PhD Viva voce Presentation 19012015 (1)

SYNTHESIS AND BIOLOGICAL STUDY OF

NOVEL HETEROCYCLIC SCHIFF BASES

AND ITS TRANSITION METAL COMPLEXES

Research Student : Sudhir Sawant

Research Guide : Dr. Ramesh S. Yamgar

Ph D Viva Voce Presentation

“ शुध बीजा पोटी , फळे रसाळ गोमटी |”

( The sweet n cute fruits are the result of purity of

seeds. )

- संत तुकाराम

Coordination Chemistry

Fe

NN

Ph

NN

Ph

Ph Ph Fe

N N

Ph

N N

Ph

PhPh

O

O

Fe

N N

Ph

N N

Ph

PhPh

Fe(II) Fe(III) Fe(III)

O2

Haemoglobin

Applied coordination chemistry

Anti cancer Platinum complexes

Jacobsen’s Catalyst N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminomanganese(III) chloride

Assymetric synthesis of (R) Fluoxetine

hydrochloride

N

CH3

O

N

CH3

OH

H2 (30 atm), (2S,4S) - MCCPM-Rh(I) cat (30 atm), (2S,4S) - MCCPM-Rh(I) cat (30 atm), (2S,4S) - MCCPM-Rh(I) cat

CH3OH S/C = 1000

50oC

N

CH3

O

F3C

. HCl

(R) - Fluoxetine hydrochloride

N

P(C6H5)2

(o-C6H11)2 P

CONHCH3

(2S,4S) - MCCPM

amino ketone 490.8% ee

Theoretical principles of coordination chemistry

Central metal atom is surrounded by

three ethylene diamine ligand

molecules.

Ethlene diamine is a chelating agent

or ligand with two nitrogen donor

atoms.

'Chele' is Greek word for crab's

claw.

X

M XX

X

M

X= O, N or S M = Metal atom

Chelate forming 5 member ring Chelate forming 6 member ring Chelate having 5 and 6 membered

rings

Physical techniques used for characterisation of

Schiff base transition metal complexes

UV – Visible spectroscopy

1H NMR and 13C NMR spectroscopy

Mass spectroscopy MS/MS

X-ray diffraction

Thermal analysis – DSC/TGA

HPLC

Aim of present work

Aldehydes + aliphatic amino compounds

Aldehydes + Aniline compounds

Transition metal complexes containing heterocyclic

Schiff base Ligands having antitubercoulosis activity

4-Methyl umbelliferone has exhibited anti cancer

activity

To prepare transition metal conjugates and explore

the biological activities using schiffs base chemistry

Introduction to the chemistry of coumarins

O O

R

CH3O

O O

CH3

OH H+

+ RR

Phenol substituted beta keto ester coumarin derivatives

Pechmann condensation using phenol and beta keto ester

NN

N

N

OH

OOCH3 CH3

1) glycerol, boric acid 150oC

2) H2SO4, H2O

OH

OCH3

OCH3

H O

Synthesis of syringaldehyde

Formylation procedures for aromatic nucleus

Reimer Teimann reaction : CHCl3/KOH Vilsmeir Haack formylation : DMF / POCl3

Gatterman formylation: HCl, HCN, AlCl3 or ZnCl2

Duff formylation : HMTA , Acetic acid

OH OH

H

O

Reagent

Reimer Tiemann reaction

Literature survey of transition metal complexes

derived from coumarins and heterocyclic anilines

OO

CH3

OH

N

H

R

R= Cl & CH3

O

O

CH3

OH

N

OH

OH OH

+

O

O

O

CH3

CH3

Resorcinol Ethylacetoacetate

Conc. H2SO4

0oC

OOH O

CH3

7Hydroxy-4-methyl coumarin

7080oC

Hexamine

HCl, water

OOH O

CH3

CHO

ophenylene diamine

reflux 45 HrsOOH O

CH3

O OHO

CH3

N N

reflux 45 Hrs ethylene diamineSchiff base I

O OHO

CH3

N

OOH O

CH3

N

Schiff base II

4- Phenyl semicarbazide

O

O

CH3

H

NN

NH O

M

O

O

CH3

H

N N

NHO

Where M = Divalent transition metal such as Mn, Co, Cu, Ni, Pd

Literature survey of 7-hydroxy-4-methyl-2-oxo-

2H- chromone-8-carbaldehyde Schiff bases

4-Methyl umbelliferone

O O

CH3

OH

CHO

O O

CH3

OH

HN

N8-Aminoquinoline, Ethanol

Refluxing, 12Hr

3 - amino pyridine

O O

CH3

OH

HN

N

O O

CH3

OH

HNNH2

1,8 - diamino napthalene

O O

CH3

OH

HN

N S

N

SH

5 - amino 1,3,4 thiadiazole 2 - thiol

Organic Syntheses : Synthesis of ortho

hydroxybenzaldehydes and heterocyclic aniline

compounds

7-hydroxy-4-methyl-2-oxo-2H

-chromene-8-carbaldehyde

O O

CH3

OH

OH

O O

CH3

OH Hexamine, Acetic acid

85 - 90 0C

Duff formylation of 4-Methyl-7-Hydroxycoumarin

-CHO

-OH

4-Methyl-Umbelliferone

Synthesis of Ethyl 2-(3-formyl-4-hydroxyphenyl)-4-

ethyl-1,3-thiazole-5- carboxylate

Chemistry of amino compounds

Nitrogen atom forms the core of many

heterocyclic drug molecules, DNA

Heterocycles form by far the largest of classical

divisions of organic chemistry

Synthesis of N,N- dimethylamino propyl amine

(DMAPA) and N-methylamino propyl amine (NMAPA)

CH2

N

CH3 NH2

OH -

CH3 NH

N

CH3 NH

NH2

CH3 N

N

CH3

CH3 N

NH2

CH3

Raney Ni / H2

Raney Ni / H2

CH3 NH CH3

Raney Ni / H2

OH

NRaney Ni / H2

OH

NH2

DMAPA

NMPDA

3Amino propanol

CH2NCH3

NH

CH3

1

2

3

4

. .

CH3

N+

CH3

N

H

CH3

-

CH3

N

CH3

N

Donor Acceptor Transition state

Michael addition mechanism

Synthesis of heterocyclic aniline compounds

OH

OH

ClN

CH3

CH3

ClH+Sodium methoxide

Chlorobenzene

O

OH

NCH3

CH3

10% NH3 in ethanol

Ra Ni catalyst

O

NH2

NCH3

CH3

4-Hydroxy benzaldehyde

2-chloro-N,N-dimethylethanamine

hydrochloride

4-[2-(dimethylamino)ethoxy]

benzaldehyde

2-[4-(aminomethyl)phenoxy]-

N,N-dimethylethanamine

"in situ"

Synthesis of 2-[4-(aminomethyl)phenoxy]-N,N-dimethylethanamine

1HNMR:[ 300 MHz, DMSO-d6] 2.22( s, 6H), 2.59 (t, 2H), 3.86( br s, 2H), 4.05(t, 2H), 6.96(d, 2H, J=6.7Hz), 7.33(d, 2H, J=7.3Hz)

MS : [M+1] 293

IR: ν NH2: 3278cm-1

Synthesis of 4-(4-aminobenzyl)-1,3-oxazolidine-2-one

NH2

OCH3

O

N+O

-

O

n Butyl Chloroformate

Na2CO3

NH

OCH3

O

N+O

-

O O

O CH3

H2 / Pd/C

NH

OCH3

O

NH2

O

O CH3

NaBH 4 / nButanol

NH

OH

NH2

O

O CH3NH

O

NH2

O

NaOMe , nButanol

4-(4-aminobenzyl)-1,3-oxazolidin-2-one

ClH

L-4-Nitrophenylalanine hydrochloride Carbamate intermediate IIIaniline intermediate IV

Intermediate V

Synthesis of 4-(1H-1,2,4-triazol-1-yl methyl) aniline

Br

N+

O-

O

1-(bromomethyl)-4-nitrobenzene

NH

N

N

NaOH, Methanol

25-30°C

+

1H-1,2,4-triazole N+

O-

O

N N

N

1-(4-nitrobenzyl)-1H-1,2,4-

triazole

NH2

N N

N

H2 / Pd/C 40 psi

Methanol

4-(1H-1,2,4-triazol-1-ylmethyl)

aniline

1H NMR (300 MHz, DMSO-d6): 5.24(s, CH2), 6.51(2H, d, J=9Hz, aromatic), 7.03( 2H, J=9Hz, aromatic), 8.02( 1H,s, triazole aromatic),

8.7(1H, s, aromatic triazole).

MS: [M+1]+ 175.

IR: ν NH2 3413cm-1

Synthesis of 2-Butyl-5-amino-1-benzofuran N

+O

-

O Br

OH

2-(bromomethyl)-4-

nitrophenol

PPh3 CHCl3 N+

O-

O

OH

PPh3Cl

O

CH3N

+O

-

O

O

CH3

2-butyl-5-nitro-1-benzofuran

+

Phosphonium ylide

NH2

O

CH3

HCOONH4 Pd/C

HCl gas in Methanol

2-Hydroxy-5-Nitro benzyltriphenyl

phosphonium bromide

2-butyl-5-amino-1-benzofuran

1H NMR:[ 300MHz, DMSO-d6] 0.97(m, 3H), 1.35( m, 2H), 1.73( m, 2H), 2.70( m, 2H), 6.66( s, 1H), 6.94 -6.96( m, 1H),

7.07( d, 1H, J=7.2Hz), 7.39( d 1H, J= 7.2Hz),

MS : [M+1]: 190, IR: νNH2 2954cm-1

Chemistry of Schiff bases R

1

R2

H

O+ R

3NH2

-H2O R1

R2

H

N R3

Formation of Schiff base by condensation reaction ( R group may be variously substituted)

+R1

R2

N

OH

H

R3

R1

R2

N H

R3

+

OH

-

R1

R2

O

H

R3 N

H

H

:

R1

R2

N

O

H

R3

H

dipolar intermediate carbinolamine

Schiff base

H2O

R1

R2

N H

R3

-

Applications of Schiff base metal complexes Catalysis

Biological & Medicinal

Fluorescent & electronic materials

Dyes

Analytical

O

OH

OH

OH

HO

O

N

HO

N

OH

O

OH

OH

OH

HO

O

MeMe

R R

I

Synthesis of novel Schiff base metal complexes 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde and N-methyl-

propane-1,3-diamine i.e. NMAPIMHMC oxalate salt

Ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate

and (4S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one i.e. HBOMMTC

Ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl-1,3-thiazole-5-carboxylate and

4-(1H-1,2,4-triazol-1-ylmethyl)aniline i.e. HTIMMTC

Ethyl- 2-{ [4-(aminomethyl)phenoxy] N,N- dimethylethylethanamine)]imino}

methyl]-4-methyl-1,3-thiazole-5-carboxylate i.e.EAPDMTC

(4S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one and salicylaldehyde i.e. HBABO

4-(1H-1,2,4-triazol-1-ylmethyl)aniline and salicylaldehyde i.e. TMPIMP

2-[4-(aminomethyl)phenoxy]-N,N-dimethylethanamine and salicylaldehyde

i.e. DMAEBIMP

Synthesis of Schiff base 7-hydroxy-4-methyl-8-[(Z)-{[3-(methylamino)

propyl]imino}methyl]-2H-chromen-2-one [NMAPIMHMC]

1H NMR DMSO(d6)1.92 (s, 3H), 2.2- 2.4 (m, 2H), 2.51(s, 3H), 2.79(m, 2H), 3.05( t, 2H), 5.24(s, 1H),5.87( d, 1H, J=9.4Hz),

6.84(d,1H J=9.4Hz) ,8.15(s, 1H azomethine).

MS: [M+1]+ 275, UV: λ max 225 nm, 313 nm

IR ( KBr) N-H 3468 cm-1 C=O (Lacton) 1715cm-1 C=N 1609 cm-1 C-O(phenolic)1313 cm-1, C-O-C 1076cm-1,

M+1

Synthesis of Schiff base Ethyl- 2-{ 4-hydroxy-3-[(Z)-(4S)-(4-

benzyl)-(1,3-oxazolidin-2-one]imino}methyl]-4-methyl-1,3-

thiazole-5-carboxylate [HBOMMTC]

1H NMR : DMSO(d6)300MHz: 1.31(t, 3H, J=9Hz), 2.68(s, 3H), 2.72(m, 2H), 2.84-2.85(m, 2H), 4.02-4.04(m, 1H), 4.25-4.33(q, 2H),

7.05-7.08(d, 1H,J=9Hz), 7.35-7.44(m, 4H), 7.84( s, 1H, oxazolidone N-H, exchangeable with D2O ), 8.01(d, 1H, J=3Hz), 8.35(d, 1H, J=3Hz),

9.12(s, 1H azomethine), 13.78(s, 1H, exchangeable with D2O).

13C NMR : DMSO(d6) 75MHz: 14.10(CH3), 17.14(CH3), 39.75(CH2), 52.38(CH), 61.07(CH2), 67.96(CH2), 117.18(CH), 119.81( C ),

120.20( C ), 121.43( CH x 2), 123.23( C ), 130.54(CH), 130.70(CH), 130.22(CH x 2), 135.56( C ),145.78( C ), 158.31( C ),160.15( C ),

161.29( C ), 162.14(HC=N- azomethine), 163.28( C=O ester), 168.42( C=O oxazolidinone ).

Mass : [M+H]+ 466

IR ( KBr) : N-H 3232 cm-1 C=O (oxazolidine) 1780 cm-1 ,C=O (ester) 1710 cm-1 C=N 1610 cm-1, C-O-C 1097 cm-1 C-O(phenolic)1317 cm-1

Characterization of Schiff base HBOMMTC

M+1

N

OH

NS

CH3O

O

CH3

HN

H

O

O

Synthesis of Schiff base Ethyl- 2-{ [4-(aminomethyl)phenoxy] N,N-

dimethylethylethanamine)]imino}methyl]-4-methyl-1,3-thiazole-5-

carboxylate [EAPDMTC]

O

OH

NS

CH3O

O

CH3

H

NH2

ON

CH3

CH3

N

ON

CH3

CH3

OH

NS

CH3O

O

CH3

H

EAPDMTC

+

Ethyl 2-(3-formyl-4-hydroxyphenyl)-

4-methyl-1,3-thiazole-5-carboxylate



EtOH

Atom no ppm group

14 168.73 C

2 166.25 C

7 165.75 C ester carbonyl

16 161.45 C azomethine

6 161.18 C

4 160.18 C

28 157.91 C

12 131.14 CH

27 130.80 CH

15 129.65 C

19 , 22 129.25 2 x CH

11 121.83 C

13 118.84 CH

18 118.51 C

20, 21 114.60 2x CH

17 65.78 CH2

23 61.01 CH2

9 59.75 CH2 ester

24 57.64 CH2

25, 26 45.50 2 x CH3 dimethyl amino

5 17.20 CH3 thiazole

10 14.13 CH3 ester

N

ON

CH3

CH3

OH

NS

CH3O

O

CH3

H

12

34

56

7

89

10

1112

1314 15 16

1718

19

20

2122

23

24

25

26

27

28

UV and HPLC of EAPDMTC

λ max

Synthesis and characterization of novel

Schiff base metal complexes Preparation of the Cu(II), Co(II), Ni(II) and Zn(II) complexes of “in situ” Schiff base

derived from 7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde and

N-methylpropane-1,3-diamine

[i] Preparation of [Zn(NMAPIMHMC)2]•2H2O complex

[ii] Preparation of [Cu(NMAPIMHMC)2]•2H2O complex

[iii] Preparation of [Ni(NMAPIMHMC)2] •2H2O complex

[iv] Preparation of [Co(NMAPIMHMC)2]•2H2O complex

OH2

OH2

N

O

H

N

O

H

M

O

O

CH3

O

O

CH3

NH CH3

NHCH3

O O

CH3

OH

NH NH

CH3

O O

CH3

OH

OH

NH2 NH

CH3

MX2. nH2O

M = Zn(II), Cu(II), Ni(II), Co(II)

EtOH, H+

"in situ"

EtOH

7-hydroxy-4-methyl-2-oxo-2H-chromene-8-carbaldehyde NMAPIMHMC

[M(NMAPIMHMC)2].2H2O

N-methylpropane-1,3-diamine

Results and discussion

OH

N

NHCH3

O

CH3

O

H NZn

O

O

N

NH

NHCH3

CH3

O

O

CH3

OO

CH3

HHOH

O

OO

CH3

H

8.17 ppm10.59 ppm

8.83 ppm

Azomethine proton shift values before and after complexation with Zn(II) metal atom

δ value in ppm Schiff

base NMAPIMHMC

δ value in ppm metal complex

[Zn(NMAPIMHMC)2]•2H2O

Multiplicity & Number of Protons Assignment

1.62-1.63 2.06 m ( 2H) C-CH2-C

2.11 2.34 s (3H) -N-CH3

2.41 2.51 s (3H) =C-CH3

2.75 2.96 t (2H) -N-CH2-

3.02 3.73 t (2H) =N-CH2

5.15 5.98 s (1H) =C-H olefinic

5.97 6.56 d (2H) aromatic

6.94 7.56 d (2H) aromatic

8.17 8.83 s (1H) =N-H azomethine

Results and discussion

1H NMR 300MHz (DMSO-d6) : 2.06(m, 2H), 2.34(s,3H), 2.96( t, 2H), 3.73( t, 2H), 5.98(s, 1H), 6.56( d, 2H, J=8.4Hz),

7.56(d, J=8.4Hz) 8.83(s, 1H azomethine).

1H NMR spectrum of [Zn(NMAPIMHMC)2]•2H2O

13C NMR Spectra assignments

NO

H

NO

H

Zn

O

O

CH3

O

O

CH3

NH CH3

NHCH3

1

2 3

4

5

67

8

9

10

11

12

13

14

1'

2'3'

4'

5'

6' 7'

8'

9'

10'

11'

12'

13'

14'

4a

4a'

8a

8a'

Atom No. 13C ppm Group

2, 2’ 162.733 C

3, 3’ 107.248 CH

4, 4’ 106.985 C

4a, 4a’ 106.322 C

5, 5’ 130.107 CH

6, 6’ 120.355 CH

7,7’ 154.867 C

8, 8’ 156.861 C

8a, 8a’ 160.229 C

9,9’ 173.636

CH

Azomethine

10,10’ 58.48 CH2

11,11’ 33.582 CH2

12,12’ 47.342 CH2

13,13’ 27.064 CH3

14,14’ 18.892 CH3

Mass spectra

[Zn(NMAPIMHMC)2].2H2O

M+1 : 612

[Cu(NMAPIMHMC)2].2H2O

M+1 : 611

[Ni(NMAPIMHMC)2].2H2O

M-L : 331

[Co(NMAPIMHMC)2].2H2O

M+1 : 606

All the mass spectra, have indicated M:2L stoichiometry confirming

bidentate nature of Schiff base Ligands.

Mass spectra

Comparison of IR spectra

Complex

Lattice

water

(H2O) cm-1

C=O

Lactonyl

cm-1

C=N

azomethine

cm-1

C-O Phenolic

cm-1

M-N

cm-1

M-O

cm-1

NMAPIMHMC• Oxalate NA 1715 1609 1313 NA NA

[Co(NMAPIMHMC)2]•2H2O 3556 1720 1623 1398 528 449

[Ni(NMAPIMHMC)2]•2H2O 3369 1720 1633 1334 536 457

[Cu(NMAPIMHMC)2]•2H2O 3314 1720 1629 1336 543 457

[Zn(NMAPIMHMC)2]•2H2O 3122 1727 1631 1371 543 453

IR spectra showed appearance of a new strong band in the

region 1620 cm-1to 1630cm-1assigned to the azomethine, ν(C=N)

linkage.

Complex Mass loss due to H2O

Calculated (%) Observed (%)

[Co(NMAPIMHMC)2]•2H2O 5.61 5.0

[Zn(NMAPIMHMC)2]•2H2O 5.55 5.1

Thermo gravimetric analysis showed significant loss in weight

indicating two molecules of water of crystallization

Conclusion

OH2OH2

N

O

H

N

O

H

M

O

O

CH3

O

O

CH3

NH CH3

NHCH3

[M(NMAPIMHMC)2]•2H2O where M = Zn(II), Cu(II), Ni(II), Co(II).

Proposed structure of [M(NMAPIMHMC)2]•2H2O complexes

OH2

OH2

N

O

H

N

O

H

Zn

N CH3

CH3

NCH3

CH3

N

S

N

S

CH3

CH3

O

O

O

O

CH3

CH3

N

OH

NS

CH3

O

O

CH3

H

N

CH3

CH3

CH3

N

CH3

NH2

OH

NS

CH3

O

O

CH3

H

O

Zn(DMAPIMMTC)2.2H2O

DMAPIMMTC

EtOH

N,N-dimethylpropane-1,3-diamine

EtOH, ZnCl2

ethyl 2-(3-formyl-4-hydroxyphenyl)-


Synthesis and characterization of novel Schiffs base

Zn(II) metal complexes ( by template method)

O

OH

NS

CH3O

O

CH3

H

2-(3-formyl-4-hydroxyphenyl)-


NH2

ON

CH3

CH3

EtOH



N

ON

CH3

CH3

OH

NS

CH3O

O

CH3

H

EAPDMTC

ZnCl 2 , EtOH

OH2OH2

N

O

H

N

O

H

Zn

O

O

N

CH3

CH3

N

CH3

CH3

S

N

S

N

CH3

CH3

O O

CH3

OO

CH3

Zn(EAPDMTC)2. 2H2O

OH2OH2

N

O

H

N

O

H

Zn

O

CH3

O

CH3

S

N

S

N

CH3

CH3

OO

CH3

O O

CH3

NH2

O

CH3O

OH

NS

CH3O

O

CH3

H

N

O

CH3

OH

NS

CH3O

O

CH3

H

EtOH, ZnCl2

EtOH



2-buty l-1-benzofuran-5-amine

EBBFCTC

Zn(EBBFCTC)2.2H2OO

NH2

N

NN

OH2OH2

N

O

H

N

O

H

Zn

S

N

S

N

CH3

CH3

OO

CH3

NN

N

N N

N

O O

CH3

O

OH

NS

CH3O

O

CH3

H

N

OH

NS

CH3O

O

CH3

H N

N

N

EtOH EtOH, ZnCl2



4-(1H-1,2,4-triazol-1-ylmethyl)aniline

HTIMMTC

[Zn(HTIMMTC)2].2H2O

Synthesis of Novel Schiffs base metal complexes

( by template method)

O

OH

H

NH

O

NH2O

NHO

N

OOH

H

OH2OH2

N

O

H

N

O

H

M

NH

O

NH

O O

O

M(HBABO)2.2H2O

M = Zn(II), Cu(II)

HBABO

MX2

salicylaldehyde

(4S)-4-(4-aminobenzyl)-1,3-oxazolidin-2-one

EtOH EtOH

O

OH

H NH2

N

NN

N

N N

N

OH

H

M(TMPIMP)2. 2H2O

M = Zn(II), Cu(II), Ni(II)

MX2. nH2O

TMPIMP

salicylaldehyde

4-(1H-1,2,4-triazol-1-ylmethyl)aniline

EtOH EtOHOH2 OH2

N

N N

N

H

O

N

NN

N

H

OZn

13C NMR spectrum of [Zn(HBABO)2] complex

Atom No. Group 13C ppm

14,14’ HC=N 163.04

5, 5’ C=O 160.26

20, 20’ C-O-Zn 158.60

10, 10’ C 146.43

7,7’ C 135.48

16, 16’ CH 133.18

18,18’ CH 132.53

8, 8’, 12, 12’ CH 130.49

9,9’,11,11’ CH 121.36

15, 15’ C 119.27

19, 19’ CH 119.10

17,17’ CH 116.55

2, 2’ CH2 67.97

3,3’ CH 52.42

6,6’ CH2 39.90

NO

H

NO

H

Zn

NH

O

NH

O O

O1

2

1'

2'

3

3'

4

4'

5

5'

6

6'

7

7'

8

8'

9

9'

10

10'

11

11'

1212'

13

13'

14

14'

15

15'

16

16'

17

17'

18

18'

19

19'

20

20'

13C NMR spectrum of [Zn(TMPIMP)2] complex

NO

H

NO

H

Zn

NN

N

N N

N

1

2

1'

2'

3

3'

4

4'

5

5'

6

6'

7

7'

8

8'

9

9'

10

10'

11

11'

12

12'

13

13'

14

14'

15

15'

16

16'

17

17'

18

18'

19

19'

20

20'

Atom No. Group 13C ppm

14,14’ HC=N 163.70

20, 20’ C-O-Zn 160.23

2, 2’ CH 151.44

10, 10’ C 147.82

5,5’ CH 144.20

7,7’ C 134.69

16, 16’ CH 133.37

18,18’ CH 132.52

8, 8’, 12,12’ 12’ CH 129.12

9,9’,11,11’ CH 121.60

15, 15’ C 119.24

17,17’ CH 119.16

19, 19’ CH 116.58

6,6’ CH2 51.77

13C Spectrum of Zn(BBFIMP)2 complex

OH2

OH2

NO

H

NO

H

Zn

O

CH3

O

CH3 1

1'

2

2'

3

3'

4

4'

5

5'

6

6'7

7'

8

8'

9

9'

10

10'11

11'

1212'

13

13'

14

14'

15

15'

16

16'

17

17'

18

18'

19

19'

20

20'

Atom No Assignment 13C PPM

14, 14’ CH Azomethine 162.23

20, 20’ C 160.79

9, 9’ C 160.21

6, 6’ C 150.34

2, 2’ C 143.30

18, 18’ CH 132.83

16,16’ CH 132.43

4, 4’ C 129.52

15, 15’ C 119.36

7, 7’ CH 119.03

17, 17’ CH 117.37

19,19’ CH 116.50

5, 5’ CH 112.46

8, 8’ CH 111.19

3, 3’ CH 102.36

10, 10’ CH2 29.14

11, 11’ CH2 27.37

12, 12’ CH2 21.86

13, 13’ CH3 13.56

PXRD study of Zn complexes

XRPD plot of [Zn(DMAPIMMTC)2]•2H2O XRPD plot of [Zn(EBBFCTC)2]•2H2O

XRPD plot of [Zn(HBABO)2]•2H2O complex XRPD plot of [Cu(TMPIMP)2]•2H2O

Conclusion

OH2OH2

N

O

H

N

O

H

M

NH

O

NH

O O

O

[M(HBABO)2]•2H2O, M= Zn(II) and

Cu(II)

OH2OH2

N

O

H

N

O

H

M

N

N N

N

NN

[M(TMPIMP)2]•2H2O, M= Zn(II),

Cu(II) and Ni(II)

OH2OH2

N

O

H

N

O

H

M

O

O

N CH3

CH3

NCH3

CH3

[M (DMABIMP)2]•2H2O, M= Zn(II),

Cu(II) and Ni(II)

OH2

OH2

NO

H

NO

H

M

O

CHO

CH3

[M(BBFIMP)2]•2H2O, M= Zn(II) and

Cu(II)

Biological study of novel Coumarine Schiff bases

and their metal complexes

Test compound Escherichia coli Aspergillus niger

Schiffs base [NMAPIMHMC] <200 <200

Co[NMAPIMHMC]2.2H2O <20 <20

Ni[NMAPIMHMC]2.2H2O <20 <20

Cu[NMAPIMHMC]2.2H2O <20 <20

Zn[NMAPIMHMC]2.2H2O <20 <20

Antimicrobial Activity (MIC, µg ml-1) of Schiff base [NMAPIMHMC]and its metal complexes

Conclusion: antimicrobial activity of the ligand is enhanced

on complex formation

Anti bacterial and antifungal studies of Zinc metal

complexes ( MIC method)

Results & discussion

Schiffs base and metal complexes comparative antifungal screening results by MIC method

Conclusion : [Zn(NMAPIMHMC)2].2H2O, [Zn(TMPIMP)2].2H2O and

[Zn(HBABO)2].2H2O complex showed most promising activity upto

3.2 - 1.6µg/ml, compared to standard Fluconazole having MIC value

8µg/ml in A. niger.

Test

Organism Test sample MIC

C.albicans

NMAPIMHMC 50

Zn(NMAPIMHMC)2 3.12

TMPIMP 50

Zn(TMPIMP)2 3.12

HBABO 12.5

Zn(HBABO)2 25

Std. Flucanazole 16

A.niger

NMAPIMHMC 0.8

Zn(NMAPIMHMC)2 0.8

TMPIMP 1.6

Zn(TMPIMP)2 3.12

HBABO 6.25

Zn(HBABO)2 3.12

Std. Flucanazole 8

Results & discussion

Conclusion: Zn(NMAPIMHMC)2].2H2O, [Zn(DMAPIMMTC)2].2H2O

and [Zn(HBABO)2].2H2O as a metal containing complex of potential

therapeutic benefit, particularly for the topical treatment as antifungal

agent against C.albicans and A.niger.

Test

Organism Test sample MIC

C.albicans

Zn(DMAEBIMP)2 12.5

Zn(HBABO)2 3.12

Zn(NMAPIMHMC)2 3.12

Zn(BBFIMP)2 100

Zn(DMAPIMMTC)2 1.6

Std. Flucanazole 16

A.niger

Zn(DMAEBIMP)2 0.4

Zn(HBABO)2 0.2

Zn(NMAPIMHMC)2 0.2

Zn(BBFIMP)2 0.2

Zn(DMAPIMMTC)2 0.4

Std. Flucanazole 8

Anti tuberculosis study of Zinc complexes

Test Organism Test sample concentration in

μg/ml

M.Tuberculosis

1. Zn(DMAPIMMTC)2 25

2. Zn(NMAPIMHMC)2 25

3. Zn(HBABO)2 12.5

4. Zn(DMAEBIMP)2 25

5. Zn(BBFIMP)2 25

Std. Pyrazinamide 3.125

Std. Steptomycin 6.25

Conclusion : Zinc(II) complexes have shown moderate activity as

compared to standard Pyrazinamide and Streptomycin against

M.Tuberculosis

List of publications 1. Ramesh S. Yamgar, Prasad Kamat and Sudhir S. Sawant, Synthesis of Schiff base zinc metal complex (MAPIMP)2Zn and

development of HPLC chromatographic method for its analysis, J. Chem. Pharm. Res., 2010, 2(5): 216-224.

2. Ramesh Yamgar, Prasad Kamat, Dileep Khandekar & Sudhir Sawant, Preparation of Schiff base Zinc Metal complex (DMAPIMP)2Zn

and Development of HPLC Chromatographic method for its analysis., J. Chem. Pharm. Res., 2011, 3(1), 188-198.

3. M. Mustapha, B. R. Thorat, Sudhir Sawant, R. G. Atram and Ramesh Yamgar

Synthesis of novel Schiff bases and its transition metal complexes, J. Chem. Pharm. Res., 2011, 3(4), 5-9.

4. Sangeeta V. Chavan, Ramesh S. Yamgar and Sudhir S. Sawant, Synthesis and Characterization of Novel Transition Metal

Complexes of Benzo-Pyranone Derivatives and Their Biological Activities, Asian J. Research Chem., 2011, 4(5), 834-837.

5. Vijaya Pawar, Sangeeta V. Chavan, Ramesh S. Yamgar, R. G. Atram, B.R. Thorat, Swati Bisht and Sudhir S. Sawant,

Synthesis and Characterization of Novel Transition Metal Complexes of 4-Methyl-7-Hydroxy-8-Formyl Coumarin and Their

Biological Activities, Asian J. Research Chem. 2011, 4(8), 1238-1242.

6. Sudhir S. Sawant , Vijaya Pawar, Shirish Janrao, Ramesh S. Yamgar and Y. Nivid,

Synthesis and Characterization of Transition Metal Complexes of Novel Schiff base 8-[(z)-{[3-(N-methylamino)propyl]imino}

methyl]-7-hydroxy-4-methyl-2h- chromen-2-one][NMAPIMHMC] and their Biological activities, International Journal of Research in

Pharmacy and Chemistry, 2013, 3(3), 636- 644.

7. Ramesh S. Yamgar, Y.Nivid and Sudhir S. Sawant, Synthesis, Characterisation and Anti tuberculosis activity of novel transition metal

complexes of heterocyclic Schiff bases, International Journal of Advanced Research in Applied Chemistry, 2013, 1(9), 1-21.

8. Ramesh S. Yamgar, Y.Nivid, Satish Nalawade, Mustapha Mandewale, R. G. Atram and Sudhir S. Sawant, Novel Zinc (II) complexes of

Heterocyclic ligands as antimicrobial agents: Synthesis, characterisation and antimicrobial studies, Bioinorganic Chemistry and

Applications, 2014, doi:10.1155/2014/276598.

Documents

PhD Viva voce Presentation 19012015 (1)