Synthesis, Theoretical Study, and Biological Evaluation of Some Metal Ions with Ligand "Methyl -6-[2-(4-Hydroxyphenyl) -2-((1-Phenylethylidene) Amino) Acetamido] -2,2-Dimethyl-5—Oxo-1-Thia-4-Azabicyclo [3.2.0] Heptane-3-Carboxyylate

: Schiff base (methyl 6-(2-(4-hydroxyphenyl) -2- (1-phenyl ethyl ideneamino) acetamido) -3, 3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0] heptane-2-carboxylate)Co(II), Ni(II), Cu (II), Zn (II), and Hg(II)] ions were employed to make certain complexes. Metal analysis M percent, elemental chemical analysis (C.H.N.S), and other standard physico-chemical methods were used. Magnetic susceptibility, conductometric measurements, FT-IR and UV-visible Spectra were used to identified. Theoretical treatment of the generated complexes in the gas phase was performed using the (hyperchem-8.07) program for molecular mechanics and semi-empirical computations. The (PM3) approach was used to determine the heat of formation (ΔH˚f), binding energy (ΔEb), and total energy (ET) for ligands and metal complexes at 298 ᴼK. To explore the reactive sites of the compounds, the electrostatic potential of the ligand (L) was computed. PM3 was used to calculate the vibrational frequencies of the ligand (L) and its metal complexes, which were then compared to experimental data. The antibacterial activity of (L) and its metal complexes against three harmful microorganisms were examined: Staphylococcus aureus (gram positive), Echerchia coli (gram negative), and Candida albicans .


Introduction:
Biological activity of Schiff base and its complexes have been discovered. Antifungal, antibacterial, antimalarial, antipyretic, larvicidal, and antiviral activities are among the qualities understudy. In addition to biological activities, Carbonylation, hydroformylation, reduction, oxidation, epoxidation, and hydrolysis, as well as corrosion and enzyme inhibition, all use Schiff base metal complexes as catalysts, as well as polymers [1][2][3] Amoxicillin is a semisynthetic penicillin derivative that is active against Gram positive and, to a lesser extent, Gram negative bacteria. 6-[D(-) Amino-p-hydroxypenyl) acetamido] peninillanic acid or -amino-p-hydroxyl benzyl penicillin is its nomenclature, according to penicillin.
Amoxicillin belongs to the penicillin group of antibiotics. Due to their particular bacterial toxicity, they are a very significant class of B-lactamic antibiotics used in therapy. All B-lactamic antibiotics have a number of probable donor sites and are known to interact efficiently with a variety of metal ions and organometallic moieties, resulting in complexes, according to coordination chemistry 4,5 .
Metals have an esteemed place in medicinal chemistry, most antibiotics do not need metal ions for their biological activities, but there are a number of antibiotics that require metal ions to function properly, such as bleomycin. Streponigrin and bacitracin drugs have gained recognition, and they are more effective than pure drugs 6 , this is due to the fact that metal ions can interact with many different kinds of biomolecules including DNA, RNA, proteins and lipids rendering their unique and specific bioactivities 7 . This work describes the process of synthesizing a new Shiff -imine ligand along with its Cu(II), Co (II) , and Ni (II), Zn (II) coordination compounds. The new synthesized compounds have been characterized by means of some spectral procedures. Biological activities of compounds have been tested by using three bacterial types.

Materials and Methods:
All metal salts used in this work were obtained from Fluka (CoCl2.6H2O, NiCl2.6H2O, CuCl2.2H2O, ZnCl2.6H2O, HgCl2). Uv-Vis 1600A Shimadzu was used to record the electronic spectra at wave length range of 190-1100 nm. A Shimadzu 8400 Fourier Infrared Transform Spectrophotometer with a wave number range of 4000-200 cm -1 was used to measure FTIR. A Perkin Elmer 500 Atomic Absorption Spectrophotometer was used to conduct the metal analysis. Conductivity Meter 220 with Gallencamp was used to calculate the molar conductivity in ethanol as a solvent at room temperature, M.F.B-600.01 was used as a melting device. Magnetic susceptibility balance model MSB-MKT was used for magnetic moment measurement.

Infrared Spectra
At 1731 and 1681 cm -1 , the ligand has two bands that correspond to the carbonyl of amide and βlactam, respectively 9 Fig 1. In all compounds, the amide group's carbonyl was moved to a lower wave number, yielding in bands at (435-470) cm -1 , which is attributed to the M-O band 10 .
The β -lactam band has remained unchanged, indicating that the oxygen atom in this group is not involved in complicated coordination of these complexes. At 1628 cm -1 , the ligand's third band corresponds to the imine (C=N) group 11 , this band was shifted to lower frequency about (17-32) cm -1 in all complexes indicating that azomethane moiety is involved in the complex formation Fig 2 FTIR for L-Co complex.
In all complexes, this band changed to a lower frequency, indicating that azomethane is involved in their creation. The appearance of a new band ranging from (540-575) cm -1 in all complexes to the M-N bond 12 supports the coordination of this group through nitrogen atoms. Table 2 contains a list of other bands.

Uv-Visible Spectra
The electronic spectra of the synthesized ligands showed several peaks between 200-400 nm which were assigned to n→π*and π→ π*transitions to the C-O, C-N, and C=C transition respectively Fig3. The spectra helped us to expect the suggested geometry according to the shape and number of observed peaks 13 For L-Co complex showed three bands in the wave number (10537, 19921, 23991) cm -1 respectively for oh geometry. Table 3 shows the  absorption bands and their assignments Fig4. L-Ni complex showed three bands in the wave number (96993,14749,26178) cm-123, L-Cu complex has two bands (12453, 23984) cm-1.
L-Zn and L-Hg with d 10 electronic configuration were not expected to show (d-d) electronic transition because of the filled (d) orbital 14,15 , this complex did not show clear band in the visible region. Table 3. Electronic Spectra data and their probable assignments, magnetic moment data of the L and new prepared complexes

Antibacterial and Antifungal Activities
Human and animal pathogenic microbes cause a variety of diseases. The discovery of Chemotherapeutic drugs has a critical role in regulating and preventing such diseases. Microorganisms can acquire resistance to these chemotherapeutic drugs, and resistant strains pose a significant difficulty in the treatment of microbial illnesses. Searching for new antimicrobial agents becomes something very necessary. As a result, much effort has been expended in the search for novel antibiotics or molecules with a good antimicrobial activity that could be exploited as chemotherapeutic drugs 15 .
The antibacterial effectiveness of the synthesized compounds was examined in vitro against two pathogenic bacteria species in this study: Antifungal Candida albicans, as well as Gram positive (Staphylococcus aureus) and Gram negative (Escherchia coli) bacteria. Furthermore, as shown in Table 4, the presence of metal ions in the complexes affects the final biological screening in vitro in a variety of ways.

Computational Chemistry
Computational chemistry is one of the chemical applications to solve chemical problems using mathematical applications based on molecular shape (sample molecular) .To build a molecular model accurately based on the electronic build method that relies on quantum mechanics , you must increase the storage capacity and increase the processor speed ,so another method (semi-empirical method ) was introduced to resolve this problem by introducing experimental spectral values for the purpose of speeding up the calculation calendar style treatment 16,17 .

Theoretical Energies and Dipole Moment
The program Hyperchem-8.07 is used to compute the heat of formation (ΔH°f), binding energy (ΔEb), and dipole moment (µ) for ligands and their formed complexes using semi-empirical and molecular mechanic approaches PM3, DFT methods, in addition to calculating some identification vibration in IR spectra and molecular orbital HOMO and LUMO for ligand 18 ,Figs. 5,6 . A comparison of experimental and theoretical vibrational frequencies for ligand and their complexes are shown in Table 6. While the heat of formation (ΔH°f), binding energy (ΔEb), and dipole moment (µ) for 1-((dicyclohexylamino) methyl)-3-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1Hpyrzol-4-ylimino) indolin-2-one and all produced complexes are shown in Table 5 the results revealed that all complexes are stable.

Computational Details
Hyper-chem8.07 was used to accomplish the current quantum chemistry computations the energy of the highest occupied molecular orbital and other molecular characteristics (EHOMO),the lowest empty molecular orbital's energy (ELUMO). The molecule's energy gap (E= ELUMO -EHOMO), dipole moment (µ), and total energy (ET) were calculated. The reactivity parameters were then calculated using the conceptual framework of DFT [19][20][21][22] . So, the chemical potential is defined as Eq.1: µp= (

∂E ∂N
)ν(r)=-χ 1 Where is the chemical potential, E is the total energy, N is the number of electrons, ν(r) is the external potential of the system and is the global electro negativity. The global hardness is given by Eq.2: µp= ( According to the definition, this index measures a chemical species' propensity to accept electrons. Good electrophile behavior is indicated by a high electrophilicity index value, whereas good nucleophile behavior is indicated by a low electrophilicity index value 24 .

Quantum Chemistry Study
The calculated quantum chemical parameters are displayed in Table 5.       (7)

Conclusions:
The new Schiff base ligand and its metal complexes were successfully synthesized and characterized. Physio-chemical and spectroscopic approaches were used to determine the mode of bonding and overall structure of the complexes. The Hyperchem-8.07 program has been used to predict the structural geometries of all compounds in gasphase using PM3 program to calculate physical parameter (∆E & ∆H). The free ligand (L) and its metal complexes showed a significant antibacterial activity. All complexes were found to be more effective than the free ligand.