The synthesis and characterization of the novel Pseudo-Octahedral complex bis[(2-hydroxybenzyl) - (2-methylpyridyl)-amine] zinc(II), [ZnII(bpa)2].2H2O as a model for astacin

Abstracts

The reaction between (2-hydroxybenzyl)(2-pyridylmethyl) amine (Hbpa) and Zn(OAc)2.2H2O (2:1) in a methanolic medium gave colorless crystals of [Zn(bpa)2].2H2O. The crystal structure of the complex was determined by X-ray diffraction in the triclinic crystal system, space group P <img width=32 height=32 src="../../../../../../img/revistas/jbchs/v8n3/a15img01.gif" align=absmiddle>(No. 2), and cell dimensions a = 9.504(1), b = 11.984(1), c = 11.966(1) Å, a = 79.36(2), b = 89.18(2), g = 78.95(2)o , V = 1314.2(2) Å3, Z = 2, Dcalc = 1.334 Mg m-3, l(MoKa) = 0.71073 Å, m = 0.991 mm-1, F(000) = 552, T = 296 K, and R = 7.1% (Rw = 11.0%), with 4846 measured reflections and 3247 observed reflections with I > 3s(I) and 326 refined parameters. The coordination environment around the Zn(II) ion is pseudo-octahedral, with the tripodal units of bpa- coordinated in a facial arrangement. To the best of our knowledge, [Zn(bpa)2].2H2O is the first structural example of an octahedral Zn2+ complex which contains phenolate in its coordination sphere.

mononuclear zinc(II) complex; X-ray analysis; [Zn(bpa)2].2H2O

A reação entre o ligante (2-hidroxibenzil)(2-metilpiridil) amina (Hbpa) e Zn(OAc)2.2H2O (estequiometria 2:1), em solução metanólica, rendeu cristais incolores de [Zn(bpa)2]. A estrutura cristalina do complexo foi determinada por difração de raios-X, no sistema cristalino triclínico, grupo espacial P <img width=32 height=32 src="../../../../../../img/revistas/jbchs/v8n3/a15img01.gif" align=absmiddle>(No. 2) e dimensões de cela a = 9,504(1), b = 11,984(1) c = 11,966(1)Å, a = 79,36(2), b = 89,18(2), g = 78,95(2)º , V = 1314,2(2) ų, Z = 2,Dcalc = 1,334 Mg m-3, l(MoKa) = 0,71073 Å, m = 0,991 mm-1, F(000) = 552, T = 296 K, R = 7,1% (Rw = 11,0%), com 4846 reflexões medidas, 3247 reflexõesobservadas com I > 3s(I) e 326 parâmetros refinados. A geometria de coordenação em torno do Zn(II) é pseudo-octaédrica com as unidades tripodais do ligante (bpa-) coordenadas facialmente. Segundo nosso conhecimento, [Zn(bpa)2].2H2O representa o primeiro exemplo estrutural de um complexo octaédrico de Zn2+ que contém fenolato na sua esfera de coordenação.

Article

The synthesis and characterization of the novel Pseudo-Octahedral complex bis[(2-hydroxybenzyl) - (2-methylpyridyl)-amine] zinc(II), [Zn^II(bpa)₂].2H₂O as a model for astacin

Ademir Neves*, Ivo Vencato, and Cláudio Nazari Verani

Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis - SC, Brazil

Received: August 16, 1996; November 20, 1996

A reação entre o ligante (2-hidroxibenzil)(2-metilpiridil) amina (Hbpa) e Zn(OAc)₂.2H₂O (estequiometria 2:1), em solução metanólica, rendeu cristais incolores de [Zn(bpa)2]. A estrutura cristalina do complexo foi determinada por difração de raios-X, no sistema cristalino triclínico, grupo espacial P (No. 2) e dimensões de celaa = 9,504(1), b = 11,984(1) c = 11,966(1)Å, a = 79,36(2), b = 89,18(2), g = 78,95(2)^o , V = 1314,2(2) ų, Z = 2,D_calc = 1,334 Mg m^-3, l(MoK_a) = 0,71073 Å, m = 0,991 mm^-1, F(000) = 552, T = 296 K, R = 7,1% (Rw = 11,0%), com 4846 reflexões medidas, 3247 reflexõesobservadas com I > 3s(I) e 326 parâmetros refinados. A geometria de coordenação em torno do Zn(II) é pseudo-octaédrica com as unidades tripodais do ligante (bpa^-) coordenadas facialmente. Segundo nosso conhecimento, [Zn(bpa)₂].2H₂O representa o primeiroexemplo estrutural de um complexo octaédrico de Zn²⁺ que contém fenolato na sua esfera de coordenação.

The reaction between (2-hydroxybenzyl)(2-pyridylmethyl) amine (Hbpa) and Zn(OAc)₂.2H₂O (2:1) in a methanolic medium gave colorless crystals of [Zn(bpa)₂].2H₂O. The crystal structure of the complex was determined by X-ray diffraction in the triclinic crystal system, space group P (No. 2), and cell dimensions a = 9.504(1), b = 11.984(1), c = 11.966(1) Å, a = 79.36(2), b = 89.18(2), g = 78.95(2)o , V = 1314.2(2) Å^3, Z = 2, D_calc = 1.334 Mg m^-3, l(MoK_a) = 0.71073 Å, m = 0.991 mm^-1, F(000) = 552, T = 296 K, and R = 7.1% (Rw = 11.0%), with 4846 measured reflections and 3247 observed reflections with I > 3s(I) and 326 refined parameters. The coordination environment around the Zn(II) ion is pseudo-octahedral, with the tripodal units of bpa^- coordinated in a facial arrangement. To the best of our knowledge, [Zn(bpa)₂].2H₂O is the first structural example of an octahedral Zn²⁺ complex which contains phenolate in its coordination sphere.

Keywords: mononuclear zinc(II) complex, X-ray analysis, [Zn(bpa)₂].2H₂O

Introduction

It is well known that zinc plays an important role in many biological processes¹. It is now evident that zinc is essential for the normal growth and development of all living matter, but, remarkably, this universal requirement has been unappreciated until quite recently^1c . Particularly of interest, are the extracellular zinc enzymes which are involved in hydrolytic processes. Astacin, a digestive zinc-endopeptidase from the crawfish Astacus astacus L.² represents the prototype for the "astacin family"³, which includes mammalian metaloendopeptidases⁴ and developmentally regulated proteins of humans⁵, fruitflies⁶, frogs⁷ and sea urchins⁸. Very recently, the X-ray crystal structure of this metalloenzyme was solved and refined to a crystallographic R-value of 0.162 using reflections from 10 to 1.8 Å⁹. The structure of the active site reveals that the Zn²⁺ lies in a trigonal-bipyramidal coordination environment, with three histidines, a water molecule, and a remote tyrosine as ligands⁹. One histidine nitrogen and the tyrosine OH group, at distances of 2.3 and 2.6 Å from the zinc, respectively, are apically connected, whereas the other three ligands are coplanar with, and 2.1 Å apart from, the central zinc. It is important to note that astacin represents the first example of a zinc enzyme which contains tyrosine ligated directly to the metal center in the active site⁹. In order to provide model compounds for this class of enzymes and subsequent reactivity and activity studies, we report here the synthesis and X-ray crystal structure of the [Zn(bpa)₂].2H₂O complex which contains the tripodal Hbpa ligand (Fig. 1), with phenolate, amine, and pyridine coordinated to Zn²⁺. This is part of our program for the preparation and characterization of metal complexes with bioinorganic relevance¹⁰.

Experimental

Materials

Salicylaldhyde, 2-(aminomethyl)pyridine, and Zn(OAc)₂ .2H₂O were obtained from Aldrich Chemical Co. All other chemicals and solvents were reagent grade.

Syntheses

The ligand (2-hydroxybenzyl)(2-pyridylmethyl) amine (Hbpa) was obtained from a condensation reaction of 2-(aminomethyl) pyridine and salicylaldehyde followed by a reduction with NaBH₄ in methanol^10c. Yield: 65%. Mp = 62 °C (lit. value: 62 °C^10c).

[Zn(bpa)₂].2H₂O (1)

Zn(OAc)₂.2H₂O (0.22 g, 1.0 mmol) was added to a solution of Hbpa (0.43 g, 2.0 mmol) in 15 mL of methanol. The clear solution was heated to 40 °C and stirred for 10 min at ambient atmosphere. After the solution was cooled to room temperature, ethylacetate (10 mL) was added, and in a few days suitable colorless crystals of 1 for X-ray crystallography were obtained. Anal. Calcd. for C₂₆H₂₆N₄O₂Zn.2H₂O: C, 59.15; H, 5.73; N, 10.61%. Found: C, 58.45; H, 6.58; N, 10.48%.

X-ray crystallography

A colorless prismatic single crystal with dimensions 0.20 x 0.30 x 0.70 mm was mounted on a glass fiber and used to collect data on a Nonius CAD-4 diffractometer¹¹ with graphite-monochromated Mo K_a radiation and w – 2q scan. The unit cell and the orientation matrix for the data collection were obtained by a least-squares fit of 25 centered reflections (17.56 < q < 19.57°). The intensities of three standard reflections were measured every 60 min and varied less than 1.2%. The intensity data were corrected for Lorentz and polarization effects, but no decay correction was applied. A Y scan-based empirical absorption correction was applied (transmission factors 0.9695 to 0.9997). The number of measured reflections was 4846 in the range of -11/11, 0/14, -13/14, with 4608 unique reflections, and 3242 were above the significance level of 3s(I). The maximum value of (sin q)/l was 0.594 Å^-1. Equivalent reflections were merged with R_int = 2.2%. Automatic peak search and indexing procedures yielded a triclinic reduced primitive cell. Inspection of the Niggli values revealed no conventional cell of higher symmetry. The intensity statistics were consistent with a centrosymmetric space group. We solved and refined this structure in P, with two half molecules in the asymmetric unit because the two Zn atoms were found at inversion centers.

The structure was solved by means of direct methods using SIR92¹² and subsequent Fourier difference synthesis. The structure was refined by full-matrix least-squares techniques which minimized Sw(DF)². A weighing scheme of w = 1/[(s(F_o2) + (0.020*F_o)² + 1.0] was used. H atoms were placed in geometrically calculated positions with C-H = 0.95 Å, the aqua H atoms were found in difference Fourier maps and their parameters were not included in the refinement. Anisotropic displacement parameters were used for all non-hydrogen atoms; each H atom was given an isotropic displacement parameter equal to 1.3 times the equivalent isotropic displacement parameter of the atom to which it is attached. At the end of the refinement an isotropic extinction correction (1 + gI_c) was applied to F_c with a coefficient of g = 2.48(1) x 10^-7. The number of refined parameters was 326, and the fit was 1.739. Residual densities of 1.32 and -0.94 e^-/ ų in the final difference map were found. Examination of the structure with PLATON¹³ showed no solvent-accessible voids in the crystal lattice. The final refinement gave R = 7.1%, Rw = 11.0% and all parameter shifts were less than 0.12 of the corresponding standard deviation. Scattering factors were taken from the International Tables for X-ray Crystallography (1974). Calculations were performed on a DEC 3000 AXP computer using the MolEN package¹⁴.

Results and Discussion

The Crystal and Molecular structure of [Zn(bpa)₂].2H₂O (1)

The structure of complex 1 consists of discrete neutral [Zn(bpa)₂] units and water molecules of crystallization. The asymmetric unit consists of two slightly different half molecules, since the whole molecules are generated by distinct inversion centers. Table 1 reports the final atomic coordinates, while Fig. 2 shows the ORTEP¹⁵ of molecule 1 with an atom-numbering scheme. Bond distances and bond angles are given in Tables 2 and 3, respectively.

The molecular structure of each molecule in 1 shows two deprotonated bpa^- ligands facially coordinated to the Zn²⁺ ion through the nitrogen (amine and pyridine) and oxygen (phenolate) donors. Since the molecules possess inversion centers, atoms of the same nature (two N_amine, two N_pyridine, and two O_phenolate) must be coordinated in trans positions with respect to each other. The six-membered chelate rings (ZnONC₃) adopt chair conformations with the torsion angles N1-C2-C22-C21 of -67(1)° and N2-C4-C42-C41 of -69(1)°. The remaining five-membered rings formed by the 2-pyridylmethyl groups are rigid and deviate slightly from planarity, with the sum of the interior angles being 526° and 527° for Zn1-N1-C1-C12-N11 and Zn2-N2-C3-C32-N31 rings, respectively. The angles N1-Zn1-N11 = 79.7(3)° in molecule 1 and N2-Zn2-N31 = 76.4(3)° in molecule 2 are significantly smaller than the ideal octahedral angle of 90° and are a reflection of the rigidity of these five-membered rings. The torsion angles N11-Zn1-N1-C1 = 30.0(6)° and Zn1-N11-C12-C1 = 1.5(9)°, and N31-Zn2-N2-C3 = 31.5(6)° and Zn2-N31-C32-C3 = 7.6(9)° give us the extent of puckering in the outer and inner regions of molecules 1 and 2, respectively. The Zn-N_amine bond lengths of 2.148(8) Å in molecule 1 and 2.186(7) Å in molecule 2 compare very well with the corresponding distances observed in the centrosymmetric pseudo-octahedral structure of the [ZnL₂](PF₆)₂ complex (L = 1,4,7-triazacyclononane), which are in the range of 2.156(5) to 2.187(5) Ź⁶, while the Zn1-N_pyridine = 2.160(8) Å and Zn2-N_pyridine = 2.167(8) Å are in good agreement with the Zn-N_pyridine bonds (average = 2.170 Å detected in [Zn(bpy)₃](ClO₄)₂¹⁷. However, these distances are significantly longer than those observed in the equatorial plane (Cu-N_amine = 2.003 Å and Cu-N_pyridine = 2.051 Å) of the [Cu(Hbpa)₂]²⁺ complex, which has a similar arrangement of the Hbpa ligand around the Cu^{2+ 18}.This may arise from the presence of cationic species in the Cu²⁺ complex, compared with the neutral complex 1. From this point of view it is consistent to consider a decrease of electron density at the Cu²⁺ center, that determines an increase of the Cu-N bond order, and consequently the shortening of the Cu-N_amine and Cu-N_pyridine bond lengths. It is important to note that the ionic radii of Cu²⁺ and Zn²⁺ with O_h symmetry are similar, at 87 and 88 pm, respectively¹⁹. The Zn-O_phenolate bonds in molecules 1 and 2 are very different with Zn1-O1 = 2.154(6) Å and Zn2-O2 = 2.076(6), and are a consequence of the distinct hydrogen contacts of the O1 and O2 atoms. Details of the hydrogen bonding scheme are in Table 4. The crystal structure is shown in projection down the c axis with the hydrogen bonds (Fig. 3). On the other hand, these bonds are significantly longer than those generally found in the equatorial plane of trigonal bipyramidal complexes, which fall in the range of 1.9-2.0 Å. This unusual structural feature can be tentatively explained as a result of a mutual trans effect caused by the phenolate groups which are coordinated in trans positions with respect to each other. Unfortunately, the lack of structural data for octahedral zinc-phenolate complexes restrict us from further comparisons. Indeed, to the best of our knowledge, [Zn(bpa)₂].2H₂O is the first structural example of an octahedral Zn²⁺ complex which contains phenolate in its coordination sphere.

Finally, we conclude that some appropriate synthetic modifications of 1 are necessary to obtain more adequate models for astacin. The synthesis of analogues of 1 in which one or two phenolates could be protonated are in progress in our laboratory and will be the subject of future reports. This has already been achieved with the corresponding copper complex¹⁸.

Supplementary Material

The list of observed and calculated structural factors, anisotropic temperature factors, and hydrogen coordinates are available from the authors (I.V.) upon request.

Acknowledgments

This research was supported by grants from CNPq, PADCT, and FINEP (Ministério da Ciência e Tecnologia - Brazil). C.N.V. wishes to thank CNPq for a fellowship.

References

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Publication Dates

• Publication in this collection
  31 Jan 2011
• Date of issue
  June 1997

History

• Received
  16 Aug 1996
• Accepted
  20 Nov 1996