 5 and 6 are actually more reactive (by 102-103 times) than are 1 and 2. It seems, then, that both the electrochemical properties of the molecules and their steric features determine whether or not the complexes will be active catalysts.Conclusion A series of square-pyramidal and trigonal-bipyramidal copper- (11) complexes formed from tetradentate pyridine- and pyrazole- containing ligands have been prepared in an attempt to uncover the predominant features which define their catalytic action. In contrast to earlier work on pyrazole-containing ligands, the results for the pyridine complexes show that trigonal- bipyramidal and square-pyramidal copper(I1) complexes can act as catalysts for the oxidation of catechols. It is clear that substantial differences in catalytic ability can be built into copper(I1) complexes by the judicious choice of ligand sets. The rate of catalysis for copper(r1) complexes is linked to both the redox potentials and the steric match between the substrate and the complex.Substantial retardation of reactivity is evident if either steric or electronic factors are not optimal. Having a reduction potential in the appropriate range is of crucial importance in defining catalytic activity, however, this is a necessary but not sufficient requirement for truly effective catalysis. Although the electronic features determine whether catalysis will proceed, the steric match between the substrate and the catalyst is also of crucial importance. In complexes with identical reduction potentials, the pyridine-containing systems have substantially higher rates of reaction than do their pyrazole counterparts. This result suggests that a more optimal steric match exists between the pyridine complexes and catechol or 0, than exists for the pyrazole systems.Efforts towards preparing copper(I1) complexes with pyridine donors which have reduction potentials of intermediate values are being undertaken to determine whether these complexes can serve as more efficient catalysts. Acknowledgements The support of this research by the Research Corporation is gratefully acknowledged (M. R. M. and R. S. K.). We are also grateful to Professor Jan Reedij k (Leiden University, Leiden), and Professor Donald Jameson (Gettysburg College, Gettysburg, PA) for stimulating discussions. References 1 D. A. Robb, in Copper Proteins and Copper Enzymes, ed. R. Lontie, CRC Press, Boca Raton, FL, 1984, vol. 2, p.207. 2 A. E. Martell and D. T. Sawyer, Oxygen Complexes and Oxygen Activation by Transition Metals, Plenum Press, New York, 1987. 3 D. E. Wilcox, A. G. Porras, K. Lerch, M. E. Winkler and E. I. Solomon, J. Am. Chem. Soc., 1985,103,4015. 4 P. K. Ross and E. I. Solomon, J. Am. Chem. Soc., 1991,113, 3246. 5 S. Kida, H. Okawa and Y. Nishida, in Copper Coordination Chemistry: Biochemical and Inorganic Perspectives, eds. K. D. Karlin and J. Zubieta, Adenine, Guilderland, NY, 1983, p, 425. 6 M. R. Malachowski, M. G. Davidson and J. N. Hoffman, Inorg. Chim. Acta, 1989,157,91. 7 M. R. Malachowski and M. G. Davidson, Inorg. Chim. Acta, 1989, 8 M. R. Malachowski, L. J. Tomlinson, M. G. Davidson and 9 B. Srinivas, N. Arulsamy and P. S. Zacharias, Polyhedron, 1991,10, 10 A. Latif Abuhijleh, C.Woods, E. Bogas and G. LeGuenniou, Inorg. 1 1 N. Oishi, Y. Nishida, K. Ida and S. Kida, Bull. Chem. Soc. Jpn., 1980, 12 M. A. Cabras and M. A. Zoroddu, Inorg. Chim. Acta, 1987,135, L19. 13 K. Moore and G. S. Vigee, Inorg. Chim. Acta, 1982,66, 125. 14 A. B. P. Lever, B. S. Ramaswamy and S. R. Pickens, Inorg. Chim. 15 S . Casellato, S. Tamburini, P. A. Vigato, A. DeStefani, M. Vidali and 16 J. S. Thompson and J. C. Calabrese, Inorg. Chem., 1985,24, 3167. 17 J. Chyn and F. L. Urbach, Inorg. Chim. Acta, 1991,189, 157. 18 R. R. Jacobson, Z. Tyeklar, A. Farooq, K. D. Karlin, S. Liu and J. Zubieta, J. Am. Chem. Soc., 1988,110, 3690. 19 N. Wei, N. N. Murthy, Q. Chen, J. Zubieta and K. D. Karlin, Inorg. Chem., 1994,33, 1953. 20 K. D. Karlin, N.Wei, B. Jung, S. Kaderli and A. D. Zuberbuhler, J. Am. Chem. Soc., 1991,113,5868. 21 K. D. Karlin, N. Wei, B. Jung, S. Kaderli, P. Niklaus and A. D. Zuberbuhler, J. Am. Chem. Soc., 1993,115,9506. 22 E. I. Solomon and M. D. Lowery, Science, 1993,259, 1575. 23 A. Voldeba and W. G. J. Hol, J. Mol. Biol., 1989,209,249. 24 E. I. Solomon, M. J. Baldwin and M. D. Lowery, Chem. Rev., 1992, 92, 521. 25 D. M. Dooley, M. A. McGuirl, D. E. Brown, P. N. Turowski, W. S. McIntire and P. F. Knowles, Nature (London), 1991,349,262. 26 S. 0. Pember, K. A. Johnson, J. J. Villafranca and S. J. Benkovic, Biochemistry, 1989, 28, 21 24. 27 M. C. Brenner and J. P. Klimman, Biochemistry, 1989,28,4664. 28 J. W. Furbee, jun., C. R. Thomas, R. S. Kelly and M. R. 29 W. L. Driessen, Reel.Trav. Chim. Pays-Bas, 1982,101,441. 30 T. N. Sorrell and D. L. Jameson, Inorg. Chem., 1982,21, 1014. 3 1 A. I. Vogel, Quantitative Inorganic Analysis, Longmans, London, 32 G. Anderegg and F. Wenk, Helv. Chim. Acta, 1967,50,2330. 33 T. N. Sorrell, Tetrahedron, 1989,45, 3. 34 E. Bernarducci, W. F. Schwindinger, J. L. Hughey, K. Krogh- Jespersen and H. J. Schugar, J. Am. Chem. Soc., 1981,103, 1686. 35 H. E. Reich and R. Levine, J. Am. Chem. Soc., 1955,77,4913. 36 G. J. van Driel, W. L. Driessen and J. Reedijk, Inorg. Chem., 1985,24, 2919. 37 K. D. Karlin, J. C. Hayes, S. Juen, J. P. Hutchinson and J. Zubieta, Znorg. Chem., 1982,21,4108. 38 J. Zubieta, K. D. Karlin and J. C. Hayes, in Copper Coordination Chemistry: Biochemical and Inorganic Perspectives, eds. K.D. Karlin and J. Zubieta, Adenine, Guilderland, NY, 1983, p. 97. 39 A. Bencini, I. Bertini, D. Gatteschi and A. Scozzartara, Inorg. Chem., 1978,17,3194. 40 B. J. Hathaway and D. E. Billing, Coord. Chem. Rev., 1970,5, 143. 41 K. J. Oberhausen, R. J. O’Brien, J. F. Richardson and R. M. Buchanan, Inorg. Chim. Acta, 1990,173, 145. 42 T. N. Sorrell, D. L. Jameson and M. R. Malachowski, Inorg. Chem., 1982,21,3250. 43 N. Makino, P. McMahill and H. S. Mason, J. Biol. Chem., 1974,249, 6062. 44 M. M. Rogic, M. D. Swerdloff and T. R. Demmin, in Copper Coordination Chemistry: Biochemical and Inorganic Perspectives, eds. K. D. Karlin and J. Zubieta, Adenine, Guilderland, NY, 1983, p. 167. 45 CRC Handbook of Chemistry and Physics, 62nd edn., ed. Robert C. Weast, CRC Press, Boca Raton, 1981, pp.D139-141. 46 S. Chen, J. F. Richardson and R. M. Buchanan, Inorg. Chem., 1994, 33, 2376. 47 T. N. Sorrell, V. A. Vankai and M. L. Garrity, Inorg. Chem., 1991,30, 207. 48 K. D. Karlin, J. C. Hayes, Y. Gultneh, R. W. Cruse, J. W. McKown, J. P. Hutchinson and J. Zubieta, J. Am. Chem. Soc., 1984,106,2121. 162, 199. M. J. Hall, J. Coord. Chem., 1992,25, 171. 731. Chim. Acta, 1992,195,67. 53,2847. Acta, 1980,46, L59. D. E. Fenton, Inorg. Chim. Acta, 1983,69,45. Malachowski, Anal. Chem., 1993,65, 1654. 1961. Received 5th July 1994; Paper 4/04079AJ. CHEM. SOC. DALTON TRANS. 1995 31Comparative Study of the Catalytic Oxidation of Catecholsby Copper(ii) Complexes of Tripodal LigandsMitchell R. Malachowski,*-e Hong B. Huynh,B Laura J. Tomlinson,a Richard S.Kellyb andJames W. Furbee jun?a Department of Chemistry, University of San Diego, Alcala Park, San Diego, CA 921 10, USAIllinois 60045, USADepartment of Chemistry, Lake Forest College, 555 North Sheridan Road, Lake Forest,Copper( 11) complexes of the ligands tris( 2-pyridylmethy1)amine (tpyma), tris( 2- pyridylet hyl) amine(tpyea), tris( 3,5-dimethylpyrazol- 1 - ylmethy1)amine (tpzma) and tris( 3.5-dimethylpyrazol- 1 -ylethyl) -amine (tpzea) were prepared. The complexes, [Cu(ligand)CI]CI or [Cu(ligand)(H,O)] [BF,],, werecharacterized by a combination of absorption and EPR spectroscopies and chemical analysis. The abilityof the complexes to oxidize 3.5-di-tert-butylcatechol to 3,5-di-tert-butyl-o-benzoquinone has beenstudied and the results show that the rate of reaction is dependent on the nature of the heterocyclicdonor, its basicity, steric considerations, the chelate ring size and the type of exogenous donorpresent.Large variations in the rate were observed with the most effective catalysts being those withpyridine donors which formed six-membered chelate rings; the complex [Cu(tpyea) (H,O)] [BF,], wasthe most active while [Cu(tpzea) (H,O)] [BF,], and [Cu(tpzea)CI]CI were inactive. Electrochemicaldata for the series of compounds show that there is a non-linear relationship between their ability tooxidize catechols and their reduction potentials. The most effective catalysts were those complexeswhich exhibited reduction potentials close to 0.00 V, while those that deviated from that potential by200-300 mV in either direction were largely inactive.Within the range of complexes which wereactive, a steric match between the substrate and the complex also largely defined their reactivity.Comparisons to the biological system tyrosinase are drawn.Tripodal ligands continue to find extensive use in the synthesisof metal complexes because of their ease of preparation, thewealth of spectroscopic and X-ray crystallographic data whichhas been generated for their metal complexes, and thepredictable changes in the physical properties of the metalcomplexes as the ligand sets are varied. We are particularlyinterested in using nitrogen-containing tripodal ligands asmodels for the protein backbone of the enzyme tyrosinase.Spectroscopic and physical studies indicate that this metal-loenzyme has two copper atoms at the active site, each boundto three nitrogens of histidine residues from the protein back-bone.14 Tyrosinase is a monooxygenase and, as is shownin Fig.1, it is responsible for the air oxidation of phenol tocatechol (benzene- 1,2-diol) (cresolase activity) and the subse-quent oxidation of catechol to o-benzoquinone (catecholaseactivity) .Models for biological systems can be designed to reproducethe structural, spectroscopic or reactivity properties of theprotein of interest. In this study we are particularly interested indeveloping a better understanding of the parameters which leadto effective catalysis for synthetic copper(@ complexes. Syntheticmodel studies of the reactivity of copper(I1) complexes towardscatechols implicate the geometry around the copper ions as themost dominant feature in determining the catalytic activity ofthe complexes.Non-planar mononuclear complexes andbinuclear complexes with the two coppers separated by ca.3-4 A catalyse the oxidatiori process, while square-planarmononuclear complexes and dinuclear complexes with a largeCu-Cu distance ( > 5 A) are generally unreactive towardscatechol.6-17 No correlation between the redox potential of thecopper complexes and the rate of the oxidation has beenuncovered; instead, the determining factor is thought to be asteric match between the substrate and the copper ion.Systematic studies which selectively change the structural andelectronic features of copper complexes and assess the effect onaoH - aoH OHaO"- OHFig.1 Reactions catalysed by tyrosinasetheir catalytic properties should help explain which features oftyrosinase are primarily responsible for its activity. In addition,studies of this type would allow for the rational design andsynthesis of more efficient catalysts.There is a rich chemistry associated with the reactivity ofcopper complexes of tripodal ligands. Germane to this workare the reactivity studies on copper(1) complexes of quinolineand pyridine tripodal ligands which have been shown to formcopper-oxygen complexes of varying stoichiometry dependingon the nature of the ligand.18*19 Kinetic and thermodynamicproperties have been determined for the reactions between0, and the copper(1) tripodal complexes which show thatligand modifications dramatically effect the rate of formationand dissociation of the Cu-0, adducts.20,21 Copper-oxygenadducts have been shown to be important intermediates in anumber of protein active sites including tyrosinase,22 haemo-cyan in^,^^.^^ amine oxidases,, phenylalanine hydroxylase 26and dopamine B-hydroxylase.' 'As part of our studies on the electron-transfer propertiesof copper(I1) complexes, we have shown that the tripodalligand tri~(3~5-dimethylpyrazol- 1 -ylmethyl)amine (tpzma)forms copper(n) complexes which are capable of mediatingelectron transfer to both negative and positively charge32 J. CHEM. SOC. DALTON TRANS. 1995proteins.' Nafion-coated glassy carbon electrodes containingthe copper(I1) complex show electron transfer to cytochromec or to tyrosinase, a result which is unobtainable with theuntreated electrode. A second-order EC (electrochemical-chemical) catalytic reaction mechanism is operative at thereduction potential of the copper complex for both thereduction of cytochrome c and tyrosinase.Along with their electron-transfer properties, we have alsobeen probing the catalytic properties of copper(rr) com-plexes.6-8 The kinetic results for the oxidation of catechol tobenzoquinone using the copper(I1) complexes of the tripodalligands tpzma and tris(3,5-dimethylpyrazol- 1 -ylethyl)amine(tpzea) have recently been reported. ' The trigonal-bipyramidaltpzma complexes were found to act as efficient catalyststowards the oxidation of catechol, while the square-pyramidalcomplexes formed from tpzea did not catalyse this oxidation.Regardless of the various permutations present (monomericor dimeric, the nature of the fifth ligand, or the counter ion),the copper(@ complexes of tpzma catalysed the oxidation ofcatechol and substituted catechols, while those of tpzea did not.The lack of reactivity exhibited by the square-pyramidaltpzea complexes is striking since simple copper(I1) salts such asCuC1, will catalyse the reaction.In order to determine whetherthe results obtained using the pyrazole-containing ligands are ageneral feature of the reactivity for trigonal-bipyramidal andsquare-pyramidal copper(I1) complexes, the pyridine analoguesof these two ligands, tris(2-pyridylmethy1)amine (tpyma) andtris(2-pyridylethy1)amine (tpyea) and a variety of their copper-(11) complexes have been prepared.The reactivity of thecomplexes towards 3,5-di-tert-butylcatechol was studied usingUV/VIS spectroscopy and the results compared to thosepreviously found for the tpzma and tpzea complexes. Inaddition, electrochemical data were obtained in order toattempt to correlate the reduction potentials to the reactivityof the complexes.ExperimentalGeneral.-All reagents and solvents were purchased fromcommercial sources and used as received unless notedotherwise. 1 -(Hydroxymethyl)-3,5-dimethylpyrazole, tris( 3,5-dimethylpyrazol-1 -ylethyl)amine (tpzea),,' tris(3,5-dimethyl-pyrazol- 1 -ylmethyl)amine (tpzma),' and [Cu(tpzea)(H,O)]-[BF,], 30 were prepared by the literature methods.Meltingpoints were obtained with the use of a Fisher-Johns apparatusand are uncorrected. The C, H and N elemental analyses wereperformed at Desert Analytical, Tucson, AZ. Metal contentswere determined complexometrically by indirect titration withNa,(H,edta) (H,edta = ethylenediaminetetraacetic acid)and zinc acetate after destruction of the sample withconcentrated nitric acid.Electronic spectroscopy was performed on a Uvikon 860spectrophotometer using methanol as the solvent, while IRspectra were recorded on a Nicolet 5ZDX instrument. ProtonNMR spectra were recorded on a Bruker WM 250 instrumentusing CDCI, as the solvent.All chemical shifts are reported inppm relative to an internal standard of SiMe,. X-Band EPRspectra were recorded on a Varian E-3 spectrophotometerat 77 K in methanol solution using diphenylpicrylhydrazyl(dpph) as the calibrating field marker. Kinetics were followed'@)3 N W )3tpzma tpzeaspectrophotometrically on a Uvikon 860 spectrophotometer byfollowing the appearance of 3,5-di-tert-butyl-o-benzoquinoneover time using the 390 nm peak. The metal complex (0.3 cm3 ofa 1 x mol dm-3 methanol solution) and a 2.0 cm3 solution(1 x lo-' mol dm-, methanol solution) of 3,5-di-tert-butyl-catechol were added together in the spectrophotometric cellat 25 "C.Electrochemistry was performed in an aqueous solution thatwas 0.1 mol dm-, in Tris [tris(hydroxymethyl)methylamine]buffer.The concentration of metal complex was 1 x lo-, moldrn-,. All complexes undergo chemically reversible oxidation-reduction reactions at a glassy carbon electrode with anAg-AgC1 reference electrode and a platinum wire as theauxiliary electrode.CAUTlO N : perchlorates may explode violently.Syntheses of Ligands.-Tris(2-pyridylmethyl)amine (tpyma).To a solution of tris(2-pyridylmethy1)ammonium perchlorate 32(6.0 g, 0.015 mol) in H 2 0 (200 cm3) was added 5 mol dm-3NaOH (40 cm3). The solution was stirred at room temperaturefor 3 h and extracted with CHCl, (3 x 50 cm3). The CHCl, solu-tion was dried over Na2S04, filtered, and evaporated to 10 cm3.After cooling overnight to - 20 "C, white crystals formed (2.66g, 61%), m.p.84-86 "C (lit.,32 84.5-86.5 "c); GH(CDC13) 4.05(6 H, s, CH,), 7.1 1-7.65 (9 H, m, py), 8.40-8.52 (3 H, d, py).Tris(2-pyridylethy1)amine (tpyea). A solution of 2-vinyl-pyridine (25.0 cm3, 0.238 mol) (purified by passage through analumina column) and ammonium acetate (3.0 g, 0.039 mol) inMeOH-H,O (2: 1, 300 cm3) was refluxed for 5 d. The solventwas evaporated, the residue dissolved in 20% NaOH (1 00 cm3)and then extracted with CH,Cl, (4 x 100 cm3). The combinedorganic solvents were dried over Na,SO,, filtered andevaporated. The product was purified using flash chromato-graphy on silica using MeOH as the eluent. A colourless oil (5.6g, 43%) was obtained; GH(CDCI,) 2.53 (6 H, t, CH,), 3.02 (6 H, t,CH,), 7.09-7.84 (9 H, m, py), 8.63-8.82 (3 H, d, py).Syntheses of Metal Complexes.-[Cu(tpyma)( H,O)] [ BF,]1.A solution of Cu(BF,),.6H2O (0.46 g, 1.3 mmol) in MeOH(25 cm3) was filtered into a solution of tpyma (0.39 g, 1.3 mmol)in MeOH (10 cm3). The solvent was reduced in volume to 5 cm3and diethyl ether was slowly added. Blue crystals (0.30 g, 43%)formed on standing at -20 "C (Found: C, 39.30; H, 4.05; Cu,11.90; N, 10.40. C,,H,oB,CuF,N,O requires C, 39.65; H, 3.70;Cu, 11.65; N, 10.25%).[Cu(tpyma)Cl]C12. A solution of CuC1,=2H2O (1.17 g, 6.88mmol) in MeOH (50 cm3) was filtered into a solution of tpyma(2.00 g, 6.88 mmol) in MeOH (25 cm3). The solution was filteredand green-blue crystals (1.52 g, 52%) formed on standing at-20 "C(Found: C, 50.55; H, 4.70; Cu, 15.25; N, 12.95.C18H,,-Cl,CuN, requires C, 50.90; H, 4.30; Cu, 14.95; N, 13.20%).[Cu(tpyea)(H,O)][BF,], 3. A solution of Cu(BF,),*6H2O(2.08 g, 6.02 mmol) in MeOH (50 cm3) was filtered into asolution of tpyea (2.00 g, 6.02 mmol) in MeOH (25 cm3). Slowevaporation of the solvent in air led to the isolation of bluecrystals (1.95 g, 55%) (Found: C, 43.20; H, 4.50; Cu, 10.85;N, 9.60. C2,H26B,CuF,N40 requires C, 42.90; H, 4.45; Cu,10.80; N, 9.55%).[Cu(tpyea)CI]CI 4. A solution of CuC1,.2H20 (1.03 g, 6.02mmol) in MeOH (50 cm3) was filtered into a solution of tpyea(2.00 g, 6.02 mmol) in MeOH (25 cm3). Green crystals (2.05 g,73%) formed on standing at -20°C (Found: C, 54.35; H,5.30; Cu, 13.70; N, 11.75. C2,H,,Cl,CuN, requires C, 54.00;H, 5.20; Cu, 13.60; N, 12.00%).[Cu(tpnna)(H,O)][BF,],-H,O 5.A solution of Cu(BF,),-6H,O (2.04 g, 5.90 mmol) in MeOH (50 cm3) was filtered into asolution of tpzma (2.00 g, 5.90 mmol) in MeOH (25 cm3).On allowing the solution to stand overnight at -20 "C, bluecrystals (1.67 g, 46%) were formed (Found: C, 35.55; H, 5.25;Cu, 10.40; N, 16.45. Cl8H3,B,CuF,N,0, requires C, 35.15;H, 5.10; Cu, 10.40; N, 15.95%)J. CHEM. SOC. DALTON TRANS. 1995 33[Cu(tpzma)Cl]C16. A solution of CuC12.2H20 (1.01 g, 5.90mmol) in MeOH (50 cm3) was filtered into a solution of tpzma(2.00 g, 5.90 mmol) in MeOH (25 cm3). The solution wasfiltered, reduced in volume to 25 an3, and cooled to -20 "Cfrom which small green crystals (1.71 g, 61%) formed (Found:C, 45.00; H, 6.00; Cu, 13.20; N, 20.55. C18H2,C12CuN, requiresC, 45.45; H, 5.75; Cu, 13.35; N, 20.60%).[Cu(tpzea)Cl)C18. To a solution of CuC12*2H20 (1.13 g, 6.60mmol) in MeOH (50 cm3) was added tpzea (2.53 g, 6.60 mmol)in MeOH (25 cm3).After filtration, the green solution wasslowly treated with diethyl ether. It was cooled to -20 "C fromyielding green crystals (1.23 g, 36%) (Found: C, 48.20; H, 6.30;Cu, 12.30; N, 18.75. C2,H3,C12CuN, requires C, 48.70; H,6.45; Cu, 12.25; N, 18.90%).ResultsSynthesis.-Pyrazole- and pyridine-containing ligands havefound extensive use in a variety of multidentate ligandscomplexed to metal ions which serve as models formetal lop rote in^.^^ The donor ligands in this study were chosenbecause of their demonstrated similarity to the biological donorimidazole. 34 Tripodal compounds are attractive candidates forligands because of the variety and predictability of geometrieswhich are possible for their subsequent metal complexes.Tris(2-pyridylmethy1)amine (tpyma) was synthesized using amodification of the method of Anderegg and Wenk32 via thecondensation of 2-(chloromethy1)pyridine and 2-(aminomethy1)-pyridine through the isolation of the intermediate perchloratesalt of the amine.Tris(3,5-dimethylpyrazol-l-ylmethyl)amine(tpzma) was synthesized from ammonium chloride and1 -(hydroxymethyl)-3,5-dimethylpyrazole using the method ofDriessen 29 for the pyrazolylmethylation of amines, whiletris(2-pyridylethy1)amine (tpyea) was prepared from ammoniumacetate and 2-vinylpyridine using an adaptation of Reich andLevine for the pyridylethylation of amines.Tris(3,Sdimethyl-pyrazol- 1 -ylethyl)amine (tpzea) was prepared from tris(2-chloroethy1)amine and the 3,5-dimethylpyrazolate anion asdescribed by Sorrel1 and Jame~on.~'A variety of copper(I1) complexes formed from these ligandswere isolated in crystalline form. A methanolic solution of theligand was added to either Cu(BF4),*6H20 or CuCl,*2H20 inmethanol from which the complexes were isolated directly.Spectroscopy.-Elemental analyses, EPR spectroscopy andelectronic spectroscopy show the complexes to exist as five-co-ordinate species of the form [Cu(ligand)(H,O)][BF41, or[Cu(ligand)Cl]Cl. In the case of tpzma with Cu(BF4),.6H2Otwo different complexes can be isolated, a blue form and a greenone. The blue compound has been identified as a dimer offormula [Cu,(tpzma),F(H,O),] [BF,] in the solid state.36Evidence for its formulation as a dimer came from elementalanalysis, solid-state EPR spectroscopy and the crystal structureof the analogous cobalt complex. However, it was shown byconductivity studies that even in nitromethane, the dimerbreaks down to monomeric cations. In our work, we haveisolated the green complex and studied its solution propertiesby EPR spectroscopy and electrochemistry (see later); neithertechnique shows evidence of a dimer in solution and theelemental analysis is consistent with the formulation [Cu-Copper(@ complexes formed from tripodal ligands typicallyexist as five-co-ordinate species of either trigonal-bipyramidalor square-pyramidal geometry, depending on the length of thearms connecting the donor atoms.It has previously been shownusing a combination of X-ray crystallography, electronicspectroscopy and EPR spectroscopy that numerous copper@)complexes formed from tpzea and tpyea (which have threeatoms separating the donor atoms) exist both in solution and inthe solid state as five-co-ordinate mononuclear species withsquare-pyramidal geometry. 30*3 ' In comparison, complexes of(tpzma)(H,O)I CBF4I 2-20.tpzma and tpyma (which have two atoms separating thedonors) generally form copper(r1) complexes with trigonal-bipyramidal geometry. 36*38 Chemical and spectroscopicanalyses of the copper(I1) complexes prepared here are in accordwith those assignments.Electronic and EPR spectroscopic data for the complexes aregiven in Table 1.The EPR spectra for complexes of tpyea andtpzea display gll > g , > 2.00 and A l l = (120-150) x lo4cm-', typical of a square-pyramidal geometry. 39 An illustrationof this is the frozen solution spectrum of [Cu(tpzea)-(H20)][BF4I2 7 which has gll = 2.23, g, = 2.09 and All =156 x lo4 cm-'. This is in contrast to complexes formed fromtpyma and tpzma which give EPR spectra consistent with atrigonal-bipyramidal geometry (8, > gll > 2.00, A l l = (60-100) x lo4 cm-I). For example, for [Cu(tpyma)Cl]C12 gll =1.98, g , = 2.26 and A l l = 80 x lo4 cm-'.Unlike the results from the solid-state analysis of [Cu2-(tpzn1a)~F(H~O),][BF~3,,~~ in the frozen solution EPRspectrum of the green complex formed from tpzma andCU(BF,)~-~H~O a half-field signal is not observed.Along withthe electrochemical results described below, we believe that thecomplex exists as [Cu(tpzma)(H,O)][BF,], in the solid stateand in solution.The electronic absorption spectra of five-co-ordinatecopper(rr) complexes also fall into two general categories.,'Square-pyramidal complexes typically show a high-energyabsorption band in the visible region with a low-energyshoulder. In contrast, trigonal-bipyramidal complexes have alow-energy absorption band with a high-energy shoulder in thevisible region. As shown in Table 1, the results for complexes 1-8 are consistent with these criteria. For example, the electronicspectrum of [Cu(tpyea)Cl]C14 shows a visible absorption bandmaximum at 660 nm (E 185 dm3 mol-' cm-') with a low-energyshoulder at 950 nm (E 54 dm3 mol-' cm-').In contrast, theelectronic spectrum of [Cu(tpzma)Cl]C16 shows a maximum at855 nm (E 225 dm3 mol-' cm-') with a high-energy shoulder at708 nm (E 77 dm3 mol-' cm-I).Electrochemistry.-The cyclic voltammetric data for com-plexes 1-8 are shown in Table 2, and cyclic voltammograms ofthe representative complexes [Cu(tpyea)(H,O)][BF,], 3 and[Cu(tpyma)Cl]Cl 2 are shown in Fig. 2. In all cases, aone-electron reduction is observed. This is of particular10Y-51-10 I WI I L0.25 0.00 -0.25 -0.50 -0.75E N vs As-AgCIFig. 2 Cyclic voltammograms for: (a) [Cu(tpyea)(H,O)][BF,], 3 (0.5mmol dm-3 solution, E, = -0.032 V, AE, = 0.15 V) and (b)[Cu(tpyma)Cl]C12 (1 -0 mmol dm-3 aqueous solution, E+ = - 0.32 V,AE, = 0.073 V).Both scans recorded in 0.1 mol dm-3 Tris buffer (pH7.0) at a scan rate of 0.050 V s-' against a Ag-AgCI reference electrod34 J. CHEM. soc. DALTON TRANS. 1995Table 1 UV/VIS absorption data and EPR spectral data for copper complexes 1-8UV/VISh,,,/nm (&/drn3 mol-' cm-')930 (205), 640 (85)855 (225), 708 (77)890 (70), 680 (240)950 (54), 660 (1 85)847 (210)708 (77), 855 (225)800 (63), 660 (61)760 (70), 630 (60)EPR8111.991.982.272.212.031.982.232.19g,2.222.262.012.022.262.262.092.061 04,4 ,I /cm-'90801601548580156150Table 2 Catalytic activities and cyclic electrochemical * data forcopper complexes 1-8Activity (pmolsubstrate per mgcatalyst per min)0.000 4710.001 3484.963.20.5230.238No reactionNo reactionE+IV-0.31-0.32- 0.03- 0.04 + 0.06-0.01 + 0.21 + 0.32* Electrochemistry was performed in a solution that was 0.1 mol dm-3in Tris buffer.The concentration of metal complex was 1 x rnoldm-3. All complexes undergo chemically reversible oxidation-reductionreactions at a glassy carbon electrode with an Ag-AgCI referenceelectrode and a platinum wire as the auxiliary electrode.importance in the case of [Cu(tpzma)(H20)][BF4], 5 since theblue form was formulated as a dimer in the solid state.36 Theelectrochemical data, along with the EPR results previouslydescribed, establish that the complex exists as a monomer insolution. The reduced forms of complexes 1-8 all displayreasonable chemical stability on the time-scale of the cyclicvoltammetry experiment; ratios of reverse to forward currents( i J Q range between 0.72 and 1 .OO at a scan rate of 0.050 V s-'.The electrochemical data show that the reduction potentialsof the bound copper(I1) species depend more on the nature of theresulting chelate ring than on the fifth donor or counter ion.Ingeneral, the E3 values for the complexes which form six-membered chelate rings (tpzea and tpyea) are more positivethan the corresponding complexes which form five-memberedrings (tpzma and tpyma). These values are in accord with whatis expected as the size of the chelate ring is ~hanged.~'Significant (and predictable) electronic differences can be builtinto metal complexes by changing the length of the tripodalarms connecting the donor atoms.When the fifth donor is changed from chloride to H,O, andthe counter ion from C1 to BF,, the reduction potentials ofcomplexes formed with the same tetradentate ligand changevery little.It can also be gleaned from the E+ values thatpyrazole-containing complexes have more positive reductionpotentials than the corresponding pyridine complexes. This isillustrated by comparing complex 7 (E+ = 0.21 V) with 3 (E+. =- 0.03 V). These results suggest that the pyrazole-containingligands are weaker ligands than the pyridine ones and that theco-ordination environment of the complexes is softer for thepyrazole c~mplexes.~' Similar results have been found for otherpyrazole and pyridine systems.42 Consequently, differences inthe chelate ring size and the nature of the heterocyclic donorlargely determine the electrochemical properties of thecomplexes.Reactivity with 3,5-Di-tert-butylcatechol.-The reactivity ofthe copper(I1) complexes 1-8 towards 3,5-di-tert-butylcatecholunder catalytic conditions (0.3 cm3 of a 1.0 x mol dm-3methanol solution of catalyst and 2.0 cm3 of a 0.1 mol dm-3methanolic solution of 3,5-di-tert-butylcatechol) in the presenceof atmospheric O2 was studied using electronic spectroscopy byfollowing the appearance of the absorption maximum of thequinone at 390 nm over time.The results of the oxidations arepresented in Table 2 and it is clear that there are profounddifferences in the ability of the complexes to catalyse theoxidation reaction.DiscussionThe two-electron oxidation of substituted o-catechols toquinones was investigated because this is one of the reactionsthat the copper-containing enzyme tyrosinase catalyses. Thereare a number of factors which need to be considered inexplaining the differences in the catalytic properties ofcomplexes 1-8. These include (a) the electrochemical propertiesof the complexes, (b) the geometry imposed by the ligands onthe metal ion, (c) the nature of any exogenous donors, ( d ) thebasicity of the donor atoms and (e) the steric features of theligands. Of these factors, (b), (c), ( d ) and (e) are inherent featuresof the molecules while factor (a) is a secondary effect derivedfrom those.All of these factors will be considered sequentially.Electrochemical Considerations.-Upon oxidizing catechol,both tyrosinase and the synthetic copper(I1) complexes studiedhere are reduced to Cut. Therefore, electrochemistry was used toestablish whether there is a correlation between the redoxpotential and catalytic capabilities of the copper complexes andto assess the ease of reduction of the complexes. A comparisonof the E+ values for the eight complexes studied with theobserved catalytic properties yields a number of interestingresults. First, the four complexes with appreciable activity inthe oxidation of 3,5-di-tert-butylcatechol (3-6) have reductionpotentials intermediate between the most positive and negativepotentials in the group.Thus, complexes exhibiting reductionpotentials close to 0.00 V demonstrate activity, while those thatdeviate from that potential by 200-300 mV in either directionlead to significant or complete loss of activity. Complexes 7 and8 have the most positive reduction potentials and, as a result,are catalytically inactive since the pyrazole donors stabilize theCu' site at the expense of the Cu" form; at the other extreme,complexes 1 and 2 have the most negative potentials and aredifficult to reduce from the Cu" state.Other attempts to compare the redox properties of copper(1r)complexes with catalytic activity have failed to show a directcorrelation.' While our data do suggest an interdependencybetween the catalytic properties of the complexes and theirredox potentials, it is clear that electronic effects do not totallycontrol the reactivity and that other factors are also at work inthe catalytic cycle. This is best illustrated by examining thereactivity of complexes 4 (63.2 pmol substrate per mg catalysJ. CHEM. soc. DALTON TRANS. 1995 35per min) and 6 (0.238 pmol substrate per mg catalyst per min)which have virtually identical reduction potentials butenormously different rates of reaction. There are otherexamples of copper(I1) complexes which have essentiallyidentical reduction potentials but drastically different catalyticproperties." The origin of these differences in reactivity will bediscussed below.Regardless of these other factors though, onecan assume that a balance between ease of reduction (morepositive reduction potential) and subsequent reoxidation (morenegative reduction potential) by molecular oxygen must bemaintained for efficient catalysis to occur; this would imply thata window of E+ values exists wherein effective catalysis can takeplace. If the reduction potential is too negative, reduction to Cu'would be unattainable; on the other hand, if the reductionpotential is too positive, the catalytic cycle would be short-circuited because once reduced to Cu', the complexes would beunable to be easily reoxidized to Cu" by 0,. Within a certainrange of E+ values catalysis is possible, while outside that rangethe drop off in rate is quite significant.It should be noted that the enzyme tyrosinase isolated frommushroom (Agaricus bisporus) has a reported value for E,of 0.36 V us. the standard calomel reference; 43 this value lies atthe positive end of the series of our complexes.It is obvioushowever, that the enzyme has been able to balance successfullythe requirements of the different oxidation states of the metal inperforming its catalytic tasks.Geometrical Effects.-The geometry of the pyrazole-contain-ing complexes was probed in our earlier work.8 The data forcomplexes 1-8 show that first, and most importantly, thesquare-pyramidal complexes [Cu(tpzea)(H20)][BF4], 7 and[Cu(tpzea)Cl]Cl 8 are unique in their inability to catalyse theoxidation of 3,5-di-tert-butylcatechol. As shown in Table 2, thesquare-pyramidal complexes [Cu(tpyea)(H,O)][BF,], 3 and[Cu(tpyea)Cl]Cl 4 do catalyse the oxidation reaction.Ouroriginal premise that a geometrical effect may be responsible forthe lack of reactivity of the square-pyramidal tpzea complexesis clearly inoperative since complexes of tpyea catalysethe reaction, as do the trigonal-bipyramidal tpzma andtpyma complexes. Therefore, in considering five-co-ordinatecopper(1r) complexes, either square-pyramidal or trigonal-bipyramidal complexes are capable of serving as catalysts foroxidation reactions so other factors must be responsible for thedifferences in rate.Exogenous Donors.-We have previously shown thatchanging the nature of the fifth donor atom, the counter ion, orany bridging group bound to the copper ions has an effect onthe rate of In addition, it has been shown thatelectron transfer from catechol to Cu" can begin only aftercatechol and the Cu" species form a Cu" catecholateintermediate; 44 this situation would require a vacant co-ordination site on the metal so that complexation of thecatechol can occur.The results for the complexes describedhere affirm that the reaction is dependent on either the rateof dissociation of the fifth donor, or the differences in thedissociation constants for the loss of the fifth donor. This isevident when one compares the reactivity of the systems havingthe same tetradentate ligand but different fifth donors, such as[Cu(tpyma)(H,O)][BF,], 1 and [Cu(tpyma)Cl]C12.In thesecases, the activities are 4.71 x lo4 and 1.34 x lo-' pmolsubstrate per mg of catalyst per min respectively. However,when comparing different ligand sets with identical fifth donors,no trend which would correlate the nature of the fifth donorwith the reactivity of the complex is apparent. The differences inrate as a result of changes in the fifth donor are relatively minorcompared to other effects described below. Since the catalysisis performed in methanol, the relatively small differences maybe a result of the formation of [Cu(ligand)(CH3OH)l2+ oiu asolvolysis reaction which occurs after dissociation of the fifthdonor.Basicity.-The fourth consideration in assessing the reactivityof these complexes is the basicity of the donor atoms.Pyrazolehas a p& value of I 1 .5 while pyridine has p& = 8.7.45 Sincethe biological donor imidazole has a p&, value of 7.0, thissuggests that if basicity alone is considered, pyridine is a bettermimic for imidazole. Analogous to results found for the tpymaligand and its quinoline (p& = 9.1) derivatives," replacingpyridine by pyrazole should result in a more stable Cu' form forthe pyrazole complexes because of its higher pK,. This featurewill affect the reduction potentials of the complexes by shiftingthe pyrazole E+ values to more positive values compared totheir pyridine counterparts. In contrasting complexes 1 with 5or 2 with 6, it can be seen that this is the case. The data areconsistent with the premise that the basicity of the donor atomsis one of the primary factors in modulating the resultantelectrochemical properties of the complexes.Steric Considerations.-There are a number of stud-ies 19.30*41 9 4 6 on complexes of tripodal ligands which haveconsidered the impact of changing the steric features of theligands on the stability of the oxidized and reduced forms of theCu'-Cu" couple; two are pertinent to the work described here.Sorrel1 and Jameson'O have shown that as the steric bulk on aseries of pyrazole ligands (one of which was tpzea) is increased,the Cu' form is stabilized resulting in more positive reductionpotentials for the sterically hindered complexes.Karlin and co-workers l9 reported similar effects when pyridine donors arereplaced by the bulkier quinoline, suggesting that the change tonon-polar quinolyl substituents leads to increased hydrophob-icity which stabilizes the lower charged species (Cu' over Cu").Karlin et aL2' have also generated oxygen complexes fromtheir tripodal species where the differences in the relativestabilities of the oxygen complexes are attributed to stericfactors.When exposed to the atmosphere at -8O"C, thecopper(r) complex [Cu(tpyma)(MeCN)] + was shown to reacto h the initial reversible formation of the 1 : 1 Cu : 0, complex[Cu(tpyma)(O,)] + which reacts reversibly with the starting Cu'species to form the 2: 1 complex [(C~(tpyma)),(O,)]~+.~' Incontrast, the complex with three quinoline donors is muchbulkier than the pyridine-containing complex and as a result isunreactive towards 0,.A similar result was found as the size ofthe alkyl substituents was increased on the pyrazole arms oftpzea." It is possible that similar copper-oxygen species existduring the reaction of the tripodal-containing complexes with3,5-di-tert-butylcatechol prepared here; however, we have notprobed the detailed mechanism of the reactions.Differences in the steric features of the ligands can bemanifested in a variety of ways. These include differences in thehydrophobicity of the complexes, accessibility of the substrateto the metal ion due to the steric bulk of the ligand, and theextent of the steric match between the substrate and thecomplex.If any of these steric considerations are important, thereactivity properties of the copper(@ complexes should beaffected. An examination of Table 2 shows that the pyridine-containing complexes [Cu(tpyea)(H,O)][BF,], 3 and [Cu-(tpyea)Cl]Cl 4 are significantly more reactive than thecorresponding pyrazole complexes [Cu(tpzma)(H,O)] [BF,] , 5and [Cu(tpzma)Cl]C16, even though their redox potentials arevery similar. Activity values for the oxidation of 3,s-di-tert-butylcatechol by mononuclear copper(r1) complexes typicallyfall in the range (0.5-1) x lo-' pmol substrate per mg ofcatalyst per min.6-8 However, complexes formed from thepyridine-containing tpyea have significantly higher rates ofreaction, and indeed are the most active catalysts that we havestudied.There are other examples of enhanced reactivity for pyridineover pyrazole containing copper complexes.The most strikingexample is the hydroxylation of aromatic moieties by N,pyridine complexes while the analogous N, pyrazole systems donot activate 0, for this r e a ~ t i o n . ~ ~ , ~ ' . ~ ~ It has beenhypothesized that the geometry needs to be optimized fo36 J. CHEM. soc. DALTON TRANS. 1995correct orientation of the bound peroxo group and the arenering in order for hydroxylation to A more optimalsteric match between complexes 3 and 4 and catechol or O2compared to that found for complexes 5 and 6 may be partlyresponsible for the differences in their reactivity towardscatechols.However, if steric factors were exclusively responsible forcontrolling the rates of reaction, then the pyrazole-basedcomplexes should have slower rates than the correspondingpyridine-based complexes.As shown in Table 2, this is notalways the case. Although complexes 3 and 4 are appreciablymore reactive than 7 and 8, the pyrazole-containing 5 and 6 areactually more reactive (by 102-103 times) than are 1 and 2. Itseems, then, that both the electrochemical properties of themolecules and their steric features determine whether or not thecomplexes will be active catalysts.ConclusionA series of square-pyramidal and trigonal-bipyramidal copper-(11) complexes formed from tetradentate pyridine- and pyrazole-containing ligands have been prepared in an attempt to uncoverthe predominant features which define their catalytic action.In contrast to earlier work on pyrazole-containing ligands,the results for the pyridine complexes show that trigonal-bipyramidal and square-pyramidal copper(I1) complexes canact as catalysts for the oxidation of catechols.It is clear that substantial differences in catalytic ability can bebuilt into copper(I1) complexes by the judicious choice of ligandsets.The rate of catalysis for copper(r1) complexes is linked toboth the redox potentials and the steric match between thesubstrate and the complex. Substantial retardation of reactivityis evident if either steric or electronic factors are not optimal.Having a reduction potential in the appropriate range is ofcrucial importance in defining catalytic activity, however, this isa necessary but not sufficient requirement for truly effectivecatalysis.Although the electronic features determine whethercatalysis will proceed, the steric match between the substrateand the catalyst is also of crucial importance. In complexes withidentical reduction potentials, the pyridine-containing systemshave substantially higher rates of reaction than do theirpyrazole counterparts. This result suggests that a more optimalsteric match exists between the pyridine complexes and catecholor 0, than exists for the pyrazole systems. Efforts towardspreparing copper(I1) complexes with pyridine donors whichhave reduction potentials of intermediate values are beingundertaken to determine whether these complexes can serve asmore efficient catalysts.AcknowledgementsThe support of this research by the Research Corporationis gratefully acknowledged (M.R. M. and R. S. K.). We arealso grateful to Professor Jan Reedij k (Leiden University,Leiden), and Professor Donald Jameson (Gettysburg College,Gettysburg, PA) for stimulating discussions.References1 D. A. Robb, in Copper Proteins and Copper Enzymes, ed. R. Lontie,CRC Press, Boca Raton, FL, 1984, vol. 2, p. 207.2 A. E. Martell and D. T. Sawyer, Oxygen Complexes and OxygenActivation by Transition Metals, Plenum Press, New York, 1987.3 D. E. Wilcox, A. G. Porras, K. Lerch, M. E. Winkler andE. I. Solomon, J. Am. Chem. Soc., 1985,103,4015.4 P. K. Ross and E. I. Solomon, J. Am. Chem. Soc., 1991,113, 3246.5 S.Kida, H. Okawa and Y. 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