Synthesis and structure of Zn(II) and Cu(II) complexes derived from 2-(aminomethyl)benzimidazole and glycine

Reactions of 2-(aminomethyl)benzimidazole di-hydrochloride (1·2HCl) and glycine with 3Zn(OH)2·2ZnCO3 or Cu(OAc)2·H2O led to the synthesis of the quaternary coordination complexes 2 and 3. X-ray diffraction showed that these complexes are composed of 2a = [Zn(L)Cl(L′)] and 2b = [Zn(L)(H2O)2(L′)], and of 3a = [Cu(L)(H2O)0.25Cl(L′)] and 3b = [Cu(L)(H2O)1.5(L′)], respectively, where L = 2-(aminomethyl)benzimidazole and L′ = glycinate. Zn(II) in 2a has an intermediate geometry between a square-pyramid and a trigonal bipyramid structure. However, the geometry about the metal ion of units 2b, 3a, and 3b is distorted octahedral. Moreover, the supramolecular structures for 2 and 3 were assembled through N–H⋯O and O–H⋯Cl hydrogen bonds. In these complexes, H2O and N–H groups serve as proton donors, whereas chloride and C=O groups serve as proton acceptors. Also π–π stacking interactions between aromatic rings contribute to the stabilization of the supramolecular structure of 2 and 3. The Zn and Cu complexes were studied by infrared and Raman spectroscopy, which indicated that 2 and 3 have similar molecular structures in the solid state. Ultrasound activation at the end of the reaction was necessary to yield 2. Graphical Abstract


Introduction
Zn(II) and Cu(II) are important in chemical and biological systems. Therefore, a wide variety of organic compounds have been used as ligands for Zn(II) and Cu(II) complexes [1,2].
Complexes derived from imidazole, benzimidazole, and amino acid ligands are model compounds of particular bioinorganic interest [3,4]. The imidazole moiety is essential in metalloproteins, and its interaction with Zn(II) and Cu(II) has profound effects on the biological actions of these macromolecules [5,6]. In this context, 2-(aminomethyl)benzimidazole 1 is a very useful ligand in coordination chemistry because it can coordinate with transition metals such as V, Co, Ni, Pd, and Cd [7][8][9][10]. Thus, 1 has been used as a molecular model to explain the substrate-metal interactions in biochemical systems [7][8][9][10]. However, even though Zn and Cu are neighboring elements in the periodic table, these metals have different chemical behavior when interacting with 2-(aminomethyl)benzimidazole. Zn(II) coordinates with one or two 1 ligands as a function of pH and can assume diverse geometries in the solid state with different assemblies through N-H⋯Cl and O-H⋯Cl hydrogen bonds, whereas Cu(II) yields square-pyramidal or distorted octahedral complexes [11][12][13]. This behavior is chemically and biologically relevant, and for this reason, we are interested in the synthesis and structure of Zn(II) and Cu(II) complexes using 1 as a ligand.
Quaternary complexes of 2-(aminomethyl)benzimidazole and leucine or gly-gly dipeptide have been reported [14,15]. However, a systematic study for the synthesis of Zn(II) or Cu(II) complexes derived from 1 and amino acids has not been reported. Aljahdali et al. proposed that the formation of 2 and 3 is thermodynamically viable in the presence of 1, glycine, and the corresponding metal ion [figure 1(A)] [10,16]. However, the formation of these complexes has not been demonstrated by spectroscopic and crystallographic methods. We believe that it is possible to promote the coordination of 2-(aminomethyl)benzimidazole, glycine, and X (Cl − or H 2 O groups) with metal by controlling the pH of the solution and the concentration of the chloride. In this article, we report on studies performed to identify the suitable reaction conditions for the synthesis of 2 and 3 in aqueous solution. The structural characterizations of 2 and 3 were performed by infrared (IR), Raman, and nuclear magnetic resonance (NMR) (only for 2) spectroscopy; elemental and thermogravimetric analysis (TGA); and X-ray diffraction.

Materials
Water was deionized prior to use. All reagents were purchased and used without purification. 2-(Aminomethyl)benzimidazole di-hydrochloride was synthesized as previously reported [17,18].

Physical and chemical measurements
The 1 H and 13 C NMR spectra were recorded on a Varian 400 MHz spectrometer. The chemical shifts (δ ppm) are relative to the external reference CH 3 OH (δ = 3.31 for proton NMR and δ = 49.1 for carbon NMR). IR and Raman spectra were recorded on a Perkin-Elmer System 200 FT-IR spectrophotometer. The elemental analyses were performed on a 2400 Perkin-Elmer Series II CHNS/O analyzer. The TGA studies were performed on a SDT Q 600 instrument. The melting points were measured on a Buchi Melting Point B-450 apparatus and were not corrected.
X-ray diffraction studies were performed on an Xcalibur Atlas Gemini diffractometer with a charge-coupled device area detector (λMoKα = 0.7107 Å, monochromator: graphite). The frames were collected at T = 301 K (2) and T = 296 (3) via ω/ϕ-rotation at 10 s per frame. The measured intensities were corrected for absorption [empirical absorption correction using spherical harmonics, implemented with the SCALE3 ABSPACK scaling algorithm (CrysAlisPro, Agilent Technologies)] [19]. The structure solution, refinement, and data output were performed using the SHELXTL-NT program package [20]. The non-hydrogen atoms were anisotropically refined. The C-H hydrogens were placed in geometrically calculated positions using a riding model with d(C-H aryl ) = 0.93 Å and U iso (H ary l) = 1.  U iso (H) = 1.5 U eq (N,O). The networks contained one water for 2 (O7 refined occupancy 0.5) and two waters for 3 (disordered O8, O9 refined occupancies of 0.25), which are disordered around the crystallographic symmetry centers. Their hydrogens could not be located by difference Fourier maps.  are drawn with DIAMOND [21] and OLEX 2 [22] using spheres of arbitrary radius.

Synthesis
The syntheses of 2 and 3 were performed at controlled pH values. Moreover, strict control of the concentrations of the ligands and metal salts was important to obtain these complexes.
2.3.1. Complex 2. A mixture of 2-(aminomethyl)benzimidazole di-hydrochloride (117 mg, 0.533 mM) and glycine (60 mg, 0.800 mM) was dissolved in 5 mL of deionized water and activated with ultrasound for 10 min. Next, 280 mg (0.510 mM) of 3Zn(OH) 2 ·2ZnCO 3 was added, and the resulting mixture was treated with ultrasound for 5 min. The solution was adjusted to pH 6.3 with 1.00 M NaOH and subjected to ultrasound for an additional 20 min (final pH 6.0). After the reaction was completed, the mixture was filtered and the solution was slowly evaporated. The helix 2 was obtained as colorless crystals (

Synthetic procedures
We performed the reaction of di-hydrochloride of 1, glycine, and ZnCl 2 in aqueous solution at different pH values [from 2.4(1) to 5.4(1) at 0.5 intervals] in an attempt to produce 2. The pH of the medium was fixed using NaOH, followed by slow evaporation. Nevertheless, 2 was not obtained under these reaction conditions. Instead of 2, 4-6 were crystallized, depending on the working pH [ figure 1(B)]. Compounds 4-6 have been reported [12]. These results should have been due to the presence of excess chloride in the reaction. To maintain a constant chloride : benzimidazole proportion (2 : 1 equivalents), we used 3Zn (OH) 2 ·2ZnCO 3 ; however, the quaternary complex was again not formed.
Cu and Zn have different chemical and structural behaviors. For example, Zn(II) has a ligand-field stabilization energy of zero and can adopt diverse geometries. However, Cu complexes generally have square, square-pyramidal or distorted octahedral geometries [25]. Moreover, Cu complexes usually have higher stability constants and are predicted to be easier to synthesize than Zn complexes [10]. For this reason, we performed the reaction of the di-hydrochloride of 1 and glycine with CuCO 3 ·Cu(OH) 2 . The process was performed at two different pH values [2.5(1) and 3.0(1)] with or without ultrasound activation. Nevertheless, the reaction preferentially yielded 7 [figure 1(C)]. Compound 7 has been reported [11,18].
In view of the results obtained with CuCO 3 ·Cu(OH) 2 , we chose to use Cu(OAc) 2 ·H 2 O because this salt is very soluble in aqueous solutions. Moreover, the acetate can be easily replaced and Cu(II) reactivity significantly increases. Again, we performed the reaction of the di-hydrochloride of 1 and glycine with Cu(OAc) 2 ·H 2 O at pH of 2.5(1), 2.8(1), and 3.3 (1) with or without ultrasound activation at the end of the reaction. In this case, the slow evaporation of the reaction yielded 3 as blue crystals. The best yield and best crystals were obtained at pH 2.8(1) without ultrasound activation and at molar ratios of 1 : 1.5 : 1.

Crystallography
Analysis by single-crystal X-ray diffraction showed that these complexes are assembled through N-H⋯O and O-H⋯Cl hydrogen bonds, producing helical supramolecular structures [with dissymmetric motifs (C 2 )] for 2 and pseudo-tubular supramolecular structures for 3.  [26].
In contrast to 2a, the coordination environments for Zn(II) in 2b have a distorted octahedral geometry whose equatorial plane is formed by 2-(aminomethyl)benzimidazole and  (7) (O7). Again, the crystallographic results agree with the elemental analysis and TGA studies, which confirm the incidence of three water molecules in 3. In 3a and 3b, Cu(II) ions have six-coordinate geometry. Thus, O8 is bonded to 3a [Cu2-O8 bond length is 2.624(13) Å], but this oxygen is distorted and has an occupancy of 0.25. Moreover, the bond length Cu2-O8 and bond angle O8-Cu2-Cl1 [169.9(3)°] support the presence of a Jahn-Teller distortion in this unit [27,28]. Otherwise, the Cu(II) in 3b is embedded in a distorted six-coordinate geometry with Jahn-Teller distorted octahedral geometry, with one of the waters situated around a symmetry center (O3, refined occupancy 0.50).

Spectroscopic characterization
The vibrational spectra of 2 and 3 are similar, which corroborates that both complexes have analogous molecular structures in the solid state. The IR spectra of 2 and 3 indicate the presence of water molecules with similar patterns of hydrogen bond interactions. In both cases, the bands from 3600 to 2660 cm −1 are strong and broad, which suggest the presence of supramolecular hydrogen interactions in these complexes [15,27,34,35]. The presence of water in these compounds is evidenced by ρ r (H 2 O) vibrations at 844 cm −1 for 2 and 846 cm −1 for 3, respectively. Whereas, the ρ w (H 2 O) vibrations appear at 528 cm −1 for 2 and 543 cm −1 for 3 [36][37][38]. Indeed, the broad signal at 672 cm −1 suggests the presence of H 2 O→Cu and H 2 N→Cu coordinated bonds in 3 [35][36][37][38]. IR spectra of 2 and 3 have the characteristic of asymmetric (1603 cm −1 for 2 and 1602 cm −1 for 3) and symmetric (1402 cm −1 for 2 and 1401 cm −1 for 3) COO stretching frequencies.
Raman spectrum of 2 confirms that carboxylate groups are unidentate [ν a (COO) = 1597 cm −1 and ν s (COO) = 1403 cm −1 ]. Likewise, the H 2 O rocking vibration at 842 cm −1 was observed. The existence of Zn-N and Zn-Cl bonds was confirmed with absorptions at 491 and 283 cm −1 , respectively [43][44][45][46]. In contrast, the Raman spectrum of 3 showed the ν a (COO) vibration at 1592 cm −1 and ν(Cu-Cl) at 242 cm −1 , respectively. 1 H and 13 C NMR spectra corroborated that 2 is present in aqueous solution. In the 1 H NMR spectrum, all resonances of 2 are shifted to low frequencies with respect to glycine and 1·2HCl. These changes are more significant in methylene hydrogen nuclei (Δδ = 0.49 for H1 and 0.13 for H10) and can be explained by the inductive effect due to the presence of N→Zn coordination bonds. The 13 C NMR spectrum of 2 has only one set of signals, and therefore, it is unlikely that a supramolecular structure exists in aqueous solution. The spectrum of 2 is asymmetric and all resonances of carbon nuclei are different. The presence of 2 with a quaternary structure is corroborated because there are chemical shifts to higher frequencies for C1-C3, C7-C8, and C10 (Δδ = 0.7-11.1). On the other hand, as in 4-6, Zn complexes are characterized by bond-breaking phenomena (L→Zn L + Zn) [12,[47][48][49]. The high coordinate flexibility of N→Zn bonds allows the occurrence of an intermolecular proton transfer mechanism of benzimidazole with D 2 O. This increases the symmetry and broadening of NMR signals. Nevertheless, in 2, the strong N→Zn coordination bond of imidazole nitrogen produces distinct aromatic signals of carbon nuclei. Whereas in 1·2HCl, and 4-6, the carbon nuclei next to imidazole nitrogen (pairs C3-C8 and C4-C7) have the same chemical shifts, the resonances of these carbon nuclei in 2 are different (δ = 134.6 for C3; 138.5 for C8; 112.7 for C4 and 117.6 for C7). Thus, it is probable that the presence of the glycinate, bonded to Zn(II), stabilizes the quaternary structure of 2. Finally, when the deutered solvent was evaporated, IR spectroscopy again demonstrated the presence of 2 in the solid state.

Conclusion
Complexes 2 and 3 were only synthesized and crystallized when low-chloride concentrations and controlled pH [5.0(1)-6.3(1) for 2 and 2.8 for 3] were used in the reaction of 1·2HCl and glycine with the corresponding metal ion [Zn(II) or Cu(II)]. Ultrasound activation was necessary to achieve the synthesis of 2. However, the use of bigger chloride concentrations yielded 4-6 [for Zn(II)] or 7 [for Cu(II)] under these reaction conditions. Moreover, in these complexes, the molecular self-assembly of the units "a" and "b" yielded helical motifs for 2 and pseudo-tubular structures for 3. The supramolecular structures are modulated by N-H⋯O and O-H⋯Cl hydrogen bonding interactions. This result is relevant because we demonstrated that it is possible to promote the synthesis of coordination compounds with supramolecular structures by controlling the concentration of the reactants and pH. The formation of the coordination compounds based on benzimidazoles and amino acid derivatives is important as these compounds have notable chemical and physical behaviors [42,[50][51][52][53][54][55].