Designer ligands. Part 14. Novel Mn(lI), Ni(II) and Zn(II) complexes of benzamide-and biphenyl-derived ligands

Manganese(II), nickel(II) and zinc(II) complexes have been prepared using various benzamide-and biphenyl-derived ligands; their structures have been investigated using infrared spectroscopy and it is apparent that, depending on the ligand, the metal centres adopt octahedral, tetrahedral and distorted tetrahedral coordination geometries. The catecholase activity of the manganese(II) complexes has also been evaluated


Introduction
Metals play important roles in biological systems and, in earlier papers, we have described the development of biomimetic complexes designed to mimic the active site of tyrosinase, 1 an enzyme capable of ortho-hydroxylating phenols (phenolase activity) and oxidising catechols to ortho-quinones (catecholase activity). 2,3Copper 4 and cobalt 5 complexes of novel ligands, prepared in our laboratory, have also been shown to exhibit catecholase activity, and our interests broadened to include other transition metal systems, viz., manganese(II), nickel(II) and zinc(II) complexes.][9][10] Nickel also plays important roles in biological systems.The first such system to be discovered, the enzyme urease, was isolated from jack beans [11][12] and shown by UVvisible spectroscopy and EXAFS studies to contain two octahedral nickel(II) ions in a nitrogenand oxygen-donor environment.Nickel has subsequently been found in other enzymes, viz., hydrogenases, CO dehydrogenases and coenzyme F 430 . 12It has been found that the hydrogenases and CO dehydrogenases have nickel(III) (low spin d 7 ) and Fe-S clusters present in their structures, 12 while nickel(II) in coenzyme F 430 , a cofactor of methyl coenzyme M reductase, exhibits square planar geometry.

Results and Discussion
The ligands 1a-c (Scheme 1) were prepared by treating benzoic acid with carbonyl diimidazole (CDI) 13 in dimethylformamide (DMF), followed by the respective primary amines, histamine, 2-(2-aminoethyl)benzimidazole and 2-(2-aminoethyl)pyridine.[Histamine had to be released from its dihydrochloride salt by treatment with sodium methoxide, while 2-(2aminoethyl)benzimidazole was prepared from 1,2-diaminobenzene and β-alanine. 16] The synthesis of the biphenyl-derived ligand 2, which also contains imidazolyl groups, has been reported previously. 13Schemes 2-5 outline the use of these ligands in the formation of manganese(II), nickel(II) and zinc(II) complexes, the structural assignments of which are based on a consideration of the microanalysis and infrared data.Microanalysis data for the various complexes are summarized in Table 1.It is apparent that the manganese complexes 3a and 3c are mononuclear while complex 4 is dinuclear; all three complexes, however, contain two chloride ions (Scheme 2).The nickel complexes 5-7 (Scheme 3) all appear to be dinuclear and each complex contains four chloride ions.The diamide-and monoamide zinc complexes [8a,c and 9a-c, respectively (Schemes 4 and 5)] all appear to be mononuclear and contain only two chloride ions.The structures proposed for the various complexes (Schemes 2-5) are consistent with the microanalysis and corresponding infrared data (Table 2).Mid-IR spectra of the complexes were used to establish whether the manganese ions coordinate through the amide nitrogen or oxygen atoms, while the environment of the coordinated chloride anions was determined by running spectra in the far-IR region.Both negative and positive shifts may be observed for the amide carbonyl band (amide I) − a negative shift indicating coordination via the amide oxygen, a positive shift coordination via the amide nitrogen.For the manganese monoamide complex 3a, the absence of any significant change in ν C=O coupled with a small positive shift (16 cm -1 ) of the benzamide NH band (relative to the free ligand) indicates coordination via the amide nitrogen, while the presence of the benzimidazole NH indicates coordination with the tertiary benzimidazole nitrogen.In the case of the pyridyl analogue 3c and the diamide complex 4, the significant positive amide NH band shifts, coupled with the negative C=O band shifts, are consistent with coordination via the amide carbonyl oxygen.The far-IR bands at 278 and 276 cm -1 are consistent with chloride ions in an octahedral environment in complexes 3a and 3c, respectively; the two, lower-frequency bands at 217 and 271 cm -1 for complex 4 are characteristic of chloride bridging. 17oordination of nickel through the amide oxygen in the diamide complex 6 is indicated by the small positive NH and negative C=O shifts.In complexes 5 and 7, coordination through the amide nitrogen is suggested by the positive amide NH shifts; complex 7 also exhibits a positive carbonyl shift, but complex 5 none.The presence of the amide NH band in all cases implies that deprotonation of the amide nitrogen has not occurred − an observation consistent with the microanalysis data for these nickel complexes.Very weak bands at 276 and 325 cm -1 in the far IR region were observed for complex 5 and are attributed to Ni-Cl stretches in a square planar environment.In the case of complexes 6 and 7 the strong bands in the 370-390 cm -1 region are attributed to chloride anions coordinated in a trans octahedral geometry. 17The X-ray crystal structure for complex 11 (Scheme 6 and Figure 1) clearly confirms the tetrahedral geometry responsible for the two relatively strong bands at 289 and 329 cm -1 ; these values are characteristic of chloride ions coordinated in a tetrahedral environment 17 − in contrast with the somewhat lower values attributed to the square-planar complex 5.For complex 8a, the small positive shifts of both the amide carbonyl and amide NH bands indicate coordination through the amide nitrogen (the apparent broadening of the amide carbonyl band is attributed to the presence of DMF).In complex 8c, no shift of the amide carbonyl band is evident and the large positive shift (ca. 100 cm -1 ) of the amide NH band points to coordination with the amide nitrogen.The negative shift of the amide CO band in complexes 9a and 9b is an indication that coordination occurs with the amide oxygen atom.From the data in Table 2 it appears that the amide functionality in these complexes is resistant to deprotonation.Two Zn-Cl bands characteristic of tetrahedral geometry are anticipated in the far-lR region (ca.295 and 327 cm -1 ) for complex 8a, but this was not observed. 17Instead, a very strong, broad band, with shoulders, is observed at ca. 287 cm -1 .This band may reflect accidental degeneracy of the symmetric and anti-symmetric Zn-Cl stretches due to a distorted tetrahedral zinc arrangement within this complex.The mononuclear zinc complexes 9a and 9b exhibit less intense bands at lower wave-numbers in the far-IR region and these are attributed to Zn-Cl stretches in an octahedral arrangement. 17 NMR analysis ( 1 H, 13 C and DEPT 135) of the zinc(II) complexes revealed broadening of the ligand signals − a phenomenon observed in other studies 18 and attributed to site-exchange processes involving coordination to the metal centre.Signal broadening is particularly marked in the 1 H NMR spectrum of complex 9b, while the corresponding 13 C spectrum reveals doubling of certain ligand signals, consistent with slow (on the NMR time-scale) site-exchange between nonequivalent structural arrangements.In the case of complex 8c, on the other hand, only slight broadening of the 1 H signals is apparent.
The phenolase and catecholase activity of the manganese(II) complexes were investigated to determine whether these complexes are capable of mimicking the active site of the enzyme tyrosinase.0][21] [3,5-DTBP is oxidized to 3,5-DTBC, which is oxidized, in turn, to 3,5-di-t-butyl-o-quinone (3,5-DTBQ); if formed, the oxidation products may be readily detected by 1 H-NMR analysis].It can be seen from the data summarised in Table 3 that while no phenolase activity was observed, catecholase activity was exhibited by the three manganese complexes 3a, 3c and 4. Phenolase activity requires initial axial binding of the phenol to the metal centre, followed by Berry pseudorotation of the trigonal bipyramidal complex, to expose the equatorial substrate to ortho-hydroxylation.This may be inhibited in these complexes and, as a consequence, no phenolase activity was observed.Catecholase activity is easier to achieve since it only requires a transfer of electrons and it is observed for complexes 3a, 3c and 4. The catecholase activities of the mangananese complexes complexes 3a and 4 are greater than those exhibited by our biphenyl dinuclear cobalt(II) complexes (≤ 88%) 5 and by our macrocyclic dinuclear copper(I) and copper(II) complexes (63% and 83% conversion, respectively), but comparable with the activity of our macrocyclic dinuclear cobalt(II) complex (100% conversion). 22The catalytic oxidation of 3,5-DTBC to 3,5-DTBQ by a series of mononuclear manganese complexes has been reported previously, 23 and our results are similar to those observed for [M II (diclofenac) 2 H 2 O)] complexes (M = Mn, Co, Ni, Cu). 24

Conclusions
It is apparent that the benzamide-and biphenyl-derived ligands examined here form complexes with manganese(II), nickel(II) and zinc(II) and that, depending on the ligand, the metal centres in these complexes adopt octahedral, tetrahedral or distorted tetrahedral coordination geometries.The structures of the complexes have been assigned using elemental analysis data, mid-and farinfrared and, where appropriate, NMR spectroscopic data.Significant catecholase activity (75 -100% conversion within 24 hours) has been demonstrated for the manganese(II) complexes 3a, 3c and 4, while complexes 3a and 4 also exhibit encouraging recyclability (100% conversion within 24 hours).

The manganese complex 3c
To a stirred solution of N-[(2-pyridinyl)ethyl]benzamide 1c (0.17 g, 0.75 mmol) in MeOH (3 mL), a solution of MnCl 2 .4H 2 O (0.17 g, 0.75 mmol) in MeOH (5 mL) was added and the reaction mixture stirred for 53 h.The solvent was removed under reduced pressure to less than half the original volume before adding Et 2 O to precipitate the product.The residual oil that precipitated was washed with Et 2 O followed by drying under vacuum to afford, as a light-brown powder, the manganese complex 3c, (0.29 g, 97%), mp 103-105°C; v max (KBr/cm -1 ) 3344 (amide NH) and 1623 (CO); v max (nujol/cm -1 ) 276 (Mn-Cl).), 4317 unique with I > 2σ(I).Hydrogen atoms were placed in calculated positions and the structure was solved by direct methods using SHELX-97; 29 full-matrix least-squares refinement converged at R 1 = 0.0494, wR 2 = 0.0979, GOF = 1.132.CCDC 704606 contains the supplementary crystallographic data for this paper.These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif

Catalytic studies
The substrates 3,5-DTBP (100 eq.) and 3,5-DTBC (100 eq.) were added to solutions of the Mn(II) complexes (0.01g) in DMF (2 mL for 3a, 4; 2.5 mL for 3c), typically containing Et 3 N (see Table 3), to give substrate:complex molar ratios of 100:1.The resulting mixtures were aerated by stirring vigorously for 24h.At the conclusion of each reaction period, the mixture was concentrated to dryness in vacuo and the residue analysed by 1 H NMR spectroscopy to determine the substrate:product ratio.After analysis of the residue, diethyl ether was added to dissolve and remove 3,5-DTBC and 3,5-DTBQ from the complex.Recyclability was established by adding fresh substrate, DMF and Et 3 N to the complex from the initial reaction, and stirring for 24 h.The solvent was evaporated in vacuo and the residual material analyzed as before.

Table 1 .
Microanalytical data for the metal complexes followed, in parentheses, by the calculated values Presence of H 2 O and/or DMF supported by IR data; see Table 2 for ν(OH 2 ) data. a

Table 2 .
Summary of the IR frequencies (V M-Cl ) and the amide frequency shifts (∆V NH and ∆V C=O ) on formation of the metal complexes a Broad H 2 O bands.b In HCBD.c In NaCl.d Shoulder.

Table 3 .
Catecholase activity of the manganese(II) complexes

Table 4 .
Atomic coordinates (x 10 4 ) for complex 11 and equivalent isotropic displacement parameters (Ǻ 2 x 10 3 ) U(eq) is defined as one third of the trace of the orthogonalized Uij tensor

Table 5 .
Bond lengths (in Angstroms) with standard deviations for complex 11

Table 6 .
Bond angles [deg] for complex 11Low resolution mass spectra were obtained on a Hewlett-Packard 5988A mass spectrometer, and high resolution analyses on a Kratos MS8ORF double focussing magnetic sector instrument (Cape Technikon Mass spectrometry unit).Microanalysis (combustion analysis) was conducted at the University of Cape Town, and the data for the zinc complexes are reported in Table1.Melting points were obtained using a Kofler hot-stage microscope and are uncorrected.Na 2 CO 3 (50 mL) was added.The mixture was extracted with EtOAc (4 x 100 mL), and the combined extracts were washed with H 2 O (100 mL) and brine (100 mL), and dried (MgSO 4 ). 2 O (7 mL).Volatiles were removed under reduced pressure, and aqueous 1 M Na 2 CO 3 (50 mL) was added to the residual oil.The mixture was extracted with EtOAc (4 x 100 mL), and the combined extracts were washed with H 2 O (100 mL) and brine (100 mL), and dried (MgSO 4 ).