New Nanosized V(III), Fe(III), and Ni(II) Complexes Comprising Schiff Base and 2-Amino-4-Methyl Pyrimidine: Synthesis, Properties, and Biological Activity

A new synthesis of mixed ligand complexes vanadium(III), iron(III), and nickel(II), [M : L1 : L2], where L1 = Schiff base 2-((E)-((4-(((E)-benzylidene)amino)phenyl)imino)methyl)-naphthalene-1-ol (C24H18N2O) as for L2 = AMPY 2-amino-4-methyl pyrimidine (C5H7N3) were prepared in powder and investigated. Element analysis, molar conductivity, FT-IR, UV-vis, and magnetic susceptibility values have been acquired to describe the generated complexes. The values of vanadium(III), iron(III), and nickel(II) compounds are, respectively, 2.88 BM, 5.96 BM, and 2.92 BM, demonstrating that all compounds conform to the recommended octahedral geometry. Thermal gravimetric analysis (TGA) is used to further assess the complexes and establish the temperature stability and degradation of the metal complexes. The calculations abstracted from XRD patterns propose nanosized complexes (average size 29–50 nm). The microstructures of the samples have also been investigated by scanning electron microscopy (SEM). The disc diffusion method was used to assess and analyze the inhibition of the growth of compounds against harmful bacterial and fungal strains. The prepared complexes were tested against three strains of bacteria, one gram-positive strain (Bacillus subtilis), two gram-negative strains (Escherichia coli and Pseudomonas aeruginosa), and one fungus (Aspergillus fumigatus). The complexes inferred antimicrobial activity against the studied organisms. Specifically, vanadium(III) and nickel(II) are more effective than iron(III), making them promising drugs.


Introduction
Te coordination complexes are made up of a core, an ion or atom, which is typically metallic, and an array of bonded ions or ions that are known as ligands or complexing agents.Transition metals are frequently found in coordination complexes [1].A wide range of structural architecture and high design abilities are supplemented (available here) by using transition elements and organic ligands in chemistry as their building components [2].Tis group of complexes has a wide range of applications in analysis, homogeneous catalysis, bioinorganic chemistry, and other felds.Because organic heterocyclic ring complexes have numerous uses in agriculture, health, pharmacy, and other industries, heterocyclic complex chemistry is a growing area of biology and chemistry [1].Mixed ligand complexes are diferent from classical complexes in that they pair the same metal ion with at least two diferent kinds of ligands.Tis increases the potential for shifting properties, increasing the researchers' interest in synthesizing mixed ligand complexes.Hence, mixed-ligand complex synthesis and characterization have drawn a great deal of attention in recent years.It is common knowledge in the scientifc community that mixed ligand complexes are crucial to the functioning of biological systems.It has been demonstrated that these complexes are biologically efective against a range of harmful microorganisms.In coordination chemistry, organic bidentate ligands are a frequent form of ligand and have a variety of applications.Oxygen and nitrogen are examples of donor atoms found in ligands.Complexes with diverse geometrical features are physiologically active as a result of their interaction with metal ions [3].Interest in the structural chemistry, catalysis, and biological properties of transitionmetal complexes containing heterocyclic molecules has been high.Amazing progress has been made in the feld thanks to the synthesis of multidentate ligands from heterocyclic compounds containing metal ions.In coordination chemistry, a variety of multidentate ligands have crucial functions to perform.Numerous attempts have been made to create multidentate ligands.Schif bases include a number of these ligands that have a C�N (azomethine) group.Tey were given the name Schif bases in honor of their discoverer, German Hugo Schif, who discovered in 1864.Simple condensing of primary amines and carbonyl compounds was used to make them [4].Here, azomethine nitrogen and phenol oxygen act as coordination partners and serve as coordination partners; it has been shown in tests that Schif's base is a superior ligand because it possesses a fexible, toothed structure [5].Te C�N connection plays a signifcant role in the demonstration of biological activity, due to the discovery that the lone pair of electrons of the nitrogen atom of the azomethine group in a sp 2 hybridized orbital has chemical and biological signifcance [6].In the chemistry of metals, coordination Schif bases are considered "privileged ligands," which means that they are employed in a variety of industries and felds, including chemistry, organic synthesis, analytical, and optical and electrochemical sensors.In addition, transition metal complexes of Schif bases are also used in the food, leather, and wood dyeing industries.It also represents a wide range of medicinal chemistry applications.A wide range of biological activities, including antifungal, antibacterial, antitumor, tuberculosis, antidiabetic, analgesic, antispasmodic, antiproliferative, antimalarial, antiinfammatory, antiviral, and antipyretic characteristics, have been demonstrated in them due to the wide range of pharmacokinetic characteristics and popularity in medication development [7][8][9].Te ability of Schif bases to automatically and spontaneously form a monolayer, with a layer on the surface to be protected, makes this one of their most signifcant characteristics [10,11].Furthermore, pyridine derivatives serve as useful chelating ligands, and the complex-forming ability of pyridine and its derivatives with transition metal ions is well known, where they function as monodentate ligands [12].Furthermore, the amino group (NH 2 ) has been reported in several papers related to pyridine derivative compounds [13].Pyrimidines are a heterocyclic ring with remarkable biological activity, which has been studied extensively because of its occurrence in living systems.Many pyrimidines and their derivatives have been used in various felds ranging from medical applications to industrial applications.Knowledge of the coordinating characteristics of the pyrimidine ring system is crucial for understanding the function of metal ions in biological systems since it ofers a potential binding site for metals [12].Te chemotherapy drug bleomycin is a useful example of pyrimidine activity.Antimicrobial, antimalarial, antispasmodic, antineoplastic, and antidiabetic and nucleic acids (cytosine and uracil) [13].Tese organic compounds (pyrimidines and their derivatives) are crucial since a repeated take of these drugs can lead to signifcant neurotic changes that afect the immunological function of the body and increase the generation of antibodies [14].Te dimethyl pyrimidine derivative-based HIV-1 CCR5 entry inhibitor (vicriviroc), nifekalant, is a category III antiarrhythmic drug, and urapidil is an antihypertensive sympatholytic drug [13].Large proportions of people die from microbial infections and among the common microbial species that threaten human civilization and pose a danger, such as Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Aspergillus fumigatus, which were used in this study.By measuring the diameter of the inhibition zone (IZ) surrounding the hole (mm), antimicrobial activity was assessed.According to the inhibitory zones discovered and the literature, all complexes are efcient against the four species [15][16][17] in that all of them showed better activity for the metal complexes compared to the original ligands (Schif base and AMPY) as expected.Te antimicrobial activities of the studied complexes were found in the following order: metal complexes > AMPY ligand > HL ligand.Te fndings demonstrate that coordination with the metal atoms increases the activity of the Schif base and it explains that, when complexation is performed, the polarity of the metal atom will be reduced by partial sharing of its positive charge with donor groups and possible π-electron delocalization throughout the ring.Tis increases the lipophilic character of the complex and favors the permeation of the complex through the lipid layer of the cell membrane.Te complex blocks metal binding sites in microorganism enzymes.As a result, they have the ability of metal complexes to inhibit microbial growth more efectively than free ligands [18,19].Previously, compounds of chromium(III), manganese (II), copper(II), and zinc(II) were reported to show antibacterial activity, anticancer, and antioxidant [3,4].Terefore, we speculate that compounds of V(III), Fe(III), and Ni(II) with 2-amino-4-methyl pyrimidine and Schif's base will show more antibacterial, anticancer, and antioxidant activity.Te preparation and characterization of mixed ligand complexes of vanadium(III), iron(III), and nickel(II), with a 1 : 1 : 1 (M : L1 : L2) ratio, are the subjects of the study given in this publication.Te Schif base, aminopyrimidyl, and its complexes were studied using elemental analysis, IR, ultraviolet-visible analysis, conductivity measurement, magnetic behavior, XRD, and thermal analysis (Figures 1(a) and 1(b)) and show the ligands employed in this investigation, HL and AMPY, respectively.FT-IR Spectrometer) was used to measure the solid-state FTIR spectra of the ligand and its complexes spanning the wave range 400-4000 cm −1 .A magnetic susceptibility balance (MSB-Auto) from Sherwood Scientifc was used to detect magnetic moments (the United Kingdom).Te absorption spectra of the solutions (DMSO, 1 × 10 -3 M) were also captured using a Shimadzu 1650-Spec UV-vis spectrometer (Shimadzu, Duisburg, Germany).At temperatures ranging from 20 to 600 °C, the compounds were thermally examined in dynamic air using a Shimadzu (DTG 60-H) thermal analyzer.Te control unit for the Philips XRD model (PW 1710) uses a Cu K anode at 40 K. V 30 M. (l � 1.54180).SEM (JEOL JSM-5400-LV feld Emission SEM) was used to conduct the research, and the morphology of the complexes was investigated through it.

Antibacterial Assignment.
Te in vitro antibacterial sensitivity of each of the complexes was tested using the disc difusion method [20].Nutrient agar medium (28 g) in 1000 ml of distilled H 2 O was then poured into Petri discs and allowed to solidify for 15 min in a sterilized zone, and plates were incubated overnight with the following bacterial strains: Bacillus Subtilis (+ve) and Escherichia coli, Pseudomonas aeruginosa (-ve).Tese were obtained from the Department of Botany and Microbiology, King Saud University.Te NPs of vanadium(III), iron(III), and nickel(II) used in the study were aliquoted until the wells were flled.Te resulting mixture was stirred until it reached incubation for 24 hours at 37 °C.Ten, the diameter of the damping zone was measured.

Antifungal Assignment. Antifungal activity studied:
Aspergillus fumigatus.Tis sample was obtained from the Department of Botany and Microbiology, King Saud University.Te PDA medium was then prepared and sterilized. 2 ml of treatment was added to 20 ml of PDA medium in a Petri dish, and the mixture was homogenized.Tis was followed by the transfer of a fungus disc, using an inoculation needle, and placing it upside down in the middle of the plate.Te samples were then placed in a party dish, which was incubated for 5 days at 27 °C.After that, the results were captured with a camera.Te diameter of the fungal growth was measured from the plate directly using a ruler, and the results were recorded and compared with the control experiment.

Synthesis of the Schif Base Ligand (HL).
Te ligand was made using the process described in the literature [4], in which 2-hydroxy-1-naphthaldehyde (3.5 g) and benzaldehyde (3.1 g) his solution were added dropwise to a fask containing (2.5 g) of p-phenylenediamine dissolved in ethanol.During the three hours that a mixture was allowed to stir while experiencing refux to form an orange precipitate, the precipitate was fltered, repeatedly, rinsed with distilled water, and then completely EtOH (Figure 2).
After the refuxing procedure, the mixture was allowed to cool to room temperature.A red product precipitated, which was fltered and cleaned with distilled water and ethanol before being placed in the oven to dry for two hours at 50 °C (Figure 3(a)).

Elemental Analysis and Physical Properties of the Ligand and Complexes.
In Table 1, the information from the ligand and its complexes' element analysis (CHN) is displayed in a 1 : 1 : 1 [M : L1 : L2] ratio.Te values obtained and those calculated using the suggested formula agree with the formula of the vanadium, iron, and nickel complexes.Table 1 displays certain physical characteristics (color and melting points) for HL, AMPY, and their complexes.Tese characteristics demonstrate that the complexes have diferent colors from those of the ligands and have a high melting point, which is greater than the melting point of the ligands.Tis demonstrates that the coordination between the ligands and their metal salts, leading to complexation, is present.In DMSO solvent, the molar conductivity of the mixed ligand chelates was measured, and the results are given in Table 1.Low values for complexes of metal ions point to nonelectrolytic activity.4 International Journal of Biomaterials 3.2.Fourier Transform Infrared Spectra.Te detailed assignment of all bands is based on the comparison with the signifcant frequencies in the IR spectra of the free ligands HL and AMPY with metal complexes (Table 2).Te intraligand hydrogen bonding that the phenolic (OH) bond engages in with an azomethine nitrogen atom's (OH. ..N) lone electron pair prevents the ligand 1 (HL) FT-IR spectra from revealing the stretching frequency of the phenolic (OH) bond.Te two azomethine groups (C�N) have strong bands at 1618,1604 cm −1 in all complexes, while the azomethine group (C�N) experiences a change that requires coordination with the metal center.In the phenolic (CO) bond, undergoing stretching at a frequency of 1310 cm −1 , the phenolic OH group is involved in chelation because the stretching frequency of the phenolic (CO) bond has changed in the stretching band of the spectra of the produced complexes.Te development of new peaks in the complexes as a result of (OH) rocking lends additional credence to this chelation.Te (C�C) medium band appears at 1540 cm −1 [4].Ligand 2 (AMPY) coordination occurs in the nitrogen amino.Stretching and bending modes for NH 2 change in free ligand 3430−3305 cm −1 to lower wave numbers as in the Ni(II) complex when the nitrogen amino is engaged in complex building, which also disappeared in C1 and C2, sometimes the complex spectra contain water coordination, which makes it challenging to interpret them since the NH 2 group of the AMPY ligand will overlap with that of the water molecules.Te δ(NH 2 ) vibration of NH 2 provides more  International Journal of Biomaterials proof that the NH 2 group is involved.Te change in the wavelength of this band between the complexes and the free ADMPY ligand from 1648 cm −1 to 1656-1665 cm −1 indicates that the NH 2 group was involved in the complex formation [4,21].At a wavelength of 3520-3030 cm −1 , the coordinated water is indicated by the stretching vibration of coordinated H 2 O (OH) in the complexes.Te bands that emerge at 612-640, 544-566, and 419-442 cm −1 , respectively, are indications of the M-O, M-N, and M-Cl bonding, respectively (Figure 5) [4].

Electronic Spectra Electronic Spectra and Magnetic
Moments.Te arrangement of the ligand in metal complexes is possibly inferred to from the electronic spectra (Figure 6).Additionally, it makes a distinction between diferent geometries.Te magnetic moment value provides accurate details on the complex's shape and paramagnetic or diamagnetic nature.Te ligands (HL) and (AMPY) showed two bands at 38,610 cm −1 returning to the transformation π ⟶ π * and 35,714 cm −1 attributed to the transition n ⟶ π * [4,22,23].Te strongest indication that coordination took place was the appearance of displacement.
Te magnetic moment values and UV-visible spectral data are provided in Table 3. Vanadium (III) exhibits a band at 20,492 cm −1 , which may be assigned to 3 T 1 (F) ⟶ 3 T 1 (P) transition in the octahedral geometry of the complex [24], magnetic moment for V(III) (2.88 BM) [25].Tree absorption bands of the iron(III) complex can be seen at 20,450, 21,598, and 25,641 cm −1 , and these are values related to transfers 4 T 1g (D) ⟶ 6 A 1g , 4 T 2g (G) ⟶ 6 A 1g , and 4 T 2g (G) ⟶ 6 A 1g , serially [26,27].Te magnetic moment shows the iron (III) (5.96 BM) [28], which indicates the presence of the Fe(III) complex in the octahedral structure.Te electronic spectra of the nickel(II) complex exhibited one band of the d-d transition at λmax 21,277 cm −1 , and these correspond to the 3 A 2g (F) ⟶ 3 T 1g (P) transition [29].Te Ni(II) complex was shown to possess two unpaired electrons and is paramagnetic because its octahedral geometry agrees with its magnetic moment value of (2.92 BM) [29].

Termal Analysis.
Termal analyses of the manufactured complexes were performed up to 550 °C.Using this method, complex composition, temperature stability, and the presence or absence of water molecules inside or outside the compound's inner coordination sphere can all be determined.TGA thermograms of the synthesized ligand and transition metal polymeric complexes showed a gradual weight reduction, indicating disintegration by fragmentation as the temperature increased.Te fndings revealed a good agreement between the calculated data and the suggested formulae for weight loss (Table 4).

[V(HL)(AMPY)(H 2 O)Cl 2 ]. Te thermogram indicates
that there are four distinct steps of mass loss.Te frst step is consistent with the release of the water molecule (calc.3.00%, found at 2.55%).Two chlorine atoms were eliminated in the second stage (calculated at.11.83% found at 11.47%).
According to the mass loss analysis, the third stage is a dissociation of the AMPY (calc.18.21%, found 17.98%).At 343 °C, the DTA trace has an endothermic action.Te remaining resulting deterioration was assigned based on mass loss consideration to the formation of 1/2 V 2 O 3 (calc.11.17%, found at 10.92%).Te DTA curve has an exothermic peak at 411 °C (Figure 7(a)).

[Fe(HL)(AMPY)(H 2 O)Cl 2 ].
Te measured mass loss of this early stage and the loss of one water molecule (calc.2.98%, found at 2.52%) are highly connected.Te observed mass drop in the second step is due to two chlorine atoms (calc.11.73%, found at 11.40%).An endothermic DTA peak        ).Te third step discarded the AMPY ligand, and the fourth stage represented the decomposition of the rest complex, respectively (calculated at 17.98% and found 17.64%), and (calculated at 57.74% and found at 57.53%) on the DTA curve, and there are endothermic peaks at 318 °C and exothermic peaks at 450 °C.At 550 °C, the fnished item is consistent with NiO (calculated at 12.30%, found at 11.72%).International Journal of Biomaterials

X-Ray Difraction (XRD).
For powder X-ray difraction experiments, the vanadium(III), iron(III), and nickel (II) complexes were used.Te complex difraction patterns are captured between 2θ, spanning 10 °to 80 °.Scherrer's formula is used to calculate the samples' particle sizes.Scherrer's equation states that the particle size is provided by the formula t � 0.9 λ/Bcosθ, where the crystal's thickness (in nm) is t, B stands for half width (measured in radians), θ for the Bragg angle, and λ for the wavelength.Te measurement of the difraction peak's half-width yields the particle size corresponding to each difraction maxima.Table 5 displays the value of the lattice parameter as well as the particle size for each of the three complexes.Te V(III) and Fe(III) complexes are triclinic, while that of the Ni(II) complex is  A HL ligand, B AMPY ligand, C Fe(III) complex, D V(III) complex, and E Ni(II) complex.
International Journal of Biomaterials a system of monoclinic crystals.Sharp peaks can be seen in all metal complexes.Te particle sizes of all complexes were found to be between 21 and 49 nm (Figure 8).International Journal of Biomaterials (AMPY) of the free ligand and complexes of vanadium(III), iron(III), and nickel(II).Tey were also tested against the fungus (Aspergillus fumigatus).

Antibacterial and Antifungal
Screening.According to the fndings, all complexes are efective in opposition to all examined species.Tese numbers exceed those for free HL and AMPY ligands, where the metal complexes showed better activity compared to the original ligands [19].Te most active ligand complexes were those containing nickel and vanadium, while the least active ligand complexes contained iron (Figure 10).It is clear from the antibacterial data that coordination with the metal atoms increased the activity of the Schif base and AMPY.Te results of the susceptibility of these bacteria to chemicals determined by the diameter of the inhibition zone (IZ) are shown in Table 6 for fungi.A clear area surrounding the disc indicates that the substance has an inhibitory efect on an organism, in the order as follows: vanadium (III) > nickel (II) > iron (III) (Figures 11 and 12).Metal complexes were more energetic than ligands; thus, chelation theory might be able to explain this rise in activity.Tis was as a result of chelation's ability to decrease the polarity of the metal ion by sharing some of its positive charge with the donor groups [30].

Conclusions
In the present study, three transition metal (II) or (III) complexes were synthesized and characterized by various spectral and physicochemical techniques.Te coordination of the frst ligand (Schif base) occurred through the phenolic -OH group and a nitrogen atom of an azomethine group (-C�N-), while the coordination of the second ligand (AMPY) occurred through the NH 2 group, according to the spectrum data.According to the suggestions acquired from overhead readings (elemental analysis, magnetic susceptibility, molar conductance, UV-visible, FTIR, TGA analysis, and XRD tests), we propose an octahedral structure for V(III), Fe(III), and Ni(II) complexes with HL ligand and other AMPY ligand.Te V(III), Fe(III), and Ni(II) complexes, respectively, are shown in Figures 13 and 14 below, while the Fe(III) complex's particles have a caulifower shape, and those of the V(III) complex have a nanorod shape.Te Ni(II) compound causes coral-like morphologies, and the molar conductivity of the complexes has the nonelectrolytic shape of all the complexes.In vitro, the efectiveness of the free ligands and their metal complexes against pathogenic organisms was tested, and the results showed that the complexes had more activity compared to the free ligands.
Based on the results in the current manuscript, the substance has an inhibitory efect on an organism, in the order as follows: vanadium (III) > nickel (II) > iron (III).

3. 4 . 3 .
[Ni(HL)(AMPY)(H 2 O)Cl 2 ].Te TGA and DTA curves of the sample Ni(II) complex are shown in Figure 7(c).Te thermal degradation processes, which have four steps, start at a heat of 76 °C, as evidenced by the TG-analysis fndings.Te frst mass loss is closely related to the discharge of water molecules.Te mass loss (calc.2.96%, found at 2.75%) points to the loss of the H 2 O molecule.Te DTA curve has an endothermic peak at 80 °C.Two chlorine atoms were removed during the second breakdown stage (142-248 °C; calculated 11.68%, found 11.31%

3. 6 .
SEM Morphological Study.Te microstructure and surface appearance of the V(III), Fe(III), and Ni(II) complexes were studied using scanning electron microscopy.Te shape of the particles of the V(III) complex particles' shape is consistent with the nanorod structure (Figure9(a)).Te morphologies of caulifower and coral, respectively, are seen for the substances Fe(III) and Ni(II) (Figures 9(b) and 9(c)).

Figure 10 :
Figure 10: Antibacterial activity of complexes (A, B, C, D, E) against values of B. subtilis, E. coli, and P. aeruginosa inhibition zones (mm).

Figure 13 :
Figure 13: A perspective view of complete coordination, SEM micrographs, and their antimicrobial activity.
Tey were purchased and used without purifcation.Te commercially available salts VCl 3 , FeCl 3 .6H 2 O, and NiCl 2 .6H 2 O were used without additional purifcation.Concentrations of carbon, hydrogen, and nitrogen were measured using a Euro vector CHN analyzer (EA3000, Italy).Agilent Technologies (Cary 600 Series

Table 2 :
FT-IR spectral data (cm −1 ) of free ligands and their metal complexes.

Table 3 :
Absorption spectra of L1 and L2 ligands with their compounds and magnetic moments.

Table 4 :
Termal decomposition data of metal compounds.

Table 5 :
Te crystal data of the complexes.

Table 6 :
Te antimicrobial activity of the complexes (A, B, C, D, E) against inhibition zone values of B. subtilis, E. coli, P. aeruginosa, and A. fumigatus.

Table 6
provides the in vitro antimicrobial screening results.Bacterial strains, including (Bacillus subtilis) which are Gram-positive and two Gram-negative strains (E-coli and Pseudomonas aeruginosa), were used to test the antimicrobial actions (HL),