The document discusses the synthesis of Schiff base ligands and their metal complexes, and characterization of the compounds. It then examines the biological activities of some complexes, including their ability to interact with DNA through intercalation, and inhibition of fungal growth through antifungal testing. The goal was to enhance knowledge of Schiff base metal complexes and investigate their potential biological applications.

1. 1

2. SYNTHESIS OF SCHIFF BASE COMPLEXES AND
THEIR BIOLOGICAL STUDIES
Supervisor:- Dr. Khalil Ahmad
Co-supervisor:- Prof. Dr. Saqib Ali(QAU)
Hafiz Muhammad Asif
2

3. 3

4. Mechanism
4

5. Schiff bases are valuable intermediate
products of organic synthesis
Schiff bases are used as inhibitors
They show their efficiency in both
homogenous and heterogeneous reactions
Schiff bases can be used as an important
intermediates in many enzymatic reactions
5

6. Aims and Objectives
 The primary goal of this study is to enhance the knowledge Schiff bases and their complexes of
Ni(II), Co(II), zinc(II), Cu(II) and Cd(II) chemistry which include,
 Synthesis of Schiff bases of metaphnylene diammine and para phenylene diammine with
pyridine-2-aldehyde.
 Synthesis of Ni(II), Co(II), zinc(II), Cu(II) and Cd(II) complexes with Schiff bases.
 Characterization of synthesized compounds by elemental analysis, IR, NMR spectroscopy.
 To investigate the anti-microbial properties (anti-fungal and ant-bacterial).
 To carry out enzymatic inhibition studies of some synthesized compounds
 To investigate the DNA interaction studies of some synthesized compounds.
6

7. EXPERIMENTAL SCHEME
Pyridine-2-aldehyde m-phenylenediamine
reflux for 3
hrs
ion
at
ex
Concentrate by Rotary evaporator
pl
m
co freeze for 5 days
Schiff base ligand Filter
A
washed,dried and characterized
B
Schiff base complexes
A= LIGAND SYNTHESIS SCHEME
B=COMPLEXATION SCHEME
Characterized Activities
7

8. + 2 O EtOH N N
H2N NH2 N -2H2O N N
O EtOH
H2N NH2 + 2 N N N
N
N -2H2O
8

9. Synthesis of complexes
N N EtOH
N N
+ 2MCl2.xH2O
N N N N
M M
Cl
Cl
Cl Cl
Cl Cl
N EtOH M
N
N N + 2MCl2.xH2O N N
N N
M
Cl Cl
9

10. Table : Melting points(0C) of compounds
Compound Melting Compound Melting
point(0C) point(0C)
B1 152 B2 149
B1Ni >300 B1Cu >300
B1Cd >300 B2Cu >300
B2Zn >300 B2Ni >300
10

11. Compound Solvent Solubility Compound Solvent Solubility Compound Solvent Solubility
B1 Methanol completely B1 Chloroform completely B1 DMSO completely
soluble soluble soluble
B1Cd Methanol not soluble B1Cd Chloroform slightly B1Cd DMSO soluble
soluble
B1Cu Methanol soluble on B1Cu Chloroform partially B1Cu DMSO completely
heating soluble soluble
B2 Methanol completely B2 Chloroform completely B2 DMSO completely
soluble soluble soluble
B2Ni Methanol not soluble B2Ni Chloroform not soluble B2Ni DMSO not soluble
B2Cu Methanol completely B2Cu Chloroform completely B2Cu DMSO completely
soluble soluble soluble
B2Zn Methanol partially B2Zn Chloroform partially B2Zn DMSO completely
soluble soluble soluble
11

12. Table : Solubility of Compounds
Compound Solubility
Methanol Chloroform DMSO Ethanol Benzene
B1 completely completely completely completely not soluble
soluble soluble soluble soluble
B1Cd not soluble slightly soluble soluble not soluble not soluble
B1Cu
B2
B2Ni
B2Cu
B2Zn
12

13. 1H-NMR Studies of B1 and its Complex
Compound 1H-NMR Values(ppm)
B1 5
8.70 d (2H, H12&H12’)
4 6 8.65 s (2H, H7 & H7’)
9 ' 7' 7 9
8.21 dd (2H,H10 & H10’)
' 8' 8 8.00 d (2H,H9 & H9’)
10 3 10
N 1 N
2 7.80 dd (1H,H5)
11'
N N 11 7.80 dd (2H,H11 & H11’)
12 '
12 7.39 d (2H,H4 & H6)
6.72 s (1H,H2)
B1Cd 5 8.83 d (2H, H12&H12’)
4 6 8.74 s (2H, H7 & H7’)
9' 7' 7 9 8.19 dd (2H,H10 & H10’)
' 8' 8
10 3 10 8.08 d (2H,H9 & H9’)
N 1 N
2
N Cd Cd N
7.92 dd (1H,H5)
11' 11
'
Cl Cl 7.71 dd (2, HH11 & H11’)
12 12
Cl Cl 7.32 d (2H,H4 & H6)
6.55 s (1H,H2)
13

14. 1H-NMR Studies of B1 and its Complex
Compound 1H-NMR Values(ppm)
B2 11' 6
8.73d (2H, H12&H12’)
12' 7' 5 9
10' N 8N
8.65 s (2H, H7 & H7’)
N 10
9'
N 8'
4
2
1 8.22 dd (2H,H10 & H10’)
3 7
12
11
7.86 d (2H,H9 & H9’)
7.37 dd (4H,H2,H3,H5 & H6)
7.28 dd (2H,H11 & H11’)
B2Zn Cl Cl 8.90d (2H, H12&H12’)
11' 12' 7' 5
6 Zn
9 8.73 s (2H, H7 & H7’)
10'
N 8' N 1
N 8N
10 8.22 dd (2H,H10 & H10’)
4
9'
Zn 3 2 7
11
7.96 d (2H,H9 & H9’)
12
Cl Cl 7.37 dd (4H,H2,H3,H5 & H6)
7.28 dd (2H,H11 & H11’)
14

15. Table:13C NMR values
Compound C1 C2 C3 C4 C5 C6 C7, C7’ C8, C8’ C9, C9’ C10, C11, C11’ C12,
C10’ C12’
B1 150.2 121.8 150.2 127.8 136.4 127.8 158.2 150.3 131.7 136.5 128.0 149.2
B1Cd 148.3 121.0 148.3 127.0 136.4 127.0 151.8 150.3 131.7 136.8 128.7 149.0
B2 149.2 122.2 122.2 149.2 122.2 122.2 154.0 160.0 121.9 136.6 125.1 149.7
B2Zn 147.5 122.2 122.2 147.5 122.2 122.2 151.8 157.0 121.9 136.6 125.1 147.0
15

16. 13C-NMR values(ppm) of B1
136.4 121.8 158.2
150.3
127.8 131.7
5
4 6
9' 7' 7 9
'
' 8 8
10 3 10 136.5
N 1 N
2
N N
11' 11
'
12 12
121.8 150.2
128.0
149.2
16

17. 13C-NMR values(ppm) of B1Cd
136.4 127.0 151.8
150.3
127.0 131.7
5
4 6
9' 7' 7 9
'
' 8 8
10 3 10 136.8
N 1 N
2
N Cd Cd N
11' Cl 11
Cl
12' Cl Cl 12
121.0 148.3
128.7
149.0
17

18. Compound Ar ― H Ar (C = C) CH = N meta- Ar (N = C)
disubstituent
B1 3002 cm-1 1567 cm-1 1590 cm-1 832 cm-1 1505 cm-1
B1Ni 3185 cm-1 1538.8 cm-1 1558cm-1 1021.0 cm-1 1472 cm-1
B1Cd 3359.7 cm-1 1591.4 cm-1 1478.6 cm-1 1015.3 cm-1 1436.2 cm-1
18

19. Compound Ar ― H Ar (C = C) CH = N para- Ar (N = C)
disubstituent
B2 3006 cm-1 1573 cm-1 1621 cm-1 822 cm-1 1506 cm-1
B2Zn 3030.7 cm-1 1580 cm-1 1590 cm-1 838 cm-1 1514 cm-1
B2Co 3052.9 cm-1 1494 cm-1 1594 cm-1 839.3 cm-1
B2Cd 3074.9 cm-1 1478 cm-1 1615.5 cm-1 840.1 cm-1 1500 cm-1
B2Cu 3050.7 cm-1 1498 cm-1 1596 cm-1 852.3 cm-1 1494.3 cm-1
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20. DNA interaction studies
Anti-fungal activity
Anti-bacterial activity
Enzymatic studies
20

21. Drug-DNA interaction by Viscometric studies
 In tested compounds viscosity of the DNA solution
increases with increasing concentration of the
complexes. The consumption of complexes by DNA
molecules shows the intercalative mode of binding of
the complexes with DNA. As with intercalation the
size of the DNA helix increases and the mobility of the
DNA molecule decrease, so the viscosity increases.
21

22. Graphical representation of DNA-Drug Interaction
B1Cu B2Cu
1.6
1.6
1.4
1.4
1.2
1.2
1
(η / η o )1/3
1
(η / η o )1/3
0.8 0.8
0.6 0.6
0.4 0.4
0.2 0.2
0 0
0 0.05 0.1 0.15 0.2 0 0.05 0.1 0.15 0.2
r = [comp]/[DNA] r = [comp]/[DNA]
22

23. DNA Interaction
B1Ni B2Zn
1.6 1.6
1.4 1.4
1.2 1.2
1
(η / ηo )1/3
1
1/3
(η / η o )
0.8 0.8
0.6
0.6
0.4
0.4
0.2
0.2
0
0
0 0.05 0.1 0.15 0.2
0 0.05 0.1 0.15 0.2
r = [comp]/[DNA]
r = [comp]/[DNA]
23

24. Metal-DNA Interaction
A=Adenine, T=Thymine C=Cytocine, G=Guanine
O NH2 N
NH2 O N
N N
T-M-A R
N R N N
N C-M-G
N N
M N
M
N
O X O X
R H2N R
24

25. Anti-fungal activity
Percent inhibition = 100 – [fungal growth in sample (cm)/fungal growth in
control (cm) x 100] (Standard drug; Turbinafine)
Compound Concentration Negative Culture Fungal % Inhibition
(mg/ 100mL) Control Length Growth of Fungal
Growth/ (in Control) Length Growth
DMSO (cm) (in Sample)
(cm) (cm)
B1 1.00 9.00 10.00 8.50 15.00
3.00 9.50 10.00 6.20 38.00
10.00 9.60 10.00 4.30 57.00
B1Cu 1.00 8.00 8.00 6.00 25.00
3.00 8.50 8.00 4.00 50.00
10.00 8.30 8.00 3.00 63.00
B1Cd 1.00 9.00 10.50 5.50 48.00
3.00 9.50 10.50 4.30 59.00
10.00 9.00 10.50 1.20 89.00
B2Zn 1.00 8.20 9.50 8.20 14.00
3.00 8.30 9.50 7.50 21.00
10.00 8.00 9.50 6.10 36.00
25

26. Zone of Inhibition = [Zone of inhibition of
the chemical compound/Zone of
inhibition of the standard
(Imipenem)]x100
Antibacterial Activity of certain chemicals against locally isolated
pathogens from (1) urinary tract infections (Indigenous uropathogens)
and (2) other hospital acquired infections. The results are given in the
table.
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27. Table: Antibacterial activity
Staphylococ Klebsiellap Micrococcu Escherichia Staphylococ Klebsiellap Micrococcu Escherichia
cus aureus neumoniae s luteus(2) coli(1) cus aureus neumoniae s luteus(2) coli(1)
(2) (1) (G +ve) (G -ve) (2) (1) (G +ve) (G -ve)
(G +ve) (G -ve) (G +ve) (G -ve)
Compound Radius % Radius % Radius % Radius %
(mm) value (mm) value (mm) value (mm) value
Imipenem 18 100 18 100 18 100 18 100
B1Cu 08 44 11 62 05 27 09 50
B1Cd 09 50 12 66 07 38 08 44
B2Ni 07 38 10 55 07 38 04 22
B2Cd 08 44 7 38 06 33 05 28
B2Zn 11 62 8 44 04 22 09 50
B1 06 33 9 50 00 00 4 22
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28. Graph: Antibacterial activity
28

29. Enzymatic studies
B1Cu(Series1),B1Cd(Series2) B2Ni(Series1),B2Cd(Series2),B2Zn(Series)
29

30. Conclusion
 Schiff bases and their complexes were synthesized.
 NMR, FT-IR, and UV-Visible spectroscopy techniques
were used to characterize the synthesized compounds.
 Melting point experiments show that the synthesized
Schiff base complexes exhibit a significant thermal
stability.
 complexes were found to be potent inhibitors of ALP.
 DNA interaction studies revealed that the ligand B2
and the complexes B1Cu, B1Cd, B2Ni, B2Cd, B2Zn have
strong interaction with DNA.
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31. Acknowledgment
 Dr. Khalil Ahmad
 Prof. Dr. Saqib Ali (QAU)
 Chairman Department of Chemistry (UAJ&K)
 All Respected Teachers
 My Class & Lab Fellows
 Special thanks to Miss. Farzana Shaheen (QAU)
 Dr. Hafiz Zia-ur-Rahman
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32. Thanks
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