Next Article in Journal
Extended Synthetic Pathways Towards Dialkyl-Substituted Phosphanylboranes
Previous Article in Journal
Tailoring Porosity and CO2 Capture Performance of Covalent Organic Frameworks Through Hybridization with Two-Dimensional Nanomaterials
Previous Article in Special Issue
Synthesis, Characterization, and Biological Activities of Rare Earth Metal Complexes with Gallic Acid
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Inorganics
Volume 13
Issue 7
10.3390/inorganics13070238
inorganics-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Synthesis, Characterization, and Anticancer Activity of 3-Chlorothiophene-2-carboxylic Acid Transition Metal Complexes

by
Baiquan Hu
1,
Qianqian Kang
1,†,
Xianggao Meng
2,†,
Hao Yin
3,
Xingzhi Yang
4,
Yanting Yang
1 and
Mei Luo
1,*
1
College of Chemistry and Chemical Engineering, Hefei University of Technology, Hefei 230009, China
2
College of Chemistry, Central China Normal University, Wuhan 430079, China
3
Instruments Center for Physical Science, University of Science and Technology of China, Hefei 230022, China
4
Active Screening Center of Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Inorganics 2025, 13(7), 238; https://doi.org/10.3390/inorganics13070238
Submission received: 11 March 2025 / Revised: 28 June 2025 / Accepted: 7 July 2025 / Published: 11 July 2025
(This article belongs to the Special Issue Synthesis, Structural Analysis and Biological Activity of Metal Complexes)
Browse Figures
Review Reports Versions Notes

Abstract

In this study, 3-chlorothiophene-2-carboxylic acid (HL) was used as a main ligand to successfully synthesize four novel complexes: [Cu(L)2(Py)2(OH2)2] (1), [Co(L)2(Py)2(OH2)2] (2) (Py = pyridine), [{Ni(L)2(OH2)4}2{Ni(L)(OH2)5}]L•5H2O (3), and [{Co(L)2(OH2)4}2{Co(L)(OH2)5}]L•5H2O (4). All four compounds were identified by elemental analysis and ESI mass spectrometry, and subsequently characterized by IR spectroscopy, UV-visible diffuse reflectance spectroscopy, electron paramagnetic resonance spectroscopy, thermogravimetric analysis, single-crystal X-ray crystallography, and cyclic voltammetry. X-ray analyses revealed that complexes 1 and 2 exhibit a centrosymmetric pseudo-octahedral coordination geometry; the copper (II) and cobalt (II) metal ions, respectively, are located at the crystallographic center of inversion. The coordination sphere of the copper (II) complex is axially elongated in accordance with the Jahn–Teller effect. Intriguingly, for charge neutrality, compounds 3 and 4 crystallized as three independent mononuclear octahedrally coordinated metal centers, which are two [ M L 2 ( O H 2 ) 4 ] complex molecules and one [ M L ( O H 2 ) 5 ] + complex cation (M = N i I I and C o I I , respectively), with the ligand anion L − serving as the counter ion. The anticancer activities of these complexes were systematically assessed on human leukemia K562 cells, lung cancer A549 cells, liver cancer HepG2 cells, breast cancer MDA-MB-231 cells, and colon cancer SW480 cells. Among them, complex 4 shows significant inhibitory effects on leukemia K562 cells and colon cancer SW480 cells.

1. Introduction

Metal complexes have become significant research topics in fields such as inorganic chemistry, biochemistry, and medicinal chemistry [1,2,3,4,5,6,7,8]. In recent years, transition metal complexes have demonstrated great potential in anticancer research [9]. For example, Wang et al. synthesized two complexes, [Zn2(H4L)2(DMF)1.3(H2O)]·H2O and [Mn2(H4L)2(DMF)2(H2O)]·H2O, employing 2,2,5,5-tetraphenyl ether tetracarboxylic acid (H4L) as the ligand through a solvothermal approach. Among them, the Zn(II) complex exhibited higher inhibitory activity against BxPC-3 cells than both the Mn(II) complex and the anticancer drug oxaliplatin, inducing apoptosis and causing cell cycle arrest at the G2 phase, suggesting potential for anticancer drug development [10]. It is noteworthy that metal complexes containing heterocyclic carboxylate ligands have become an important direction in the development of novel anticancer drugs [11,12,13]. For instance, Zhang and co-workers [14] synthesized two Pt(IV) complexes: [Pt(NH3)2Cl2(L1)2] (1) and [Pt(NH3)2Cl2(L2)2] (2), with L1 = 3-chlorobenzo[b]thiophene-2-carboxylic acid and L2 = 3-chloro-6-methylbenzo[b]thiophene-2-carboxylic acid. complex 2 exhibited an IC50 value of only 0.4 ± 0.3 μM against A2780 cells and demonstrated significant anticancer activity with low toxicity in mice.
Carboxylate ligands, due to their rich coordination modes and flexible structural tunability, have become preferred ligands for designing anticancer metal complexes [15,16]. For example, the research group of Tabassum [17,18] synthesized five metal complexes using bilastine and found that all the complexes could bind to ct-DNA. Among them, the Cu(II) complex showed superior DNA binding affinity and cytotoxicity against cancer cells compared to the Co(II) and Zn(II) complexes, indicating that the metal ion type and complex structure significantly influence biological activity. Moreover, carboxylate complexes also exhibit potential application value in areas such as catalysis [19,20,21] and optoelectronic materials [22,23]. For instance, Zhang and colleagues [24] synthesized a Cu-MOF material by reacting a flexible ligand containing imidazole and carboxyl groups with copper salts. It efficiently catalyzed the reaction of CO2 with epoxides to form cyclic carbonates under mild conditions, and could also be used as a fluorescent probe, showing good detection capabilities for Fe3+ (limit of detection: 0.53 μM) and Cr2O72− (limit of detection: 0.23 μM).
With the continuous advancement of anticancer drug research, the potential of metal complexes as anticancer agents has drawn increasing attention. Compared to traditional platinum-based drugs [25] (e.g., cisplatin), metal complexes exhibit lower toxicity and reduced drug resistance, positioning them as attractive alternatives for anticancer therapy [12,26,27,28]. Building on this context, in this study, four thienylcarboxylic acid metal complexes were synthesized using 3-chlorothiophene-2-carboxylic acid as the ligand via a solution synthesis method (Scheme 1).
Their inhibitory effects on various cancer cell lines [29], including human leukemia K562 cells, lung cancer A549 cells, liver cancer HepG2 cells, breast cancer MDA-MB-231 cells, and colon cancer SW480 cells, were assessed by the MTS assay (an MTT analog, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium). Furthermore, characterization of the synthesized complexes was performed using techniques such as elemental analysis (EA), UV-visible diffuse reflectance spectroscopy (UV-vis DRS), infrared spectroscopy (IR), Electron paramagnetic resonance (EPR), thermogravimetric analysis (TGA), electrospray ionization mass spectrometry (ESI-MS), and single-crystal X-ray diffraction (XRD).

2. Results and Discussion

2.1. Crystal Structure Analyses of Complexes 1–4

Single-crystal X-ray diffraction analysis shows that complex 1 adopts a monoclinic crystal system with space group P21/c (Figure 1); The Cu1 center is coordinated by four oxygen atoms and two nitrogen atoms, including oxygen atoms from carboxylate groups (O1, O1#i), aqua ligands (O3, O3#i), and nitrogen atoms from pyridine ligands (N1, N1#i), forming a distorted octahedral coordination geometry. The equatorial Cu–O (Cu1–O1/O1#i) and Cu–N (Cu1–N1/N1#i) bond lengths are 1.9866(12) Å and 2.0039(15) Å, respectively, which are consistent with those reported for similar structures in the literature [15]. The axial Cu–O (Cu1–O3/O3#i) bond is elongated due to the Jahn–Teller effect arising from the d9 configuration of the central Cu2+ ion, with a bond length of 2.4473(14) Å, consistent with observations in other copper(II) octahedral complexes [30,31]. As shown in Table 1, the cis coordination angles of complex 1 deviate slightly from the ideal 90°, ranging from 0.57° to 3.6°, while the trans coordination angles are essentially linear, indicating a distorted octahedral geometry. As shown in Table S1, intramolecular hydrogen bonds are formed between the hydrogen atoms of water molecules and the uncoordinated oxygen atoms of the carboxylate ligands (O3–H3A···O2#i; #i = −x + 1, −y + 2, −z + 1) and intermolecular hydrogen bonds (O3–H3B···O2#ii; #ii = −x, −y + 2, −z + 1), with hydrogen bond lengths of 1.86 Å and 2.09 Å, respectively. These hydrogen bonds enhance the overall stability of the crystal lattice [32].
The copper (II) ( d 9 configuration) and cobalt (II) ( d 7 configuration) complexes 1 and 2, respectively, are isostructural in that they are both centrosymmetric (Figure 1), but differ in that the six-coordinate geometry of the latter is not tetragonally distorted since this complex is singly degenerate. The equatorial C o I I – O c a r b o x y l a t e [Co1–O1/O1#i = 2.0744(9) Å] and C o I I – N p y [Co1–N1/N1#i = 2.1341(11) Å], and the axial C o I I – O a q u a [Co1–O3/O3#i = 2.1419(9) Å] are normal. According to Table 1, the cis angles show a slight deviation from the ideal 90°, ranging from 0.4° to 1.25°, while the trans angles are nearly linear, suggesting that the complex adopts a slightly distorted octahedral geometry. As listed in Table S1, hydrogen atoms of the water molecule form intramolecular hydrogen bonds with uncoordinated oxygen atoms from carboxylate ligands (O3–H3A···O2#i; #i = −x + 1, −y + 1, −z + 1) and intermolecular hydrogen bonds (O3–H3B···O2#ii; #ii = x − 1, y, z), with corresponding hydrogen bond lengths of 1.88 Å and 2.05 Å, respectively, suggesting that these hydrogen bonds contribute to the overall crystal stability.
The crystal structure of Complex 3 shows that its space group is P 1 ¯ , belonging to the triclinic system (Figure 1). Its asymmetric unit contains one and a half coordination unit, Ni1 atom lies at an inversion center and Ni2 atom lies at a general position. For these metal centers, they are both coordinated by six oxygen atoms: Ni1 with two carboxylate ligands (O1 and O1#i) and four water molecules (O3, O3#i, O4, and O4#i), and Ni2 with one carboxylate ligand (O5) and five water molecules (O7, O8, O9, O10, and O11), each forming an octahedral geometry. According to the crystal data (Table 1), the opposite Ni-O bond lengths around Ni1 are equal with corresponding bond angles of 180°, while those around Ni2 are unequal with bond angles deviating from 180° [15]; the adjacent Ni-O bond angles around Ni1 are pairwise equal, ranging from 84.96(10)° to 95.04(10)°, whereas those around Ni2 vary, ranging from 87.53(14)° to 92.81(11)°, indicating that the octahedral geometries formed by Ni1 and Ni2 are both distorted octahedra. The uncoordinated carboxylate ligand forms intramolecular hydrogen bonds with free water molecules and water molecules coordinated to Ni2, while hydrogen bonds also exist between other coordinated water molecules and carboxylate ligands (Table S1), enhancing the stability of the complex [33]. The structure of Complex 4 is similar to that of Complex 3, with only the metal center changed from Ni2+ to Co2+, with detailed bond lengths and angles in Table 1 and hydrogen bond parameters in Table S1.

2.2. Infrared Spectra of Complexes 1–4

Infrared spectra of complexes 1–4 are displayed in Figure 2. The broad absorption bands between 3200 and 3600 cm−1 are attributable to the ν(O–H) for the aqua ligands. In the IR spectra of complexes 3 and 4, these absorptions are conspicuously more intense due to the presence of the solvent molecules of crystallization. In general, if the difference between the asymmetric and symmetric stretching vibrations of the COO− group exceeds 200 cm−1, the carboxyl group is coordinated in a monodentate manner; if it is less than 200 cm−1, bidentate or bridging coordination may be suggested [34]. The IR spectrum of complex 1 shows a peak at 3530 cm−1 corresponding to O–H stretching vibration, while the peaks at 3217 cm−1 and 3114 cm−1 are assigned to C–H stretching vibration [35]. The peak at 1609 cm−1 corresponds to the asymmetric stretching of the COO− group, and the one at 1423 cm−1 corresponds to the symmetric stretching. Since the difference between these peaks is less than 200 cm−1, it is likely that a hydrogen bond forms between the uncoordinated carboxyl oxygen atom and the coordinated water molecule, resulting in a “pseudo-bridging” structure [34], indicating monodentate coordination, consistent with single-crystal X-ray diffraction results. The absorption bands at 1561 cm−1 and 1505 cm−1 are assigned to the stretching vibrations of the aromatic ring skeleton. Additionally, the peaks at 1369 cm−1, 1214 cm−1, 1068 cm−1, and 614 cm−1 are attributed to in-plane bending vibrations of C–H groups, and the peak at 908 cm−1 corresponds to in-plane bending of the aromatic ring. The absorption bands at 795 cm−1 and 759 cm−1 correspond to stretching vibrations of the C–S and C–Cl bonds, respectively [36,37]. The peaks at 729 cm−1 and 699 cm−1 are due to out-of-plane bending of the C–H groups, while those at 489 cm−1 and 441 cm−1 are attributed to out-of-plane bending of the aromatic ring. Notably, the peak at 665 cm−1 is attributed to the Cu–O stretching vibration, and the one at 642 cm−1 to the Cu–N stretching vibration [15,38,39]. The IR spectrum of complex 2 is similar to that of complex 1 (Figure 2) and is not further discussed here.
The IR spectrum of complex 3 shows an absorption peak at 3418 cm−1, attributed to the stretching vibration of the O–H group. A peak at 1616 cm−1 indicates the asymmetric stretching of the COO− group, while the 1421 cm−1 peak denotes the symmetric stretching. The difference is less than 200 cm−1, which is attributed to hydrogen bonding between the uncoordinated carboxyl oxygen and the coordinated water molecule, forming a “pseudo-bridging” structure, indicating monodentate coordination of the COO− group, consistent with single-crystal X-ray diffraction results [34]. The absorption band at 1558 cm−1 corresponds to the stretching vibration of the aromatic ring skeleton; additionally, peaks at 1369 cm−1, 1110 cm−1, and 607 cm−1 are due to C–H bending vibrations, and the 903 cm−1 peak is attributed to in-plane bending of the aromatic ring. The absorption band at 787 cm−1 corresponds to the stretching vibration of the C–S bond [36,37], while the peak at 711 cm−1 is due to out-of-plane bending of the C–H group. Notably, the absorption peak at 668 cm−1 is attributed to the Ni–O bond stretching vibration [15,39].
In the IR spectrum of complex 4, the asymmetric stretching of the COO− group and the aromatic ring skeletal vibration overlap around 1553 cm−1, resulting in a broad absorption peak. The symmetric stretching vibration of the COO− group appears at 1426 cm−1. Similar to complex 3, hydrogen bonding between the uncoordinated carboxyl oxygen and the coordinated water molecule leads to a difference of less than 200 cm−1 between asymmetric and symmetric stretching vibrations [34], indicating that the carboxylate ligand coordinates in a monodentate fashion to the metal center. Other absorption peaks are similar to those of complex 3 (Figure 2) and are not discussed further here.

2.3. UV-Visible Diffuse Reflectance Spectra of Complexes 1–4

Figure 3 shows the UV-visible diffuse reflectance spectra of complexes 1–4 and the 3-chlorothiophene-2-carboxylic acid ligand in the range of 200–800 nm. The results reveal the presence of ligand-based absorption bands due to π–π* transitions in the 210–250 nm range and n–π* transitions in the 300–310 nm range. All the complexes exhibit absorption bands associated with ligand π–π* transitions, red-shifted compared to the free ligand, primarily occurring within the 210–280 nm region [15]. For complex 1, an absorption band appears in the range of 350–360 nm, attributed to a red-shifted n–π* transition after coordination with the metal; a broad band in the 600–800 nm range is ascribed to d–d transitions induced by Cu2+ coordination [40]. Complexes 2 and 4 display broad absorption peaks in the 470–530 nm range, ascribed to d–d transitions arising from Co2+ coordination with the ligand [38]. The absorption band of complex 3 at 340–360 nm is attributed to the red-shifted n–π* transition of the ligand, while the broad bands at 400–420 nm and 660–750 nm originate from d–d transitions induced by Ni2+ coordination [39].

2.4. Electron Paramagnetic Resonance Spectrum of Complex 1

Figure 4 displays the X-band electron paramagnetic resonance (EPR) spectrum of complex 1 in its crystalline powder form at 298 K. For complex 1, g ⊥ = 2.08, g ∥ = 2.24, both larger than the free electron g-factor ( g e = 2.0023), indicating that the coordination geometry of Cu(II) in complex 1 is an axially elongated distorted octahedron. This inference is consistent with single-crystal X-ray diffraction data (Cu1-O3/O3#i = 2.4473(14) Å). Additionally, the magnitude of the hyperfine parameters g ∥ > g ⊥ > 2.0 indicates an axially symmetric crystal field around the Cu2+ ion. Its ground-state orbital is identified as d x 2 − y 2 , a singly occupied molecular orbital (SOMO) [32,41].

2.5. Thermogravimetric Analysis of Complexes 1–4

Figure 5 shows the thermogravimetric analysis (TGA) curves of complexes 1–4. The thermal decomposition of complex 1 in the range of 30–150 °C occurs in three stages, with corresponding weight losses of 9.7%, 5.9%, and 9.9%. A significant weight loss of 44.4% is observed between 150 and 250 °C. Between 30 and 100 °C, complex 2 exhibits thermal stability. When the temperature exceeds 100 °C, the decomposition of complex 2 occurs in three stages: 100–170 °C (23.4%), 170–250 °C (9.9%), and 250–390 °C (34.9%). Complex 1 exhibits lower thermal stability than complex 2, which may be attributed to weaker coordination bonds caused by the Jahn–Teller effect, making it more prone to decomposition. Complex 3 undergoes three-stage thermal decomposition, with weight losses of 24.5% (30–200 °C), 33.4% (200–370 °C), and 12.6% (370–600 °C). Similarly, the thermal decomposition of complex 4 occurs in three stages, with weight losses of 21.6% (30–180 °C), 28.9% (270–390 °C), and 11.1% (390–690 °C).

2.6. Electrospray Ionization Mass Spectrometry Analysis of Complexes 1–4

Figure 6 displays the electrospray ionization mass spectra (ESI-MS) of complexes 1–4. The theoretical mass-to-charge ratio (m/z) of complex 1 is 579.91, and the observed value is 579.79 [M–H]+, corresponding to the molecular formula [Cu(L)2(Py)2(OH2)2]. The theoretical m/z for complex 2 is 575.29, and the observed value is 574.79 [M–H]+ (molecular formula: [Co(L)2(Py)2(OH2)2]). The calculated m/z of complex 3 is 1468.86, while the observed value is 1469.29 [M–H]+, corresponding to the molecular formula [{Ni(L)2(OH2)4}2{Ni(L)(OH2)5}]L•5H2O. The theoretical m/z of complex 4 is 1469.52, and the observed value is 1469.23 [M–H]+ (molecular formula: [{Co(L)2(OH2)4}2{Co(L)(OH2)5}]L•5H2O).

2.7. Reduction Potential and Stability Analysis of Complexes 1–4

The pharmacological activity and DNA-binding ability of many metal complexes are related to their reduction potential and stability [42]. Therefore, before evaluating their anticancer activity, we first measured the reduction potentials of the four complexes and assessed their stability under physiological conditions [43]. The cyclic voltammetry analysis showed that the reduction potentials of complexes 1–4 are −0.90 V, −0.89 V, −0.92 V, and −0.90 V, respectively (Figure S2). All reduction potentials were calculated relative to the Ag/AgCl electrode. These values are slightly lower than that of Pt(IV) complexes [43,44], indicating that they are more difficult to reduce. Stability tests indicated that all complexes remained good stability within 24 h in phosphate-buffered saline (PBS, pH = 7.4) containing 5% DMSO (Figure S3).

2.8. Cytotoxicity Assays of Complexes 1–4

Table 2 and Figure 7 present the inhibition rates of complexes 1–4 against five cancer cell lines. The results indicate that complex 3 exhibited the highest inhibition rate against the breast cancer MDA-MB-231 cell line, reaching 43.98 ± 1.02%. Complex 4 exhibited the highest inhibition rates among four other cell lines: leukemia K562, lung cancer A549, liver cancer HepG2, and colon cancer SW480, with values of 62.05 ± 1.15%, 36.93 ± 2.04%, 46.38 ± 1.86%, and 66.83 ± 1.05%, respectively. Complexes 1 and 2 exhibited relatively lower inhibitory activity against all five cell lines. These findings provide experimental support for further investigation into the anticancer potential of this class of complexes.

3. Experimental Section

3.1. Materials and Methods of Characterization

Unless otherwise stated, all experiments were conducted at 298 K. 3-Chlorothiophene-2-carboxylic acid was sourced from J&K CHEMICAL, and CoCl2•6H2O, (CH3COO)2Cu•H2O, (CH3COO)2Co•4H2O, NiCl2•6H2O, NaOH, C5H5N(pyridine), CH3OH and CH3CH2OH were procured from China National Pharmaceutical Group Corporation, Phosphate-buffered saline (PBS) was purchased from Beijing Pusitang Biotechnology Co., Ltd., Beijing, China, Tetrabutylammonium hexafluorophosphate ([n-Bu4N][PF6]) was purchased from Jiangsu Aikon Biopharmaceutical R&D Co., Ltd., Nanjing, China, All reagents were of commercial grade and used without further purification. IR spectra were recorded in the range of wavenumbers using KBr pellet technique on a Nicolet IS50 iN10 FTIR spectrometer (Thermo Fisher Scientific, Waltham, MA, USA), with absorption bands reported in cm−1. Elemental analyses were carried out using a VARIO ELIII elemental analyzer. Single-crystal X-ray diffraction data were collected using a Bruker D8 Venture diffractometer. UV–vis diffuse reflectance spectra (UV–vis DRS) were recorded using a CARY 5000 spectrophotometer from Agilent Technologies, with a wavelength range of 200–800 nm. UV–vis absorption spectra were also measured using the CARY 5000 spectrophotometer. Melting points were determined using an X-4S microscopic melting point apparatus (Shanghai JingSong Instrument Co., Ltd., Shanghai, China). Electrospray ionization mass spectrometry data were obtained using a Vanquish Q Exactive Plus LC-Q Orbitrap MS system (Thermo Fisher Scientific, Dreieich, Germany), with samples dissolved in methanol prior to injection. Thermogravimetric analysis (TGA) was performed using a TGA8000 instrument (PerkinElmer, Waltham, MA, USA) under nitrogen atmosphere, with a heating rate of 5 °C/min over a temperature range of 30–900 °C. Electron paramagnetic resonance (EPR) spectra were recorded by a Bruker E500-10/12 spectrometer (Bruker Biospin GmbH, Ettlingen, Germany) from Germany at a microwave frequency of 9.42 GHz. Cyclic voltammetry (CV) measurements were performed in a three-electrode system, with a glassy carbon working electrode, a platinum auxiliary electrode, and an Ag/AgCl as the reference electrode. All electrochemical measurements were conducted at room temperature using a CHI660E electrochemical workstation. The supporting electrolyte was 0.1 M tetrabutylammonium hexafluorophosphate ([n-Bu4N][PF6]), and the scan rate was set to 100 mV/s. The potential was calibrated using Ag/Ag+ as an internal reference standard.

3.2. Single-Crystal X-Ray Structure Determinations

X-ray diffraction data for complexes 1–4 were collected at low temperature using a Bruker D8 Venture diffractometer with graphite-monochromated Ga-Kα radiation (λ = 1.34139 Å). The structures of complexes 1–4 were solved using SHELXT [45] and refined with SHELXL-2018/3 [46]. Molecular graphics were prepared with MERCURY (MERCURY 4.2.0/2019) [47], and structure visualization was performed using OLEX2 (OLEX2-1.5) [48]. All non-hydrogen atoms in complexes 1–4 were refined anisotropically [29], while hydrogen atoms were placed in calculated positions and refined using a constrained isotropic model [38]. Crystallographic data and refinement parameters for complexes 1–4 are summarized in Table 3, and hydrogen bonding interactions are detailed in Table S1.

3.3. Cytotoxicity Assay

This study utilized the MTS cell viability assay to evaluate the viability of five human cancer cell lines (leukemia K562, lung cancer A549, liver cancer HepG2, breast cancer MDA-MB-231, and colon cancer SW480). The cell lines were sourced from ATCC (Manassas, VA, USA) [29], and the MTS assay kit was obtained from Promega (Madison, WI, USA). The MTS assay evaluates cell viability by detecting the amount of formazan generated via the metabolic reduction in MTS by mitochondrial succinate dehydrogenase in living cells. The amount of formazan is directly proportional to the number of viable cells and is quantified by measuring the optical density (OD) at 492 nm using a microplate reader.
Experimental procedure: Cell suspensions (in DMEM or RPMI-1640 medium supplemented with 10% fetal bovine serum) were seeded into 96-well plates at 5000 cells per well and incubated for 12–24 h. Complexes were tested at a concentration of 100 μM, dissolved in DMSO, with each group set up in triplicate. After 48 h of incubation, the culture medium was discarded, and MTS solution was added to each well for color development over 2–4 h [39,40]. Three blank control wells were included simultaneously. Absorbance was measured at 492 nm using a microplate reader (MULTISKAN FC), and the data were recorded. After data processing, inhibition curves were plotted with complex numbers on the x-axis and cell inhibition rates on the y-axis.
Synthesis of complex 1: 3-Chlorothiophene-2-carboxylic acid (0.163 g, 1.0 mmol) was dissolved in a mixed solvent containing 10 mL of CH3CH2OH and 10 mL of H2O and stirred for several minutes until completely dissolved. Subsequently, 1 mL of pyridine was added, and stirring was continued. Next, (CH3COO)2Cu•H2O (0.200 g, 1.0 mmol) was dissolved in 5 mL of CH3CH2OH, and the resulting solution was added to the above system, followed by refluxing at 90 °C with stirring for 72 h. After completion of the reaction, the mixture was hot-filtered to remove insoluble materials, and the filtrate was allowed to evaporate naturally at room temperature. Blue crystals were obtained from the solution after 24 h (Scheme 1), purified by washing with petroleum ether and n-hexane, affording a final yield of 88% with a melting point of 220–225 °C. IR peaks at (KBr; υ , cm−1): 3530, 3217, 3114, 1609, 1581, 1561, 1505, 1423, 1369, 1214, 1068, 908, 795, 759, 729, 699, 665, 642, 614, 489, 441. For [C20H18Cl2CuN2O6S2], Anal. Calcd., %: C, 41.35; H, 3.12; N, 4.82. Found, %: C, 41.40; H, 3.36; N, 4.53.
Synthesis of complex 2: The synthesis followed the same procedure as for complex 1, differing only in the substitution of (CH3COO)2Cu•H2O with (CH3COO)2Co•4H2O (0.249 g, 1.0 mmol). After the reaction, the filtrate was left standing at room temperature for 24 h, yielding purple crystals from the solution (Scheme 1), which were washed with petroleum ether and n-hexane, with a final yield of 76% and a melting point exceeding 300 °C. IR peaks at (KBr; υ , cm−1): 3449, 3119, 3064, 1604, 1579, 1550, 1505, 1423, 1365, 1216, 1069, 903, 800, 772, 755, 701, 663, 630, 612, 472, and 431. For [C20H18Cl2CoN2O6S2], Anal. Calcd., %: C, 41.68; H, 3.15; N, 4.86. Found, %: C, 41.22; H, 3.19; N, 4.73.
Synthesis of complex 3: 3-Chlorothiophene-2-carboxylic acid (0.098 g, 0.6 mmol) was added to a flask, followed by NaOH (0.020 g, 0.5 mmol), 5 mL H2O, and 5 mL CH3OH, and stirred until fully dissolved. Subsequently, NiCl2•6H2O (0.143 g, 0.6 mmol) was dissolved in 2.5 mL H2O and 2.5 mL CH3OH, and the resulting solution was added to the above system. The mixture was refluxed with stirring at 90 °C for 24 h; upon completion, it was filtered hot to remove insoluble impurities, and the filtrate was allowed to evaporate naturally at room temperature, producing green crystals after 72 h (Scheme 1), which were washed with petroleum ether and n-hexane, achieving a final yield of 92% and a melting point above 300 °C. IR peaks at (KBr; υ , cm−1): 3418, 1616, 1558, 1421, 1369, 1110, 903, 787, 711, 668, and 607. For [C30H48Cl6Ni3O30S6], Anal. Calcd., %: C, 24.52; H, 3.29; N, 0.00. Found, %: C, 24.75; H, 3.15; N, 0.48.
Synthesis of complex 4: The synthesis was conducted using the same method as for complex 3, with the only difference being the replacement of NiCl2•6H2O with CoCl2•6H2O (0.143 g, 0.6 mmol). Upon completion of the reaction, the filtrate was allowed to stand at room temperature for 72 h, resulting in the precipitation of purple crystals from the solution (Scheme 1), which were subsequently washed with petroleum ether and n-hexane, achieving a final yield of 93% and a melting point above 300 °C. IR peaks at (KBr; υ , cm−1): 3406, 3105, 1553, 1510, 1426, 1369, 1168, 1112, 907, 791, 737, 711, 668, and 607. For [C30H48Cl6Co3O30S6], Anal. Calcd., %: C, 24.50; H, 3.29; N, 0.00. Found, %: C, 24.99; H, 2.93; N, 0.00.

4. Conclusions

Under one-pot reaction conditions, this study successfully synthesized four complexes: [Cu(L)2(Py)2(OH2)2] (1), [Co(L)2(Py)2(OH2)2] (2), [{Ni(L)2(OH2)4}2{Ni(L)(OH2)5}]L•5H2O (3), and [{Co(L)2(OH2)4}2{Co(L)(OH2)5}]L•5H2O (4). The four complexes underwent comprehensive structural characterization, including EA, UV-vis DRS, IR, EPR, TGA, ESI-MS, and XRD, alongside an assessment of their anticancer activities, particularly their inhibitory effects on human leukemia K562 cells, lung cancer A549 cells, liver cancer HepG2 cells, breast cancer MDA-MB-231 cells, and colon cancer SW480 cells. The results show that Complex 4 exhibits significant inhibitory effects on leukemia K562 cells, lung cancer A549 cells, liver cancer HepG2 cells, and colon cancer SW480 cells, but the overall effect remains unsatisfactory. In view of this, our research team will continue to focus on synthesizing complexes with higher anticancer activity and, based on this, strive to develop candidate drugs with potential clinical applications.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/inorganics13070238/s1, Table S1: Hydrogen bond lengths (Å) and bond angles (°) for complexes 1–4; Figure S1:IR spectra of complexes 1–4 in the 4000–400 cm−1 region; Figure S2: Cyclic voltammogram of complexes 1–4 in DMF containing 0.1 M [n-Bu4N][PF6] at a scan rate of 100 mV/s using a glassy carbon as a working electrode; Figure S3: UV-vis spectra of complexes 1–4 in PBS with 5% DMSO under physiological conditions (pH 7.4) at 0 and 24 h.

Author Contributions

B.H.: Writing—original draft, Methodology, Investigation, Formal analysis, Visualization. Q.K.: Writing—review and editing, Formal analysis. X.M.: Visualization, Resources, Formal analysis. H.Y.: Resources, Formal analysis. X.Y.: Resources, Formal analysis. Y.Y.: Writing—review and editing. M.L.: Writing—review and editing, Resources, Validation, Supervision, Conceptualization, Project Administration, Funding Acquisition. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The original contributions presented in this study are included in the article/Supplementary Materials. Further inquiries can be directed to the corresponding author.

Acknowledgments

This work was supported by the Hefei University of Technology and State Key Laboratory of Photochemistry and Plant Resources in West China.

Conflicts of Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References

  1. Erxleben, A. Transition metal salen complexes in bioinorganic and medicinal chemistry. Inorg. Chim. Acta 2018, 472, 40–57. [Google Scholar] [CrossRef]
  2. Ott, I. On the medicinal chemistry of gold complexes as anticancer drugs. Coord. Chem. Rev. 2009, 253, 1670–1681. [Google Scholar] [CrossRef]
  3. Gasser, G.; Metzler-Nolte, N. The potential of organometallic complexes in medicinal chemistry. Curr. Opin. Chem. Biol. 2012, 16, 84–91. [Google Scholar] [CrossRef]
  4. Voloshin, Y.Z.; Varzatskii, O.A.; Bubnov, Y.N. Cage complexes of transition metals in biochemistry and medicine. Russ. Chem. Bull. 2007, 56, 577–605. [Google Scholar] [CrossRef]
  5. Dalia, S.; Afsan, F.; Hossain, M.; Khan, M.N.; Zakaria, C.; Zahan, M.K.-E.; Ali, M. A short review on chemistry of schiff base metal complexes and their catalytic application. Int. J. Chem. Stud. 2018, 6, 2859–2866. [Google Scholar]
  6. Soldevila-Barreda, J.J.; Metzler-Nolte, N. Intracellular Catalysis with Selected Metal Complexes and Metallic Nanoparticles: Advances toward the Development of Catalytic Metallodrugs. Chem. Rev. 2019, 119, 829–869. [Google Scholar] [CrossRef]
  7. Williams, C.K.; Nozaki, K. Metal Complexes for Catalytic Polymerizations. Inorg. Chem. 2020, 59, 957–959. [Google Scholar] [CrossRef]
  8. Oehninger, L.; Rubbiani, R.; Ott, I. N-Heterocyclic carbene metal complexes in medicinal chemistry. Dalton Trans. 2013, 42, 3269–3284. [Google Scholar] [CrossRef]
  9. Dasmahapatra, U.; Maiti, B.; Alam, M.M.; Chanda, K. Anti-cancer property and DNA binding interaction of first row transition metal complexes: A decade update. Eur. J. Med. Chem. 2024, 275, 116603. [Google Scholar] [CrossRef]
  10. Wang, L.; Chong, S.; Wu, S.; Sun, Y.; Zhang, Y.; Sun, C.; Zhu, M. Construction of Zn (II)/Mn (II) complexes based carboxylic acid ligands and their drug delivery, antiproliferation and DNA interaction. J. Mol. Liq. 2025, 425, 127187. [Google Scholar] [CrossRef]
  11. Guan, Q.; Shi, X.; Shen, J.; Zhao, G. Antimicrobial, anticancer and DNA binding studies of transition metal(II) complexes containing 2-phenyl-4-selenazole carboxylic acid. Sci. China Chem. 2013, 56, 588–594. [Google Scholar] [CrossRef]
  12. Garcia-Valdivia, A.A.; Jannus, F.; Garcia-Garcia, A.; Choquesillo-Lazarte, D.; Fernandez, B.; Medina-O’donnell, M.; Lupianez, J.A.; Cepeda, J.; Reyes-Zurita, F.J.; Rodriguez-Dieguez, A. Anti-cancer and anti-inflammatory activities of a new family of coordination compounds based on divalent transition metal ions and indazole-3-carboxylic acid. J. Inorg. Biochem. 2021, 215, 111308. [Google Scholar] [CrossRef]
  13. Tamer, Ö.; Mahmoody, H.; Feyzioğlu, K.F.; Kılınç, O.; Avci, D.; Orun, O.; Dege, N.; Atalay, Y. Synthesis of the first mixed ligand Mn (II) and Cd (II) complexes of 4-methoxy-pyridine-2-carboxylic acid, molecular docking studies and investigation of their anti-tumor effects in vitro. Appl. Organomet. Chem. 2019, 34, e5416. [Google Scholar] [CrossRef]
  14. Zhang, S.; Zhong, X.; Yuan, H.; Guo, Y.; Song, D.; Qi, F.; Zhu, Z.; Wang, X.; Guo, Z. Interfering in apoptosis and DNA repair of cancer cells to conquer cisplatin resistance by platinum(iv) prodrugs. Chem. Sci. 2020, 11, 3829–3835. [Google Scholar] [CrossRef]
  15. Zhang, L.; Yin, H.; Zhang, J.-C.; Luo, M.; Meng, X.-G. Synthesis, crystal structure and anticancer activity of 4-chloro-2-methoxybenzoic acid transition metal complexes. J. Mol. Struct. 2024, 1316, 139080. [Google Scholar] [CrossRef]
  16. Wang, X.; Yan, M.; Wang, Q.; Wang, H.; Wang, Z.; Zhao, J.; Li, J.; Zhang, Z. In Vitro DNA-Binding, Anti-Oxidant and Anticancer Activity of Indole-2-Carboxylic Acid Dinuclear Copper(II) Complexes. Molecules 2017, 22, 171. [Google Scholar] [CrossRef]
  17. Rijwan; Arjmand, F.; Tabassum, S. Synthesis, spectroscopic, single crystal X-ray diffraction studies of Bilastine, BLA(bpy)2Cu(II) & Zn(II) complexes as anticancer chemotherapeutic agents: Validation of their cytotoxic potency on cancer cell lines. J. Mol. Struct. 2025, 1328, 141244. [Google Scholar]
  18. Rijwan; Arjmand, F.; Tabassum, S. Repurposing the antihistamine drug bilastine as an anti-cancer metallic drug entity: Synthesis and single-crystal X-ray structure analysis of metal-based bilastine and phen [Co(II), Cu(II) and Zn(II)] tailored anticancer chemotherapeutic agents against resistant cancer cells. Dalton Trans. 2024, 53, 10126–10141. [Google Scholar] [PubMed]
  19. Li, H.-M.; Li, G.-D.; Li, J.-Y.; Zhang, T. An Iodine-Functionalized Metal–Organic framework for catalytic alkene bromination. Inorg. Chem. Commun. 2022, 141, 109529. [Google Scholar] [CrossRef]
  20. Prakash, A.; Saini, S.; Basappa, S.; Gupta, D.K.; Mao, L.; Bose, S.K. Metal-Organic Frameworks for Catalytic Construction of C−B Bond and Related Reactions. ChemCatChem 2022, 15, e202201156. [Google Scholar] [CrossRef]
  21. Koner, S. Catalytic epoxidation of olefin over metal-organic framework solids: A mini-review. J. Organomet. Chem. 2025, 1025, 123449. [Google Scholar] [CrossRef]
  22. Xie, H.; Bai, M.; Wang, A.; Chen, Z.; Chang, F.; Lian, J.; Xu, S. Antenna-based optimization of triplet radioluminescence of Tb-organic complex scintillator for efficient X-ray detection. J. Colloid Interface Sci. 2024, 676, 45–51. [Google Scholar] [CrossRef]
  23. Psalti, A.E.; Andriotou, D.; Diamantis, S.A.; Chatz-Giachia, A.; Pournara, A.; Manos, M.J.; Hatzidimitriou, A.; Lazarides, T. Mixed-Metal and Mixed-Ligand Lanthanide Metal-Organic Frameworks Based on 2,6-Naphthalenedicarboxylate: Thermally Activated Sensitization and White-Light Emission. Inorg. Chem. 2022, 61, 11959–11972. [Google Scholar] [CrossRef]
  24. Zhang, Y.; Xu, S.; Huang, K.; Zhang, X.-Y.; Qin, D.-B.; Zhao, B. A Novel 2D Copper–Organic Framework for Catalyzing CO2 Chemical Fixation and Luminescence Sensing. Cryst. Growth Des. 2023, 23, 7873–7881. [Google Scholar] [CrossRef]
  25. Kelland, L. The resurgence of platinum-based cancer chemotherapy. Nat. Rev. Cancer 2007, 7, 573–584. [Google Scholar] [CrossRef]
  26. Fernández, C.Y.; Rocha, A.; Azam, M.; Alvarez, N.; Min, K.; Batista, A.A.; Costa-Filho, A.J.; Ellena, J.; Facchin, G. Synthesis, Characterization, DNA Binding and Cytotoxicity of Copper(II) Phenylcarboxylate Complexes. Inorganics 2023, 11, 398. [Google Scholar] [CrossRef]
  27. Fernandez, C.Y.; Alvarez, N.; Rocha, A.; Mendes, L.F.S.; Costa-Filho, A.J.; Ellena, J.; Batista, A.A.; Facchin, G. Phenanthroline and phenyl carboxylate mixed ligand copper complexes in developing drugs to treat cancer. J. Inorg. Biochem. 2024, 260, 112700. [Google Scholar] [CrossRef] [PubMed]
  28. Mandal, P.; Sonkar, C.; Dhankhar, S.S.; Nagaraja, C.M.; Mukhopadhyay, S. Ruthenium(II)-arene complexes containing ferrocenamide ligands: Synthesis, characterisation and antiproliferative activity against cancer cell lines. J. Organomet. Chem. 2020, 916, 121247. [Google Scholar] [CrossRef]
  29. Umar, Q.; Huang, Y.; Nazeer, A.; Yin, H.; Zhang, J.C.; Luo, M.; Meng, X.G. Synthesis, characterization and anticancer activities of Zn2+, C(2+, Co2+ and Ni2+ complexes involving chiral amino alcohols. RSC Adv. 2022, 12, 32119–32128. [Google Scholar] [CrossRef]
  30. Rostami, L.; Golchoubian, H. Copper(II) complexes containing hemilabile tridentate ligand as chromotropic probes. J. Coord. Chem. 2017, 70, 3660–3676. [Google Scholar] [CrossRef]
  31. Klanicová, A.; Houck, J.D.; Baran, P.; Trávníček, Z. Synthesis, X-ray structures, properties and SOD-like activity of ternary copper(II) complexes showing the N4O2 coordination with a combination of monodentate and bidentate N-donor ligands. Inorg. Chim. Acta 2012, 384, 47–53. [Google Scholar] [CrossRef]
  32. Santana, F.S.; Briganti, M.; Cassaro, R.A.A.; Totti, F.; Ribeiro, R.R.; Hughes, D.L.; Nunes, G.G.; Reis, D.M. An Oxalate-Bridged Copper(II) Complex Combining Monodentate Benzoate, 2,2′-bipyridine and Aqua Ligands: Synthesis, Crystal Structure and Investigation of Magnetic Properties. Molecules 2020, 25, 1898. [Google Scholar] [CrossRef] [PubMed]
  33. Song, X.; Wang, Y.; Wang, C.; Wang, D.; Zhuang, G.; Kirlikovali, K.O.; Li, P.; Farha, O.K. Design Rules of Hydrogen-Bonded Organic Frameworks with High Chemical and Thermal Stabilities. J. Am. Chem. Soc. 2022, 144, 10663–10687. [Google Scholar] [CrossRef] [PubMed]
  34. Deacon, G. Relationships between the carbon-oxygen stretching frequencies of carboxylato complexes and the type of carboxylate coordination. Coord. Chem. Rev. 1980, 33, 227–250. [Google Scholar] [CrossRef]
  35. Kim, M.C.; Cho, S.H.; Lee, S.B.; Kim, Y.; Boo, J.H. Characterization of polymer-like thin films deposited on silicon and glass substrates using PECVD method. Thin Solid Films 2004, 447–448, 592–598. [Google Scholar] [CrossRef]
  36. Layman, K.A.; Bussell, M.E. Infrared Spectroscopic Investigation of Thiophene Adsorption on Silica-Supported Nickel Phosphide Catalysts. J. Phys. Chem. B 2004, 108, 15791–15802. [Google Scholar] [CrossRef]
  37. Sainz-Díaz, C.I.; Francisco-Márquez, M.; Vivier-Bunge, A. Molecular structure and spectroscopic properties of polyaromatic heterocycles by first principle calculations: Spectroscopic shifts with the adsorption of thiophene on phyllosilicate surface. Theor. Chem. Acc. 2009, 125, 83–95. [Google Scholar] [CrossRef]
  38. Luo, M.; Guo, C.C.; Li, Y.Z.; Zhang, J.C. Syntheses and crystal structure of copper (II) and cobalt (II) complexes containing N-heterocyclic compounds. J. Iran. Chem. Soc. 2017, 15, 415–420. [Google Scholar] [CrossRef]
  39. Nazeer, A.; Umar, Q.; Yang, Y.; Luo, M. Zn (II), Cu (II), Co (II), and Ni (II) complexes bearing aza-heterocyclic ligands: Synthesis, characterization, and anticancer activities. J. Iran. Chem. Soc. 2024, 21, 1599–1609. [Google Scholar] [CrossRef]
  40. Luo, M.; Li, H.M. One-pot synthesis and biological and catalytic applications of organometallic complexes involving oxazolines and (R)/(S)-a-phenylethylamine. J. Iran. Chem. Soc. 2019, 17, 963–971. [Google Scholar] [CrossRef]
  41. Maślewski, P.; Wyrzykowski, D.; Witwicki, M.; Dołęga, A. Histaminol and Its Complexes with Copper(II)—Studies in Solid State and Solution. Eur. J. Inorg. Chem. 2018, 2018, 1399–1408. [Google Scholar] [CrossRef]
  42. Muhammad, N.; Sadia, N.; Zhu, C.; Luo, C.; Guo, Z.; Wang, X. Biotin-tagged platinum(iv) complexes as targeted cytostatic agents against breast cancer cells. Chem. Commun. Camb. 2017, 53, 9971–9974. [Google Scholar] [CrossRef] [PubMed]
  43. Zhang, S.; Yuan, H.; Guo, Y.; Wang, K.; Wang, X.; Guo, Z. Towards rational design of RAD51-targeting prodrugs: Platinum(IV)-artesunate conjugates with enhanced cytotoxicity against BRCA-proficient ovarian and breast cancer cells. Chem. Commun. Camb 2018, 54, 11717–11720. [Google Scholar] [CrossRef] [PubMed]
  44. Guo, Y.; Zhang, S.; Yuan, H.; Song, D.; Jin, S.; Guo, Z.; Wang, X. A platinum(iv) prodrug to defeat breast cancer through disrupting vasculature and inhibiting metastasis. Dalton Trans. 2019, 48, 3571–3575. [Google Scholar] [CrossRef]
  45. Sheldrick, G.M. SHELXT—Integrated space-group and crystal-structure determination. Acta Crystallogr. A Found. Adv. 2015, 71, 3–8. [Google Scholar] [CrossRef] [PubMed]
  46. Sheldrick, G.M. Crystal structure refinement with SHELXL. Acta Crystallogr. C Struct. Chem. 2015, 71, 3–8. [Google Scholar] [CrossRef]
  47. Macrae, C.F.; Edgington, P.R.; McCabe, P.; Pidcock, E.; Shields, G.P.; Taylor, R.; Towler, M.; van de Streek, J. Mercury: Visualization and analysis of crystal structures. J. Appl. Crystallogr. 2006, 39, 453–457. [Google Scholar] [CrossRef]
  48. Dolomanov, O.V.; Bourhis, L.J.; Gildea, R.J.; Howard, J.A.K.; Puschmann, H. OLEX2: A complete structure solution, refinement and analysis program. J. Appl. Crystallogr. 2009, 42, 339–341. [Google Scholar] [CrossRef]
Inorganics 13 00238 sch001
Scheme 1. Synthetic Routes to Complexes 1–4.
Scheme 1. Synthetic Routes to Complexes 1–4.
Inorganics 13 00238 sch001
Inorganics 13 00238 g001
Figure 1. Crystal structures of complexes 1–4. For clarity, these solvent molecules and counter anions are omitted in complexes 3 and 4. In (1), #i − x + 1, −y + 2, −z + 1; In (2), #i − x + 1, −y + 1, −z + 1, In (3), #i − x + 2, −y + 2, −z + 1, In (4), #i − x + 2, −y + 2, −z + 1.
Figure 1. Crystal structures of complexes 1–4. For clarity, these solvent molecules and counter anions are omitted in complexes 3 and 4. In (1), #i − x + 1, −y + 2, −z + 1; In (2), #i − x + 1, −y + 1, −z + 1, In (3), #i − x + 2, −y + 2, −z + 1, In (4), #i − x + 2, −y + 2, −z + 1.
Inorganics 13 00238 g001
Inorganics 13 00238 g002
Figure 2. IR spectra of complexes 1–4 in the 4000–400 cm−1 region.
Figure 2. IR spectra of complexes 1–4 in the 4000–400 cm−1 region.
Inorganics 13 00238 g002
Inorganics 13 00238 g003
Figure 3. UV-visible diffuse reflectance spectra of complexes 1–4 in the range 200–800 nm.
Figure 3. UV-visible diffuse reflectance spectra of complexes 1–4 in the range 200–800 nm.
Inorganics 13 00238 g003
Inorganics 13 00238 g004
Figure 4. X-band EPR spectrum for complex 1 (polycrystalline sample) at 298 K at a microwave frequency of 9.42 GHz.
Figure 4. X-band EPR spectrum for complex 1 (polycrystalline sample) at 298 K at a microwave frequency of 9.42 GHz.
Inorganics 13 00238 g004
Inorganics 13 00238 g005
Figure 5. TGA curves of complexes 1–4 at 30–900 °C in nitrogen atmosphere.
Figure 5. TGA curves of complexes 1–4 at 30–900 °C in nitrogen atmosphere.
Inorganics 13 00238 g005
Inorganics 13 00238 g006aInorganics 13 00238 g006b
Figure 6. ESI-MS spectra of complexes 1–4 in methanol.
Figure 6. ESI-MS spectra of complexes 1–4 in methanol.
Inorganics 13 00238 g006aInorganics 13 00238 g006b
Inorganics 13 00238 g007
Figure 7. Cell inhibition (%) of complexes 1–4 to the different tumor cell lines.
Figure 7. Cell inhibition (%) of complexes 1–4 to the different tumor cell lines.
Inorganics 13 00238 g007
Table 1. Selected bond lengths ( Å ) and bond angles (°) of complexes 1–4.
Table 1. Selected bond lengths ( Å ) and bond angles (°) of complexes 1–4.
complex 1
BondLength/ Å BondLength/ Å
Cu(1)-O1 1.9866(12)Cu1-O1#i 1.9866(12)
Cu1-N1 2.0039(15)Cu1-N1#i 2.0039(15)
Cu1-O3 2.4473(14)Cu1-O3#i 2.4473(14)
BondAngle/(°)BondAngle/(°)
O1#i-Cu1-O1180.00(8)O1-Cu1-O386.40(49)
O1#i-Cu1-N1#i89.43(6)N1-Cu1-O391.41(53)
O1-Cu1-N1#i90.57(6)N1#i-Cu1-O388.59(53)
O1#i-Cu1-N190.57(6)O1#i-Cu1-O3#i86.40(49)
O1-Cu1-N189.43(6)O1-Cu1-O3#i93.60(49)
N1#i-Cu1-N1180.0N1-Cu1-O3#i88.59(53)
O1#i-Cu1-O393.60(49)N1#i-Cu1-O3#i91.41(53)
O3-Cu1-O3#i180.00(4)
complex 2
BondLength/ÅBondLength/Å
Co1-O1 2.0744(9)Co1-O1#i 2.0744(9)
Co1-N1 2.1341(11)Co1-N1#i 2.1342(11)
Co1-O3 2.1419(9)Co1-O3#i 2.1420(9)
BondAngle/(°)BondAngle/(°)
O1#i-Co1-O1180.0O1-Co1-O389.13(4)
O1#i-Co1-N191.25(4)N1-Co1-O390.40(4)
O1-Co1-N188.75(4)N1#i-Co1-O389.60(4)
O1#i-Co1-N1#i88.75(4)O1#i-Co1-O3#i89.13(4)
O1-Co1-N1#i91.25(4)O1-Co1-O3#i90.87(4)
N1-Co1-N1#i180.0N1-Co1-O3#i89.60(4)
O1#i-Co1-O390.87(4)N1#i-Co1-O3#i90.40(4)
O3-Co1-O3#i180.00(4)
complex 3
BondLength/ÅBondLength/Å
Ni1-O3 2.043(2)Ni2-O5 2.031(2)
Ni1-O3#i 2.043(2)Ni2-O11 2.051(3)
Ni1-O1 2.065(2)Ni2-O10 2.059(3)
Ni1-O1#i 2.065(2)Ni2-O8 2.059(3)
Ni1-O4#i 2.084(2)Ni2-O7 2.075(3)
Ni1-O4 2.084(2)Ni2-O9 2.078(3)
BondAngle/(°)BondAngle/(°)
O3-Ni1-O3#i180.00(4)O5-Ni2-O11179.46(12)
O3-Ni1-O184.96(10)O5-Ni2-O1089.81(11)
O3#i-Ni1-O195.04(10)O11-Ni2-O1089.76(12)
O3-Ni1-O1#i95.04(10)O5-Ni2-O891.86(12)
O3#i-Ni1-O1#i84.96(10)O11-Ni2-O888.57(13)
O1-Ni1-O1#i180.0O10-Ni2-O8178.13(12)
O3-Ni1-O4#i91.76(10)O5-Ni2-O792.81(11)
O3#i-Ni1-O4#i88.24(10)O11-Ni2-O787.53(14)
O1-Ni1-O4#i89.88(10)O10-Ni2-O791.90(12)
O1#i-Ni1-O4#i90.12(10)O8-Ni2-O788.87(14)
O3-Ni1-O488.24(10)O5-Ni2-O988.78(11)
O3#i-Ni1-O491.76(10)O11-Ni2-O990.89(14)
O1-Ni1-O490.12(10)O10-Ni2-O989.05(11)
O1#i-Ni1-O489.88(10)O8-Ni2-O990.14(14)
O4#i-Ni1-O4180.0O7-Ni2-O9178.16(12)
complex 4
BondLength/ÅBondLength/Å
Co1-O3#i 2.067(3)Co2-O5 2.065(4)
Co1-O3 2.067(3)Co2-O11 2.078(4)
Co1-O1#i 2.116(3)Co2-O9 2.103(4)
Co1-O1 2.116(3)Co2-O10 2.103(4)
Co1-O4 2.124(4)Co2-O8 2.111(4)
Co1-O4#i 2.124(4)Co2-O7 2.134(4)
BondAngle/(°)BondAngle/(°)
O3#i-Co1-O3180.0O5-Co2-O11178.32(19)
O3#i-Co1-O1#i84.70(14)O5-Co2-O990.97(15)
O3-Co1-O1#i95.30(14)O11-Co2-O990.37(19)
O3#i-Co1-O195.30(14)O5-Co2-O1089.05(15)
O3-Co1-O184.70(14)O11-Co2-O1089.97(16)
O1#i-Co1-O1180.0O9-Co2-O1088.44(16)
O3#i-Co1-O491.94(14)O5-Co2-O891.68(16)
O3-Co1-O488.07(14)O11-Co2-O889.32(17)
O1#i-Co1-O488.15(14)O9-Co2-O890.21(19)
O1-Co1-O491.85(14)O10-Co2-O8178.48(19)
O3#i-Co1-O4#i88.06(14)O5-Co2-O790.81(16)
O3-Co1-O4#i91.93(14)O11-Co2-O787.87(19)
O1#i-Co1-O4#i91.85(14)O9-Co2-O7177.90(16)
O1-Co1-O4#i88.15(14)O10-Co2-O792.70(16)
O4-Co1-O4#i180.0O8-Co2-O788.63(18)
Equivalent atoms are generated by symmetry transformations: complex 1: #i −x + 1, −y + 2, −z + 1 complex 2: #i −x + 1, −y + 1, −z + 1 complex 3: #i −x + 2, −y + 2, −z + 1 complex 4: #i −x + 2, −y + 2, −z + 1.
Table 2. Cell inhibition (%) of complexes 1–4 to the different tumor cell lines.
Table 2. Cell inhibition (%) of complexes 1–4 to the different tumor cell lines.
ComplexK562A549HepG2MDA-MB-231SW480
Cell Inhibition (%)
15.34 ± 2.066.01 ± 2.576.04 ± 0.2825.48 ± 2.0917.61 ± 2.60
212.48 ± 1.456.71 ± 0.986.54 ± 0.8213.06 ± 3.0526.24 ± 2.40
349.96 ± 0.3121.91 ± 1.568.57 ± 2.6743.98 ± 1.0224.32 ± 3.49
462.05 ± 1.1536.93 ± 2.0446.38 ± 1.8639.78 ± 2.8666.83 ± 1.05
Table 3. Crystallographic data for complexes 1–4.
Table 3. Crystallographic data for complexes 1–4.
Complex1234
Empirical formulaC20H18Cl2CuN2O6S2C20H18Cl2CoN2O6S2C30H48Cl6Ni3O30S6C30H48Cl6Co3O30S6
Formula mass580.92576.311469.871470.53
Temp (K)100(2) K100(2)100(2)200(2)
Wavelength (Å)1.34139 Å1.341391.341391.34139
Crystal systemMonoclinicMonoclinicTriclinicTriclinic
Space groupP21/cP21/c P 1 ¯ P 1 ¯
a (Å)6.8852(3)6.7286(4)7.5046(3)7.5626(8)
b (Å)8.7665(4)9.0683(5)11.0363(4)11.0377(12)
c (Å)19.5603(8)19.1980(11)16.0898(6)16.1607(17)
α (°)909088.6166(15)88.380(4)
β (°)97.221(2)94.914(2)86.0285(15)85.918(4)
γ (°)909088.3027(14)88.693(4)
Volume (Å3)1171.28(9)1167.10(12)1328.50(9)1344.7(2)
Z2211
Dcalcd (Mg/m3)1.6471.6401.8371.816
μ (mm−1)7.7706.7799.5908.820
F (000)590586750747
θ range (°)3.964 to 72.6494.021 to 72.5472.395 to 52.0882.385 to 52.095
Total reflec.24271277292300121832
Independent reflections3495 [R(int) = 0.0654]3496 [R(int) = 0.0444]4418 [R(int) = 0.0504]4487 [R(int) = 0.0690]
R1, wR2 [I > 2σ(I)]0.0395, 0.10580.0291, 0.07630.0433, 0.10230.0607, 0.1438
R1, wR2 [all data]0.0441, 0.10840.0307, 0.07730.0469, 0.10480.0680, 0.1475
Residuals (e.Å3)1.125, −0.8770.874, −0.8840.827, −0.5250.822, −0.675
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Hu, B.; Kang, Q.; Meng, X.; Yin, H.; Yang, X.; Yang, Y.; Luo, M. Synthesis, Characterization, and Anticancer Activity of 3-Chlorothiophene-2-carboxylic Acid Transition Metal Complexes. Inorganics 2025, 13, 238. https://doi.org/10.3390/inorganics13070238

AMA Style

Hu B, Kang Q, Meng X, Yin H, Yang X, Yang Y, Luo M. Synthesis, Characterization, and Anticancer Activity of 3-Chlorothiophene-2-carboxylic Acid Transition Metal Complexes. Inorganics. 2025; 13(7):238. https://doi.org/10.3390/inorganics13070238

Chicago/Turabian Style

Hu, Baiquan, Qianqian Kang, Xianggao Meng, Hao Yin, Xingzhi Yang, Yanting Yang, and Mei Luo. 2025. "Synthesis, Characterization, and Anticancer Activity of 3-Chlorothiophene-2-carboxylic Acid Transition Metal Complexes" Inorganics 13, no. 7: 238. https://doi.org/10.3390/inorganics13070238

APA Style

Hu, B., Kang, Q., Meng, X., Yin, H., Yang, X., Yang, Y., & Luo, M. (2025). Synthesis, Characterization, and Anticancer Activity of 3-Chlorothiophene-2-carboxylic Acid Transition Metal Complexes. Inorganics, 13(7), 238. https://doi.org/10.3390/inorganics13070238

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop