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SYNTHESIS OF SCHIFF BASE COMPLEXES AND THEIR BIOLOGICAL STUDIES

Supervisor:- Dr. Khalil AhmadCo-supervisor:- Prof. Dr. Saqib Ali(QAU)

Hafiz Muhammad Asif

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Introduction Schiffbase A Schiff base, named after Hugo Schiff, is a compound with a functional group that contains a carbon-nitrogen double bond with the nitrogen atom connected to an aryl or alkyl group, not hydrogen. The general formula of the Schiff bases is R1R2C=N-R3, where, R3 = aryl or alkyl group that makes the Schiff base a stable imine.

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Mechanism

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Uses of schiff base complexes

Schiff bases are valuable intermediate products of organic synthesisSchiff bases are used as inhibitorsThey show their efficiency in both homogenous and heterogeneous reactionsSchiff bases can be used as an important intermediates in many enzymatic reactions

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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.

 

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EXPERIMENTAL SCHEME

reflux for 3 hrs

Concentrate by Rotary evaporator

freeze for 5 days

Filter

washed,dried and characterized

Schiff base ligand

A

B

Schiff base complexes

Characterized Activities

A= LIGAND SYNTHESIS SCHEMEB=COMPLEXATION SCHEME

Pyridine-2-aldehyde m-phenylenediamine

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Synthesis of 1,3 and 1,4-bis (iminopyridyl)benzene(SCHIFF BASES)

NN

N NH2N NH2

+ 2

N

O EtOH

-2H2O

NNH2N + 2N

O EtOH

-2H2ONH2 N N

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Synthesis of complexes

NN

N N

EtOHNN

N N+ 2MCl2.xH2O

M MCl

Cl Cl

Cl

NN

EtOHN N

M

M

ClCl

Cl Cl

NNN N

+ 2MCl2.xH2O

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Table : Melting points(0C) of compounds

Compound Melting point(0C)

Compound Melting point(0C)

B1 152 B2 149

B1Ni >300 B1Cu >300

B1Cd >300 B2Cu >300

B2Zn >300 B2Ni >300

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Table : Solubility of Compounds

Compound

Solvent Solubility Compound

Solvent Solubility Compound

Solvent Solubility

B1 Methanol completely soluble

B1 Chloroform

completely soluble

B1 DMSO completely soluble

B1Cd Methanol not soluble B1Cd Chloroform

slightly soluble

B1Cd DMSO soluble

B1Cu Methanol soluble on heating

B1Cu Chloroform

partially soluble

B1Cu DMSO completely soluble

B2 Methanol completely soluble

B2 Chloroform

completely soluble

B2 DMSO completely soluble

B2Ni Methanol not soluble B2Ni Chloroform

not soluble B2Ni DMSO not soluble

B2Cu Methanol completely soluble

B2Cu Chloroform

completely soluble

B2Cu DMSO completely soluble

B2Zn Methanol partially soluble

B2Zn Chloroform

partially soluble

B2Zn DMSO completely soluble

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Table : Solubility of CompoundsCompound

Solubility

Methanol Chloroform DMSO Ethanol Benzene

B1 completely soluble

completely soluble

completely soluble

completely soluble

not soluble

B1Cd not soluble slightly soluble soluble not soluble not soluble

B1Cu

B2

B2Ni

B2Cu

B2Zn

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1H-NMR Studies of B1 and its Complex

Compound 1H-NMR Values(ppm)

B1 8.70 d (2H, H12&H12’)8.65 s (2H, H7 & H7’)8.21 dd (2H,H10 & H10’)8.00 d (2H,H9 & H9’)7.80 dd (1H,H5)7.80 dd (2H,H11 & H11’)7.39 d (2H,H4 & H6)6.72 s (1H,H2)

B1Cd 8.83 d (2H, H12&H12’)8.74 s (2H, H7 & H7’)8.19 dd (2H,H10 & H10’)8.08 d (2H,H9 & H9’)7.92 dd (1H,H5)7.71 dd (2, HH11 & H11’)7.32 d (2H,H4 & H6)6.55 s (1H,H2)

NN

N N

12

3

4

5

6

78

9

10

11

12

7'

8'9'

10'

11'

12'

NN

N N

12

3

4

5

6

78

9

10

11

12

7'

8'9'

10'

11'

12'

CdCdCl

Cl

Cl

Cl

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1H-NMR Studies of B1 and its Complex

Compound 1H-NMR Values(ppm)

B2 8.73d (2H, H12&H12’)8.65 s (2H, H7 & H7’)8.22 dd (2H,H10 & H10’)7.86 d (2H,H9 & H9’)7.37 dd (4H,H2,H3,H5 & H6)7.28 dd (2H,H11 & H11’)

B2Zn 8.90d (2H, H12&H12’)8.73 s (2H, H7 & H7’)8.22 dd (2H,H10 & H10’)7.96 d (2H,H9 & H9’)7.37 dd (4H,H2,H3,H5 & H6)7.28 dd (2H,H11 & H11’)

NNN N

123

4

56

7

8

9

10

1112

7'12'

8'9'

10'

11'

NNN N

123

4

56

7

8

9

10

1112

7'12'

8'9'

10'

11' Zn

Zn

Cl

Cl Cl

Cl

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Table:13C NMR values

Compound

C1 C2 C3 C4 C5 C6 C7, C7’

C8, C8’ C9, C9’

C10, C10’

C11, C11’

C12, 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

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13C-NMR values(ppm) of B1

NN

N N

12

3

4

56

78

9

10

11

12

7'

8'9'

10'

11'

12'

150.2121.8

127.8

136.4 121.8 158.2150.3

131.7

136.5

128.0

149.2

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13C-NMR values(ppm) of B1Cd

NN

N N

12

3

4

56

78

9

10

11

12

7'

8'9'

10'

11'

12'

148.3121.0

127.0

136.4 127.0 151.8150.3

131.7

136.8

128.7

149.0

CdCd

Cl

ClCl

Cl

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I.R Values of B1 & its complexes

Compound Ar ― H Ar (C = C) CH = N meta-disubstituent

Ar (N = C)

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

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I.R Values of B2 & its complexesCompound Ar ― H Ar (C = C) CH = N para-

disubstituent

Ar (N = C)

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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BIOLOGICAL STUDIES

DNA interaction studies

Anti-fungal activity

Anti-bacterial activity

Enzymatic studies

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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.

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Graphical representation of DNA-Drug Interaction

B1Cu B2Cu

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

0 0.05 0.1 0.15 0.2

r = [comp]/[DNA]

(η /

ηo)1

/3

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

0 0.05 0.1 0.15 0.2

r = [comp]/[DNA]

(η /

ηo

)1/3

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DNA Interaction

B1Ni B2Zn

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

0 0.05 0.1 0.15 0.2

r = [comp]/[DNA]

(η /

ηo)1/

3

0

0.2

0.4

0.6

0.8

1

1.2

1.4

1.6

0 0.05 0.1 0.15 0.2

r = [comp]/[DNA]

(η /

ηo)1/

3

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Metal-DNA Interaction

A=Adenine, T=Thymine C=Cytocine, G=Guanine

N

N

O

N

N

H2N

M

X

NH2 O

N

N

R

R

T-M-A

N

N

O

N

NM

X

N

N

R

R

O NH2

C-M-G

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Anti-fungal activityPercent inhibition = 100 – [fungal growth in sample (cm)/fungal

growth in control (cm) x 100] (Standard drug; Turbinafine)

Compound

Concentration(mg/ 100mL)

Negative Control Growth/ DMSO(cm)

Culture Length(in Control)(cm)

Fungal Growth Length(in Sample)(cm)

% Inhibition of Fungal Growth

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

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Anti-bacterial activity

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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Table: Antibacterial activity

Staphylococ

cus aureus

(2)

(G +ve)

Klebsiellap

neumoniae

(1)

(G -ve)

Micrococcu

s luteus(2)

(G +ve)

Escherichia

coli(1)

(G -ve)

Staphylococ

cus aureus

(2)

(G +ve)

Klebsiellap

neumoniae

(1)

(G -ve)

Micrococcu

s luteus(2)

(G +ve)

Escherichia

coli(1)

(G -ve)

Compound Radius

(mm)

%

value

Radius

(mm)

%

value

Radius

(mm)

%

value

Radius

(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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Graph: Antibacterial activity

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Enzymatic studies

B1Cu(Series1),B1Cd(Series2)B2Ni(Series1),B2Cd(Series2),B2Zn(Series)

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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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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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Thanks