2D and 3D Supramolecular Structures of trans– and cis–Octahedral Coordination Compounds of Ethyl–5–methyl–4–imidazolecarboxylate with Transition Metal Ions

Víctor Adán Barrera–Guzmán, Raúl Ramírez–Trejo, Edgar Omar Rodríguez–Hernández, and Noráh Barba–Behrens*

Departamento de Química Inorgánica, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, México, D.F., 04510, México. Tel/fax: +52–55–622–3810, norah@unam.mx

Received February 1, 2011. ]]> Accepted June 6, 2011.

Abstract

Ethyl–5–methyl–4–imidazolecarboxylate (emizco) is an important intermediate in the synthesis of pharmacological active compounds. In this work, there were synthetized and characterized the following coordination compounds with emizco: trans–[Co(emizco)₂(H₂O)₂](NO₃)₂ 1, trans–[Ni(emizco)₂(H₂O)₂](NO₃)₂ 2, trans–[Cd(emizco)₂(H₂O)₂](NO₃)₂ (3) and cis–[Cd(emizco)₂Br₂] (4). 2D or 3D supramolecular arrangements were stabilized. All nitrate trans octahedral compounds stabilized a 3D supramolecular arrangement via hydrogen bonding, throughout the nitrate anions, the ligand and the coordinated water molecules; the cis–octahedral halide complex formed a 2D pleated sheet arrangement, by intermolecular π stacking and halide–hydrogen bonding.

Key words: Emizco, cobalt(II), nickel(II), cadmium(II), coordination compounds, supramoleular arrangements.

Resumen

El etil 5–metil–4–imidazolcarboxilato (emizco) es un intermediario importante en la síntesis de compuestos con actividad farmacológica. En el presente trabajo se sintetizaron y caracterizaron los siguientes compuesto de coordinación con emizco: trans–[Co(emizco)₂(H₂O)₂](NO₃)₂ 1, trans–[Ni(emizco)₂(H₂O)₂](NO₃)₂ 2, trans–[Cd(emizco)₂(H₂O)₂](NO₃)₂ (3) y cis–[Cd(emizco)₂Br₂] (4). Estos compuestos estabilizan estructuras supramoleculares en 2D ó 3D; todos los compuestos de nitrato con geometría trans octaédrica estabilizan arreglos en 3D por medio de puentes de hidrógeno entre los iones nitrato, emizco y las moléculas de H₂O; mientras que el compuesto de coordinación del haluro cis octaédrico tiene un arreglo en forma de hoja plegada en 2D, por medio de interacciones intermoleculares de tipo apilamiento–π y puente de hidrógeno–haluro.

Palabras clave: Emizco, cobalto(II), niquel(II), cadmio(II), compuesto de coordinación, arreglos supramoleculares.

The interaction of imidazole derivatives with metal ions is a subject of continuous interest. It is well known that a number of imidazole derivatives have biological activity, e.g. presenting pharmaceutical, antibacterial or fungicidal properties [1–3], among others. Within this class of compounds, nitroimidazoles have been used in the treatment of tropical diseases, in protozoal, anaerobic bacteria and the eradication of Helicobacter pylori infections [4–9], as in medical creams for treating acne, seborrheic dermatitis, rosacea and folliculitis [10]. Their biological activity as radiosensitizers, or as hypoxic cytotoxins has been studied [11–19]. Furthermore, these molecules may easily coordinate to transition metal ions, giving stable coordination compounds. The nitro group adjacent to an imidazolic nitrogen may occupy a coordination site, stabilizing chelate metal complexes, while the hydroxyethyl and nitro groups act as supramolecular synthons, with the option to generate hydrogen–bonded networks of different dimensions. The number, orientation and type of hydrogen bonding drive the formation of mono and two dimensional networks. The contribution of metal ions in metronidazole coordination compounds is shown in the stabilization of different aggregate structures, as we have informed [20]. Ethyl 5–methyl–4–imidazolecarboxylate (hereafter abbreviated emizco), is used as an intermediate in the synthesis of a variety of imidazolic compounds with pharmacological properties [21, 22]. Previously, we have investigated the coordination compounds of emizco with copper(II) [23], and the biological activity of its transition metal complexes on photosynthesis. They showed to be inhibitors of the photosynthetic electron flow and ATP–synthesis [24, 25]. In the copper(II) coordination compounds, the imidazole nitrogen atom and its neighbouring ester group are active sites for binding the Cu²⁺ atom, giving place to mono– or bi–dentate coordination modes, therefore stabilizing tetrahedral or octahedral geometries. In this paper we present the synthesis and the structural characterization of coordination compounds of emizco with cobalt(II), nickel(II) and cadmium(II) salts. This work was undertaken to contribute to a better understanding of the coordination behavior of this biologically relevant compound towards metal ions, the geometries and isomers that the metal atoms may adopt in these compounds, as the contribution of the counterion on the stabilization of 2D and 3D molecular aggregates.

Results and Discussion

When the reaction syntheses of emizco was carried out with the corresponding nitrate salts, the octahedral trans complexes: 1, 2 and 3 were obtained, while with cadmium bromide the cis compound 4 was isolated. These reactions are summarized in Scheme 1.

Spectroscopic characterization

In Table 1, spectral and magnetic data of emizco and its coordination compounds are presented. The IR spectrum of emizco showed absorption bands corresponding to the stretching modes v(C=O), v_as(C–O–C), v_s(C–O–C) of the ester functional group at 1693, 1321 and 1180 cm^–1 respectively, and for the v(C=N) at 1508 cm^–1. For compounds 1–4, the ester bands are shifted, upon coordination, with respect to the respective bands in the free ligand; the v(C=O) stretching band is shifted to lower energies (1644–1678 cm^–1), while v(C=N) is shifted to higher energy (1509–1528 cm¹), indicating that the emizco ligands are coordinated to the metal ion in a bidentate mode, through the C=O of the ester group and the imidazolic nitrogen, in agreement with their X–ray structures.

Reflectance spectrum of [Co(emizco)2(H₂O)₂](NO3)2 1 is characteristic of a cobalt(II) in an octahedral geometry, with a band centered at 9100 cmr¹ assigned as v₁ ⁴T_2g(F)⁴T_1g(F), in addition to a band at 20892 cm^–1 corresponding to v₃ ⁴Ti_g(P)⁴T_1g(F) [27]. The [Ni(emizco)2(H₂O)2](NO3)2 2 compound exhibits three bands at 9803 cm , v₁ = ³T_2g(F)³A_2g(F), 15852 cm^–1, v₂ = ³T_lg(F)³A_2g(F), and 25809 cm^–1, v₃ = ³T_lg(P)³A_2g(F). These transitions are within the expected range for a nickel(II) ion with an octahedral geometry [26]. In this compound the first transition (9803 cmr¹) corresponds to the 10 Dq, indicative of a weak crystal field splitting.

Magnetic susceptibility and electrical conductivity

For [Co(emizco)₂(H₂O)₂](NO₃)₂, an effective magnetic moment of 4.82 B.M. was observed, which is within the expected range for a high spin Co²⁺ ion with three unpaired electrons. The nickel(II) compound [Ni(emizco)₂(H₂O)₂](NO₃)_2, presented a magnetic moment of 3.17 B.M., as expected for this metal ion in an octahedral geometry. Their molar conductivities are characteristic for 1:2 electrolytes, for the nitrate complexes 1 and 2 are within the range of 222–257 μS/cm (in water), and for compound 3 a conductivity of 78 μS/cm (in DMSO) was found.

X–ray crystal structures of compounds 1–4

Suitable crystals for X–ray diffraction studies were obtained for the coordination compounds 1–4. The nitrate complexes 1 3 correspond to a centrosymmetric trans–octahedral geometry (Fig. 1), and the bromide compound 4 to a cis–octahedral geometry (Fig. 2).

The stabilization of these isomers was controlled by the counterion used in the reaction synthesis. The nitrate anions favors the centrosymmetric trans–octahedral cationic complexes [M(emizco)₂(H₂O)₂](NO₃)₂, where M = Co²⁺, Ni²⁺ and Cd²⁺(compounds 1, 2 and 3), whereas the bromide favor the cis geometry, [Cd(emizco)₂Br₂] 4, as it was previously observed for the copper(II) complexes trans–[Cu(emizco)₂(H₂O)₂](NO₃)₂ and cis–[Cu(emizco)₂X₂] (X^– = Cl, Br) [27]. The stabilization of the cis or trans geometry is driven by steric factors.

For the trans compounds 1–3, [Cd(emizco)₂(H₂O)₂](NO₃)₂ 3 presents the longest coordination bond lengths and the smallest chelate angle 73.22(5)°, whereas for the cobalt(II) and nickel(II) compounds as the coordination bond lengths get shorter, the chelate angle increases (Tables 2 and 3). Two intramolecular hydrogen bonds in the emizco ligand, O6^...C7 2.707 Å and O7^...C9 3.078 Å, [23] are conserved in all coordination compounds, as depicted for [Co(emizco)₂(H₂O)₂](NO₃)₂ 1 (Fig. 3).

A partial electronic delocalization on the chelate ring is observed, N3=C4 1.377(3) Å, C4–C6 1.450(3) Å, C6=O6 1.224(3) Å. The angles O1–M–O6 and N3–M–O1 have values in the range of 87–94°, as expected for this geometry.

The compound cis [Cd(emizco)₂Br₂] 4, has the smallest chelate angles, O6–Cd1–N3 66.58(9)° and O16–Cd1–N13 68.11(9)° (table 3), with the longest coordination bond lengths, N3–Cd 2.218(3) Å, O6–Cd 2.757(3) Å, N13–Cd 2.227(3) Å and O16–Cd 2.645(3) Å (figure 4, table 2).

Supramolecular arrangements

Trans–octahedral compounds 1–3

A 2D ribbon is build up by hydrogen bonds between the nitrate ions, the amino group of emizco ligands and the water molecules, in figures 5 and 6 these is shown for the cobalt(II) compound 1. The NH of the imidazolic rings form bifurcated hydrogen bonds with the nitrate ion, N1–H1B 02N2 (Nl 02 3.051 Ǻ) and N1–H1B 03N2 (Nl 03 2.854 Ǻ), forming a chain, that grows in the a axis direction. Additionally, one coordinated water molecule forms bifurcated hydrogen bonds with the ionic nitrate, O1^...O3N2, (2.907 Ǻ, 172.85°) and O1^...O4–N2 (3.044 Ǻ, 134.91°), Figure 5.

In tables 4 and 5 are included the intermolecular hydrogen bond lengths and angles for the nitrate trans compounds.

A 3D supramolecular structure is built up by parallel planes, linked by hydrogen bonds between the axial acua ligands and the nitrate ions, Figure 7.

Cis–octahedral compound 4

In this compound, there are two types of intermolecular interactions: hydrogen bonding and π stacking. The intermolecular hydrogen bonds are formed between N1–H of imidazole ring and the Br2 of a neighbouring molecule, which is shorter than the sum of van der Waals radii of Br and N atoms (Σ_rvwBr–N: 3.51 Ǻ) [29]. In Figure 8 is shown the π stacking and hydrogen bonding, which extend the crystal lattice in the bc crystallo–graphic plane, stabilizing a 2D supramolecular arrangement. Similar interactions were found in the analogous copper(II) compound [23].

All trans–octahedral nitrate compounds stabilized a 3D supra–molecular arrangement via hydrogen bonding, between the nitrate anions, the N–H from the ligand and the coordinated water molecules. The c/s–octahedral halide complex forms a 2D pleated sheet arrangement, by intermolecular π stacking and halide–hydrogen bonding. A similar behavior was observed previously for similar nitrate and halide copper(II) compounds, which implies that an anion directed assembly allows the formation of 2D or 3D supramolecular structures.

Experimental

Reagents

Emizco, metal salts: CdBr₂, Co(NO₃)₂·6H₂O, Ni(NO₃)₂·6H₂O, Cd(NO₃)₂, and solvents were purchased from Aldrich Chem., Merck and J.T. Baker and were used as received.

Spectroscopic measurements

IR spectra in the range 4000–400 cm¹ were recorded in KBr pellets (Perkin Elmer FTIR 1605). Electronic spectra of powdered crystalline samples were measured by the diffuse reflectance method on a CARY–5000 Varian spectrometer, over the range 250–2000 nm (40,000–5,000 cm¹). Elemental analyses were carried out with a Fisons EA 1108 analyzer (CHNS–O) using a cystine standard. Magnetic susceptibility measurements at room temperature of powdered samples were recorded on a Johnson–Matthey type MSB model MK II 13094–3002, using the Gouy method at a temperature of 297 +/– 2 K.

Crystallography

Suitable single crystals of compounds 14 were mounted on a glass fiber. Data were colleted at 293 K. Crystal data, data collection and structure refinement details are given in Table 6. All data were measured using standard procedures on a Oxford Diffraction Gemini "A" instrument with CCD area detector using graphitemonochromated Mo Ka radiation at 293 K. Intensities were measured using φ + ω scans. A summary of data collection and refinements is given in Table 6. All structures were solved using direct methods, using SHELX97 program [30] and the refinement (based on F² of all data) was performed by full–matrix least squares techniques with SHELX97 program [30]. All non hydrogen atoms were refined anisotropically. For all compounds, all non aromatic hydrogen atoms were found in the difference map and their positions refined, whereas all the aromatic hydrogen atoms were localized in the difference map and allowed to ride on their respective atoms.

Coordination compounds were prepared in all cases using methanol as solvent and employing a 2:1 (ligand:M²⁺) ratio for the cobalt(II) and nickel(II) compounds, and a 1:1 ratio for the cadmium(II) compounds. The emizco ligand was dissolved in 5 mL of hot methanol, and the metallic salts were dissolved separately in 10 mL of hot methanol. The metal salt solution was added to the ligand solution and refluxed, after that the solution was allowed to stand at RT. The resulting crystals were washed with methanol and dried in vacuo.

[Co(emizco) ₂(H₂0)₂](NO₃)₂ (1)

Cobalt(II) nitrate hexahydrate (0.580 g, 2 mmol) was dissolved in hot methanol (10 mL) and added to a solution of emizco (0.154 g, 1 mmol) in hot methanol (5 mL). The red solution was refluxed for 6 h and then allowed to stand for 4 weeks. The resulting red crystals were filtered off, washed with methanol and dried in vacuo. Yield: 99.43%.

Molar conductivity (H₂O): [μS/cm] 257. IR v_max [cm¹] 1678 (C=O), 1509 (C=N), 1316 (COO_as), 1214 (COO_s), 1384 (NO₃). Anal. Found: C, 31.46; H, 4.69; N, 15.88%. Calcd. for C1₄H₂₄CoN₆O1₂:C, 31.88; H, 4.58; N, 15.93%.

[Ni(emizco)₂(H₂0)₂](N0₃)₂(2)

Nickel(II) nitrate hexahydrate (0.290 g, 1 mmol) was dissolved in hot methanol (10 mL) and added to a solution of emizco (0.308 g, 2 mmol) in hot methanol (5 mL). The green solution was refluxed for 6 h and then allowed to stand for 5 weeks. The resulting lime green crystals were filtered off, washed with methanol and dried in vacuo. Yield: 30.13%. Molar conductivity (H₂O): [μS/cm] 222. IR v_max [cm^–1] 1644 (C=O), 1528 (C=N), 1217 (COO_s), 1384 (NO₃). Anal. Found: C, 31.63; H, 4.65; N, 16.22%. Calcd. for C₁₄H₂₄NiN₆O₁₂: C, 31.90; H, 4.59; N, 15.94%.

[Cd(emizco)₂(H₂0)₂](N0₃)₂ (3)

Cadmium(II) nitrate (0.236 g, 1 mmol) was dissolved in hot methanol (10 mL) and added to a solution of emizco (0.154 g, 1 mmol) in hot methanol (5 mL). The colorless solution was refluxed for 6 h and then allowed to stand for 4 weeks. The resulting colorless crystals were filtered off, washed with methanol and dried in vacuo. Yield: 32.38%. Molar conductivity (DMSO): [μS/cm] 78.8. IR v_max [cm^–1] 1655 (C=O), 1525 (C=N), 1335 (COO_as), 1163 (COO_s), 1384 (NO₃). Anal. Found: C, 28.75; H, 4.30; N, 14.12%. Calcd. for C₁₄H₂₄CdN₆O₁₂: C, 28.95; H, 4.16; N, 14.47%.

4 [Cd(emizco)₂Br₂](4)

Supplementary material

Supplementary crystallographic data for this paper have been deposited with the CCDC: 810798 to 810801. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

Acknowledgements

This work was supported by the project DGAPA–UNAM IN212210 We acknowledge R.P. Fierro for technical support.

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Note

Dedicated to Estela Sánchez Quintanar, friend and colleague, in recognition of her contribution to the biochemistry of maize.