**Low-Dimensional Compounds Containing Bioactive Ligands. Part XIX: Crystal Structures and Biological Properties of Copper Complexes with Halogen and Nitro Derivatives of 8-Hydroxyquinoline**


**Abstract:** Six new copper(II) complexes were prepared: [Cu(ClBrQ)<sup>2</sup> ] (**1a**, **1b**), [Cu(ClBrQ)<sup>2</sup> ]·1/2 diox (**2**) (diox = 1,4-dioxane), [Cu(BrQ)<sup>2</sup> ] (**3**), [Cu(dNQ)<sup>2</sup> ] (**4**), [Cu(dNQ)<sup>2</sup> (DMF)<sup>2</sup> ] (**5**) and [Cu(ClNQ)<sup>2</sup> ] (**6**), where HClBrQ is 5-chloro-7-bromo-8-hydroxyquinoline, HBrQ is 7-bromo-8-hydroxyquinoline, HClNQ is 5-chloro-7-nitro-8-hydroxyquinoline and HdNQ is 5,7-dinitro-8-hydroxyquinoline. Prepared compounds were characterised by infrared spectroscopy, elemental analysis and by X-ray structural analysis. Structural analysis revealed that all complexes are molecular. Square planar coordination of copper atoms in [Cu(XQ)<sup>2</sup> ] (XQ = ClBrQ (**1a**, **1b**), BrQ (**3**) and ClNQ (**6**)) and tetragonal bipyramidal coordination in [Cu(dNQ)<sup>2</sup> (DMF)<sup>2</sup> ] (**5**) complexes were observed. In these four complexes, bidentate chelate coordination of XQ ligands via oxygen and nitrogen atoms was found. Hydrogen bonds stabilizing the structure were observed in [Cu(dNQ)<sup>2</sup> (DMF)<sup>2</sup> ] (**5**) and [Cu(ClNQ)<sup>2</sup> ] (**6**), no other nonbonding interactions were noticed in all five structures. The stability of the complexes in DMSO and DMSO/water was evaluated by UV-Vis spectroscopy. Cytotoxic activity of the complexes and ligands was tested against MCF-7, MDA-MB-231, HCT116, CaCo2, HeLa, A549 and Jurkat cancer cell lines. The selectivity of the complexes was verified on a noncancerous Cos-7 cell line. Antiproliferative activity of the prepared complexes was very low in comparison with cisplatin, except complex **3**; however, its activity was not selective and was similar to the activity of its ligand HBrQ. Antibacterial potential was observed only with ligand HClNQ. Radical scavenging experiments revealed relatively high antioxidant activity of complex **3** against ABTS radical.

**Keywords:** copper complexes; derivatives of 8-hydroxyquinoline; crystal structure; bromination; biological properties

### **1. Introduction**

Cancer treatment by using cisplatin spread widely after discovery of its anti-neoplastic activity [1]. Since then, some derivatives, such as carboplatin, oxaliplatin, nedaplatin, heptaplatin, lobaplatin and miriplatin, were prepared and used as anticancer agents, too [2]. Nowadays, nearly half of all cancer diseases are being treated by platinum-based drugs. These compounds are exceptionally successful against a broad spectrum of cancers, which

**Citation:** Kepe ˇnová, M.; Kello, M.; Smolková, R.; Goga, M.; Frenák, R.; Tkáˇciková, L'.; Litecká, M.; Šubrt, J.; Potoˇc ˇnák, I. Low-Dimensional Compounds Containing Bioactive Ligands. Part XIX: Crystal Structures and Biological Properties of Copper Complexes with Halogen and Nitro Derivatives of 8-Hydroxyquinoline. *Inorganics* **2022**, *10*, 223. https:// doi.org/10.3390/inorganics10120223

Academic Editors: Peter Segl'a and Ján Pavlik

Received: 7 November 2022 Accepted: 22 November 2022 Published: 25 November 2022

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

is caused by their high reactivity [3]. Unfortunately, due this property, some negative phenomena are observed. Treatment with platinum-based drugs negatively influences healthy cells, which causes side-effects, such as neurotoxicity, renal toxicity, vomiting, and damage to the gastrointestinal tract, hair follicles and other tissues [4]. Another observed negative impact is the development of resistance, by which cancer cells try to escape apoptosis [5]. The necessity to reduce the negative impacts widely opened a new research field focused on other metal complexes as biological agents.

The quinoline family, including 8-hydroxyquinoline (8-HQ) and its derivatives, represents compounds with interesting pharmacological properties. For these compounds, anticancer, antibacterial, antifungal, antimalaria, antineurodegenerative and antiHIV effects were described [6–8]. These ligands can be coordinated to different metal atoms by oxygen and nitrogen atoms, and the resulting complexes often show increased anticancer activity. As an example, we can mention several complexes of Pd [9,10], Zn [11,12], Ga [13–15], Ru [16,17] and lanthanides [18–21], among which complexes with halogenand nitro-derivatives of 8-HQ exhibited the highest activity. However, information on the anticancer activity of copper complexes rarely appears in the literature [12,22–25]. Therefore, we decided to prepare a series of copper complexes with commercially unavailable halogen- and nitro-derivatives of 8-HQ (HClBrQ = 5-chloro-7-bromo-8-hydroxyquinoline, HClNQ = 5-chloro-7-nitro-8-hydroxyquinoline and HdNQ = 5,7-dinitro-8-hydroxyquinoline), as well as with the commercially available, but hitherto unstudied HBrQ (HBrQ = 7-bromo-8-hydroxyquinoline) ligand: [Cu(ClBrQ)2] (**1a**, **1b**), [Cu(ClBrQ)2]·1/2 diox (**2**), [Cu(BrQ)2] (**3**), [Cu(dNQ)2] (**4**), [Cu(dNQ)2(DMF)2] (**5**) and [Cu(ClNQ)2] (**6**). In this paper, we present synthesis of these complexes and the results of infrared and UV-Vis spectroscopy, and elemental and monocrystal X-ray structural analysis. Moreover, we also discuss their antiproliferative activity against seven cancer cell lines and, using one non-cancerous Cos-7 cell line, we evaluate their selectivity. We also compare their anticancer activity with the activity of the corresponding ligands and cisplatin. Finally, we present the antimicrobial activity of the complexes and ligands against one gram-positive and one gram-negative bacteria, as well as their antioxidant activity.

### **2. Results and Discussion**

### *2.1. Syntheses*

The described copper complexes were synthesised by a simple mixing and stirring of solutions of corresponding ligand and copper(II) salt at laboratory (**1a**) or higher temperature (**1b**–**6**). While HClQ and HBrQ ligands used in the syntheses of complexes were obtained commercially, the HClNQ, HdNQ and HClBrQ ligands were first synthesised by previously described synthetic routes [26–28]. Interestingly, in the synthesis of **1a**, where CuBr<sup>2</sup> was used, in situ bromination of HClQ ligand was observed. The mechanism of bromination of organic substances using CuBr<sup>2</sup> was described in the literature [29,30]. This motivated us to prepare HClBrQ ligand and use it for the synthesis of **1b** to compare its structure with the structure of **1a**, because, in the case of in situ bromination, only 85% of the ligand molecules were brominated, as confirmed by semiquantitative EDS analysis (Figure S1) and X-ray structural analysis. Crystals of all prepared complexes suitable for X-ray structural analysis were obtained by slow crystallisation from corresponding solutions.

The composition of the prepared complexes was suggested by elemental (**1b**–**4**, **6**) and X-ray structural analysis (**1a**, **1b**, **3**, **5**, **6**). Crystals of **5** were unstable in air, due to the releasing of DMF from the structure, and crystals of **1a** were not prepared in sufficient quantity, and, therefore, they could not be characterised by elemental analysis.

### *2.2. Infrared Spectroscopy*

All complexes were first characterised by IR spectroscopy (Figure 1) to confirm the presence of the ligands or solvates in the complexes. The presence of XQ ligands in the prepared compounds was confirmed by several bands, including very weak bands of

*ν*(C–H)ar vibrations observed at 3075–3098 cm−<sup>1</sup> . Coordination of the ligands to the copper central atom was supported by the absence of *ν*(O–H) vibration, from the hydroxyl group, which should be observed in uncoordinated 8-hydroxyquinoline and its derivatives as a broad band in the 3700–3400 cm−<sup>1</sup> region [31–35]. Characteristic bands of halogen functional groups in positions 5 and 7 presented, in the ranges 973–984 (*ν*(C5–Cl) vibrations in (**1a**, **1b**, **2**, **6**) and 861–873 cm−<sup>1</sup> (*ν*(C7–Br) vibrations in (**1a**–**3**). The presence of a nitro group in **4**–**6** was manifested by bands of *ν*(N–O)as vibrations observed at 1561–1569 cm−<sup>1</sup> and *ν*(N–O)sym vibrations at 1323 cm−<sup>1</sup> [35]. *Inorganics* **2022**, *10*, x FOR PEER REVIEW 4 of 18

**Figure 1.** FT–IR spectra of **1**–**6**. **Figure 1.** FT–IR spectra of **<sup>1</sup>**–**6**.

If we compare the IR spectra of **2** and **5** with the spectra of **1b** and **4**, respectively, we can clearly identify characteristic bands of used solvents in the IR spectra of the first two complexes. The bands of *ν*(CH2) vibrations at 2965, 2912, 2887, 2849 cm−<sup>1</sup> and ring breathing vibrations at 613 and 1182 cm−<sup>1</sup> confirmed the presence of 1,4-dioxane in **2** [36–38]. Molecules of DMF in **5** manifested themselves as weak bands of *ν*(C–H)al vibrations at 2968, 2928, and 2860 cm−<sup>1</sup> , as a band at 1098 cm−<sup>1</sup> , which belonged to the deformation vibrations of the methyl group, and as a strong band of *ν*(C=O) vibrations at 1651 cm−<sup>1</sup> [39].

### *2.3. UV-Vis Spectroscopy*

A study of the stability of the prepared complexes (**1b**–**4**, **6**) was performed by comparison of the UV-Vis spectra of the complexes freshly suspended in Nujol with the spectra of the complexes in DMSO and DMSO/water (1:1) solutions, which were remeasured every 24 h over 3 days. As can be seen in Figure 2, the spectra of **1b** in DMSO and DMSO/water

measured for 3 days were identical and very similar to the spectrum of **1b** prepared in Nujol, which suggested the stability of **1b** in the solutions. Similar results were obtained for **2**, **4** and **6**, but this was not the case for **3.** Figure 2 shows its UV-Vis spectra and it was obvious that the spectra in DMSO/water did not coincide with the spectra in Nujol or DMSO. This might be explained by a very low concentration of **3** in the DMSO/water solution, due to its continuous precipitation from this solution. and DMSO/water measured for 3 days were identical and very similar to the spectrum of **1b** prepared in Nujol, which suggested the stability of **1b** in the solutions. Similar results were obtained for **2**, **4** and **6**, but this was not the case for **3.** Figure 2 shows its UV-Vis spectra and it was obvious that the spectra in DMSO/water did not coincide with the spectra in Nujol or DMSO. This might be explained by a very low concentration of **3** in the DMSO/water solution, due to its continuous precipitation from this solution.

A study of the stability of the prepared complexes (**1b**–**4**, **6**) was performed by

remeasured every 24 h over 3 days. As can be seen in Figure 2, the spectra of **1b** in DMSO

*Inorganics* **2022**, *10*, x FOR PEER REVIEW 5 of 18

*2.3. UV-Vis Spectroscopy* 

**Figure 2.** UV-VIS spectra of **1b** (**top**) and **3** (**bottom**). **Figure 2.** UV-VIS spectra of **1b** (**top**) and **3** (**bottom**).

### *2.4. X-ray Structure Analysis*

*2.4. X-ray Structure Analysis*  The crystals of **1a**, **1b**, **3**, **5** and **6** were suitable for X-ray structural analysis, which confirmed their molecular character. Complexes **1a**, **1b** and **6** crystallised in the monoclinic space group *P*21/*c*, while **3** crystallised in *P*21/*n* space group. Their unit cells contained two [Cu(XQ)2] molecules with copper atoms sitting on inversion centres. The central atoms were chelate-coordinated by two deprotonated corresponding XQ ligands (XQ = ClBrQ, BrQ and ClNQ) via oxygen and nitrogen atoms in a distorted square planar fashion (Figures 3 and S2). The shape of their polyhedral coordination was confirmed by bond lengths and angles (Table 1). Cu1–O1 bonds (1.920(2)–1.926(2) Å) were slightly shorter than Cu1–N1 bonds (1.953(2)–1.964(2) Å), due to the smaller covalent radius of the The crystals of **1a**, **1b**, **3**, **5** and **6** were suitable for X-ray structural analysis, which confirmed their molecular character. Complexes **1a**, **1b** and **6** crystallised in the monoclinic space group P21/c, while **3** crystallised in P21/n space group. Their unit cells contained two [Cu(XQ)2] molecules with copper atoms sitting on inversion centres. The central atoms were chelate-coordinated by two deprotonated corresponding XQ ligands (XQ = ClBrQ, BrQ and ClNQ) via oxygen and nitrogen atoms in a distorted square planar fashion (Figures 3 and S2). The shape of their polyhedral coordination was confirmed by bond lengths and angles (Table 1). Cu1–O1 bonds (1.920(2)–1.926(2) Å) were slightly shorter than Cu1–N1 bonds (1.953(2)–1.964(2) Å), due to the smaller covalent radius of the oxygen atom. Similar bond distances and angles were observed in other copper complexes with derivatives of 8-hydroxyquinoline [11,23,40,41].

oxygen atom. Similar bond distances and angles were observed in other copper complexes with derivatives of 8-hydroxyquinoline [11,23,40,41]. Even though the crystals of **5** were not stable, being out of the maternal solution, collected X-ray data was sufficient to solve the structure. Complex **5** crystallised in the triclinic space group *P*-1. Cu1 atom, sitting on an inversion centre, was hexacoordinated by pairs of oxygen and nitrogen atoms in *trans*-positions from two molecules of dNQ, and axial positions were occupied by two oxygen atoms from two molecules of DMF (Figure 4). As can be seen in Table 2, the shape of the coordination polyhedron could be described as elongated tetragonal bipyramid, due to the Jahn–Teller effect. Nevertheless, the Cu1–O1

*Inorganics* **2022**, *10*, x FOR PEER REVIEW 6 of 18

80% or 50% (**3**) probability levels. Symmetry code: i = −*x*, −*y* + 1, −*z* + 1.

*Inorganics* **2022**, *10*, x FOR PEER REVIEW 6 of 18

and Cu1–N1 bond lengths were close to those observed in **1a**, **1b**, **3** and **6**. All carbon atoms of DMF were disordered over two positions with site occupation factors being 0.62 and 0.38. **Table 1.** Selected bond lengths [Å] and angles [°] for **1a**, **1b**, **3** and **6**. **1a 1b 3 6** 

**Figure 3.** Molecular structure of **1b**, **3** and **6** (left to right). Displacement ellipsoids are drawn at the

**Figure 3.** Molecular structure of **1b**, **3** and **6** (left to right). Displacement ellipsoids are drawn at the 80% or 50% (**3**) probability levels. Symmetry code: i = −*x*, −*y* + 1, −*z* + 1. **Figure 3.** Molecular structure of **1b**, **3** and **6** (left to right). Displacement ellipsoids are drawn at the 80% or 50% (**3**) probability levels. Symmetry code: i = −*x*, −*y* + 1, −*z* + 1. triclinic space group *P*-1. Cu1 atom, sitting on an inversion centre, was hexacoordinated by pairs of oxygen and nitrogen atoms in *trans*-positions from two molecules of dNQ, and

**Table 1.** Selected bond lengths [Å] and angles [◦ ] for **1a**, **1b**, **3** and **6**. axial positions were occupied by two oxygen atoms from two molecules of DMF (Figure


O1–Cu1–N1 85.10(11) 85.24(8) 85.43(9) 84.19(9) Symmetry code: i = −*x*, −*y* + 1, −*z* + 1.

**Figure 4.** Molecular structure of **5**. Displacement ellipsoids are drawn at the 50% probability level. Only one position of carbon atoms of DMF is shown because of clarity. Symmetry code: i = −*x* + 1, −*y* + 1, −*z*. **Figure 4.** Molecular structure of **5**. Displacement ellipsoids are drawn at the 50% probability level. Only one position of carbon atoms of DMF is shown because of clarity. Symmetry code: i = −*x* + 1, −*y* + 1, −*z*.



Only one position of carbon atoms of DMF is shown because of clarity. Symmetry code: i = −*x* + 1, Symmetry code: i = −*x* + 1, −*y* + 1, −*z*.

−*y* + 1, −*z*. **Table 2.** Selected bond lengths [Å] and angles [°] for **5**. **Bonds Angles**  Cu1–O1 1.9508(14) O1–Cu1–N1 i 96.82(7) From the above-described structures, only structures with nitro groups (**5** and **6**) were stabilised by hydrogen bonds. Two hydrogen bonds presented in **5** (Table S1) created a layer parallel with the (01-1) plane (Figure 5). Only one hydrogen bond in the structure of **6** (Table S1) created a layer parallel with the (100) plane (Figure 5). No other significant intermolecular interactions were present in the structures of the complexes.

Cu1–N1 1.9706(17) O1–Cu1–N1 83.18(7) Cu1–O2 2.4920(19) O1–Cu1–O2 94.14(6) N1–Cu1–O2 91.91(7)

O1i

N1i

From the above-described structures, only structures with nitro groups (**5** and **6**) were stabilised by hydrogen bonds. Two hydrogen bonds presented in **5** (Table S1) created a layer parallel with the (01-1) plane (Figure 5). Only one hydrogen bond in the structure of **6** (Table S1) created a layer parallel with the (100) plane (Figure 5). No other significant intermolecular interactions were present in the structures of the complexes.

Symmetry code: i = −*x* + 1, −*y* + 1, −*z*.

–Cu1–O2 85.86(6)

–Cu1–O2 88.09(7)

**Figure 5.** Layers formed by hydrogen bonds (dashed lines) in **5** (**top**) and **6** (**bottom**). Hydrogen **Figure 5.** Layers formed by hydrogen bonds (dashed lines) in **5** (**top**) and **6** (**bottom**). Hydrogen atoms not involved in hydrogen bonds are omitted because of clarity.

#### atoms not involved in hydrogen bonds are omitted because of clarity. *2.5. Antiproliferative Activity*

In the present work, four copper(II) complexes (**1b**, **3**, **4** and **6**) and their ligands were screened for potential antiproliferative activity. Furthermore, cisplatin, as a common chemotherapy agent, was used as a standard. There is evidence that copper complexes should be studied for their pro-apoptotic potential, also due to the fact that cancer cells take up larger amounts of copper than normal cells, as reviewed in [42]. Moreover, it was published that copper complexes with quinoline induced apoptosis and had cytotoxic effects on cancer cell lines [43–45]. In our study, the most potent novel copper(II) complex was **3** with IC<sup>50</sup> values in the range 5.3–6.0 µM on all tested cancer cell lines (Table 3). However, we did not observe selectivity towards non-cancerous Cos-7 cells (IC<sup>50</sup> = 5.8 µM). This complex was more efficient than cisplatin and its ligand HBrQ. Other tested complexes (**1b**, **4** and **6**) showed IC<sup>50</sup> values above 200 µM on all tested cell lines, except for Caco-2 cells,

where complex **1b** showed IC<sup>50</sup> 106.8 µM and complex **4** around 46.4 µM with a selectivity towards Cos-7 cells, but lower effectivity than cisplatin. Based on the literature [46–51] the antiproliferative activity of copper(II) chloride against the seven cancer cell lines under study was not tested, because CuCl<sup>2</sup> displayed inconsequential in vitro toxicity.


**Table 3.** IC<sup>50</sup> values of tested copper(II) complexes and their ligands.

NT: not tested.

### *2.6. Antibacterial Activity*

The antibacterial activity of the prepared complexes and their ligands were tested against gram-positive (*S. aureus*) and gram-negative (*E. coli*) bacteria (CuCl<sup>2</sup> was not tested, due to its inactivity against bacteria [52]). The RIZD, as well as MIC, were performed. Only ligand HClNQ in RIZD exhibited test inhibition against gram-positive bacteria *S. aureus* as well as gram-negative bacteria *E. coli*. The RIZD for *S. aureus* was 153% and for *E. coli* 123% (Table 4), whereas the inhibition of gentamicin sulfate as positive control was 100%. Other complexes were not suitable for antibacterial activity in concentration of 33.6 µM. This concentration was still possible, due to the solubility of the tested compounds.

**Table 4.** Antibacterial activity of tested complexes. RIZD (%) means percentage of relative inhibition zone diameter. All complexes were tested against *E. coli* and *S. aureus* in 3 replicates (n = 3, ±SD).


NA: no activity.

MIC was tested with ligand HClNQ in all dilutions (1:1; 1:2; 1:4; 1:8). For *E. coli*, as well as *S. aureus*, the absorbance in dilutions 1:1 and 1:2 was lower and comparable with negative control (average 0.042 ± 0.005). Dilutions 1:4 and 1:8 showed higher absorbance, due to turbidity caused by the growing bacteria (Table 5).

**Table 5.** MIC (minimal inhibition concentration) of tested complex HClNQ with dilution ratio. Values mean absorbance. Absorbance was based on the cloudiness of the sample. Higher value means that bacteria were growing. Positive control represents bacterial growth without any treatment.


### *2.7. Radical Scavenging Activity*

Radical scavenging activity was tested for complexes **1b**, **3**, **4** and **6**, along with free parental ligands against ABTS and DPPH radicals. Ligands HClBrQ and HdNQ showed low radical scavenging activity, while HClNQ was completely inactive within the measured range. Among the prepared compounds only **3** was active against both radicals (Table 6); however, its parental ligand HBrQ showed even stronger antioxidant activity [53]. The lower activity of studied complexes in comparison with free ligand molecules suggested that the radical scavenging mechanism involved reaction of radicals with 8-hydroxyquinoline derivatives, rather than Cu(II) central atoms. Antioxidant activity was more pronounced against ABTS radical than DPPH radical for all active compounds. This trend was previously observed for analogous metal complexes with the derivatives of 8-quinolinol [54,55].

**Table 6.** ABTS and DPPH radical scavenging activity (IC<sup>50</sup> in µM; and SC% for 200 µM antioxidant concentration) for complex **3**, free ligands and L-ascorbic acid.


Complexes **1b**, **4** and **6** and ligand HClNQ were inactive in the measured range 0–200 µM. <sup>a</sup> Data from [53].

### **3. Materials and Methods**

### *3.1. Materials and Chemicals*

The coordination compounds to be investigated were prepared using copper(II) chloride dihydrate, p.a. (Lachema, Neratovice, Czech Republic), copper(II) bromide, 99% (Sigma Aldrich, Bratislava, Slovakia), 5-chloro-8-hydroxyquinoline (HClQ), 95% (Sigma Aldrich), 7-bromo-8-hydroxyquinoline (HBrQ), 97% (Sigma Aldrich), N,N-dimethylformamide, 99% (Merck KGaA, Darmstadt, Germany), 1,2-dimethoxyethane, 99% (Alfa Aesar, Karlsruhe, Germany), ethanol, 96% (BGV, Hniezdne, Slovakia), methanol, p.a. (Centralchem, Bratislava, Slovakia), 1,4-dioxane, 99% (Centralchem), dimethyl sulfoxide, ≥99.9% (Sigma Aldrich). All commercially available chemicals were used without further purification. HdNQ, HClNQ and HClBrQ ligands were synthesised.

### *3.2. Syntheses*

### 3.2.1. Synthesis of [Cu(ClBrQ)2] (**1a**)

The HClQ (35.9 mg, 0.2 mmol) was dissolved in DMF (10 mL). While continuously stirring, 10 mL of DMF solution of CuBr<sup>2</sup> (44.7 mg, 0.2 mmol) was added. After 30 min of stirring, the beaker was laid down at room temperature. After three months, yellow needles of **1a** had formed, and were filtered off, and dried in the air.

[Cu(ClBrQ)2] (**1a**)—Calc. for C18H8.30Br1.70Cl2N2O2Cu (554.85 g·mol−<sup>1</sup> ): C, 38.96; H, 1.51; N, 5.05%. Found: not measured. IR (ATR, cm−<sup>1</sup> ): *ν*(C–H)ar 3075 (vw), *ν*(C=C)ar 1595 (w), 1578 (w), 1555 (m), 1485 (m), *ν*(C=N) 1448 (m), *ν*(C–C) 1370 (s), 1223 (m), 1135 (m), *ν*(C–O) 1114 (m), *β*(C–H) 1045 (m), *ν*(C5–Cl) 973 (m), *ν*(C7–Br) 864 (m), *γ*(C–H) 806 (m), Ring breathing 779 (m), 748 (m), *β*(CCC) 723 (m), 654 (s), *β*(CNC) 596 (m), *β*(C5–Cl) 508 (w), *γ*(CCC) 485 (m).

### 3.2.2. Synthesis of [Cu(ClBrQ)2] (**1b**)

HClBrQ (25.9 mg, 0.1 mmol) was dissolved in ethanol (10 mL) and warmed to 60 ◦C. While continuously stirring, 10 mL of DMF solution of CuCl<sup>2</sup> (8.5 mg of CuCl2·2H2O, 0.05 mmol) (warmed to 60 ◦C) was added. After 30 min of stirring, the beaker was laid

down at room temperature. After five days, yellow needles of **1b** had formed, and were filtered off, and dried in the air.

[Cu(ClBrQ)2] (**1b**)—Calc. for C18H8Br2Cl2N2O2Cu (578.73 g·mol−<sup>1</sup> ): C, 37.37; H, 1.39; N, 4.84%. Found: C, 37.72; H, 1.58; N, 4.65%. IR (ATR, cm−<sup>1</sup> ): *ν*(C–H)ar 3074 (vw), *ν*(C=C)ar 1594 (w), 1578 (w), 1555 (m), 1485 (m), *ν*(C=N) 1448 (m), *ν*(C–C) 1370 (s), 1223 (m), 1136 (m), *ν*(C–O) 1114 (m), *β*(C–H) 1045 (m), *ν*(C5–Cl) 974 (m), *ν*(C7–Br) 863 (m), *γ*(C–H) 806 (m), Ring breathing 779 (m), 750 (m), *β*(CCC) 723 (m), 654 (s), *β*(CNC) 596 (m), *β*(C5–Cl) 509 (w), γ(CCC) 484 (m).
