Synthesis, Characterization, PXRD Studies, Theoretical Calculation, and Antitumor Potency Studies of a Novel N,O-Multidentate Chelating Ligand and Its Zr(IV), V(IV), Ru(III), and Cd(II) Complexes

A new series of Zr(IV), V(IV), Ru(III), and Cd(II) complexes with the ligand N-((5-hydroxy-4-oxo-4H-pyran-3-yl)methylene)-2-(p-tolylamino)acetohydrazide (H2L) have been prepared. FT-IR, 1H-NMR, electronic spectra, powder X-ray, and thermal behavior methods were applied to elucidate the structural composition of new compounds. Geometry optimization for all synthesized compounds was conducted using the Gaussian09 program via the DFT method, to obtain optimal structures and essential parameters. Moreover, the antibacterial and antitumor activity of the ligand and its complexes were studied, where the Cd(II) complex acquires probably the best antibacterial activity followed by the Ru(III) complex towards bacterial species than others when using ampicillin and gentamicin were used as standard drugs. The complexes exhibited interestingly antitumor potential against the MCF-7 breast cancer cell line. The cytotoxicity of the new complexes has been arranged to follow the order: Ru(III) complex > Cd(II) complex > Zr(IV) complex > V(IV) complex > ligand. Molecular docking was performed on the active site of ribosyltransferase and obtained good results. Structure-based molecular docking is used to identify a potential therapeutic inhibitor for NUDT5.

From the previous work and the wide applications of acetohydrazide and carbaldehyde derivatives, the ligand N'-((5-hydroxy-4-oxo-4H-pyran-3-yl)methylene)-2-(p-tolylamino)acetohydrazide was synthesized, which is considered a modification of a previously used ligand and used as a chelator of Ru(III), Cd(II), Zr(IV), and V(IV) where the characterization, theoretical calculation, and the effect of these compounds on the bacterial species and MCF7 cancer cell lines were studied.
e ruthenium(III) complexes have been synthesized for their eclectic cytotoxic effects in vitro and hopeful anticancer properties in vivo, leading to a few candidates in developed clinical experiments aiming at treating the stability, solubility, and cellular uptake issues of depressed molecular weight Ru(III)-based components [41,42].Cd(II) complexes with Schiff base ligand can be used as an active emitting layer and exhibit photophysical properties [43] and showed anticancer activities against human liver cancer HepG2 cell line and human colon cancer HCT116 cell line [44].Moreover, they showed excellent antibacterial activity against different bacterial strains [45,46].e Zr(IV) cation with its relatively small ionic radius and high positive charge number shows the characteristics of a hard Lewis acid, and it is perfect for strong complexation [47].Zr(IV) complexes have a metalorganic framework that can be used for a variety of catalytic processes, industrial purposes, and pharmaceutical applications [44,48,49].V(IV) complexes are reported to show various biological characteristics including antitumor, antimicrobial, antiobesity, antihyperlipidemic, and antihypertension activities, insulin-enhancing action, and improvement of oxygen-carrying efficiency of hemoglobin and myoglobin [50][51][52][53].Vanadium complexes are also used for lowering of blood glucose [54][55][56] and natriuretic and diuretic effects.
e resulting precipitate was filtered off, washed several times with ethanol and diethyl ether, and then dried in a vacuum. C

Synthesis of Metal Complexes.
In the boiling flask, a stoichiometric amount of the appropriate metal salt (1 mmol; 0.178 g Zr(IV); 0.163 g of V(IV); 0.207 g of Ru(III); and 0.174 g of Cd(II)) was added to 0.301 of the ligand (1 mmol) in the same solvent EtOH (20 ml) in accordance with a general procedure (Scheme 1).e reaction mixture was then refluxed at 60 °C and stirred for 6 hr.
e resulting product was filtered off from the mixture, thoroughly washed with ethanol to remove any traces of unreacted starting materials, and then dried in a vacuum [39].e purity of the complexes was checked by TLC.
e yields and characterization details for the complexes are presented as follows.

Physical Measurements.
e Fourier transform infrared (FT-IR) spectrum was measured (4000-400 cm −1 ) in KBr discs using Nenexeus-Nicolidite-640-MSA FT-IR, ermo-Electronics Co.In the DMF solution, the UV-visible absorption spectra were measured using a 4802 UV-Vis double-beam spectrophotometer.e 1 H-NMR spectra have been recorded in DMSO-d6 as a solvent using a Varian Gemini 200 NMR spectrophotometer and Varian-Oxford Mercury at 300 MHz, respectively.ermal analysis (TG/ DTG) was obtained using a Shimadzu DTA/TG-50 ermal Analyzer with a heating rate of 10 °C/min in a nitrogen atmosphere with the rate of 20 mL/min using platinum crucibles in the range of ambient temperature up to 800 °C.Mass spectra were acquired by the electron impact (EI) ionization technique at 70 eV on a Hewlett-Packard MS-5988 GC-MS instrument at the Microanalytical Center, National Research Center, Egypt.X-ray powder diffraction analyses of solid samples were measured using a APD 2000 PROModel GNR-X-ray diffractometer (NRC, Tanta University, Egypt).X-ray diffractometer is ready with Cu Kα radiation (λ �1.540 56 Å).Most powder diffractometers use Bragg-Brentano parafocusing geometry.e X-ray tube applied was a copper tube operating at 40 KV and 30 mA. e scanning range (2θ) was 5 °-90 °with a step size of 0.050 °and a counting time of 2 s/step.Quartz was utilized as the standard material, accurate for the instrumental extension.is identification of the complexes was done by a known method from the fit identified Scherer formula, and the average crystallite size (D) is where λ is the X-ray wavelength in nanometers, K is a factor related to crystallite shape, with a value of about 0.9, and β is the peak width at half-maximum height.e value of β in the 2θ pivot of diffraction shape should be in radians.θ is the Bragg angle and can be in radians since the Cosθ is suitable with the same number.

Kinetic and ermodynamic Parameters for the Complexes.
e kinetic and thermodynamic parameters of the decomposition stages of the complexes (C, D) were determined from the TGA thermogram using the Coats-Redfern equation [57].e values of the activation energy E * , Arrhenius constant A, activation entropy S * , activation enthalpy H * , and free energy of activation G * are calculated by applying Coats-Redfern equation for n � 1.
where x is the fraction decomposed, R is the gas constant, and θ is the heating rate.Since (1-2RT/E * ) ≃ 1, a plot of the left-hand side of equation ( 2) against 1/T gives a straight line from its slope and intercept, and E * and A were calculated.e entropy of activation S * , enthalpy of activation H * , and the free energy change of activation G * were calculated using the following equations: where k is Boltzmann's constants and h is Planck's constants.

Quantum Chemical Calculation (QCC).
e input files of all compounds were prepared with GaussView 5.0.8 [58].Gaussian 09 rev.A.02 [59] software was used for all calculations by the DFT/B3LYP method.6/31G and LANL2DZ are the standard basis sets for the synthesized ligands and their metal complexes.All docking steps were done using MOE 2008 (Molecular Operating Environment) software to simulate the binding model of these compounds into ATP binding sites of 3GEY transferase and the NUDT5 proteins.
e protein crystal structures were obtained from the Protein Data Bank (PDB).

Antibacterial Assay.
e antimicrobial activity of synthesized compounds was determined by the agar well diffusion method [60].All the compounds were tested in vitro for their antibacterial activity against Staphylococcus aureus (ATCC:13565) and Streptococcus mutans (ATCC:25175) (Gram-positive bacteria) and Escherichia coli (ATCC:10536) and Klebsiella pneumonia (ATCC:10031) (Gram-negative bacteria) using nutrient agar medium.Ampicillin and gentamicin were utilized as standard medications for Gram-4 Bioinorganic Chemistry and Applications positive and Gram-negative bacteria.DMSO was used as a control solvent.
e cell suspension was diluted with a complete medium to a concentration of 5 × 10 4 cell•mL −1 .
e cell suspension (100 μL) was pipetted into each well of a 96-well plate (about 5000 cells per well).e 96-well tissue culture plate was inoculated with 1 × 10 5 cells/ml (100 μL/well) and incubated at 37 °C for 24 hours to develop a complete monolayer sheet.e growth intermediate was poured from 96-well microtiter plates after a confluent sheet of cells was created, and the cell monolayer was washed twice with washing media.Two-fold dilutions of the tested sample were made in RPMI medium with 2% serum (maintenance medium).0.1 ml of each dilution was tested in various wells, leaving 3 wells as control, thus only receiving a maintenance medium.e plate was incubated at 37 °C and then examined.Cells were scanned for any toxicity physical signs, e.g., partial or complete absence of the monolayer, rounding, retractability, or cell granulation.e solution of MTT was prepared (5 mg/ml in PBS) (BIO BASIC CANADA INC).A 20 μL MTT solution was added to each well and then placed on a vibration table, 150 rpm for 5 minutes, to completely combine the MTT into the media.ereafter, it was incubated (37 °C, 5% CO 2 ) for 1-5 hours to allow the MTT to be metabolized.e medium was then dumped off.A dry plate was placed on paper towels to remove remains if necessary.Resuspended formazan (MTT metabolic product) was resuspended in 200 μL DMSO and then placed on a vibration desk, at 150 rpm for 5 minutes, to completely combine the formazan into the solvent.e optical density was recorded at 560 nm, and the background at 620 nm was subtracted, since it is important to directly correlate optical density with cell quantity [61][62][63].

Results and Discussion
3.1.Physicochemical Properties.All metal chelates are colored and stable towards air and moisture.
e analytical results for the complexes are consistent with the proposed molecular formulas and confirm the formation of 2 : 1 of Zr(IV), 2 : 2 of V(IV), 1 : 2 of Ru(III), and 1 : 1 (M : L) of Cd(II) complexes (Table 1).e molar conductance values for the complexes in 10 −3 M DMF solution are in the range of 46-89 Ω −1 cm 2 •mol −1 for Zr(IV), V(IV), Ru(III), and Cd(II) complexes.e values of the Zr(IV) and Ru(III) reveal their nonelectrolytic nature, while the values of the V(IV) and Cd(II) complexes reveal their electrolytic nature [64,65]. 13C-NMR Spectra.

1 H-NMR and
e 1 H-NMR spectrum of the ligand was verified in DMSO-d6.It exhibits one signal at d 5.94 ppm assigned to the NH proton and a broad single peak observed at 11.1 ppm assigned to the NHC � O proton.Furthermore, the spectrum displays multiple signals at (6.70-6.75ppm) assigned to aromatic ring protons.Moreover, the spectrum depicts singlet signals (7.11 ppm) corresponding to pyrene protons.us, the 1 H-NMR result supports the assigned geometry.e 1 H-NMR spectrum of the ligand was verified in DMSO-d6 solution (d ppm) (Figure S1A).e 1 H-NMR spectrum exhibited a signal at 2.36 (s, 2H, CH 2 ), 4.14 (br, 1H, NH), 6.58-7.63(m, 8H, aromatic system), 5.94 (s, 1H, CH), and 11.36 (s, 1H, NH) (amide a to hydrazone linkage).
e 13 C-NMR spectrum of the ligand (DMSO-d6) (Figure S1B) features a signal at 19.2 ppm corresponding to the methyl group, while the methylene carbon was assigned at 45.3 ppm.e aromatic carbons of the phenyl ring are observed at 113.4, 126.8, 129.8, 129.8, and 144.6 ppm, whereas the pyrane ring carbons appeared at 116.8, 128.0, 163.1, 179.1, and 179.5 ppm.In addition, two carbon atoms appeared at 154.7 and 173.5 ppm that corresponded to (C � N) and (C � O), respectively.

FT-IR Spectra.
FT-IR spectra of the ligand and its metal complexes are depicted in Table 2, Figure 1, and Figure S2.
e ligand spectrum shows a band at 1604 cm −1 which corresponds to the (−C � N) stretching vibration [66].On complexation, this band is shifted to a lower frequency (1582, 1595, 1553, and 1603 cm −1 ) for Zr(IV), V(IV), Ru(III), and Cd(II) complexes, respectively.e red shift is a proof that the azomethine nitrogen atoms get shared in complex formation.e IR spectrum of Bioinorganic Chemistry and Applications the ligand additionally showed a broad band at 3202 cm −1 due to the stretching vibration of the ν(N-H) group.On complexation, the IR spectra of all complexes displayed that the bands of the imine groups have been shifted to a lower wave number (3100, 2625, 2925, and 3104 cm −1 ) for Zr(IV), V(IV), Ru(III), and Cd(II) complexes, respectively, than those of the free Schiff base ligand.e broad bands in the 3392 cm −1 region are due to the hydroxy group, and this band was shifted to higher frequencies (3399, 3434, 3433, and 3422 cm −1 ) for Zr(IV), V(IV), Ru(III), and Cd(II) complexes, respectively, which did not participate in the complex formation, where we note the appearance of new bands within the ranges 560-   6 Bioinorganic Chemistry and Applications complexation, which excludes the possibility of the participation of the hydroxyl group.e presence of two strong bands at 1375 and 1315 cm −1 was assigned to ν as (NO 3 ) and ν s (NO 3 ), indicating monodentate nitrate groups [68,69].

e Electronic Spectra and Magnetic Data.
e UV-Vis spectra of the hydrazone ligand and its complexes of Zr(IV), V(IV), Ru(III), and Cd(II) were recorded in 10−3 DMF solution in the range of 200-800 nm at room temperature.
e values of the maximum absorption wavelength (λ max ) and magnetic moments (μ eff ) are listed in Table 3, and the spectra are presented in Figure 2. e absorption spectrum of the ligand showed two absorption bands in the ultraviolet region [70].e first high-intensity bands were observed at λ max � 341 nm, and the second low-intensity bands were observed at λ max � 399 nm. e two bands are attributed to the (n-π * ) transition associated with the azomethine group [60].
e band of the high wavelength side exhibited a bathochromic shift relative to its free ligand.e absorption bands of the first wavelength in the ligand slightly changed for metal complexes, while the second band strongly changed, where the electronic spectra of Zr(IV), V(IV), and Ru(III) complexes of this band were shifted to (338-479), (351-555), and (340-519) nm. e first band of complexes at 338, 351, and 340 is attributed to the (n-π * ) transition.However, the second band in the visible region at 479, 555, and 519 is considered to arise from (d-d) transitions.e electronic spectrum of the Cd(II) complex exhibited two bands at 338 and 378 nm, referring to (n-π * ) transition associated with the azomethine group.At room temperature, the magnetic moment values of the V(IV) complex is 1.6 ppm, according to spin-spin interaction between the V ion in the binuclear complex causing low value of the magnetic moment [53], Ru(III) complex is 1.74 B.M. which are close to the spin-only value of one unpaired electron.However, the Cd complex showed a diamagnetic character.
ese results indicated that the ligand coordinates to Zr(IV), V(IV), Ru(III), and Cd(II) are in accordance with the results of other spectral data.According to modern molecular orbital theory [71], any factors that can influence the electronic density of the conjugated system must result in the bathochromic or hypsochromic shift of absorption bands.Here, in the case of the metal complexes with the same ligand, the main reason for bathochromic shifts is generally related to the electronegativity of the different metal ions [72].

ESI-MS Spectra.
e mass spectrum has been increasingly used to demonstrate the molecular structure of the ligand and complexes.Figure S3 shows the mass spectrum of the ligand and its complexes of Zr(IV) and V(IV).e mass spectrum of the ligand gave a molecular ion peak at m/ z � 302.21  .On complexation, the mass spectra of Zr(IV) and V(IV) complexes display molecular ion peaks at m/z 621.11 (40%) and 965.62 (42%), and these data are in good agreement with the proposed molecular formulas for complexes (calc.620.66 and 964.63 amu), respectively.e mass fragmentation pattern of the ligand and complexes are presented in Scheme S1, where the multipeak pattern of the mass spectra gives a series of peaks corresponding to the various fragments.

X-Ray Diffraction.
Since the growth of single crystals of the synthesized complexes failed, PXRD was performed.e powder diffraction patterns of the ligand and its complexes of Zr(IV), Ru(III), and Cd(II) were recorded over 2θ � 5-80 °(Table 4 and Figures 3, S4, and S5).
e position of the highest intensity peak was determined, along with the width of this peak at half-maximum and the d spacing.e diffractogram of ligand displays a reflection with a maximum at 2θ � 15.822 °, corresponding to a d value of 0.559119.e patterns reveal well-defined crystalline peaks indicating the crystalline nature of the ligand and Cd complex, while Zr(IV) and Ru(III) complexes are amorphous in nature [60,63].
e average particle sizes of the ligand and Cd  complexes were calculated using the Scherer equation [66,73], which were 37.48 (ligand) and 42.42 (Cd/ligand) nm.

ermal Studies.
ermogravimetric analysis (TGA) was carried out to probe the thermodynamic stability of the obtained compounds, as well as to collect information about the lattice guests.e TG and differential thermogravimetric (DTG) analyses for the ligand and Zr(IV), V(IV), Ru(III), and Cd(II) metal complexes over the 10 °-800 °C temperature range are shown in Table 5 and Figures 4(a)-4(e).e TG curves for the ligand showed two weight-loss events.e first decomposition was conducted at 197 °-391 °C and was accompanied by a weight loss of 60 In continuation of the thermal investigation, the kinetic and thermodynamic data of complexes (C and D) are listed in Table S1.ese data can be summarized in the following:   Bioinorganic Chemistry and Applications (1) e negative ΔS * indicates that the reactants or intermediates are in a more ordered activated state or have a more rigid structure than the reactants or intermediates, and therefore, the reactions are slower than usual [74] (2) Because ΔH * has positive values, the decomposition processes are endothermic (3) ΔG * has a positive sign, suggesting that the final product's free energy is higher than that of the initial compound and that all degradation steps are nonspontaneous [67] (4) e correlation coefficients of the Arrhenius plots of the thermal decomposition steps were 0.98, showing a good fit with the linear function

Geometric Study.
e geometric optimization was carried out for the investigated ligand and its synthesized complexes (Zr(IV), V(IV), Ru(III), and Cd(II)) with the numbered ring system, as seen in Figure 5. e values of optimization energy, dipole moment, energy gap and hardness (η), ionization potential (I), electron affinity (A), absolute electronegativity (χ), absolute hardness (η), and softness (S) are mentioned in Table 6.
ese molecular properties can be calculated as follows: hardness, η � (I − A)/2; softness (S), S � 1/2η; chemical potential (μ), μ � −(I + A)/2; and electronegativity (χ), χ � (I + A)/2.e reactivity of the complexes under the study follows the order V(IV) > Zr(IV) > Cd(II) > Ru(III).As the energy gap of the studied complexes decreases, the reactivity of the complexes increases.e polarity of the ligand increased after complexation by their coordination with Zr(IV) and  Cd(II) metal ions and vice versa through its coordination with V(IV) and Ru(III), as indicated by the magnitude of their dipole moments.e lower value of the energy gap is defined as corresponding to a soft molecule, and it explains the charge transfer interactions within the molecule, which influences the molecule's biological activity [65].e geometric changes observed in the studied ligand moiety are interesting.us, most of the bond lengths were increased upon complexation with different metal ions.Analysis of the data of the bond lengths is presented in Table 7. us, we can conclude that the bond lengths of C4-O5, N6-N7, and N7-C8 become longer in all complexes, as the coordination takes place via N atoms of the (C � N) azomethine[Rh] and O5 of the carbonyl group.However, C14-O16 bond length was elongated in all complexes except for the Ru(III) complex because O16 carbonyl group shares in coordination with all-metal ions except for Ru(III). is finding is due to the formation of the M-O and M-N bonds, which make the C-O and C � N bonds weaker [Rh].
e bond angles of the ligands are altered relatively upon coordination, as pointed out in Table 7. e atomic charge distribution of the ligand and its complexes is determined by Mulliken population analysis (MPA).
e distribution of positive and negative charges is important from the perspective of an increase or decrease in the bond length between atoms.
e results showed that the best negative atomic charges are related to O16 (−0.470),O5 (−0.430), and N7 (−0.115) atoms in the studied ligand.us, the metal ions preferred the coordination through O5, N7, and/or O16, forming membered rings.Upon chelation, the charge of the coordinated atoms had a slight decrease in its negative value with the decrease in the remaining surrounding atoms that are relative to the ligands because of their involvement in coordination with the metal ions.e atomic charges in Cd and Ru complexes as representative examples were changed to O16 (−0.402),O5 (−0.421 and −0.294), and N7 (−0.218 and −0.072) atoms, respectively.e electron density on the center of V(IV), Cd(II), Zr(IV), and Ru(III) atoms increased to V(0.757), Cd(1.020),Zr(1.354), and Ru(0.177) after complexation because of the charge transfer from the examined ligand to the central metal ions, i.e., L ⟶ M. erefore, the theoretical calculations confirmed the results obtained from the analysis tools, which were discussed in the previous characterization part.
e generated molecular orbital energy diagrams HOMO and LUMO are presented in Figure 6.    14 Bioinorganic Chemistry and Applications

Study on Antibacterial Activity.
e antibacterial of the ligand and its complexes (Zr(IV), V(IV), Ru(III), and Cd(II)) were screened against bacterial species such as Gram-negative bacteria (Escherichia coli and Klebsiella pneumonia) and Gram-positive bacteria (Staphylococcus aureus and Streptococcus mutants).Ampicillin and gentamicin were used as standard drugs for antibacterial studies.
e results of the antibacterial activity of the ligand and complexes are given in Table 8 and Figure 7. ese results suggested that the complexes act as a potent antibacterial agent more than the ligand due to their chelation ability.Furthermore, the Cd(II) complex acquired probably the best antibacterial activity followed by the Ru(III) complex towards bacterial species than others, when ampicillin and gentamicin were used as standard drugs.
e docking results revealed interesting interactions between the investigated compounds and the active site amino acids of ribosyltransferase (code: 3GEY).e OH and NH are the most active functional groups that interact with the protein amino acids, as mentioned in Table 9 and Figure 8.According to the scoring energy value, we found the antibacterial activity order of investigated compounds is Ru complex > V complex > Zr complex > Cd complex > ligand.
Experimentally, the inhibition zone values are in good agreement with the previous scoring energy order.But, based on the number of interactions between compounds and the active amino acids of protein, Cd complex gave excellent agreement with the values of zone of inhibition for all studied microorganisms.us, we can rearrange the activity sequence to be Cd complex > Ru complex > V complex > ligand > Zr complex.Classically, the polarity of a substance can be specified by its dipole moment property.It has been reported that the drug solubility in water increases with increasing dipole moment; i.e., the dipole moment is an important criterion for deciding the penetration of the drug through the cell membrane of the organism and for the speed of excretion.e lip solubility of the compound increases with decreasing dipole moment, thereby favoring its permeation through the lipid layer of the microorganism more efficiently [75,76].Consequently, devastating them more aggressively means that the less-polar drug assists in the penetration of the cell wall and then shifting to the more toxic drug within the cellular environment.e V, Ru, and Cd complexes reflected the lower liposolubility behavior that explains their high antibacterial activities than the ligand and Zr complex.

Cytotoxicity.
e in vitro cytotoxicity of the novel Zr(IV), V(IV), Ru(III), and Cd(II) complexes against the human MCF-7 breast cancer cell line was determined using the MTT assay.
e mitochondrial dehydrogenase movement was estimated as a sign of cell viability in terms of optical thickness.e absorbance values were evaluated by nonlinear regression methods to determine the IC 50 values for the tested compounds in the MCF-7 breast cancer cell line.e cytotoxicity results for the ligand and its complexes of divalent ions Cd(II), trivalent ions Ru(III), and tetravalent ions against the MCF-7 breast cancer cell line at concentrations of 31.25, 62.5, 125, 250, 500, and 1000 μg/ml based on the surviving fraction results and IC 50 values for the different compounds are shown in Figure 9.  Bioinorganic Chemistry and Applications Among the tested compounds, Ru(III) complex (IC 50 � 94.37 μg/ml) exhibited the greatest activity against the MCF-7 breast cancer cell line.e IC 50 values for Cd(II), Zr(IV), and V(IV) complexes and the ligand are in the range of 107.97, 108.5, 180.19, and 192.37 μg/ml, respectively, and they were comparable with that of vinblastine (4.58 μM) [77].
e IC 50 values followed the order vinblastine < Ru(III) L < Cd(II)L < Zr(IV)L < V(IV)L < L. From the obtained results, it is obvious that the prepared ligand and its complexes are potent agents against the MCF-7 breast cancer cell lines.Importantly, the Ru(III) complex, in particular, was more potent than the other complexes and showed concentrationdependent effects, which could suggest its potential use in cancer therapy.
It is known that NUDT5 (nucleotide diphosphate hydrolase type 5) is an upstream regulator of tumor drivers and a biomarker for cancer stratification, as well as a target for drug discovery towards the treatment of aggressive cancer types and metastasis [78].e enzyme NUDT5 catalyzes the ADP (adenosine diphosphate) ribose derived from hydrolysis of poly(ADP-ribose), and pyrophosphate (PPi) is converted to ATP. us, NUDT5 is an attractive target for drug design against breast cancer.e amino acid residues involved in the binding pockets with synthesized molecules are thus predicted.Six possible binding residues mentioned in Table 10 and Figure 10 were involved in interaction with our compound inhibitors.e theoretical sequence interaction activity was compatible with all compounds except for the Ru complex.It may be due to the mechanism of its action being more effective with other types of significant target proteins that control the breast tumor progression.
e structures of the ligand and its complexes were proposed based on the results of different characterization techniques, which confirm the formation of 2 :1 of Zr(IV), 2 : 2 V(IV), 1 : 2 of Ru(III), and 1 :1 (M : L) of Cd(II) complexes.e nonelectrolytic nature of the chelates was observed by their molar conductance values, except for the V(IV) and Cd(II) complexes, which are ionic.e thermal stability of the ligand and complexes was also confirmed.e antibacterial efficacy was tested against a variety of bacteria strains and compared to the well-known standard drugs, ampicillin and gentamicin.ese results suggested that complexes act as a potent antibacterial agent than the ligand due to their chelation ability.Furthermore, the Cd(II) complex acquired better antibacterial activity, followed by the Ru(III) complex towards bacterial species than others.Moreover, the prepared ligand and its complexes are potent agents against the MCF-7 breast cancer cell lines.e IC 50 values followed the order Vinblastine < Ru(III)L < Cd(II) L < Zr(IV)L < V(IV)L < L. DFT calculation was carried out for the prepared compounds.e synthesized ligand and its allmetal complexes had a satisfactory spectrum for their antibacterial activity against bacterial species.e docking simulation pointed out the binding model of all compounds.e interactions with active site amino acids of ribosyltransferase (code: 3GEY) and NUDT5 (PDB code : 5NWH) of interest in treating bacterial infection and breast cancer, respectively, involved the hydrogen bond formation and arenecation interaction.erefore, the current findings provide a new chance for the development and discovery of antimicrobials to beat the ever-increasing drug resistance problem.

3 Scheme 1 :
Scheme 1: e suggested chemical structures of the ligand and its metal complexes.
455 (]M-N) and 621-571 (]M-O) cm −1 and which confirms the participation of N atom of the azomethine group [67] and (carbonyl) O atom in formation of the complexes to form a hexagonal ring with the carbaldehyde moiety, where the bands at ranges (571, 506), (621, 553), (605, 560), and (587, 455) cm −1 corresponded to ν(M-O)and ν(M-N) for Zr(IV), V(IV), Ru(III), and Cd(II) metal complexes, respectively[39].On the other hand, the broad band at 1677 and 1639 cm −1 was assigned to the (ν(C � O) side and ring) and shifted to 1692 and 1644 in the Zr(IV) complex, 1692 and 1644 in the Ru(III) complex, 1689 and 1650 in the V(IV) complex, and 1669 and 1638 cm −1 in the Cd(II) complex, confirming the participation of (ν(C � O) side and ring) in the

Figure 1 :
Figure 1: FT-IR spectra of the ligand and Cd(II) complex (D).

Figure 3 :Figure 4 :
Figure 3: PXRD powder pattern of the ligand and Cd(II) complex.

Figure 5 :
Figure 5: Optimized geometry of the ligand and its metal complexes.

Figure 6 :
Figure 6: Molecular graphs of the ligand and its metal complexes.

Figure 7 :
Figure 7: In vitro antibacterial activity of the ligand and its metal complexes.

50 Figure 9 :
Figure 9: IC 50 values of the ligand and its complexes against the MCF-7 breast cancer cell line.

Table 1 :
Physicochemical parameters of the ligand and its complexes of Zr(IV), V(IV), Ru(III), and Cd(II) ions.

Table 3 :
e electronic spectra and magnetic data of the ligand and its Zr(IV), V(IV), Ru(III), and Cd(II) complexes.

Table 6 :
Ground-state properties of the ligand and its metal complexes by using B3LYP/6-311G and B3LYP/LANL2DZ, respectively.

Table 8 :
Results of antibacterial bioassay of the ligand (H2L) and its complexes of Zr(IV), V(IV), Ru(III), and Cd(II) against different strains of bacteria.

Table 10 :
Binding affinity of compounds against the breast cancer regulator NUDT5 (PDB code : 5NWH).