The use of schiff base metal complexes has attracted considerable interest because of their wide-ranging applications in the fields of coordination chemistry and biological sciences. A straightforward simple condensation methodology with acid catalyst approaches was used to synthesize a (E)-4-((anthracen-9-ylmethylene)amino)-N-(pyridin-2-yl) benzenesulfonamide schiff base ligand. The followed by the synthesis of the metal–ligand complexes encompassed the coordination of the Schiff base ligand to the transition metal ion in an ethanolic medium. Subsequent structural characterization and their properties were predicted using spectroscopic and analytical techniques. Furthermore, we evaluated the biological properties exhibited by these complexes, with a specific emphasis on their potential applications as antimicrobial, anticancer, antioxidant, and enzyme inhibition agents. The findings derived from this investigation yield significant perspectives regarding the formulation and advancement of innovative metal– organic complexes that exhibit augmented therapeutic attributes.
Research Article
Synthesis and characterization of (E)-4-((anthracen-9-ylmethylene) amino)-N- (pyridin-2-yl) benzenesulfonamide and its metal complexes: Evaluation of potential against the colon cancer cell line COLO-205 and biological activity profiles
https://doi.org/10.21203/rs.3.rs-3435682/v1
This work is licensed under a CC BY 4.0 License
Version 1
posted
You are reading this latest preprint version
Schiff Base
Antibacterial
Antifungal
Antioxidant
Anti-Larvicidal
and Anti-Inflammatory
DNA Cleavage
Colon Cancer Cell
The current state of global change has necessitated the urgent development of an alternative synthetic methodology for biologically and synthetically significant compounds. In the realm of biological processes, it is widely recognised that inorganic compounds hold significant importance. Furthermore, extensive research has demonstrated that numerous organic compounds utilized in medicine undergo activation through the intricate process of metal ion metabolism. Schiff base ligands and their corresponding metal complexes have been extensively investigated because of their wide range of applications in various fields such as biology, clinical research, analytical chemistry, and industrial processes [1].The intriguing phenomenon of coordination chemistry involving Schiff base compounds and transition metal ions, along with their significant contributions to chemical, medical, and industrial processes, warrants their recognition as potential candidates for the synthesis of novel complexes [2]. Exploration of Schiff base ligands and their metal complexes for cancer treatment is a promising avenue in the fight against cancer. These organic compounds, which contain a pivotal imine functional group, can form coordination complexes with metal ions, exhibiting enhanced anticancer properties compared with their non-metal counterparts. They can be tailored with various functional groups, allowing for the fine-tuning of their properties. Metal complexes formed with Schiff base ligands display increased cytotoxicity toward cancer cells, making them promising candidates for chemotherapy. Functionalized Schiff base ligands enable the design of targeted drug delivery systems that selectively transport metal complexes to tumour sites, minimize damage to healthy tissues, and reduce side effects. Some metal complexes can interact with DNA through intercalation or binding, leading to DNA cleavage, inhibition of replication, and induction of apoptosis in cancer cells. Methods of action for Schiff base metal complexes include inhibiting critical enzymes involved in cancer cell metabolism, angiogenesis, and proliferation, generation of reactive oxygen species (ROS) in photodynamic therapy (PDT), immune-modulation, and antioxidant properties. Future directions for research into Schiff base ligands and metal complexes for cancer treatment include optimizing ligand and metal combinations for enhanced anticancer activity, developing targeted drug delivery systems for precision medicine, conducting clinical trials to assess safety and efficacy in human patients, and exploring combination therapies involving Schiff base complexes with traditional treatments or immunotherapies. In conclusion, the exploration of Schiff base ligands and their metal complexes in cancer treatment represents a promising avenue in the fight against cancer, with the goal of enhancing patient outcomes and quality of life.
Numerous investigations have been conducted in the previous period on various metal complexes featuring schiff base compounds, owing to their extensive range of potential applications [3–6]. Schiff bases and their corresponding metal complexes are of paramount importance in elucidating the intricate nuances of coordination chemistry of transition metal ions [7]. The chemistry of transition metal complexes featuring ligands containing oxygen, nitrogen, and sulfur donor atoms has garnered significant attention. This is primarily due to the observed carcinostatic, antitumor, antiviral, antifungal, and antibacterial activities of these complexes, as well as their various industrial applications [8]. Furthermore, the inclusion of nitrogen and oxygen donor atoms within the complexes renders these compounds highly efficient and stereospecific catalysts for various chemical reactions such as oxidation, reduction, and hydrolysis. In addition, they exhibit notable biological activity and facilitate diverse transformations within the realms of both organic and inorganic chemistry. It is widely acknowledged in scientific literature that the activity of certain drugs has been observed to exhibit enhancement upon administration in the form of metal complexes [9–10]. In contemporary times, there has been a surge in scientific investigations of sulfonamides and their complexes with transition metals, primarily driven by their promising prospects in the fields of chemistry, biology, and medicine [11–15]. The investigation of the synthesis of compounds incorporating both Schiff base and sulfonamide fragments has been sparsely documented in the scientific literature [12]. A considerable quantity of Schiff bases, which have been derived from sulfa drugs, have been synthesized and employed as ligands for the preparation of highly effective metal complexes [13–15]. The coordination chemistry of metal complexes derived from Schiff bases, which are formed by combining sulfa drugs, has garnered significant attention because of their notable biological activity [15]. Antioxidants play a crucial role as inhibitors of oxidative damage. Antioxidant supplements are employed to assist the human organism in mitigating oxidative harm caused by free radicals and active oxygen species [15–16].
This article describes the condensation reaction between sulphapyridine and 9-anthracene carboxaldehyde, which is the first step in the production of a novel Schiff base ligand as (E)-4-((anthracen-9-ylmethylene) amino)-N-(pyridin-2-yl) benzenesulfonamide. The ligand, hereafter SPA, is utilized in the synthesis of Schiff base metal complexes involving Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) ions. Following a sequential progression, the metal complexes currently under scrutiny undergo a meticulous examination employing an extensive array of spectroscopic and analytical methodologies. In addition, we hereby provide a comprehensive report on the individual biological functions exhibited by each entity.
2.1. Materials
All chemicals and solvents used in the current study were of analytical grade. The compound known as sulpha pyridine was procured from the supplier High media. The compound 9-Anthracene carboxaldehyde was procured from Sigma Aldrich. The metal nitrates and solvent were procured from Merck, a reputable supplier.
2.2. Synthesis
The SPA ligand was synthesized by combining 9-Anthracene carboxaldehyde and sulphapyridine with ethanol in equal molar ratios. This mixture is then subjected to reaction conditions at a temperature of 60°C for a period of 2 h, during which a condensation process occurs, leading to the formation of the Schiff base. During the reaction, the acid catalyst employed was a 1M hydrochloric acid solution. Subsequently, the reaction mixture underwent a cooling process until it reached ambient temperature, at which point it was carefully transferred into a container filled with distilled water that had been chilled to the temperature of ice. The Schiff base SPA ligands undergo precipitation, resulting in the formation of solid materials with a distinct yellow coloration [17]. The desired product undergoes filtration and is subsequently rinsed with water and dried in the presence of air, as depicted in Fig. 1.
2.3 Synthesis of the Schiff base metal complexes
The synthesis of SPA ligand–metal complexes involved the addition of an aqueous solution containing transition metal (II) nitrate salts, which are soluble in ethanol. Subsequently, two equivalent SPA ligands were added to this solution in ethanol. The resulting mixture underwent thermal treatment at a temperature range of 60°C to 70°C for 12 h. Subsequently, the observed change in the color of the solution was attributed to the presence of specific metals [18]. The formed metal complexes were precipitated and subsequently settled within the RB flask. The solid materials were obtained via filtration, subsequently subjected to washing with ethanol and hot water, and ultimately subjected to a drying process at 90°C (as indicated in Fig. 2).
2.4. Characterization methods
The ligand and metal complexes underwent elemental analysis using the Elemental model VarIII. The acquisition of the IR spectra was performed by employing KBr pellets within the wavelength range of 4000 − 400 cm− 1, utilising the JASCO FTIR 4100 instrument. The UV–visible spectrum of the complexes was recorded in the wavelength range of 200–1100 nm using a Thermoelectron Nicolet evolution 300 UV–visible spectrophotometer. The complexes were subjected to thermogravimetric (TG), differential thermal analysis (DTA), and differential thermogravimetric (DTG) analyzes under a controlled nitrogen atmosphere. This analysis was conducted using a Perkin Elmer Pyres Diamond TG/DTA Analyzerat a heating rate of 100°C /min. The acquisition of 1H nuclear magnetic resonance (NMR) spectra was performed in a solution of deuterated chloroform (CDCl3) using a Bruker AVAVCE III 400 MHz NMR spectrometer. Trimethylsilane (TMS) was utilized as the internal standard for reference.
2.5. Biological studies
2.5.1 In vitro antibacterial study
The synthesized Schiff base ligand and its corresponding metal complexes were subjected to a screening process to evaluate their antibacterial activity against Gram-positive bacteria, specifically Bacillus subtilis and Staphylococcus aureus, as well as Gram-negative bacteria, including Pseudomonas aeruginosa, Enterobacter aerogenes, and Escherichia coli. This evaluation was conducted using the disk diffusion method [19]. A stock solution of the test chemical, measuring 100 µL, was prepared using a DMSO solvent. The initial concentration of the stock solution was subjected to further dilution using sterilised distilled water, creating multiple dilutions. Aseptic, unmarked antibacterial susceptibility discs were exposed to the introduction of test chemicals at different concentrations. The bacterial specimens underwent sub-culturing in a medium comprising Muller–Hinton agar, with a volume of 20 mL. Following the aforementioned procedure, the discs were carefully positioned on the agar medium. The Petri dishes were incubated at a temperature of 37°C for a period of 24 h. The antibacterial agent gentamycin, commonly used in conventional medical procedures, underwent screening protocols resembling those used for experimental compounds to enable comparative analysis. Quantification of growth inhibition zones observed in the vicinity of the discs enabled the determination of activity. Growth inhibitory effects were evaluated in relation to the standard pharmaceutical agent. To elucidate the influence of the solvent dimethyl sulfoxide (DMSO) on biological activity, a discrete collection of discs was exclusively subjected to treatment with DMSO, thereby serving as the control group. Significantly, the observed control group displayed no detectable activity against the bacterial strains investigated.
2.5.2 in vitro Antifungal Study
The Schiff base ligands that were synthesized, along with their respective metal complexes, were subjected to a screening process to evaluate their in vitro antifungal activity. This evaluation was performed using the disc diffusion method. The experiment was performed to assess the effects on the fungal species Penicillium notatum, Aspergillus niger, and Rhizopus. The stock solution (100 µL) of the test chemical was prepared using a DMSO solution. The stock solution was subjected to further dilution using sterilized distilled water to obtain various dilutions expressed in micrograms per milliliter (µg/mL). Aseptic, devoid of microorganisms, antimicrobial susceptibility discs were exposed to the introduction of test compounds at different concentrations. The fungal specimens were sub-culturing on a medium known as potato dextrose agar (PDA). The resulting mycelial discs were then preserved in the same medium. The Petri dishes were subjected to a 48-h incubation period at a temperature of 28°C. Nystatin, a frequently employed antifungal agent, was exposed to identical experimental conditions for comparative analysis. The data that were recorded encompassed the quantification of growth inhibition zones that surrounded the disks. To elucidate the effects of the solvent dimethyl sulfoxide (DMSO) on the evaluation of antifungal properties, isolated discs were exclusively supplemented with DMSO and used as a control. Notably, no detectable activity against the fungal strains was observed.
2.5.3 In vitro analysis of larvicidal activity
The synthesized Schiff base ligands and their respective metal complexes underwent in vitro analysis of larvicidal activity, following the methodology outlined in reference [20]. The mosquito larvae were obtained from aquatic habitats situated in Nagercoil, Kanyakumari District, using a receptacle with a wide aperture. The mosquito samples were transferred to the laboratory and underwent morphological identification using well-established manual techniques. The aforementioned samples were subsequently employed for conducting activity studies. To establish a regulated environment, we chose to employ aseptic beakers and subject them to a thorough cleansing process. In these glass containers, a collective sum of 20 first-stage larvae belonging to the Culex species were introduced, accompanied by 100 mL of tap water. A quantity of 100 ppm of synthesised complexes was introduced into the system. A cohort comprising 20 larvae was exposed to an aqueous solution derived from tap water, which was intentionally devoid of any copper complex, with the aim of establishing a control group. The beakers underwent different durations of 24, 48, 72, and 96 h to evaluate the mortality rate of Culex quinquefasciatus mosquito larvae.
3.1 Structural analysis
3.1.1 Infrared spectral
Table 1 presents the most pertinent IR spectral bands, accompanied by their provisional assignments. The spectral data are depicted in Figures S1–S6. The FT-IR spectrum of the ligand is juxtaposed with that of the complexes to determine the alterations that occur during complex formation. Upon complexation, the -C = N bands located at 1616 cm− 1 of the Schiff base exhibit a shift toward lower frequencies in the spectra of all complexes. This shift strongly suggests the coordination of the azomethine nitrogen atom [21]. The Schiff base ligand (SPA) coordinates via the azomethine nitrogen atom, functioning as a monobasic monodentate ligand. The emergence of novel bands within the spectra of all complexes depicted in Figs. 8.2 to 8.6, specifically within the frequency range of 1481 to 1473 cm− 1 and 590 to 561 cm− 1, has been designated as vibrations associated with the M – NO3 bond and the M–N bond, respectively. This observation provides supplementary support for the notion that coordination occurs through the N-atom and NO3− ion. The observed spectral bands located at wavenumbers 1136 − 1130 cm− 1 and 3367 − 3348 cm− 1 are attributed to the vibrational modes of S = O and N–H, respectively, for the ligand (SPA) and its corresponding metal complexes. This observation confirms that the sulphonamide group does not participate in complexation.
| Ligands / complexes | νC=N | νC=C | νS=0 | νN−H | νC−H Aromatics | νNO3 | νM−N |
|---|---|---|---|---|---|---|---|
| SPA | 1616 | 1519 | 1130 | 3348 | 3012 | - | - |
| Mn(SPA)2(NO3)2 | 1591 | 1516 | 1134 | 3354 | 3120 | 1481 | 563 |
| Co(SPA)2(NO3)2 | 1591 | 1516 | 1136 | 3356 | 3051 | 1474 | 561 |
| Ni(SPA)2(NO3)2 | 1608 | 1519 | 1136 | 3367 | 3086 | 1480 | 584 |
| Cu(SPA)2(NO3)2 | 1591 | 1517 | 1134 | 3356 | 3116 | 1480 | 590 |
| Zn(SPA)2(NO3)2 | 1591 | 1521 | 1132 | 3350 | 3012 | 1473 | 586 |
3.1.2 1H NMR spectra
The proton nuclear magnetic resonance (1H NMR) spectra of the Schiff base ligand and one of its metal complexes were obtained in CDCl3 and exhibited subsequent signals. As shown in Figures S7 and S8, the azomethine protons, which are part of the Schiff base ligand (SPA), exhibit a chemical shift at 8.924 ppm. The presence of multiple signals within the chemical shift range of 6.7–7.9 ppm can be attributed to aromatic protons originating from the Schiff base ligand (SPA). The observed peak at 10.577 ppm can be attributed to the N– H proton of the amide tautomer. The spectroscopic detection of the compound (SO2NH) exhibited a resonance signal at a chemical shift of 2.41 ppm, corresponding to the presence of sulfur (S) and two hydrogen atoms. The nuclear magnetic resonance (NMR) spectrum of the [Zn(SPA)2(NO3)2] complex was compared with that of the ligand (SPA). It was observed that the signal of the azomethine proton in the complexes experienced a downfield shift, specifically at 7.950 ppm. This shift indicates that the -C = N group has undergone deshielding because of coordination with the metal ion. Signals originating from the SO2NH, and aromatic hydrogen groups in the ligand were observed in the metal complex without any significant alterations. Based on the preceding discourse, it has been determined that the functional groups -SO2 and -NH do not participate in coordination processes [22]. On the basis of the aforementioned investigations, the proposed configuration of the recently formed coordination complex derived from the ligand (SPA) is visually depicted in Fig. 3.
3.1.3 Elemental analysis
The observed complexes exhibit a remarkable degree of stability in the presence of atmospheric conditions and lack hygroscopic properties. The compounds exhibit solubility in commonly employed solvents such as ethanol, methanol, N,N-dimethylformamide (DMF), and dimethyl sulfoxide (DMSO). The empirical evidence presented in Table 2 demonstrates a high level of concurrence between the observed and calculated percentages of elements. The formation of metal (II) complexes occurs through the binding of one metal ion to two ligands, resulting in a metal-to-ligand ratio of 1:2.
| Ligands / Complexes | Molecular formula | Molecular weight | Elemental Analysis Calculated (Experimental) in % | ||||
|---|---|---|---|---|---|---|---|
| C | H | N | S | M | |||
| SPA | C26H19N3O2S | 437.34 | 71.4 (71.86) | 4.34 (4.02) | 9.61 (9.89) | 7.33 (7.75) | - |
| Mn(SPA)2(NO3)2 | C52H38Mn N8O10S2 | 1053.63 | 59.06 (58.89) | 3.61 (3.38) | 10.64 (10.95) | 6.09 (5.52) | 5.21 (5.96) |
| Co(SPA)2(NO3)2 | C52H38Co N8O10S2 | 1057.62 | 59.05 (58.79) | 3.59 (3.80) | 10.59 (10.01) | 6.06 (5.86) | 5.57 (5.69) |
| Ni(SPA)2(NO3)2 | C52H38Ni N8O10S2 | 1057.38 | 59.06 (59.51) | 3.59 (3.16) | 10.60 (10.30) | 6.06 (6.36) | 5.55 (5.13) |
| Cu(SPA)2(NO3)2 | C52H38Cu N8O10S2 | 1062.24 | 58.79 (59.01) | 3.58 (3.13) | 10.55 (10.85) | 6.04 (5.86) | 5.98 (5.48) |
| Zn(SPA)2(NO3)2 | C52H38Zn N8O10S2 | 1064.07 | 58.70 (58.21) | 3.57 (3.94) | 10.53 (10.12) | 6.03 (6.48) | 6.14 (5.86) |
3.1.4 XRD analysis
The powder XRD patterns for the ligand (SPA) and its metal complex Zn(SPA)2(NO3)2 were obtained, and the XRD data are listed in Tables 3 and 4. The diffractograms for the ligand and metal complexes are shown in Figs. S9–S10. The large feeble peaks in the ligand (SPA) indicate their microcrystalline nature. The strong broad peak in [Zn(SPA)2(NO3)2] confirms complex formation. The grain sizes of the ligand and complex were calculated using Scherer’s formula.
From the observed XRD pattern, the average crystallite sizes of the ligand (SPA) and [Zn(SPA)2(NO3)2] complexes were found to be 7.05 and 4.1804 nm,, respectively. This suggested that the ligand (SPA) and Zn(SPA)2(NO3)2 complex are microcrystalline [23].
| Pos. [°2Th.] | Height [cm] | FWHM [°2Th.] | d-spacing [Å] | Rel. Int. [%] |
|---|---|---|---|---|
| 30.102 | 900.51 | 0.296 | 2.965 | 12.2 |
| 24.993 | 1650.05 | 0.290 | 3.559 | 56.8 |
| 19.941 | 2450.23 | 0.278 | 4.447 | 100 |
| 19.266 | 1000.94 | 0.301 | 4.606 | 17.6 |
| 9.926 | 1150.87 | 0.294 | 8.901 | 30 |
| 4.946 | 1750.43 | 0.356 | 17.847 | 62.2 |
| Pos. [°2Th.] | Height [cm] | FWHM [°2Th.] | d-spacing [Å] | Rel. Int. [%] |
|---|---|---|---|---|
| 30.1681 | 309.76 | 0.1171 | 2.9625 | 26.26 |
| 25.0861 | 1063.96 | 0.1338 | 3.7395 | 90.20 |
| 23.7943 | 5.77.05 | 0.1338 | 3.7396 | 48.92 |
| 20.0636 | 1179.54 | 0.2342 | 4.4257 | 100.00 |
| 19.3736 | 919.33 | 0.1338 | 4.5818 | 77.94 |
| 15.6363 | 338.13 | 0.2007 | 5.6674 | 19.17 |
3.2. Molar conductance
The molar conductance values for the synthesized metal SPA ligand– metal complexes
are depicted in Table 5. It falls within the range of 9.21–18.48 ohm− 1 cm2 mol− 1 showing their non-electrolytic nature. This is useful to confirm that the nitrate ions are coordinated with the metal ions and are present inside the coordination sphere in all complexes [24]. The observed trend in conductance across the Cu, Co, and Mn complexes indicates that the conductance increases as we move from Cu to Co to Mn. Specifically, Cu exhibits the lowest conductance, whereas Co displays the highest conductance within this series of complexes. This observation implies that the complexes exhibit an enhanced electrical conductivity gradient when traversing from the leftmost to the rightmost position within the aforementioned list. The observed trend suggests a positive correlation between the conductance and the atomic number of the metals. The observed pattern becomes increasingly evident as we traverse horizontally across the periodic table. Mn possesses a greater atomic number than Co, which, in turn, exhibits a higher atomic number than Cu (Cu). The conductance of a system can be modulated by the characteristics of the ligands and counter ions present. The conductance of these complexes can also be influenced by ligands (SPA) and counter ions (NO3). The solvation and dissociation of ions in solution can be influenced by various ligands and counter ions, thereby potentially affecting conductance. The observed phenomenon of the Cu complex exhibiting the lowest conductance can be attributed to the inherent characteristics of the ligands and counter ions present within the Cu complex, as well as the tendency of copper ions to possess a comparatively lower charge when compared to other metallic elements such as cobalt or manganese. In essence, the data elucidate pertinent details regarding the comparative conductance exhibited by these metal complexes when dissolved in solution. The conductance values may be subject to influence from several factors, including the inherent characteristics of the metal, the ligands involved, and the counter ions that coexist within the complex.
| S. No. | Complexes | Conductance ohm− 1cm2mol− 1 |
|---|---|---|
| 1 | Mn(SPA)2(NO3)2 | 16.21 |
| 2 | Co(SPA)2(NO3)2 | 18.48 |
| 3 | Ni(SPA)2(NO3)2 | 11.73 |
| 4 | Cu(SPA)2(NO3)2 | 9.21 |
| 5 | Zn(SPA)2(NO3)2 | 13.11 |
3.3. Optical characteristics
The absorption bands and the assignments of the ligand and metal complexes are given in Table 6. The electronic absorption spectra of the Schiff base ligand have bands at 238and327 nm. These are assigned to π-π* and n-π* transitions, respectively. These bands were hypsochromically shifted in the spectra of the ligand to the metal complexes. The metal complexes also display some d–d transitions along with electronic transitions. The spectrum of [Mn(SPA)2(NO3)2] gave a single d–d transition band at 458 nm assignable to forbidden 6A1→4A1 transition and two charge transfer bands at 342 and 383nm, which are typical of tetrahedral manganese(II) complexes [25]. The spectra of [Co(SPA)2(NO3)2] complex showed absorption bands at 563 nm and 632nm, which could be attributed to the 4A2(F) →4T1(P) and 4A2→4T1(F) d– d transitions, respectively, corresponding to the tetrahedral geometry [10]. The [Ni(SPA)2(NO3)2] complex exhibits an intense band at 623 nm assignable to 3T1(F) →3T1(P) transition, indicating tetrahedral geometry. The spectra of [Cu(SPA)2(NO3)2] complex showed an intense band at 659 nm assignable to the 2B1g →2A1g transition, indicating square planar geometry. In the [Zn(SPA)2(NO3)2] complex, a tetrahedral geometry is proposed and the diamagnetic behavior is confirmed.
| S. No. | Ligands / Complexes | λmax (nm) | Electronic Transition | Charge transfer | Geometry |
|---|---|---|---|---|---|
| 1 | SPA | 238, 327 | π-π* n-π* | - | - |
| 2 | Mn(SPA)2(NO3)2 | 247, 339 342, 383, 458 | π-π* π-π* | Charge transfer (CT) Charge transfer (CT) 6A1→4T2 | Tetrahedral |
| 3 | Co(SPA)2(NO3)2 | 245, 337 563,632 | π-π* n-π* | 4T1(P) ←4A2(F) 4A2→4T1(F) | Tetrahedral |
| 4 | Ni(SPA)2(NO3)2 | 249, 336 623 | π-π* n-π* | 3T1(F) →3T1(P) | Tetrahedral |
| 5 | Cu(SPA)2(NO3)2 | 243, 335 659 | π-π* n-π* | 2B1g→2A1g | Square planar |
| 6 | Zn(SPA)2(NO3)2 | 251, 342 441 | π-π* n-π* | L → M (CT) | Tetrahedral |
3.4 Magnetic susceptibility measurements
The calculated and observed magnetic moment values of the complexes are shown in Table 7. The µeff value of the Mn(SPA)2(NO3)2 complex was found to be 6.20 BM, as expected for a high-spin d5 tetrahedral system. The Co(SPA)2(NO3)2 complex exhibited a magnetic moment value of 4.59 BM. This value is within the expected range for tetrahedral Co(II) complexes. The Ni(SPA)2(NO3)2 which in the normal range observed for tetrahedral Ni(II) complexes [26]. The magnetic moment of the Cu(SPA)2(NO3)2 complex is 1.91 BM, which suggests a square planar geometry for this complex [27]. The Zn(SPA)2(NO3)2 complex shows zero magnetic moment, which indicates that this complex is diamagnetic in nature with d10 system of electronic configuration. The magnetic moment values are in good agreement with the theoretical values. This confirmed that the [Mn(SPA)2(NO3)2], [Co(SPA)2(NO3)2], Ni(SPA)2(NO3)2], and [Zn(SPA)2(NO3)2] complexes are in tetrahedral geometry and that the [Cu(SPA)2(NO3)2] complex has a square planar geometry around transition metal(II) ions. The effective magnetic moment serves as a quantitative indicator of the magnetic characteristics of a compound, thereby offering valuable insights into the intricate interplay between its electronic structure and magnetic properties. In brief, empirical evidence indicates that the aforementioned metal complexes exhibit heterogeneous magnetic properties, in which certain complexes demonstrate paramagnetic characteristics (Manganese, Cobalt, and Copper, possessing unpaired electrons), while others exhibit diamagnetic attributes (Zinc, devoid of unpaired electrons). The effective magnetic moments observed in these complexes align with the anticipated behaviours derived from the electronic configurations of the metal ions. The magnetic properties exhibited by these metal complexes hold significant value in elucidating the intricate electronic structure and reactivity of these complexes within diverse chemical and biological frameworks.
| S. No | Ligands / Complexes | µeff (BM) calculated | µeff (BM) observed |
|---|---|---|---|
| 1 | Mn(SPA)2(NO3)2 | 5.91 | 6.20 |
| 2 | Co(SPA)2(NO3)2 | 4.2–4.88 | 4.59 |
| 3 | Ni(SPA)2(NO3)2 | 3.2–4.1 | 3.43 |
| 4 | Cu(SPA)2(NO3)2 | 1.73 | 1.91 |
| 5 | Zn(SPA)2(NO3)2 | Diamagnetic | Diamagnetic |
3.5 Thermal studies
Thermogravimetric and differential thermogravimetric analyzes were performed on one of the newly synthesized metal(II) complexes. The thermogravimetric curves of [Zn(SPA)2(NO3)2] complex were recorded at a heating rate of 10 °C/min under nitrogen atmosphere in the temperature range from room temperature to 800 °C. The complex is stable up to 320 °C as shown in Fig. S11. From the literature, the TG curves indicate that in the temperature range 230–400 °C the compounds start to lose nitrate ions. In the temperature range
400–800 °C the schiff base molecule is lost. In all cases, the final product is metal oxides. The [Zn(SPA)2(NO3)2] complex started to decompose at 320 °C with a loss of mass 21%. This indicates that the nitrate ion is coordinated with the metal ion in the Zn(II) complex. Decomposition at 668 °C with a loss of mass 6.6% confirms the formation of Schiff base molecules. The results are in good agreement with the composition of the coordination compound.
The stages of thermal decomposition of the [Zn(SPA)2(NO3)2] complex are described below [28].
3.6. SEM Analysis
The examination of the complexes’ surface morphology was conducted using a scanning electron microscope, and the corresponding images are presented in Fig. 4a and b. Scanning electron microscopy (SEM) images reveal that the ligand (SPA) and metal complex [Zn(SPA)2(NO3)2] exhibit microcrystalline characteristics. Specifically, the ligand displays a structure resembling gravel, whereas the metal complex exhibits a structure resembling ice cubes [29]. Both molecules demonstrate a crystalline nature and possess porous surfaces. This characteristic can augment the efficacy of biological activities by promoting the binding of microorganisms and drugs within a host– guest framework.
3.7 Biological screening
3.7.1 Antibacterial activity
The in vitro antibacterial activity of the Schiff base ligand (SPA) and its metal complexes was assessed against various Gram-positive and Gram- negative bacteria. The results of this screening are presented in Table 8 and subsequently analysed and visualised in Fig. 5. The data are compared with the standard antibiotic gentamycin as the reference. The observed phenomenon demonstrates varying levels of antimicrobial effectiveness when tested against a wide array of bacterial strains. The empirical findings suggest that the substance demonstrates a moderate inhibitory impact on Bacillus subtiles, Pseudomonas aeruginosa, and Escherichia coli, as evidenced by the measured inhibition zones of 10 9 and 14 mm, respectively. Mn(SPA)2(NO3)2 exhibits notable antimicrobial potency against a diverse array of bacterial strains that were subjected to rigorous experimentation. The zones of inhibition exhibited the highest degree of prominence when subjected to experimentation against Pseudomonas aeruginosa, displaying a diameter of 20 mm, and Escherichia coli, exhibiting a diameter of 23 mm. The inhibitory effects demonstrated efficacy against Bacillus subtiles, exhibiting a diameter of 17 mm, as well as Enterobacter aerogenes, with a diameter of 18 mm. Cu(SPA)2(NO3)2 demonstrates remarkable antimicrobial efficacy against all bacterial strains investigated, encompassing the entire spectrum. The experimental findings indicate the existence of significant zones of inhibition against Staphylococcus aureus (24 mm), Bacillus subtilis (26 mm), and Escherichia coli (24 mm). The inhibitory effects observed were determined to be statistically significant when tested against Pseudomonas aeruginosa, yielding a mean diameter of 12 mm, and Enterobacter aerogenes, demonstrating a mean diameter of 21 mm. The compound (Zn(SPA)2(NO3)2), exhibits a degree of antimicrobial efficacy that can be categorized as moderate. The inhibitory effects observed in this study were determined to be statistically significant when tested against Bacillus subtitles (14 mm), Pseudomonas aeruginosa (15 mm), Escherichia coli (24 mm), and Enterobacter aerogenes (20 mm). The observed in vitro antibacterial activity indicates that the complexes exhibit superior antibacterial properties compared with the ligand. This observed phenomenon may explain the tendency of chelation to enhance the ligand’s efficacy as an antibacterial agent, rendering it more potent and effective. Tweedy’s theory posits that chelation decreases the polarity of the metal atom. This occurs because of the partial sharing of the metal atom’s positive charge with a donor group. Consequently, the chelate ring allows for the potential delocalization of π-electrons throughout its entirety [30]. This can enhance the lipophilicity of the central metal atom, thereby promoting its ability to permeate lipid layers and increase the likelihood of obstructing the metal binding site in the enzyme of a microorganism [31]. Other factors, such as solubility, conductivity, and band length, contribute to the enhancement of metal and ligand activity. The experimental findings also suggest that the complexes [Co(SPA)2(NO3)2], [Ni(SPA)2(NO3)2, [Cu(SPA)2(NO3)2] exhibit the most pronounced inhibitory effects on the growth of the tested bacteria. The complexes [Mn(SPA)2(NO3)2] and [Zn(SPA)2(NO3)2] exhibit moderate activity, whereas all the metal complexes demonstrate noteworthy antibacterial activity against Escherichia coli and limited activity against Staphylococcus aureus. The findings of this study indicate that these complexes exhibit enhanced biological activity, thereby suggesting their potential utility as novel pharmaceutical agents. Furthermore, it is crucial to elucidate the chemical geometry of these compounds to understand the underlying mechanisms responsible for their biological activity.
| Ligand/complex | Zone of inhibition (mm) | ||||
|---|---|---|---|---|---|
| Bacillus subtitles | Staphylococcus aureus | Pseudomonas aeruginosa | Enterobacteraerogenes | Escherichia coli | |
| SPA | 10 | - | 9 | - | 14 |
| Mn(SPA)2(NO3)2 | 17 | - | 20 | 18 | 23 |
| Co(SPA)2(NO3)2 | 25 | 24 | 26 | 20 | 29 |
| Ni(SPA)2(NO3)2 | 22 | 18 | - | 25 | 26 |
| Cu(SPA)2(NO3)2 | 26 | 17 | 12 | 21 | 24 |
| Zn(SPA)2(NO3)2 | 14 | - | 15 | 20 | 24 |
| Gentamycin | 27 | 28 | 27 | 26 | 31 |
3.7.2. Antifungal studies
The recently produced Schiff base ligand (SPA) and its corresponding metal complexes were subjected to screening for their antifungal activity against specific fungal cultures using the disc diffusion method in vitro. The standard drug employed in this study was nystatin. The experimental findings are documented in Table 9 and subsequently analyzed and presented in a graphical format in Fig. 6. This study evaluated the fungicidal characteristics of a newly synthesised Schiff base ligand (SPA) and its associated metal complexes against targeted fungal strainsusing the disc diffusion methodology. The drug used in this study was nystatin, which adhered to the established standard. The results revealed a restricted or non-existent capacity to inhibit the growth of fungi in the examined strains (Pencillium Notatum and Aspergillus niger), exhibiting a comparatively feeble influence on Rhizopus (7 mm) in comparison with alternative substances. The compound Mn(SPA)2(NO3)2 demonstrated a moderate level of antifungal effectiveness against Pencillium Notatum (10 mm) and Rhizopus (11 mm). Nevertheless, no discernible antifungal efficacy was detected within the framework of Aspergillus niger. The compound Co(SPA)2(NO3)2, demonstrated significant antifungal efficacy against multiple fungal strains. Particularly noteworthy were the observed inhibitory zones of 17 and 15 mm against Rhizopus and Aspergillus niger, respectively. The compound Ni(SPA)2(NO3)2, demonstrated discernible antifungal efficacy against all the fungal strains subjected to experimentation. Quantification of inhibitory effects was conducted by measuring the diameter of the zones of inhibition. The obtained results indicate that the inhibition zones for Pencillium Notatum, Aspergillus niger, and Rhizopus were 12 mm, 13 mm, and 15 mm, respectively. The compound Cu(SPA)2(NO3)2 demonstrated a notable spectrum of antifungal characteristics, manifesting substantial inhibitory effects targeted specifically toward Rhizopus and Aspergillus niger. In brief, this investigation has produced noteworthy findings concerning the antifungal effectiveness of SPA and its metal complexes against diverse fungal strains. In summary, metal complexes composed of cobalt (Co), nickel (Ni), and copper (Cu) typically exhibit a diverse spectrum of antifungal properties against the fungal strains being studied, displaying varying levels of effectiveness against different species. The intrinsic antifungal activity of the ligand SPA is limited although it does demonstrate noticeable effectiveness against Rhizopus. Based on empirical evidence, it can be observed that these chemical compounds demonstrate noteworthy characteristics as antifungal agents, particularly when coordinated with specific metal ions. The effectiveness of these compounds depends on the specific metal ion and fungal strain being examined. Nystatin standard is a potent antifungal agent with high efficacy. It is commonly used as a positive control in experiments to facilitate comparison. The experimental findings indicate that cobalt chelates exhibit a higher level of toxicity than other metal chelates when tested against various microorganisms, all of which were subjected to identical conditions. Metal chelates exhibit superior antifungal efficacy compared with unbound ligands. The observed increase in the activity of metal chelates could be attributed to the influence exerted by the metal ion on regular cellular processes. The elucidation of this phenomenon can be facilitated through the use of Tweedy’s chelation theory [32]. All metal chelates demonstrated significant efficacy against Rhizopus. The effectiveness of the [Co(SPA)2(NO3)2] complex in combating Rhizopus is comparable to that of conventional fungicides.
| Ligand/metal complexes | Zone of inhibition (mm) | ||
|---|---|---|---|
| PencilliumNotatum | Aspergillusniger | Rhizopus | |
| SPA | - | - | 7 |
| Mn(SPA)2(NO3)2 | 10 | - | 11 |
| Co(SPA)2(NO3)2 | 14 | 15 | 17 |
| Ni(SPA)2(NO3)2 | 12 | 13 | 15 |
| Cu(SPA)2(NO3)2 | 13 | 14 | 12 |
| Zn(SPA)2(NO3)2 | - | 12 | 14 |
| Standard/Nystatin | 15 | 16 | 19 |
3.7.3 Larvicidal Activity
The larvicidal activity of the recently synthesized ligand SPA and its corresponding metal complexes were investigated in relation to their effects on culex quinquefasciatus. The resulting data have been organized and presented in Table 10, and a graphical representation and analysis of the findings can be found in Fig. 7. The SPA ligand demonstrates minimal larvicidal activity at time intervals of 24 and 48 h. However, its effectiveness undergoes a significant increase at a time interval of 96 h. The compound Mn(SPA)2(NO3)2 exhibited no discernible larvicidal activity during the initial 24 h period. Nevertheless, following a time span of 48 h, it manifests larvicidal properties, thereby inducing a mortality rate of 40%. Significantly, the observed larvicidal activity exhibited a notable augmentation over time. The compound Co(SPA)2(NO3)2 does not exhibit any discernible larvicidal activity within a 24-h period. Nevertheless, over time, it progressively manifests larvicidal properties, leading to a mortality rate of 29% after duration of 96 h. The observed mortality rate exhibited a progressive escalation, ascending to 59% and ultimately attaining a value of 81% after the identical 96-h duration. The compound Ni(SPA)2(NO3)2 displays minimal larvicidal activity within a 24-h timeframe. However, it exhibits a progressive enhancement in effectiveness, achieving larvicidal activities of 38%, 65%, and 90% after duration of 96 h. The compound Cu(SPA)2(NO3)2 exhibited no discernible larvicidal activity during the initial 24-h period. Subsequently, the observed phenomenon began to exhibit larvicidal properties, thereby leading to a mortality rate of 27%. The observed phenomenon exhibits a progressive escalation, culminating in mortality rates of 63% and 84%, respectively, at the conclusion of a 96 h period. The compound Zn(SPA)2(NO3)2 exhibited no discernible larvicidal activity during the initial 24 h period. Nevertheless, over time, it progressively demonstrated larvicidal efficacy, leading to a mortality rate of 35% following duration of 96 h. The observed mortality rate exhibits a progressive escalation, rising to 83% initially and subsequently attaining a final value of 97% over the same period. Metal complexes frequently exhibit larvicidal activity against mosquito larvae and exhibit diverse levels of efficacy. The observed larvicidal activity of the ligand SPA is evident, albeit at a diminished magnitude. The observed larvicidal activity demonstrates a positive correlation with longer periods of exposure, suggesting potential as a larvicidal agent, particularly when combined synergistically with specific metal ions.
| Ligands / Complexes | Larvicidial activity (%) | |||
|---|---|---|---|---|
| 24 h | 48 h | 72 h | 96 h | |
| SPA | 0 | 0 | 20 | 43 |
| Mn(SPA)2(NO3)2 | 0 | 40 | 79 | 95 |
| Co(SPA)2(NO3)2 | 0 | 29 | 59 | 81 |
| Ni(SPA)2(NO3)2 | 0 | 38 | 65 | 90 |
| Cu(SPA)2(NO3)2 | 0 | 27 | 63 | 84 |
| Zn(SPA)2(NO3)2 | 0 | 35 | 83 | 97 |
3.7.4 Antioxidant study
An antioxidant can be defined as a substance that, when present in relatively lower concentrations compared with the oxidizable substrate, exhibits the remarkable ability to significantly impede or decelerate the process of oxidation of said substrate. In vitro antioxidant screening was conducted for recently synthesized compounds using the DPPH assay method. The outcomes of this screening are presented in Table 11 and further elucidated in Fig. 8. The focus of this investigation pertains to the analysis of the scavenging effectiveness of metal complexes, particularly those comprising manganese (Mn), cobalt (Co), nickel (Ni), and copper (Cu), along with their potential application as agents possessing antioxidant properties. The ligand SPA exhibits scavenging activity, which is positively correlated with increasing concentrations. At the highest concentration, SPA demonstrates a scavenging activity of 16%, a value that is relatively modest compared with the metal complexes and ascorbic acid. Manganese bis(salicylaldoximato) nitrate and cobalt bis(salicylaldoximato) nitrate demonstrate significant scavenging properties comparable to those observed in ascorbic acid. Both Ni(SPA)2(NO3)2 and Cu(SPA)2(NO3)2 exhibit significant scavenging activity. The compound Zn(SPA)2(NO3)2 demonstrates scavenging activity, albeit with a diminished magnitude compared with the alternative complexes. Ascorbic acid, a widely recognised antioxidant, demonstrates significant scavenging abilities throughout various concentrations, with a maximum efficacy of 94% observed at a volume of 200 µL. The empirical observation of the scavenging behaviour exhibited by metal complexes indicates a highly favorable prospect for their use as agents with antioxidant properties. The isolated ligand SPA demonstrates a reduced level of scavenging activity compared with both the metal complexes and ascorbic acid. In contrast, the compound Zn(SPA)2(NO3)2 exhibits a moderately significant degree of scavenging activity. As the concentration of the DPPH solution increases, a corresponding increase in the percentage of scavenging free radicals is observed. The complex [Mn(SPA)2(NO3)2] exhibits the most significant level of free radical scavenging activity compared with other metal chelates, with a percentage of approximately 76%. The Schiff base ligand exhibits a significantly lower proportion of free radical scavenging activity than metal chelates, approximately 16%. In contrast to standard ascorbic acid, these metal chelates exhibit a moderate level of free radical scavenging activity. Consequently, these chelates can serve as antioxidant drugs, but further investigation into their in vivo antioxidant activity. Functional groups play a crucial role in augmenting antioxidant activity. The presence of a sulphonomide group in the metal complexes elevates the percentage of activity associated with scavenging free radicals. Therefore, the compounds [Mn(SPA)2(NO3)2] and [Ni(SPA)2(NO3)2] display notable antioxidant properties, as reported in reference [22]. Based on the observations made, it can be inferred that these compounds display promising antioxidant properties, which necessitate additional exploration for various potential applications.
| S. No. | Ligands / Complexes | Scavenging Activity (%) | |||
|---|---|---|---|---|---|
| Concentrations(µL) | |||||
| 25 | 50 | 100 | 200 | ||
| 1 | SPA | 5.32 | 9.48 | 11.24 | 16.79 |
| 2 | Mn(SPA)2(NO3)2 | 27.49 | 50.48 | 63.86 | 76.13 |
| 3 | Co(SPA)2(NO3)2 | 20.28 | 43.14 | 54.86 | 76.13 |
| 4 | Ni(SPA)2(NO3)2 | 24.86 | 50.48 | 61.86 | 70.25 |
| 5 | Cu(SPA)2(NO3)2 | 23.86 | 45.77 | 54.86 | 64.32 |
| 6 | Zn(SPA)2(NO3)2 | 10.86 | 25.49 | 44.83 | 48.48 |
| 7 | Ascorbic Acid | 51.86 | 62.14 | 78.49 | 94.82 |
3.7.4 Anti-inflammatory activity
The recently synthesized ligand (SPA) and its corresponding metal complexes were subjected to in vitro screening for their anti-inflammatory activity using a 3% solution of serum albumin. The experimental data are organized and presented in Table 12, while the corresponding analysis and interpretation are visually depicted in Fig. 9. The experimental findings illustrate that the SPAC ligand exhibits a discernible level of inhibition against protein denaturation at various concentrations, with a corresponding augmentation in inhibition observed as the concentration escalates. At a maximum concentration of 200 µL, the substance demonstrates an inhibitory impact on the process of protein denaturation, leading to an estimated decrease of approximately 20%. The compound Mn(SPAC)2(NO3)2 demonstrates a remarkable ability to hinder the process of protein denaturation, with the level of inhibition increasing in direct proportion to higher concentrations. The observed phenomenon of inhibition in the cobalt complex is noteworthy, as it is observed to start at a concentration of 18.19% when administered at a volume of 25 µL. Furthermore, this inhibition demonstrates a progressive escalation, reaching a substantial level of 89.12% when the volume is increased to 200 µL. The inhibition percentages observed for the nickel complex demonstrated a moderate level of inhibition, with values varying from 19.48% at a volume of 25 µL to 61.84% at a volume of 200 µL. The experimental findings indicate a significant increase in the inhibitory impact of the copper complex. This increase begins at 21.29% when the administration volume is 25 µL and gradually climbs to approximately 72% as the volume is increased to 200 µL. The empirical findings suggest that the zinc complex exhibits the utmost degree of inhibition in protein denaturation. Furthermore, it was observed that with increasing concentrations of the zinc complex, there was a corresponding upward trend in the inhibition percentages. The results obtained exhibit promising potential for advancing our understanding of the therapeutic and biological implications of these complexes on protein stability and functionality. The utilization of metal ions for the coordination of bioactive molecules is a widely employed approach to enhance the therapeutic efficacy and mitigate the potential toxicity of pharmaceutical agents. The metal complexes that arise from this process often exhibit enhanced lipophilicity profiles compared with the unbound ligands, thereby facilitating their transmembrane permeability and enabling them to exert their biological effects more effectively. The user’s text, "[33]," remains unchanged. When bioactive ligands are coordinated with metal ions, they generate metal complexes that exhibit anti-inflammatory and other biological activities. The findings of the current investigation concur with the aforementioned assertions. The anti-inflammatory activity of the metal complexes surpasses that of the ligand. Among the various metal complexes investigated, the cobalt complex exhibited the most significant degree of inhibition in protein denaturation, with a remarkable percentage of approximately 89.12%. Moderate anti-inflammatory activity was exhibited by all metal complexes. In the future, it is plausible that by making slight alterations to the structure of metal complexes, they could serve as pharmaceutical agents for combating inflammation.
| S. No. | Ligands / Complexes | Inhibition of protein denaturation (%) | |||
|---|---|---|---|---|---|
| Concentrations (µL) | |||||
| 25 | 50 | 100 | 200 | ||
| 1 | SPAC | 10.34 | 11.45 | 14.78 | 20.38 |
| 2 | Mn(SPAC)2(NO3)2 | 20.78 | 43.48 | 67.87 | 82.48 |
| 3 | Co(SPAC)2(NO3)2 | 18.19 | 42.89 | 69.84 | 89.12 |
| 4 | Ni(SPAC)2(NO3)2 | 19.48 | 31.29 | 58.49 | 61.84 |
| 5 | Cu(SPAC)2(NO3)2 | 21.29 | 42.89 | 60.82 | 72.89 |
| 6 | Zn(SPAC)2(NO3)2 | 6.83 | 21.48 | 42.47 | 63.87 |
3.7.6 DNA cleavage study
The DNA cleavage activities of the Schiff base ligand (SPA) and its metal complexes were investigated at a concentration of 1 µm. PUC18 DNA (2 µg) was used as the substrate in the presence of H2O2 and buffer solution while being exposed to UV light irradiation. A diagram depicting the gel electrophoresis process is presented in Fig. 10.
The cleavage efficacy of the complexes, in comparison with the control, is attributed to their proficient DNA binding capability. The metal chelates exhibited a high degree of efficacy in inducing the transformation of supercooled DNA into its open circular conformation. The cleavage reaction was restrained by the presence of free radical scavengers containing hydroxyl radicals or peroxy derivatives, thereby enhancing the cleavage process. Based on the data presented in Fig. 20, it can be observed that the DNA gel electrophoresis experiment involving the PUC18 DNA, SPA, and their respective metal complexes, conducted in the presence of H2O2 as an oxidant, did not exhibit significant cleavage. The observation of a smear within the gel diagram is indicative of radical cleavage, as previously reported [34]. This investigation elucidates the inherent ability of plasmid DNA, a vital component of DNA, to undergo cleavage when subjected to various metal complexes, including plasmid DNA. The control lane, which functions as a control, demonstrates the unaltered, immaculate plasmid DNA. The plasmid DNA, upon interaction with different metal complexes (Mn(SPA)2(NO3)2, Co(SPA)2(NO3)2, Ni(SPA)2(NO3)2, Cu(SPA)2(NO3), and Zn(SPA)2(NO3), does not display any observable signs of cleavage. This implies that the metal complexes lack the capability to induce cleavage. Preservation of plasmid DNA integrity was observed consistently across all samples, indicating that the metal complexes not compromise the structural integrity of the DNA. Therefore, these metal complexes maintain their potential for use in various DNA manipulation and research applications. Based on the empirical observations, it can be deduced that none of the metal complexes, including plasmid DNA, demonstrated the capacity to elicit cleavage of the plasmid DNA within the confines of the conducted experiments. The collection of these data is of great importance in understanding the potential consequences of these metal complexes on DNA and their possible applications in DNA manipulation or scientific investigation.
3.7.7 Anticancer activity
The experiment involved conducting an anticancer activity assessment on the [Co(SPA)2(NO3)2] complex, which has demonstrated the highest level of biological activity compared with other metal complexes. Our scientific investigation involved the estimation of the anticancer activity of the [Co(SPA)2(NO3)2] complex against the COLO-205 human colon cancer cell line. Adriamycin was used as the positive control in this experiment. The findings of the anticancer activities have been compiled and presented in a Table 13. Figure 12 illustrates the growth curve of the human colon cancer cell line COLO-2015 when exposed to Co(II) complex and adriamycin. The Co(II) complex of the Schiff base ligand (SPDB) was analyzed at four distinct concentrations, namely 10, 20, 40, and 80 (µg/ml). The growth of the human colon cancer cell line COLO-205 was inhibited by the presence of the metal, as observed in the percentage control growth line. The lowest observed growth rate (93.7) was recorded at a concentration of 80 µg/ml. Adriamycin exhibits a robust inhibitory effect on the growth of the control group, with a maximum observed effect of 29.8% at a concentration of 80 µg/ml. The LC50, TGI, and G150 values for the Co(II) complex were not estimable (NE), not estimable (NE), and greater than 80, respectively. In contrast, for adriamycin, the LC50, TGI, and G150 values were not estimable (NE), not estimable (NE), and less than 10, respectively. The table displays the lethal concentration value (LC, measured in micrograms per millilitre), total growth inhibition (G150) for the tested sample, and the corresponding values for adriamycin [35]. The microscopic examination of the anticancer activity is depicted in Fig. 12.
| Human colon cancer cell line COLO – 205 | ||||
|---|---|---|---|---|
| Drug concentrations (µg/ml) | 10 | 20 | 40 | 80 |
| [Co(SPA)2 (NO3)2] | ||||
| Experiment 1 | 75.6 | 101.0 | 102.3 | 87.0 |
| Experiment 2 | 75.3 | 76.9 | 88.5 | 87.2 |
| Experiment 3 | 70.3 | 89.8 | 83.0 | 106.8 |
| Average values | 73.7 | 89.2 | 91.3 | 93.7 |
| Adriyamyycin (ADR) | ||||
| Experiment 1 | 0.1 | 2.6 | 22.1 | 48.8 |
| Experiment 2 | -9.9 | 28.3 | 16.2 | 30.6 |
| Experiment 3 | 0..1 | 2.7 | 21.7 | 9.9 |
| Average values | -3.2 | 19.0 | 20.0 | 29.8 |
| Drug concentrations (µg/ml) calculated from graph | |||
|---|---|---|---|
| COLO-205 | LC50 | TGI | G150 |
| Co(SPA)2(NO3)2 | NE | NE | > 80 |
| Control Adriamycin | NE | NE | < 10 |
In this study, a novel Schiff base ligand (SPA) and its metal complexes were prepared by condensation of sulphapyridine and 9-anthracene carboxaldehyde. They formed stable complexes (2:1) with transition metal ions such as Mn(II), Co(II), Ni(II), Cu(II), and Ni(II) in ethanol. The ligand and its complexes were characterized using spectral and analytical data. From the spectral and elemental analyzes, a tetra-coordinated nature was assigned to the metal complexes. The ligand binds through the azomethine nitrogen atom and nitrate units of the metal salt used in the preparation. PXRD and SEM studies revealed that the complexes are microcrystalline. Biological studies such as antibacterial activity, antifungal activity, larvicidal, antioxidant, anti-inflammatory, anticancer, and DNA cleavage studies were performed. All biological screening showed that metal complexes were more active than free ligands, suggesting that some selected complexes may be used as drugs against bacterial and fungal strains after in vivo studies. Anticancer activity tests showed that [Co(SPA)2(NO3)2] complex does not help control the growth of the human colon cancer cell line COLO-205.
Ethical approval
Not applicable
Competing Interests
The authors have no relevant financial or non-financial interests to disclose
Funding
The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.
Authors’ contributions
PJ and PSS contributed to the study conception and design. Material preparation, data collection, and analysis were performed by PJ, SR,SA and NS. The first draft of the manuscript was written by PJ, PRK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Acknowledgements
We are grateful to SAIF-Cochin University for providing morphological analysis and spectral investigation services.
Data Availability
All data generated or analysed during this study are included in this published article [and its supplementary information files].
1. Madhavan Sivasankaran Nair & Raphael Selwin Joseyphus 2012, ‘Synthesis, characterization, antifungal, antibacterial and DNA cleavage studies of some heterocyclic schiff base metal complexes’, Journal of Saudi chemical society, vol. 16, no. 1, pp. 83-88.
2. IbticalKadhim kareem,Fawzi Yahya Waddai,Ghusoon Jawad Abbas,(2019),”Synthesis characterisation and biological activity of some transition metal complexes with new Schiff base ligand type(NNO) Derivative from Benzoin”,Journal of pharmaceutical sciences and Research”vol11(1),pp. 119-124
3. P. Mishra, M. Khare and S. K. Gautam, Synthesis, Physico-Chemical Characterization, and Antibacterial Studies of Some Bioactive Schiff Bases and Their Metal Chelates, Synth. React. Inorg. Met.-Org. Chem., 32, 1485 (2002).
4. . S. M. El-Medani, Structural Studies of Some Chromium, Molybdenum and Tungsten Complexes of N-salicylidene-2-hydroxyaniline, J. Coord. Chem., 57, 115 (2004).
5. R. C. Maurya, R. Verma and T. Singh, Synthesis, Magnetic, and Spectral Studies of Some Mono- and Binuclear Dioxomolybdenum(VI) Complexes with Chelating Hydrazones Derived from Acid Hydrazides and Furfural or Thiophene-2-Aldehyde, Synth. React. Inorg. Met.-Org. Chem., 33, 309 (2003).
6. T. D. Thangadurai, M. Gowri and K. Natarajan, Synthesis and Characterization of ruthenium(III) Complexes Containing Monobasic Bidentate Schiff Bases and their Biological Activities, Synth. React. Inorg. Met.-Org. Chem., 32, 329 (2002).
7. C. Celik, M. Tumer and S. Serin, Complexes of Tetradentate Schiff Base Ligands with Divalent Transition Metals, Synth. React. Inorg. Met.-Org. Chem., 32, 1839 (2002).
8. R. Ramesh and M. Sivagamasundari, Synthesis, Spectral, and Antifungal Activity of Ru(II) Mixed-Ligand Complexes, Synth. React. Inorg. Met.-Org. Chem., 33, 899 (2003).
9. E. Canpolat, A. Yazici and M. Kaya, Studies on Mononuclear Chelates Derived from Substituted Schiff-base Ligands (part 10): Synthesis and Characterization of a New 4-Hydroxysalicyliden-p-aminoacetophenoneoxime and Its Complexes with Co(II) Ni(II), Cu(II) and Zn(II), J. Coord. Chem., 60, 473 (2007).
10. S. Dayan, A. Cetin, N. Burcu Arslan, N. Kalaycioglu Ozpozan, N. Ozdemir and O. Dayan, Palladium(II) Complexes Bearing Bidentate Pyridyl-Sulfonamide Ligands: Synthesis and Catalytic Applications, Polyhedron, 85, 748 (2015).
11. S. Dayan, N. Kalaycioglu, Ozpozan, N. Ozdemir and O. Dayan, Synthesis of Some Ruthenium(II)-Schiff Base Complexes Bearing Sulfonamide Fragment: New Catalysts for Transfer Hydrogenation of Ketones, J. Organomet. Chem., 770, 21 (2014).
12. H. Ebrahimi, J. S. Hadi and H. S. Al-Ansari, A New Series of Schiff Bases Derived from Sulfa Drugs and indole-3-carboxaldehyde: Synthesis, Characterization, Spectral and DFT Computational Studies, J. Mol. Struct., 1039, 37 (2013).
13. M. Kratky, J. Vinsova, M. Volkova, V. Buchta, F. Trejtnar and J. Stolarikova, Antimicrobial Activity of Sulfonamides Containing 5-chloro-2-hydroxybenzaldehyde and 5-chloro-2-hydroxybenzoic acid Scaffold, Eur. J. Med. Chem., 50, 433 (2012).
14. K. Lal and R. K. Shukla, Studies on the Coordination Behavior of the Schiff-Bases Derived from Some Sulpha-Drugs and Substituted 2-hydroxyacetophenones, J. Indian Chemistry, 58, 115 (1981).
15. G. Miliauskas, P. R. Venskutonis and T. A. Van Beek, Screening of Radical Scavenging Activity of Some Medicinal and Aromatic Plant Extracts, Food Chem., 85, 231 (2004).
16. G. K. Keser, N. A. Kiymaz, I. Erden and A. Peksel, Antioxidative Properties of Recently Synthesized D-Pi-D type Schiff-Base Ligands, J. Chem. Research, 6, 340 (2010).
17. Isac Sobana Raj, C, Allen Ganana Raj, G & Antilin Princela 2015, ‘Synthesis and charactersation of Bioactive transition metal complexes of Zr(IV) and Th(IV) using di-r-formylmethoxy bis(s-pentadecenglphenyl) methane(DFMPM) derived from cardanol. Asian Journal of Chemical and Pharmaceutical Research, vol. 3, no. 1, pp. 208-214.
18. Isac Sobana Raj, C, Sofia, CM & Antilin Princela, M 2014, ‘Synthesis and characterization of bioactive transition metal complexes from cardanol.’, Asian Journal of Research in Chemistry, vol. 7, no. 8, pp. 711-716
19. Bauer, AW, Kirby, MMW, Sherries, JC & Truck, M 1966, ‘Antibiotic susceptibility testing by a standardizedsinglediskmethod’Am.J.Clin.Pathol.vol.45,pp. 493.
20. Arruda, Eduardo de et al. 2010, ‘Evaluation of toxic effects with transition metal ions, EDTA, SBTI and acrylic polymers on Aedes aegypti (L., 1762) (Diptera: culicidae) and Artemiasalina (artemidae)’,Braz.Arch.Boil,vol.53,n.2, pp. 335-341.
21. Hammam, AM, Gahami, MAEL, Khafagi, ZA, Salini, MSAL & Ibrahim, SA 2015, ‘Synthesis and characterization of some New Antimicrobial transition metal complexes with 1,2,4-Traizole-3-thione schiff bases’, Journal of material Environmental science, vol. 6, no. 6, pp. 1596-1605
22. Senthil Kumaran, J, Priya, S, Jayachandramani, N & Mahalakshmi, S 2013, ‘Synthesis, spectroscopic characterization and biological activities of transition metal complexes derived from a tridentate schiff base’, Journal of chemistry, vol. 2013, p. 10.
23. Amani S. Alturique, Abdel-Nasser MA Alaghaz, Reda A. Ammar & Mohamed E Zayed 2018, ‘Synthesis, spectral characterization and thermal and cytotoxicity studies of Cr(III), Ru(III), Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes of schiff base derived from 5-hydroxymethylfuran-2-carbaldehyde, Journal of Chemistry,
vol. 2018, p. 17.
24. Lekha, L 2014, ‘Studies on the synthesis, characterization and antimicrobial applications of rare earth metal schiff base complexes’, Ph.D thesis,
B.S. Abdur Rahman University Vandalur, Chennai
25. Iniama, GE, Olanrele, OS & Lorkpiligh, TL 2015, ‘Synthesis, structure, characterization and antimicrobial activity of Manganese(II) and Copper(II) complexes of Isatin phenyl hydrazone’, The international Journal of science and Technology, vol. 3, no. 8, pp. 229-233.
26. Cotton, FA and Wilkinson, G 1989,‘Advanced Inorganic Chemistry’, Wiley, New York.
27. Gudasi, KB, Patil, MS, Vadavi, RS, Shenoy,RV & Nethaji, PSAM 2007,‘X-ray crystal structure of phenyl glycine hydrazide synthesis and spectroscopic studies of its transition metal complexes’, Spectrochimica Acta A, vol. 67,
no. 1, pp. 172-177.
28. Surabhi, AK & Pradeep Kumar, K 2016 ‘Synthesis and characterization of fluorescent schiff bases and their copper complexes from salicylaldehyde’, ISOR Journal of Applied Chemistry, vol. 9, no. 11, pp. 11-18
29. T.J.Saritha,P.Metilda,2021,”synthesis,spectroscopic characterisation and biological applications of some novel Schiff basetransition metal (II) complexes derived from curcumin moiety”,Journal of Saudi chemical society,2021(25)101245
30. E. A. Nyawade, H. B. Friedrich, B. Omondi, H. Y. Chenia,M. Singh, and S. Gorle(2015), “Synthesis andcharacterization of newα,α′-diaminoalkane-bridged dicarbonyl(η 5-cyclopentadienyl)ruthenium(II) complex salts: antibacterial activity tests of η 5-cyclopentadienyl dicarbonyl ruthenium(II) amine complexes,”Journal of Organometallic Chemistry, vol. 799-800, pp. 138–146,
31. Biju Bennie, R, Theodore David, S, Siva Sakthi, M, Asha Jeba Mary, S, Seethalakshmi, M, Daniel Abraham, S, Joel, C & Antony R 2014, ‘Synthesis, special characterization and microbial studies of Schiff base transition metal complexes derived from cuminaldehyde and 4-Aminoantipyrine’, chemical science transaction, vol. 3(3), pp. 937-944.
32. Manohar V. Lokhandr 2015, ‘Synthesis of some ferrocene schiff base complexes with Mn(II), Ni(I), Co(II), Cu(II), Zn(II) and Pt(II) and its anti-microbial activity, ‘International Journal of current Research in chemistry and pharmaceutical sciences, vol. 2, no. 3, pp. 89-98.
33. Noureen, A, Salum, S, Fathima, T, Masood, SH and Mirza, B 2013, ‘Synthesis characterization and biological evaluation and QSAR of some schiff base esters: promising new antitumor, antioxidant and anti-inflammatory agents’, Pakistan Journal of Pharmaceutical Sciences, vol. 26, no. 1, pp. 113-124
34. Raman, N, Johnson Raja, S, Joseph, J & Dhaveethu Raja, J 2007, ‘Synthesis, spectral characterization and DNA cleavage study of heterocylic schiff base metal complexes’, Journal of the Chilean chemical society, vol. 2007, pp. 1138-1141.
35. Halime Güzin Aslana , Senem Akkoçb, , Zülbiye Kökbudak, (2019)”Anticancer activities of various new metal complexes prepared from a Schiff base on A549 cell line” ,Journal of Inorganic Chemistry Communications,vol 111,2020,pp 107645
No competing interests reported.