Synthesis and Characterizations Schiff Base New and Use it as Antagonists Antibacteria

 

The number of algorithms available for ligand-protein interactions is many and constantly increasing. This diversity in computational algorithms provides a large number of techniques to address modern drug design problems. Prediction of both the binding and affinity between ligand and protein is referred to as doking[11]. Understanding the structural determinants of the protein-ligand interaction and knowing the free energy (ΔG bind) are of great importance in the manufacture of pharmaceutical compounds, since it is a useful approach in the early stages of the drug discovery process, which helps to save time, effort and costs. Molecular docking is one of the most established methods for visualizing the interaction between a ligand and a protein and evaluating the binding mode of small molecules within the receptor binding site[11].

 

Nuclear Magnetic Resonance Spectra (1H-NMR (

NMR spectra of free ligands were recorded in DMSO-2.51. H-NMR of L1 shows the signals (ppm) at (7.5572- 7.8722), (4H, Ar-H), (1H- N=CH),) (1H, C-H-triazole), and (14.72) replace (1H, N-H). H-NMR of L2 shows the signals (ppm) at (7.5572- 7.8722), (4H, Ar-H), (1H- N=CH),) (1H, C-H-triazole), and (14.72) replace (1H, N-H) and showed (6H) at 3ppm replace to (CH3) 2-N. H-NMR of L3 shows the signals (ppm) at (7.5572- 7.8722), (4H, Ar-H), (1H,- N=CH),) (1H, C-H-triazole), and  (14.72) replace (1H, N-H) and showed (6H) at1.5ppm replace to ( CH3) 2-C and 1H at 5ppm replace to C.

 

Figure (2) showed of H-NMR SPECTRUM Ligand6

 

Figure (3) showed of H-NMR SPECTRUM Ligand 7.

 

Figure (4) showed of H-NMR SPECTRUM Ligand9.

 

H NMR spectrum of ligand shows the signals (ppm) at 13 ppm( s-H),4H at 6.9-7.50ppm replace to (C-H) aromatice,1H at 8.71ppm N=C-H and 6H at 3ppm replace to N-(CH₃)2  HNMR of L2

 

H NMR spectrum of ligand shows the signals (ppm) at 13.23 ppm( s-H ),3H at 1.79ppm replace to (-CH₃),1H at 8.10ppm N=C-H and 2H at 1.4-1.6 ppm replace to C=CH₂

 

Fig (5) 1H-NMR spectra of the ligands (4).

 

Fig (6) 1H-NMR spectra of The ligands(8). 1-2-    FT-IR Spectra

 

 

FT-IR of the complex ligand and its complexes was carried out from the KBr tweak to its ligand and Cs-I to the complexes.  The Five bonding showed four main bands at (3100) cm-1, (2900) cm-1, (1608) cm-1, (825) cm-1, (1735) and (1327) which were attributed to (C-H), (υ H - N) imine, (C=N), (C-CL) (N-C), and movement ranges of the structure respectively, as shown in Table 1.

 

Table 1. IR frequencies (cm-1) of the compound and their metal complexes.

 

Figure (6)IR frequencies (cm-1) of the compound and their metal complexes of L7.

 

FT-IR of the complex ligand and its complexes was carried out from the KBr tweak to its ligand and Cs-I to the complexes.  The sex bonding showed four main bands at (2984) cm-1, (2905) cm-1, (1618) cm-1, cm-1, (825) and (1735) which were attributed to (C-H), (υ H – N) imine, (C=N), (C-CL) (N-C), and movement ranges of the structure respectively, as shown below in Table 2.

 

Table 2. IR frequencies (cm-1) of the compound and their metal complexes

 

Figure (7)IR frequencies (cm-1) of the compound and their metal complexes of L1.

 

FT-IR of the complex ligand and its complexes was carried out from the KBr tweak to its ligand and Cs-I to the complexes.  The sex bonding showed four main bands at (3237) cm-1, (2960) cm-1, (1617) cm-1, (1560) cm-1, (1478) and (1757) which were attributed to (C-H), (υ H = N) imine, (C=N), (C-CL) (N-C), and movement ranges of the structure respectively, as shown below in Table 3.

 

Table 3. IR frequencies (cm-1) of the compound and their metal complexes.

 

Figure (8)IR frequencies (cm-1) of the compound and their metal complexes of L3.

 

FT-IR Spectra

FT-IR Spectra FT-IR of the synthesized ligand  were carried out KBr disc to ligand and CsI for complexes. The free ligand exhibited six major bands at (2924.09) cm-1, (1608) cm-1,(1481) cm-1,(1327) cm-1, which are attributable to (υ MN), (υ SH),  (υ C=N) imine,(υ C-s-C) , (N-C), asy and structure movement bands respectively, as shown below (table1). New bands were formed attributed to the coordinated (CBr) bonds and appeared at the region (536,578,536) cm-1. This indicates that the coordinate occurred through the (N)and (S) atoms (Table 2). 

 

Fig (9) FT.IR spectrum of the ligands.

 

Table 3. IR frequencies (cm-1) of the compounds.

 

Molecular docking

Molecular docking was conducted using AutoDock software  . The 3D crystal structures of the E.coli protein (PDB ID: 2Q85) were retrieved from the Protein Data Bank. We used the AutoDock 4.2 to study the interactions between the protein and ligands. We submitted the PDB format of the protein and ligand in preparation for docking. Protein structures uploaded in PDB format to AutoDock are automatically cleaned with all water molecules removed and hydrogen polar atoms added to the structure using MGL Tools. After that, the active sites in the crystal structures of the protein . To visualize the molecular structures, we employed Discovery Studio 2021 Client[12].

 

Molecular docking analysis

The interaction between ligand 11 and E.coli was studied using AutoDock . The complex with least binding affinity −9.11 kcal/mol  was selected for protein ligand interaction study. Fig. 1 showed the interaction between recombinant compound 11 with E.coli . The amino acids involved in catalytic activity of E.coli were determined through docking. Our docking observation suggested the involvement of TYR-125A, GLY-126A and TYR-190A residues in the formation of recombinant compound11-E.coli complex with bond length of 2.20, 2.10 and 1.77 Ao respectively. These docking results suggests that, TYR-125A, GLY-126A, and TYR-190A are critical for compound11-E.coli interaction. The surrounding hydrophobic amino acids further stabilized the complex and enhanced enzyme activity and thermo stability [13] .

 

Fig (9) : Predicted 3D and 2D  structure of compound11-E.coli complex

 

Molecular docking

Molecular docking was conducted using AutoDock software. The 3D crystal structures of the E.coli protein (PDB ID: 2Q85) were retrieved from the Protein Data Bank. We used AutoDock 4.2 to study the interactions between the protein and ligands. We submitted the PDB format of the protein and ligand in preparation for docking. Protein structures uploaded in PDB format to AutoDock are automatically cleaned with all water molecules removed and hydrogen polar atoms added to the structure using MGL Tools. After that, the active sites in the crystal structures of the protein. To visualize the molecular structures, we employed Discovery Studio 2021 Client [12, 13-19].

 

Molecular docking analysis

The molecular fusion results for the compounds were as shown in Table 4

 

Table 4 : Molecular docking results for the compounds under study

 

The hydrogen bonds of the studied compounds were as shown in Table 5

 

Table 5: Hydrogen Bonds and Amino acids   and bond Length

 

As that Hydrophobic Interactions and π-Stacking were as shown in Table 6.

 

Table 6: Hydrophobic Interactions and π-Stacking

 

The associations between the compounds and the protein are shown as in table 7.

 

Table 7: Bonding of compounds with the target proton in 2D and 3D

 

The interaction between ligand 11 and E.coli was studied using AutoDock . The complex with least binding affinity −9.11 kcal/mol  was selected for protein ligand interaction study. Fig. 1 showed the interaction between recombinant compound 8 with E.coli . The amino acids involved in catalytic activity of E.coli were determined through docking. Our docking observation suggested the involvement of TYR-125A, GLY-126A and TYR-190A residues in the formation of recombinant compound11-E.coli complex with bond length of 2.20, 2.10 and 1.77 Ao respectively. These docking results suggests that, TYR-125A, GLY-126A, and TYR-190A are critical for compound11-E.coli interaction. The surrounding hydrophobic amino acids further stabilized the complex and enhanced enzyme activity and thermo stability.

 

Fig (11): Predicted 3D and 2D  structure of compound8-E.coli complex

 

Method for preparing a standard solution saturated with the prepared materials

1-A measured amount of each compound was taken at a concentration of 0.05M, and the weight was calculated according to the law of molar concentration.

2- Each ligand was dissolved in a 20ml conical boat with DMSO solvent, and the volume was completed to the end.

3- Tests of the effectiveness of these substances against bacteria were carried out at the Biotechnology Center, Al-Nahrain University

 

Table It shows the use of weights and concentrations of solutions for each ligand

 

 

The antibacterial activity of the prepared compounds was studied against a type of Escherichia coli (Gram-negative bacteria) as shown in Table No. (8): -

 

Table 9: Antibacterial activity test data (inhibition area in mm) for the prepared compounds.

(+++) ; high active – inhibition zone = 20 mm , (++) :moderate active - inhibition zone =14-20 mm , (+) : slighly active - inhibition zone = 9-14 mm , (-) : inactive

 

Figure (12):- The biological effect of the compounds on Escherichia coli bacteria

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