Synthesis, Characterization and Antimicrobial Activity ...

Republic of Iraq Ministry of Higher Education & Scientific Research University of Baghdad/ College of Education For Pure Science/ Ibn Al-Haitham Department of Chemistry

Synthesis, Characterization and Antimicrobial Activity Studies of New Schiff Base Chelate With Some Metal Ions

A Thesis Submitted to the council of collage of Education for Pure Sciences Ibn Al Haitham University of Baghdad in partial fulfillment of the requirements for the degree of Master of science in Chemistry By Ghassan Thabit Shinain

B.Sc. 2002 Supervisor Prof . Dr. Taghreed Hashim Al-Noor

2017 A.D.

1438 A.H .

‫بسم اهلل الرمحن الرحيم‬

‫(لقد خلقنا اإلنسن يف‬ ‫كبد)‬

‫صدق اهلل العلي العظيم‬ ‫سورة البلد‪...‬‬

‫اآلية(‪)4‬‬

Supervisor I am certify that this thesis

certification was prepared under our supervision at

Department of Chemistry, College of Education for Pure Science Ibn-Al Haitham at University of Baghdad in partial requirement for the Degree of Master of Science in Chemistry .

Dr. Taghreed Hashim Al- Noor Title : Professor Member (Supervisor) Data: 2 / 10

/ 2017

In view of the available recommendations, I forward this thesis for debate by the examining committee.

Signature: Dr. Najwa Issac Abdulla Head of Chemistry Department

Data:

/

/ 2017

Dedication

To. whom Allah has sent as a light in darkness and messenger to guide as. prophet Mohammed (oh Allah , bless Mohammed and his family) To those who taught me how to make my dream and leave me the first way .............. (my mother and father) May God have mercy on them To those who stood with me in time of distress and prosperity ................ (my wife who is precious) To my love my heart ............................. my daughter (Adian) To my little hero ........................ My son (Ibrahim) To my life flower ............................ My daughter (Rayyan)

Ghassan

ACKNOWLEDGEMENT Thanks to Allah the one the single for all this blessing during my study and all my life. I would like to express my special thanks and gratitude to my supervisor Prof. Dr Taghreed Hashim Al-Noor , in my first step in choosing the right title and giving me the main lines for my researchs, and for her encouragement and support., Also, my grateful thanks are to the staff of members of the College of Education Ibn AL–Hiatham especially prof. Dr. Sajed Mahmood, Thanks are also Dr. Ahmed Thabit and extended to all members of the staff and my Colleagues.

.

Abstract The work presented in this thesis deals with the synthesis and characterization of: A) The Schiff base ligand (L) : 4-4-((4-amino-5-(3,4,5-trimethoxybenzyl) Pyrimidin -2-yl)imino)pentan-2-one derives from selected Trimethoprim (TMA) antibiotic with acetylacetone (aac). The ligand containing (N ,O) as donor atoms type (N.N.N and O). The synthesized ligand (L) was characterized by (1H-NMR) and (13C-NMR) spectra , FT-I.R , U.V–Vis spectroscopy, (C.H.N.S), melting point, According to the results obtained from 1H-NMR , 13C-NMR and FT-IR, U.V/vis, . The proposed molecular structure Ligand (L) was drawing by using Cs chem office 3D Ultra program package (2015). As shown in Figure below (three dimensional view of ligand).

B) prepared of mixed ligand complexes : 1) Schiff base ligand (L) uses as primary ligand with Oxalic acid (H2Ox= H2C2O4 ) as a secondary ligands with M (II) and Cr(III) 2) Trimethoprim (TMA) use as primary ligand with Oxalic acid, as a secondary ligands with M (II) and Cr (III) shown table below:

i

Primary ligand

Secondary ligand

Compositions

L

[M (Ox) (L)] Oxalic acid

Schiff base C19H24N4O4 Trimethoprim

M= Co(II), Ni(II),Cu(II),Zn(II) H2Ox= H2C2O4

and [Cr (Ox) (L)]Cl

Oxalic acid

K2[M (Ox)2(TMA) (H2O) ] . M=Mn(II), Co(II),

TMA

Ni(II),Cu(II),Zn(II) and K [Cr

C14H18N4O3

(Ox)2(TMA)].

Products were found to be solid powder complexes, which have been characterized through the following techniques : Molar conductivity ,spectroscopic Method (FT-IR),(UV-Vis)and A.A.S additional measurement magnetic susceptibility. The measurement magnetic susceptibility with the electronic spectra data suggested an octahedral geometry for all the complexes . .The antimicrobial activity of the synthesized compound as well as their free ligand was studied by the zone of inhibition (ZI) technique .

ii

CHAPTER ONE ( INTRODUCTION ( (1)

General introduction

1

(1.1)

Antimicrobial drugs

1

(1.2)

Metal complexes in biological system

4

(1.2.1)

Metal complexes in medicinal biochemistry

4

(1.2.2)

Antibiotic - metal complexes

7

(1.3)

Schiff base metal complexes

10

(1.4)

Oxalic acid.

18

(1.5)

Acetyle acetone

18

(1,6)

Trimethoprim antibiotic drug(TMA)

18

(1.4.1)

Oxalic acid as ligand

19

(1.4.2)

Oxalic acid complexes

19

(1.5)

Acetyl acetone chemistry

26

(1.5.1)

Acetyl acetone as ligand

26

(1.5.2)

Acetylacetone complexes

26

(1.5.3)

Acetyl acetone derivatives

30

(1.6)

Trimethoprim (TMP) chemistry

34

(1.6.1)

Trimethoprim as ligand

34

(1.7)

Aims of the research

39

CHAPTER TWO Experimental 2

The Experimental

40

(2.1)

Chemicals

40

(2.2)

Instruments and apparatus

40

(2.2.1)

The melting point (M.P) measurement

40

(2.2.2)

Conductivity measurements (ΛM)

41

(2.2.3)

(FT-IR) Spectroscopy

41

(2.2.4)

(U.V-Vis) spectra

41

(2.2.5)

Total metal content (Metal % )

41 iii

(2.2.6)

Magnetic susceptibility (μeff)

42

(2.2.7)

(1H ,13C NMR) spectrascopy

42

(2.2.8)

Elemental micro analysis

42

(2.3)

Chloride analysis (Cl % )

42

(2.4)

The proposed molecular structure

43

(2.5)

Synthesis of Schiff Base Ligand

43

(2.6)

Synthesis of (mixing ligands) complexes with some metal ions

44

(2.6.1 )

(L- M-oxalic acid) Complexes : Set 1

44

(2.6.2 )

(TMA- M-oxalic acid) Complexes : Set 2

44

(2.6 .1.1)

potassium oxalate solution

45

(2.6.1.2)

General method for synthesis (L- M-oxalic acid) Complexes : Set 1

45

(2.6.2)

General method for synthesis (L- M-oxalic acid) Complexes : Set 2

47

(2.6.2.1)

Potassium oxalate

47

(2.6.2.2)

General method for synthesis of the mixedligand metal (II) Complexes:

and Cr(II)

47

Chapter Three (Results and Discussion) 3

Results and Discussion

49

(3.1.1)

General methodology

49

(3.1.2)

Physical properties and elemental analysis results of the synthesized ligand (L):50

(3.1.3)

Solubility

51

(3.2)

FT-IR spectra of the ligands and starting materials

51

(3.2.1)

FTIR spectrum of the ligand

54

(3.3)

(U.V-Vis) spectra of the ligands

57

(3.4)

NMR spectra of the ligand

59

(3.4.1)

1

H NMR spectrum of the ligand

59

(3.4.2)

1

3C NMR spectrum of the ligand

61

(3.5)

Structures and names of the synthesized ligand

iv

63

(3.6)

Characterization of mixed-ligand metals complexes

63

(3.6.1)

Characterization (L- M-oxalic acid) complexes

63

(3.7)

FT-IR spectra of [Cr (OX) (L)]Cl (1), [Co (OX) (L)] (2),

67

[Ni(OX) (L)] (3),[Cu(OX)2(L)] (4), and [Zn(OX)2(L)](5) complexes (3.8)

The ultra violet visible spectra and Magnetic measurements for the complexes

74

(3.8.1)

The ultra violet visible spectra and Magnetic measurements(eff) for the mixedligand metal complexes [Cr (OX) (L)]Cl (1), [Co(OX) (L)] (2), [Ni(OX)( (L)] (3), [Cu(OX)2(L)] (4), and [Zn(OX)2(L)] (5) complexes

77

(3.8.1.1)

[Cr(L)( OX)]Cl

79

(3.8.1.2)

[Co(OX) (L]

80

(3.8.1.3)

[Ni(OX) (L)]

81

(3.8.1.4)

[Cu(OX) (L)]

82

(3.8.1.5)

[Zn (OX) (L)]

83

(3.9)

The proposed molecular structure for studying complexes

83

(3-10)

Characterization of (TMA- M-oxalic acid) complexes

85

(3.10.1)

. FT-IR spectra of K [Cr( OX )2(TMA) (H2O)] (1),

87

K2[Mn(OX)2(TMA) (H2O)] (2), K2[Co (OX)2(TMA)(H2O)] (3), K2[Ni(OX)2(TMA) (H2O] (4), K2[Cu(OX)2(TMA) (H2O)](5), and K2[Zn(OX)2(TMA) (H2O)](6) complexes (3.10.2 )

The ultra violet visible spectra and magnetic measurements(eff) for the mixed ligand complexes : K [Cr ( OX )2(TMA) (H2O)](1), K2[Mn(OX)2(TMA) (H2O)] (2), K2[Co (OX)2(TMA) (H2O)] (3), K2[Ni(OX)2(TMA) (H2O] (4),K2[Cu(OX)2(TMA) (H2O)] (5), and K2[Zn(OX)2(TMA) (H2O)] (6)

93

(3.10.2.1)

K [Cr (OX)2(TMA) (H2O)]

95

(3.10.2.2) K2 [Mn (OX)2(TMA) (H2O)]

96

(3-10.2.3) K2 [Co (OX)2(TMA) (H2O)]

97

(3.10.2.4) K2 [Ni ( OX )2(TMA) (H2O)]

98

(3.10.2.5) K2 [Cu (OX)2(TMA) (H2O)]

99 v

(3.10.2.6) The K2[Zn(OX)2(TMA) (H2O)] complex

100

(3.11)

101

The proposed molecular structure for studying complexes Chapter Four Biological Activity

(4)

Biological activity

102

(4.1)

Introduction

102

(4.2)

Material and equipment's

102

(4.3)

Principle of antimicrobial susceptibility test

103

(4.4)

Types of pathogenic bacteria and bacterial infections in

this study 104

(4.4.1)

Escherichia coli: (Gram- negative)

104

(4.4.2)

Enterobacter cloacae : (Gram- negative)

105

(4.4. 3)

Staphylococcus S.P :( Gram-positive )

105

(4.4.4)

Bacillus subtilis (Gram-positive)

106

(4.5)

Results and Discussion:

106

(4.5.1)

The biological effect of the prepared compounds:

106

(4.5.2 )

Anti bacterial activities of the Schiff Base metal-mixed ligands complexes

107

(4.5.3)

Anti bacterial activities of the metal-mixed ligands complexes

114

vi

NO

Tables

page

(1-1)

Timeline of antimicrobial drugs.

1

(1-2)

Some medical and prospective medical uses of

3

inorganic compounds (1-3)

Metal complexes in medicinal biochemistry

5

(1-4)

Selected examples of acetyl acetone complexes

27

(1-5)

Trimethoprim –amino acids complexes

37

(2-1)

Chemicals used in this work and their Suppliers

40

(3-1)

Compositions of compounds

49

(3-2)

Some physical properties for the starting materials and (C.H.N.)

50

(3-3)

Solubility of the starting materials and synthesized Schiff bases ligands in different solvents

51

(3-4)

FT-IR spectral data (ύ) cm-1 for the (TMA)

52

(3-5)

FT-IR spectral data (ύ) cm-1 for the (aac)

53

(3-6)

Infrared spectral data(wave number ύ) cm-1 of the { L)

56

(3-7)

Electronic data of (TMA) and synthesized ligand (L) and molar conductivity

59

(3-8)

Some Physical Properties and (AAS ) Results of the

65

(L-M-OX) Complexes (3-9)

The solubility of the ( L- Metal -Oxalte) complexes in different solvents

66

(3-10)

Molar Conductivity )Ω−1cm2mol−1 ) in some solvents

67

(3-11)

Infrared spectrum data (wave number ύ) cm-1 for the (H2OX)

69

(3-12)

Infrared spectral data(wave number ύ) cm-1 for the mixed ligand (L1-OX)metal complexes.

73

(3-13)

spectral region

76

(3-14)

Electronic spectral data of the mixedligand (L-MOX) complexes

78

vii

(3-15)

Some physical properties and atomic absorption results of the (L-M-Ox) complexes

86

(3-16)

The solubility of the ) TMA - Metal - OX) complexes in different solvents

87

(3-17)

Infrared spectral data (wave number ύ) cm-1 for the mixedligand (L- Metal –OX]complexes.

89

(3-18)

Electronic spectral data of the mixedligand

94

(TMA - M-OX) metal complexes (4-1)

The antibacterial activity (IZ mm) data of

108

set Schiff base Metal-mixed ligands complexes (4-2)

The antibacterial activity (IZ mm) data of metal-mixed ligands complexes,

viii

114

Gradation

Figures

page

(1-1)

Different oxidation states in haemocyanins

4

(1-2)

Structure of Pt(II)-piroxicam

7

(1-3)

Complexes of rhodium and iridium with cephalexin

7

(1-4)

Metal antibiotics- cellulose- complexes

8

(1-5)

Structure of antibacterial drug cephardine

8

(1-6)

[Zn(Ciprofloxacin)2.H2O] Complex

9

(1-7)

The proposed structural formulae of (Sulphametrole) and

13

Arelaldehyde) complexes (1-8)

Sulfamethoxazole Schiff base derivative with Cu(II)and Hg(II)

(1-9)

Schiff base copper(I/II) complexes [Cu2I4]2− bridges

17

(1-10)

Schiff base salisaladehyed with ortho / (m-/p- o-)benzyl

17

(1-11)

Two-dimensional of 2 [M(ox)(bpy)]complex

20

(1-12)

Molecular structure and 3D of oxaliplatin

20

(1-13)

Suggested structure of the of the Fe(III) -H2L - Ox complex.

21

(1-14)

[Pd(obap)]−(above) KH[Pd(obap)]2·3H2O complex

14

23

(below).and schematic diagram and 3D [Pd(obap)]−/12-mer picture (along with an electrostatic surface (map) (1-15)

Crystal structure of [Tb(CHO2)-(C2O4)]n}

24

(1-16)

Perspective view structure of

25

[(PyH)2[Mo2O4(C2O4)2(Py)2]complex (1-17)

A ball model acetyl acetone structure

26

(1-18)

Schiff bases type(ONNO), (L1), L2) and (L3)

29

(1-19)

Schiff bases (L1-L3) chelates with Sn(II

30

(1-20)

Shows the molecular structure of compounds(I, II, III)

31

ix

(1-21)

Proposed structure for the complexes

34

(1-22)

Molecular structure and 3D of trimethoprim

34

(1-23)

Proposed structure M= Co(II), Cd(II) complexes of (TMA)

35

(1-24)

[Ag(I)-TMA –NO3 ] complexes

36

(1-25)

[Metal (II) -TMA –NA ] complexes

38

(3-1)

FT-IR spectrum of ( TMA)

52

(3-2)

FT-IR spectrum of (acac )

54

(3-3)

FT-IR spectrum of (L)

55

(3-4)

Electronic spectrum of (H2OX)

57

(3-5)

Electronic spectrum of (TMA)

58

(3-6)

Electronic spectrum of Schiff base (L)

58

(3-7)

Number of different types of protons in (L)

60

(3-8)

1H NMR spectrum of (L) in DMSO-d6

61

(3-9)

13

62

Structure of (Z)-4-((4-amino-5-(3,4,5-trimethoxybenzyl)

63

(3-10)

C NMR spectrum of (L )in DMSO- d6

Pyrimidin -2-yl)imino)pentan-2-one ( L) and as 3D model (3-11)

FT-IR spectrum of Oxalic acid(H2OX)

69

(3-12)

FT-IR spectrum of [Cr (OX) (L)]Cl complex

70

(3-13)

FT-IR spectrum of [Co (OX) (L)] complex

70

(3-14)

FT-IR spectrum of [Ni (OX) (L)] complex

71

(3-15)

FT-IR spectrum of [Cu (OX) (L)] complex

71

(3-16)

FT-IR spectrum of [Zn (OX) (L)] complex

72

(3-17)

Types of charge transfer (CT)

74

x

(3-18)

Electronic spectrum of [Cr(OX) (L)]complex

79

(3-19)

Electronic spectrum of [Co(OX) (L)]complex

80

(3-20)

Electronic spectrum of [Ni (OX) (L)]complex

81

(3-21)

Electronic spectrum of [Cu (OX) (L)]complex

82

(3-22)

Electronic Spectrum[Zn(OX)(L)]

83

(3-23)

3D molecular modeling proposed [Cr(L)(Ox)]Cl complex

84

(3-24)

3D molecular modeling proposed [M(L)(Ox)] complexes

84

M= Co(II), Ni(II) and Cu(II) and Zn(II) (3-25)

spectrum of K [Cr(OX)2(TMA) (H2O)]complex

90

(3-26)

FT-IR spectrum of K2[Mn (OX)2(TMA) (H2O)]complex

90

(3-27)

FT-IR spectrum of K [Co (OX)2(TMA) (H2O)]complex

91

(3-28)

FT-IR spectrum of K2[Ni (OX)2(TMA) (H2O)]complex

91

(3-29)

FT-IR spectrum of K2[Cu (OX)2(TMA) (H2O)]complex

92

(3-30

FT-IR spectrum of K2[Zn(OX)2(TMA) (H2O)]complexs

92

(3-31)

Electronic spectrum of K [Cr (OX)2(TMA) (H2O)] complex

96

(3-32)

Electronic spectrum of K[Mn (OX)2(TMA)(H2O)] complex

97

(3-33)

Electronic spectrum of K2[Co (OX)2(TMA) (H2O)] complex

98

(3-34)

Electronic spectrum of K2[Ni(OX)2(TMA) (H2O]] complex

99

(3-35)

Electronic spectrum of K2 [Cu(OX)2(TMA) (H2O)] complex

100

(3-36)

Electronic spectrum of [K2[Zn(OX)2(TM) (H2O)] complex

100

(3-37)

3D molecular modeling proposed

101

[M(Ox)2(TMA) (H2O)] complexes M= Mn(II), Co(II), Ni(II), Cu(II) ,Zn(II), n=2 M=Cr(III) , n =1

xi

(3-38)

Structure of the oxalate anion (Ox -2)

101

(4-1)

Antibiotic sensitivity testing

104

(4-2)

Escherichia coli

104

(4-3)

Enterobacter cloacae

105

(4-4)

(a) S. aureuscells and (b) skin infection by S. aureus

105

(4-5)

Bacillus subtilis

106

(4-6)

Effects of compounds on bacillus subtitis

109

(4-7)

Effects of compounds on enterobacter cloacae

110

(4-8)

Effects of compounds on Esherichia coli

111

(4-9)

Effects of compounds on Staphylococeus aureus

112

(4-10)

Effects of compounds on Enterobacter

116

(4-11)

Effects of compounds on Esherichia coli

116

(4-12)

Effects of compounds on Staphylococcusaureu

117

(4-13)

Effects of compounds on bacillus

117

xii

List of Schemes NO

Scheme

page

(1-1)

Schematic diagram prepresent the preparing of

10

complexes( nicotinamide and cephalexin (1-2)

Mechanism pathway of the protonated of Schiff base

11

(1-3)

Reaction of (NH2) with (C=O) catalytic mechanism in enzyme to

12

produce Schiff bases (1-4)

Schiff base (ATS)and its Cu(II), Ni(II), Mn(II),Co(II)and Zn(II) complexes

14

(1-5)

Preparation of salicyildene gemifloxacin

15

(1-6)

Preparation of salicyildenegemifloxacin-Zn(II)complex

15

(1-7)

The proposed molecular structure of Schiff base (HL)

16

(1-8)

16-membered macrocycle Schiff base

18

(1-9)

Reaction scheme (H3obap) ligands

22

(1-10)

Synthesis of (PyH)2[Mo2O4(C2O4)2(Py)2]complex

25

(1-11)

Synthesis of Schiff base (HL) macrocyclic ligand.

32

(1-12)

Synthesis of novel macrocyclic [HLMX2] complexes

33

(2-1)

The synthesis route of Schiff base (L)

44

(2-2)

Represented experimental scheme synthesis

46

(L - M-oxalic acid)complexes : Set 1 (2-3)

Represented experimental synthesis (TMA- M -Oxalic acid) complexes : Set 2

xiii

48

LIST OF ABBREVIATION AND SYMBOLS AAS

Atomic Absorption Spectroscopy

M.p

Melting point

BM

Bohr Magneton

DMF DMSO-d6 dec MLCT C L-F

N,N’-Dimethyl Formamide Deuterated dimethylsulfoxide Decomposition Metal to ligand charge transfer Concentration Ligand field

λmax

Wave length of maximum absorbance

ΛM

Molar conductance

Κ μeff

Specific conductance Effective magnetic moment

%

Percentage

χg

Gram magnetic susceptibility

χM

Molar magnetic susceptibility

χcorrM

Corrected magnetic susceptibility

K

Kelvin

δ

Chemical shift

M.Wt

Molecular weight

Ceph

Cephalexin

Ampi

Ampicillin

Amox

Amoxicillin

xiv

Chapter One

Introduction and Literatures Review

http://edumefree.com/welcome/lesson/752/163421. General Introduction A large number of compounds are important from the biological point of view [1] . The field of

organometallic chemistry

and

bioinorganic

chemistry, which deals with the study of the role of metal complexes in biological system, has opened a new exceed for scientific research in coordination compounds [1] 1.1. Antimicrobial Drugs Antimicrobial drugs or (Antibiotics) are the drugs that fight infections caused by bacteria or other microbes. The most useful classification system, is shown in table (1-1). Table (1-1) Timeline of antimicrobial drugs [1,2]. antibiotics (Time) Sulfanilamide (1936)

Benzylpenicillin (1941)

Streptomycin(1944)

1

Chapter One


Chloramphenicol(1947)

Chlorotetracycline(1948)

Semi-ntheticpenicillin(1958)

Cephalosporin(1960)

Fluoroquinolones(1980)

2

Chapter One


Introducing metal ions into a biological system may be carried out for diagnostic purposes, or therapeutic and overlap in many cases [3]. Many organic drugs require interaction with metals for activity [4]. see table (1-2):

Table (1-2) Some medical and prospective medical uses of inorganic compounds [4] Elements

Compounds and Trade (Names/comments)

Uses

Bi(sugar) polymers Bi

(Pepto-Bismol; Ranitidine Bismutrex;

antacid

De-Nol) Mn

Mn chelates (SOD mimics)

Anticancer agents

As

As2O3 (Trisenox)

Anticancer agents

Ln

La(CO3)3 Hyperphosphatemia

Anticancer agents

Ag

AgNO3 Ag(Sulfadiazine)1% cream (Flamazine; Silvadene ) Cis-[Pt (amine)2X2]

Pt

Treatment of burns Anticancer agents

Platinol; Paraplatin; Eloxatine Testicular,ovarian, colon cancers

Au

Hg

Acetylthioglucose derivative (Ridaura. Orally active)

Rheumatoid arthritis

Hg-organic compounds\ (Thiomersal; mercurochrome)

3

(Antibacterial, Antifungal

Chapter One


1.2. Metal complexes in biological System Metal complex is a structure consisting of a central atom or ion (metal) bonded with anions (ligands). Metals are Lewis acids because of their positive charge (+), coordination bonds are usually much-weaker than covalent bonds and so ligand substitution reactions will be common and have an esteemed place in medicinal chemistry [2]. A number of diseases and their treatment depends on the metabolism of inorganic constituents. (2-4).

1.2.1. Metal complexes in medicinal biochemistry. Metals have an important place in medicinal biochemistry. [1-8 ] see Table (1-3) .Transition metals exhibit different oxidation states and can interact with a number of negatively charged (-) molecules. As in the case of haemocyanins , the ferrous centers become ferric centers, and the (O) atom is converted to peroxide .[1]

Figure(1-1).Different oxidation states in haemocyanins

4

Chapter One


Table (1-3)Metal complexes in medicinal biochemistry complexes

cyclam(1,4,8,11-tetraazacyclotetradecane)

ruthenium-based ant metastatic agent

[4]

[5]

Bismuth –Methylthiosalicylate [5] [5] Titanium

anticancer

agents

that

have Bismuth-containing Antiulcer Drugs

undergone clinical trials [ 6]

[ 6]

[6]

5

[6]

Chapter One


Antimony-based antiparasitic agents[6]

Vanadium compound in treatment of diabetes. [7]

[7] [7] Au anti arthritis compounds

Gold complex of anti parasitic agents. [7]

[7] [7]

X-Ray crystal structure of [AuIII(TPP)]+ H2TPP = tetraphenylporphyrin Trans-platinum compounds as potential anticancer compounds [7]

6

Chapter One


1.2.2. Antibiotic - metal complexes Metal complexes Pt(II)-piroxicam =[(PtCl2)(C2H4).(Hpir)]0.5C2H5OH complex was synthesized by Leo et.al, (1998), [8]. Figure (1-2)

1

Figure (1-2). Structure of Pt(II)-piroxicam

Rhodium (Rh) and iridium(Ir) with cephalexin complexes synthesized and spectral properties are reported by Saud and Resayes (2001) [9] , Figure (1-3).

Figure (1-3). Complexes of rhodium and iridium with cephalexin

7

Chapter One


Chomplexes of Co(II), Zn(II) and Mn(II) cellulose- antibiotics figure (1-4) were synthesized by Tella et al,(2011) . [10] .

Figure (1-4). Metal antibiotics- cellulose- complexes Some matel (II) complexes of antibacterial drug cephradine have been prepared and characterized by Zahid, and co-workers (2000) [11] Figure (1-5).

Figure (1-5). Structure of antibacterial drug Cephardine

8

Chapter One


Marija et al. (2001) (12) have reported the crystal structure of the prepared [Zn(Ciprofloxacin)2]H2O complex . Figure (1-6)

HN

N

F

O O

O Zn

O

O

O

F

N

N H

Figure (1-6) .Zn(Ciprofloxacin)2.H2O complex

Taghreed et al., (2013) [13] have reported the synthesis mixed ligand complexes composition [M(Ceph)(NA)3]Cl , (where NA = Nicotinamide and ceph - = cephalexinate ion Scheme (1-1)

9

Chapter One

Introduction and Literatures Review O

1

NH2

H

H S N

N H

N

CH 3

O

. H 2O + 3

C O

NH 2

MCl2

OH

Cephalexin

Nicotinamide

H

H

N H O H

+

O

S

CH 3

N

MeOH

O

N

O

O

M

H

KOH

Stirring 5 hours

Cl

N

N N

H 2N

O

C O

O

C

C NH 2

NH2

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

.

Scheme (1-1) . Schematic diagram represent the preparing of ) nicotinamide and cephalexin( complexes

1.3.Schiff base metal complexes In (1864) Schiff’s base was first reported by Hugo Schiff . Schiff’s bases are an important class of ligands can be prepared by condensing amines (-NH2) and carbonyl (C=O) compounds with the elimination of (H2O) molecules. The common structural of Schiff’s base is the azomethine (imine) group with a general formula RHC=N-R’ , where R and R’ are ( alkyl,. aryl,. heterocyclic or cyclo alkyl)groups in different conditions and in different solvents. [14] ,See (Scheme 1-2).

10

Chapter One


Scheme (1-2) . Mechanism pathway of the protonated of Schiff base The interaction of Schiff’s bases and (metal) ions gives complexes of different geometries used to (anticancer, antibacterial. , antiviral, design medicinal compounds, antitumor metallic-organic chemistry ,catalytic applications, chemical analysis, geology and corrosion inhibition). The Schiff bases complexes can be synthesized by direct mixing of the Schiff base with metal ions in appropriate (organic solvents) using refluxing. One of the most dominant kinds of catalytic mechanism in enzyme) is usually that of a amino acid L- lysine(Lys) residue with a carbonyl group (C=O) of the compound to get Schiff base [14-15], Scheme (1-3).

11

Chapter One


Scheme (1-3) . Reaction of (NH2) with (C=O) catalytic mechanism in enzyme to produce Schiff bases

Fe(III) and UO2(II) complexes of Schiff base resulted from the condensation of 2-thiophenecarboxaldehyde(C5H4OS) and anthranilic acid (C7H7NO2) have been reported [15] were checked for their biological activity against some pathogenic bacteria.

Mohamed et al.,2010 [16] have reported the synthesis metal complexes of Schiff base derived from condensation of (sulphametrole) and arelaldehyde)

12

Chapter One


Figure (1-7) . The proposed structural formulae of (Sulphametrole and arelaldehyde) complexes

El-Sherif and Eldebss, (2011), [17] have reported the synthesis of Schiff base (ATS) = 2-Aminomethylthiophenyl-4bromosalicylaldehyde(C14H12BrNO2S) and its Cu(II), Ni(II), Mn(II),Co(II) and Zn(II) complexes ,Scheme (1-4).

13

Chapter One

.


Scheme (1-4) . Schiff base (ATS)and its Cu(II), Ni(II), Mn(II),Co(II)and Zn(II) complexes

Bharti et al., (2013) [18] have reported the synthesis metal complexes of Cu(II) and Hg(II) have been synthesized with Schiff base of sulfamethoxazole derivative and salicylaldehyde. figure (1-8).

Figure (1-8) . Sulfamethoxazole Schiff base derivative with Cu(II)and Hg(II)

14

Chapter One


Farzana et al., (2013) [19] have reported two Schiff base (salicylaldehyde) with (salicylidenegemifloxacin and gemifloxacin)antibiotics. schemes (1-5 and1-6) the ft-ir study showed that ligand is a bidentate and coordinate to the central metal ion though the (-c=N ) and the (O) of phenol groups.

Scheme (1-5). Preparation of salicyildenegemifloxacin

Scheme (1-6) . Preparation of salicyildenegemifloxacin-Zn(II)complex

15

Chapter One


Taghreed et al., (2014) [20] have reported the synthesized Schiff base (HL )via condensation of 4-dimethylaminobenzaldehyde( C9H11NO) and amoxicillin. Scheme (1-7)

Scheme (1-7) . The proposed molecular structure of Schiff base

Hong et al., 2014. [21] have reported Schiff base Cu (I/II) complexes with [Cu2I4]2− iodine–copper cluster as bridges under solvothermal conditions and characterized by (C.H.N), (IR), (TGA), and (X-ray )single-crystal/powder diffraction. The results show that 2 is a 0-D discrete structure from an assembly of one [Cu2I4]2− unit and two [2 × 2] molecular grids . Figure (1-9)

16

Chapter One


Figure (1-9). Schiff base copper(I/II) complexes [Cu2I4]2− bridges Hanaa (2016) [22] was reported synthesized and characterized Schiff base of salisaladehyed with o-benzyl, m-benzyl, p-benzyl aniline Figure (1-10)

Figure (1-10) . Schiff base salisaladehyed with ortho / (m-/p- o-)benzyl

Ali akbar et al (2017) [23] have reported the synthesis and structural characterization of a new (16-membered macrocycle Schiff base) compound derived from( 3,3′- imethoxy-2,2′-(propane-1,3-diyldioxy)-dibenzaldehyde and 1,3-propanediamine )Scheme (1-8).The quantum chemical method was used to obtain geometrical parameters and to calculate the FT-IR spectrum of the compound. 17

Chapter One


Scheme (1-8).16-membered macrocycle Schiff base Starting materials and Ligands and related compounds in this study: 1.4 - Oxalic acid. 1.5 -Acetyl acetone. 1 .6 -Trimethoprim antibiotic drug (TMA) .

18

Chapter One


1.4. Oxalic acid 1.4.1. Oxalic acid as ligand Ethanedioic acid or (oxalic acid) and other names wood bleach formula is (C2 H 2 O 4) pertain to the family of carboxylic acids. ,a colorless, crystalline, toxic organic compound and its usual form is that of the crystalline hydrate, (COOH)2·2H2O.[24] ,The first prepared synthetically in (1776) and is strong acid, despite being a carboxylic acid [25-26]. (oxalic acid) have a carbonyl (C=O) and an alcohol (OH) group they share some basic physico-chemical properties with (alcohols, aldehydes, and ketones) [27].

1.4.2. Oxalic acid complexes Jack et al . (1999) [28].have reported the hydrothermal synthesis and properties of 2 [m(ox)(bpy)] as polymer M = Fe(II), Co(II), Ni(II), Zn(II); bpy = 4,4′bipyridine and ox = C2O4 2-

19

Chapter One


Figure (1-11) .Two-dimensional of 2 [M(ox)(bpy)]complex .

Platinum(Pt) -based drugs, which limits their clinical use [29]. Oxaliplatin Figure (1-12) has been designed and clinically approved for the treatment of colorectal cancer, which is resistant to cisplatin [30].

Figure (1-12 ).molecular structure and 3D of oxaliplatin

20

Chapter One


Mahmoud et ,al(2004) [31]. have reported the mixed‐ligand complexes of a schiff base 4‐dihydroxybenzylidenethiosemicarbazide (H2L)-, oxalic acid and with, M(II) = Cu, Zn, Ni and Fe(III) Ions .The (H2L) is coordinated to the metal atom as a neutral, monoanionic and/or dianionic tetradentate type (ONNO) ligand in complexes. Figure (1-13).

Figure (1-13) . Suggested structure of the of the [Fe(III) -H2L – Ox] complex

The tetradentate (N.N.N.O.) ligand , H3Obap [32] was prepared by reacting ethyl oxalyl chloride (C4H5Cl2O2 )with anthranilic acid (AnthH) in order to prepare (ethyl oxamate benzoic acid) was intermediate compound further condensation with 1,3-propanediamine. Scheme (1-9)

21

Chapter One


Scheme (1-9). Reaction scheme (H3Obap) ligands.

The Pd(II) ion with (H2apox /or H3obap as primary ligands and nucleosides (Cyt or Ado) as secondary ligands. Figure (1-14).

22

Chapter One


Figure (1-14). [Pd(Obap)]−(above) KH[Pd(obap)]2·3H2O complex (below).and Schematic diagram and 3D [Pd(obap)]−/12-mer picture (along with an electrostatic surface (map)

23

Chapter One


In (2015) Chainok et al ,[33]. have reported the crystal structure of a mixedligand Tb (III)coordination polymer poly [Tb(CHO2)- (C2O4)]n}, containing (C2O4 2-) ligand, Figure(1-15).The Tb (III) ion is (9) coordinated in a (distorted tricapped trigonal–prismatic) by (2) chelating _COO- groups from ( 2 C2O4 2_) ligands, two carboxylate (O )atoms from another (2 C2O4 -2) ligands and (3 O) atoms from (3CHO2 ) ligands.

Figure (1-15 ) . Crystal structure of [Tb(CHO2)-(C2O4)]n}

Quan-Liang Chen (2016) [34]. has reported synthesis and structural characterization of a trans-(PyH)2[Mo2O4(C2O4)2(Py)2] in aqueous solution. Scheme (1-10). The (Py) ligand coordinates to (Mo )atom through (N)atom. The oxalato ligand coordinates to each (Mo) atom through (2-Carboxylate Oxygens) in a bidentate chelating manner. Figure (1-16).

24

Chapter One


Scheme (1-10). Synthesis of (PyH)2[Mo2O4(C2O4)2(Py)2]complex

Figure (1-16) . Perspective view structure of [(PyH)2[Mo2O4(C2O4)2(Py)2]complex.

25

Chapter One


1.5. Acetyl acetone chemistry 1.5. 1.Acetyl acetone as ligand Acetyl acetone (acac) (Pentane-2,4-dione ) = (acac) is an organic compound a common bidentate ligand [35] figure (1-17) A ball model of acetylacetone .

Figure (1-17 ): A ball model acetylacetone structure

1.5. 2. Acetylacetone complexes The acetylacetonate anion, acac−, forms complexes with many metal ions, Table (1-4). Selected examples of acetylacetone complexes

26

Chapter One


Table (1-4) Selected examples of acetyl acetone complexes Acetyl acetone complexes

Structure

Ref [36]

Vanadyl(IV) acetylacetonate

Chromium(III) acetylacetonate and

[37-38]

Manganese(III) acetylacetonate

Aluminium(III) acetylacetonate

[36]

Copper(II) acetylacetonate

[39]

27

Chapter One

Introduction and Literatures Review [40]

Nickel(II) acetylacetonate

[41] Eu(OCC(CH3)3CHCOC3F7)3 = Eu(fod)3

[42- 43]

Iridium acetylacetonate Ir(O2C5H7)3

[44]

Zinc acetylacetonate

28

Chapter One


Sadeek and Refat (2006), [45] have reported preparation and characterization complexes of { N,N’- Xphenylenebis(acetylacetoneimine)}Schiff base type(ONNO),X as ortho = (L1), as meta=(L2) as para = (L3). with {Sn(II)}atom .

Figure (1-18 ) .Schiff bases type(ONNO), (L1), L2) and (L3)

Three Schiff bases (L1-L3) chelates with Sn(II) as a tetradentate through the (2 N ) and (O) atoms as shown in figure ( 1-19 ) and in the ketoamine form (III). Figure (1-18).

29

Chapter One


Figure (1- 19) . Schiff bases (L1-L3) chelates with Sn(II)

1.5. 3.Acetyl acetone derivatives Adnan dib [46] (2013) carried out the Schiff base derived from cetylacetone were characterized by FT-IR, 1H ,13C NMR and (C.H.N). Hyper Chem-6 program has been used to predict structural geometries of Schiff base in (gas phase). Figure (1-20). The (ΔHf º) and (ΔEb) at 298 ºK for the free Schiff base was calculated by PM3 method.

30

Chapter One


Figure (1-20). Shows the molecular structure of compounds (I, II, III)

Gajendra .et al , (2012) [47] have reported the synthesis macrocyclic Schiff base ( HL) by refluxing Thio-carbohydrazide (2 mmol) and acetyl acetone (2 mmol) in ethanol with addition of ( 5 ) drops of concentrate HCl.

31

Chapter One


Scheme (1-11) . Synthesis of Schiff base (HL) macrocyclic ligand. The M(III) - (HL) macrocyclic complexes of the type [HLMX2] where X = OAc = CH3COO - ,Cl- and M = Cr(III), Mn(III), Fe(III) have been synthesis characterized . The analytical data is in the favor of (Oh) geometry of the complexes. Scheme (1-12).

32

Chapter One


Scheme (1-12). Synthesis of novel macrocyclic [HLMX2] complexes .

Santhi and Namboori, (2013 ) [48] have reported the synthesis of Schiff base derived from acetoacetanilide (C10H11NO2) and 1,3diaminopropane(C3H10N2), [MX3(LH2)], where M= { Gd(III), Dy(III) and Sm(III)}, X = NO3−, Cl−,NCS− ) have been synthesized in alcohol and characterized by (C.H.N.S), spectral, electrical conductance and magnetic susceptibility measurements In these compounds. Figure (1-21)

33

Chapter One


Figure (1-21) . Proposed structure for the complexes.

1.6. Trimethoprim (TMP) chemistry 1.6. 1. Trimethoprim as ligand Trimethoprim is an antibiotic used for treatment of an antimalarial and bladder infections , alone as an [49] Figure (1-22). Trimethoprim

Figure (1-22) . molecular structure and 3D of Trimethoprim

34

Chapter One


Trimethoprim L- Alanine were condensed to give macrocyclic ligand by the reported method [49] Adedibuet and Tella [50] carried out the two metal complexes of [Cd(II) and Co(II)] - (Trimethoprim) were synthesized and characterized by both spectroscopic and analytical methods. They are 4-coordinate complex containing 2 molecules of (TMP) and two chloride ions. Distorted (Th ) geometry is suggested for their complex where (Trimethoprim) behaves as a monodentate ligand. through the N(pyrimidine)group. Figure (1-23)

Figure (1-23) .Proposed structure M= Co(II), Cd(II) complexes of (TMA)

Air stable silver Ag(I) complexes [51] of trimethoprim drugs has been synthesized and characterized by (C.H.N) (FTIR) (UV-Vis)and conductivity measurement. The complexes formed (4) coordinate geometry with the (TMA) acting as a monodentate molecule bonding to the (Ag) ion. Figure (1-24)

35

Chapter One


Figure (1-24) : Silver Ag(I)-TMA –NO3 complexes

In continuation of our efforts (2015 - 2016) , we reported many literatures [52-54] synthesis the antibiotics Trimethoprim (TMA) as primary ligand with amino achds =Anthranilic acid (AnthH) , L-proline (ProH) and L-alanine (AlaH) as a secondary ligands with M(II) as shown in Table (1-5).

36

Chapter One


Table (1-5). Trimethoprim –amino acids complexes

Mixed ligand-Metals Complexes

Compositions

Ref.

[M (Pro)2 (TMP)(H2O)] M= Zn(II),Cd(II),Co(II), Ni(II), Cu(II), Zn(II),Cd(II) and Hg(II)

[52]

[M (Ala)2 (TMP)(H2O)] M= Zn(II),Cd(II),Co(II), Ni(II), Cu(II), Zn(II),Cd(II) and Hg(II)

[53]

TMp + L-prolin+ Metal Chloride Trimethoprim+ amino acid( L-Alanine)+ MCl2.

[54] [M (Anth)2 (TMP) (H2O)] M= Zn(II),Cd(II),Co(II), Ni(II), Cu(II), Zn(II),Cd(II) and Hg(II)

TMp +Anthranilic acid + Metal Chloride

37

Chapter One


Lawal et al (2017) have reported the synthesis series of metal ions from nicotinamide (NA) and tmp.[ 55 ] .Moreover, the complexes were the analytical data which show the {(NA) and tmp }act as bidentate towards the (metal ) ion and 2(H2O) molecules coordinated to the [M= Ni(II), Cu(II)] ions within the coordination sphere, to give an (Oh) geometry for all synthesized complexes. Figure (1-25).

Figure (1-25) .[ Metal (II) -TMA –NA] complexes M= Ni(II), Cu(II)

38

Chapter One


1.7. Aims of the research This research work aims to: 1. Synthesize, new Schiff base (L) derived from antibiotics (Trimethoprim) and acetyl acetone namely: Z)-4-(4-amino-5-(3,4,5-trimethoxybenzyl)pyrimidin-2-yl)imino)pentan-2-one 2. Synthesize mixed -ligand complexes derived from Schiff bases ligand (L ) and ( Oxalic acid) with some bivalent metal ions and Cr(III). 3. Synthesize mixed -ligand complexes derived from antibiotics (Trimethoprim) and oxalic acid with some bivalent metal ions and Cr(III). 4. Study and characterization the Schiff base that has been obtained using different techniques such as .infrared, ultraviolet/visible, H NMR,C13 NMR) spectroscopies micro analysis of the elements (C.H.N.S) . 5. Characterize the syntheses mixed ligand metal complexes depending on the results of infrared spectroscopy and UV-Vis spectroscopy in addition to the results of atomic absorption spectroscopy and the results of magnetic moments and conductivity measurement, which collectively reached to suitable geometrical structure of the prepared complexes. 6. Compare the antimicrobial activities of the syntheses Schiff base (L) and their mixed ligand complexes against 2-bacteria gram positive (+G) and gram negative(_G) bacteria.

39

Chapter Two

The Experimental

2. Experimental 2.1. Chemicals The Chemicals used in this thesis and their supplies are listed in table (2-1). All these chemicals were used without further purification. Table (2-1) Chemicals used in this work and their suppliers Purity Company source Material percentage of supply (%) Acetic acid glucial BDH 99 Acetone Merch 99 Acetyl acetone Fluka 99 Chloroform BDH 99 Chromium (III) chloride hexahydrate Merck 99 Cobalt(II) chloride hexahydrate Riedial – Dehaen 99 Copper (II) chloride dihydrate Merck 99 Dimethyl form amide (DMF) Fluka 99 Dimethyl sulfoxide (DMSO) CDH > 99.5 Ethanol Merck 99 Manganese(II) chlorid tetrahydrate Merck 99 Methanol BDH 99 Nickel (II) chloride hexahydrate Fluka 99 Sigma Oxalic Acid 98 Potassium hydroxide Riedial-Dehaen 99 Trimethoprim DSM (Spain) 99 Zinc (II) chloride Fluka 99

2.2. Instruments and apparatus The following measurements were used to characterize the ligands (oxalic acid, trimethoprim and schiff base) and their complexes.

2.2.1. The melting point (M.P) measurement. The melting point of the all compounds in this study was determined in open glass capillaries with Stuart SRS (USA) digital melting point apparatus.

40

Chapter Two

The Experimental

2.2.2. Conductivity measurements (ΛM) Electrical conductivity measurements(ΛM) of the compounds were recorded at (25ºC) for (10-3 mole.L-1) solution of the samples in H2O and DMSO by using an Multi 740, Tram Germany [57]

m 

1000 L C

L Specific conductivity ,(Ω-1 cm-1) ΛM Molar conductance, (Ω-1 cm2 mol-1) C Concentration , (mole/ L)

2.2.3. (FT-IR) spectroscopy FT-IR spectra of compounds ( two ligands and complexes) were recorded as (KBr) disc by using Shimadzu, (4800S) (FTIR) spectrophotometer: in the range (400-4000) cm-1, in Ibn sena cenrtral of science.

2.2.4. (U.V-Vis) spectra The electronic spectra of the compounds were obtained by using

[Shimadzu spectro photometer] at range (200-900) nm, with quartz cell of (1.0 cm) length and the concentration of (1× 10 -3 mole L-1), [in Ibn Sena Cenrtral of Science and Department of Chemistry, College of Science, Al-Mustansiriyah University.].

2.2.5.Total metal content

(Metal % )

The metal % contents of the complexes were determined by atomic absorption Shimadzu (A.A620) spectrophotometer,In[Ibn–Sina Company Baghdad, Iraq]. [56] 41

Chapter Two

The Experimental

2.2.6. Magnetic susceptibility (μeff) The magnetic susceptibility (μeff) measurements were obtained at 25ºC , [58] by balance magnetic susceptibility of Bruke Magnet B.M.6, England. In the College of Science, Al-Nahrain University. The following calculations were made to arrive at the magnetic moments of the metal in the complex. χM = χg × M.Wt.

χM = molar magnetic susceptibility χg=gram magnetic susceptibility

μeff = 2.828(χM corr .T) 1/2 μeff = effective magnetic moment and T = temperature in K. The χM is subjected to diamagnetic correction using pascal constants to obtain corrected (χM corr), the magnetic moment is finally calculated as;

2.2.7. (1H ,13C NMR) spectroscopy 1

H, 13C NMR spectra were recorded in Department of Chemistry Labcentral,

Tehran , (Iran). using Brucker (DRX) system 500 (500 MHzcorrelation,. The chemical shift values are expressed as  (ppm) using DMSO d6 as internal standard. The coupling constant ( J ) is given in (Hz).

2.2.8. Elemental micro analysis Elemental micro analysis(C.H.N.S.)

for the ligands was performed on a

analyzer from EURO EA(EA3000) elemental analyzer at department of Chemistry, College of Science, Al-Mustansiriyah University.

2.3. Chloride analysis (Cl % ) The complexes were analyzed for their chloride content were determined by standard methods [56] As follow: To the resultant solution of the complexes, aqueous solution of AgNO3 was added, white precipitate of AgCl was formed in the case of metal complexes has Chloride content in any . 42

Chapter Two

The Experimental

2.4. The proposed molecular structure The proposed molecular structures of the compounds were drawing by using Ultra Chem .Draw. office program, 3DX (2015) PerkinElmer.

2.5 Synthesis of Schiff base ligand (L)

The Schiff base ligand (L) was prepared by condensation of {1.176 gm(4 mmole)} of trimethoprim in ethanol (20 mL) and (0.4gm,4mmol) of acetyl acetone in ethanol (20 mL) for 8-hr with addition of 4-5 drops of acetic acid scheme (2-1) Then the volume of reaction mixture reduced by slow evaporation at room temperature was left to stand overnight. [52- 54] The obtained off white precipitate was washed several times with ethanol absolute, then dried at room temperature and recrystallized from ethanol to get a pure sample, Yield: 86%, M.P: 185 oC . M. wt = 372.43 gm.mole-1 and general formula (C19H24N4O4). % Theoretical % Experimental :

:

C: 61.28, H: 6.50 ,

C: 62.06 , H: 5.56 ,

43

N: 15.04,

N: 13,99

Chapter Two

The Experimental

Scheme (2-1) .The synthesis route of Schiff base (L)

2.6. Synthesis of mixedligand metal complexes with some metal ions : 2.6.1 : (L- M-oxalic acid) complexes : Set 1 2.6.2 : (TMA- M-oxalic acid) complexes : Set 2 2.6.1 : Synthesis of (L- M-oxalic acid) Complexes :Set 1(five complexes) The 1:1:1 (Schiff base Matel - Oxalic acid) complexes were prepared from MCl2 .nH2O .n=0-6.and CrCl3 .6H2O M =Co(II),Cu(II),Ni(II),Zn(II) and… Cr(III). Schiff base (L) as a primary ligand and oxalic acid (H2C2O4) as secondary ligand .

44

Chapter Two

The Experimental

All complexes were prepared by the following general procedure:

2.6.1. 1.Potassium oxalate solution : A solution of (oxalic acid dihydrate in 1:1 ethanol: water (10

mL)

(C2H2O4·2H2O

) (0.126 gm,1 m mole)

with KOH ( 0.112gm, 2 mmol), was added and

stirred at room temperature, the solution was deprotonated according to the (scheme 1-2).

2.6.1. 2.General method for synthesis (L- M-oxalic acid) complexes : Set 1 Set of metal(II) chloride and Cr (III) solution (1 mmol) was prepared by dissolving ( 0.23793, 0.23769, 0.17048, 0.17228and 0.26635) (gm,1.mol),of(CoCl2.6H2O,NiCl2.6H2O,CuCl2.2H2O, ZnCl2,andCrCl3.6H2O respectively in 10 mL of ethanol. [(0.372 gm,1mmole of (L)] was dissolved in (10 mL) of (ethanol) and the solution of (potassium oxalate) that has been prepared in (2.7.1.1) were added at the same time to each of the metal chloride solution in a flask mentioned above by using stoichiometric amount [(1:1:1) [(M:(K+OX-):(L)] molar ratios, and mixture stirred magnetically for 4 h. at room temperature and the residue was left to stand overnight. After (one day ) a colored powder was obtained The precipitate of the complex which was filtered and washed with ethanol and recrystallized from ethanol and finally dried in room temperature . The yields range from 79 to 85 %. The solubility of the compounds were tested using various solvents .

45

Chapter Two

The Experimental

Scheme (2-2) Represented experimental scheme synthesis ( L- M-oxalic acid)complexes :Set 1

46

Chapter Two

The Experimental

2.6. 2.General method for synthesis (L- M-oxalic acid) complexes : Set 2 (six complexes) 2.6.2.1: Potassium oxalate: A solution of (oxalic acid dihydrate (C H O ·2H O ) (0.252 gm,2 m mole) in 2

2

4

2

1:1 ethanol: water (10 mL) with KOH (0.224gm,4 mmol), was added and

stirred at room temperature, the solution was deprotonated according to the (scheme 2-2) 2.6.2.2 General method for synthesis of the mixedligand metal (II) and Cr(II) ( Complexes: see Scheme (2-6) The 1:1:2 [M: TMA: 2OX] complexes were prepared from ,trimethoprim as a primary ligand and oxalic acid (H2C2O4) as secondary ligand.

All complexes were prepared by the following general procedure : Set of metal salts = M(II) as

mentioned in [set 1 and Mn (II)] ,Cr(III) were prepared

by dissolving solution (1 mmol) in 10 mL of 1:1 ethanol: water. [(0.29 gm ,1mmole of (TMA)] was dissolved in (10 mL) of of 1:1 ethanol: water 'and the solution of ( K2+ OX-) that has been prepared in (2.7. 2.1) were added at the same time to each of the metal chloride solution in a flask mentioned above by using stoichiometric amount [(1:1:2) [(metal :(TMA) :2(K2OX)] molar ratios, and mixture stirred magnetically for 4 h. at room temperature and the residue was left to stand overnight. After (one day ) a colored powder was obtained The precipitate of the complex which was filtered and washed with (ethanol), and recrystallized from ethanol and finally dried in room temperature . The yields range from 82 to 90 %. The solubility of the compounds were tested using various solvents .

47

Chapter Two

The Experimental

Scheme (2-3). Represented experimental synthesis (TMA- M-oxalic acid) complexes : Set 2

48

Chapter Three


complexescomplexescomplexes3.

Results and Discussions

3.1. General methodology: Trimethoprim-C14H18N4O3(TMA)antibiotic, IUPAC = 2,4-Diamino-5-(3,4,5trimethoxybenzyl)pyrimidine has been selected to synthesize : A) Schiff base ligand (L) containing (N.N.N and O) as donor atoms type (NNNO) derived from (TMA) antibiotic and acetylacetone (acac) with the formula (C19H24N4O4) . B) Mixed -ligand metal complexes by using Schiff base ligand (L) as primary ligand and oxalic acid ( H2OX ) = (H2 C2O4)), as a secondary ligand with M(II) and Cr (III).

C) Mixed - ligand metal complexes by using Trimethoprim antibiotic as a primary ligand and oxalic acid as secondary ligand with M(II) and Cr (III). See Table (3-1).

Table (3-1) Compositions of compounds Primary ligand

Secondary ligand

Compositions

[M (OX) (L)]

L Schiff base

Oxalic acid

H2Ox= H2C2O4

C19H24N4O4 Trimethoprim TMA

M= Co(II), Ni(II),Cu(II),Zn(II) and [Cr (OX) (L)]Cl K2[M (OX)2(TMA) (H2O) ] .

Oxalic acid

M=Mn(II), Co(II), Ni(II),Cu(II),Zn(II) and K [Cr (OX)2(TMA)].

C14H18N4O3

49

Chapter Three


3.2. Physical properties and elemental analysis results of the synthesized ligand (L). The Physical properties and (C.H.N.S) of the synthesized ligand (L) are given in table (3-2).The Elemental Analysis data reported a good agreement between the (theoretical and experimental )values and supported the proposed formulae of the synthesized ligand.

Table (3-2) Some physical properties for the starting materials and (C.H.N.)

Trimethoprim

C14H18N4O3

Oxalic Acid

C2H2O4. 2H2O

.2H2O

Schiff base

C19H24N4O4

(exprement )

Color

M.P °C

formula

Theoretical

g/mol

Compound

Molecular weight

Compound

results for synthesized ligand (L)

C%

H%

N%

290.32

283

white

57.92

6.25

19.30

90.03

101

white

26.68

2.24

-----

372.43

185

Off white

61.28 (60.68)

6.50 (6.00)

15.04 (16.1)4

50

Chapter Three


3.1.3. Solubility The solubility data of the starting material and Schiff base ligand (L) in various solvents are summarized in table (3-3) which shows that(L)was soluble in DMF, DMSO, and C2H5OH.

Table (3-3) Solubility of the starting materials and synthesized Schiff bases ligands in different solvents Compound H2O DMF DMSO CH3OH C2H5OH acetone chloroform TMA

+

+

+

+

+

–

–

H2OX

+

+

+

+

+

–

–

L

+

+

+

÷

+

–

–

(+) Soluble, (–) Insoluble, (÷) Sparingly

3.2. FT-IR spectra of the ligands and starting materials The (FT-IR) spectrum of the starting material (TMA) figure (3-1) ,was summarized in Table (3-4) exhibits a very strong band at(3468and 3317) cm-1 ascribed to the υ(NH2) group asym andsym [65-66], while the bands at (1128) cm−1 appointed to the υ (OCH3 aromatic groups) and υ ( C-O-C ) (asym.) and (sym.) at (1263) and (1236) cm−1 respectively and a sharp very strong frequency band at (1508and1635) cm−1 ascribed to the υ (C=N).pyrimidine nitrogen ) group . [52- 54,65,67]. Figure (3-2).

51

Chapter Three

Results and Discussion Table (3-4): FT-IR spectral data (ύ) cm-1 for the (TMA)

υ (N-H)

υ (N-H)

υ (C=N)

υ

asym

sym

Pyrimidine

(C=C)

υ (C-O-C)asym Str

υ (C-O-C)sym

υ (-OCH3)

Str

nitrogen 3468vs

3317

1635vs

1562s

1265s

1234vs

1593vs

Figure (3-1) FT-IR spectrum of ( TMA)

52

1126vs

Chapter Three


The (FT-IR) spectrum of the acetaylaceton (acac) figure (3-2) , was summarized in Table (3-5) . In (2002) Tayyari and Milani [67] have reported vibrational assignment of ( acac) at 1620 cm-1 region a broad and strong . [ 65-67 ], the enol form of all beta-diketones exhibits an extremely broad band in the υ (3500–2200) cm−1.the bands at (3248) and (2997) cm-1 were ascribed to υ(CH3)asymmetry and symmetry stretching vibration respectively. The bands at (1709) cm-1 were ascribed to υsy C=C–C=O) . A broad and strong band at (1624) cm-1 was ascribed to υsy C=C–C=O). [ 67-68 ]. Table (3-5): FT-IR spectral data (ύ) cm-1 for the (acac)

vibration υ OH

3429

υ CH3 asym (in plane)

3248

υ CH3 sym (in plane)

2997

υsy C=C–C=O

1709

υ as C=C–C=O

1624 vs

δ CH3

1423

(in plane)

δ C–C+ δ C–C=C+ δ OH

53

1321

Chapter Three


Figure (3-2) : FT-IR spectrum of (acac )

3.2.1. FTIR spectrum of the ligand (L) The (FT-IR) spectrum of the ligand (L), figure (3-3) displays a sharp band around (3448,3425) cm-1 is ascribed to the stretching vibration of the asymmetric and symmetric primary amine υ (NH2) respectively.The bands at (3344) and(2997)cm-1were ascribed to υ(CH3)asymmetry and symmetry stretching vibration respectively .[ 69-70] The spectrum displays a new very strong band at (1658) cm-1 was ascribed to the υ( -C=N-) group stretching mode with disoutshoot the bands which ascribed to the stretching vibration of the primary amine in the (TMA) spectrum and strong band at (1593) cm-1 was ascribed to the υ υ(C=O) group. [65] The bands at (2935, 2831) cm-1, (30 43) cm-1, (1258) cm-1 and (1508) cm-1 were ascribed to the stretching vibration of υ(C-H) aliphatic,υ(C–H) aromatic, 54

Chapter Three


υ(C–C) aliphatic and υ(C=C) aromatic respectively [65-66].The band at (1211) cm1

is due to the stretching vibration of υ(C–N). The band at (1126) cm-1 was ascribed

to the stretching vibration of υ(C–O) [67-70]. The bands at 1334 and 1238 cm−1 which account for υ (C-O-C) str. (asym.) and υ (C-O-C str. (sym.)respectively.[69]. The assignment of the characteristic bands for the starting materials, and the shiff base are summarized in table (3-6) Figure (3-3).

Figure (3-3) : FT-IR spectrum of (L)

55

L

Compounds

Table (3-6) Infrared spectral data(wave number ύ) cm-1 of the { L)

Primary υ CH3

asym,( sym) C-O-C

asym,( sym)

1334

υ(C=O)

υ(-C=N-)

1593

υ(C=C)

arom.

1508

υ(C-C)

aliph.

1258

υ(C-N)

1211

υ(C-O)

1161

arom.

30 43

υ(C-H)

υ(N-H)

amine

56

υ = stretching , arom. = aromatic , aliph = aliphatic , br = broad

1658

2831

2935,

aliph.

(2997) (1238)

3344

υ(C-H)

3425br

3448

Chapter Three Results and Discussion

Chapter Three


3.3. (U.V-Vis) Spectra of the Ligands: The electronic spectral studies of ligands [Table (3-7), Figure (3-4)] were carried out in DMSO (10-3M) solution. [71] Oxalic acid H2OX in DMSO solvent showed two high intensity peak at 262 nm (38167 cm-1) appointed to (π→ π*) and at 310 nm (28490cm-1) appointed to (n → π*) respectively.

Figure (3-4) Electronic spectrum of (H2OX)

The spectrum of free ligand (TMA) Figure (3-5) shows strong peaks at 274 nm (36496 cm-1) which may be ascribed to π → π* and another at 313nm (31948 cm-1) due to n → π* (overlap 2 peaks) aromatic ring of the pyrimidine groups]and (C=N) groups .

57

Chapter Three


Figure (3-5) Electronic spectrum of [TMA]

The spectrum of free ligand (L) Figure (3-6) shows a strong peak at 281 nm(35587 cm-1) which may be ascribed to π → π* electronic transitions within the organic ligand.

Figure (3-6) Electronic spectrum of Schiff base (L)

58

Chapter Three


Table (3-7) Electronic data of (TMA) and synthesized ligand (L) and molar conductivity

λ nm

Symbol

Molar

Є max -1

-1

molar .cm

υ' cm-1

Assignment

Conductivity (ohm-1.cm2.mol-1) In DMSO

TMA

H2C2O4= OX L

274

1614

313

1131

262

38167

310 281

π→π*

1.41

166

π → π*

2.4

28490

1141

n→π*

2166

35587

π→π*

36496 31948

0.4

3.4. NMR spectra of the ligand (L) 3.4.1. 1H NMR spectrum of the ligand (L) The integral intensities of each signal in the 1H NMR spectrum of ligand (L) was found to agree with the number of different types of protons present as Figure (3-7) was drawn by Chem office .

59

Chapter Three


Figure (3-7) Number of different types of protons in (L) In the 1H NMR spectrum in DMSO-d6 solvent of the ligand (L= (Z)-4-((4amino-5-(3,4,5-trimethoxybenzyl)pyrimidin-2-yl)imino)pentan-2-one, Figure (3-8) . The signal noticed at δ (6.45 ,7.48) ppm represented to proton of the amine. and 2-pyrimidine respectively . The peaks appeared as singlet at range δ (3.71 - 3.51) ppm attributed to (-CH3) in methoxy (-OCH3)groups. The chemical shift of CH groups in benzene ring appeared at δ(6.24,) ppm. [79, 80]. The chemical shift of methylene(CH2) at δ(3. 48 and 2. 51) ppm, The chemical shift of methyl group , (CH3) at δ(2. 49 and 1. 68) ppm . [72-73] The NMR spectral data of (L) was compared with the spectral data for the ligand reported by using chem .office program .

60

Chapter Three


Figure (3-8) 1H NMR spectrum of (L) in DMSO-d6

3.4.2. 13C NMR spectrum of the ligand (L): The 13C NMR spectrum of the ligand [L] in DMSO-d6 solvent is shown in Figure (3-9). exhibits chemical shift [δ ppm] azomethine group -C=N carbon (C1) at 162ppm ,note 3c in pyrimidine ring in in Schiff base at δ= ( 162 .365 ,162.310 and 161.844)ppm. [74 ] The chemical shift of carbon atom of (C=C-OH ) at δ= 172.547 ppm. The carbon atoms of aromatic ring at range (δ=105.619-135.70-1052.27) ppm. The chemical shift 61

Chapter Three


of carbon atom of (N=C-CH3 ) at 162ppm.The chemical shift of carbon atom of aliphatic ( -CH2 ) at δ=38.83 ppm. The chemical shift of carbon atom of (CH3) aliphatic at range (δ=59.93-21.38) ppm.

Figure (3-9) 13C NMR spectrum of (L in DMSO-d6

This observation was also supported by the FT-IR data of the ligand discussed earlier. The NMR spectral data of L was compared with the spectral data for the

similar ligands reported in literatures. [71-73]

62

Chapter Three


3.5. Structures and names of the synthesied ligand (L) In the present study new class of

Schiff base ligand (L) was synthesized

according to the general method shown in Chapter (Two). Systematic (IUPAC) name:(Z)-4-((4-amino-5-(3,4,5-trimethoxybenzyl)pyrimidin-2-yl)imino)pentan2-one structures (3D) as shown in figure (3-10).

Figure (3-10): Structure of

(Z)-4-((4-amino-5-(3,4,5-trimethoxybenzyl)

Pyrimidin -2-yl)imino)pentan-2-one ( L) and as 3D model

3.6. Characterization of mixed-ligand metals complexes Analyses of the ligands and the corresponding complexes are based on previous (Ft-IR) and (UV-Vis) assignments of similar compounds. [71-76]

3.6.1. Characterization (L- M-oxalic acid) complexes. Generally, the metal chloride salts reacted with the two ligands according to the following proposed general equation: H2C2O4 +2KOH → K2C2O4 + 2H2O MCl2 .nH2O + L + K2C2O4 → [M (L) (C2O4)] + 2KCl + n H2O Where ; L = Schiff base (primary ligand). 63

Chapter Three


C2O4 -2 = OX-2 ( Oxalate ion as asecondary ligand). n =0-6 [M (L) (OX)] M= Co(II), Ni(II),Cu(II) and Zn(II). and [Cr (L) (OX)]Cl All complexes were prepared by reacting the respective MCl2 . nH2O with the ligands using 1:1:1 (L : M :OX-2 ) mole ratios. All the complexes were, stable in air at room temperature and appear as powders. The (M. wt) , (M.P) and (Flame - AAS) analysis of the complexes were carried out by the direct method which gave total metal content [57].The (experimental and calculated ) values of M% in each complex are in fair agreement. The test for negative (- ) except chloride ions in all complexes with (AgNO3 solution) were for [Cr(L)( OX)3]Cl positive indicating that chloride ion is outside of coordination sphere for [Cr (L) (OX)3]Cl complex only.[57]. These results are very supportive of the proposed formulae of the complexes . See table (3-8)

64

Chapter Three


Table (3-8) Some physical properties and (AAs )results of the ) (L-M-OX) Complexes (Λm) No.

M.P °c

Chemical

M.wt

Formula

Color

(De.)

M% Theoretical

°c

(exp)

Molar Conductivity (ohm-1.cm2.mol-1) In DMSO

[Cr (OX) (L)]Cl

(285)

547.89

1

Dark green

[Co(OX) (L )]

pink

[Ni(OX)(L)]

523.99

Off white

11.31

18.6

(10.2 ) 253-255

4

5

25.88

(10.85)

Light-green

[Cu(OX) (L)]

11.35

216

519.14

3

37.88

( 10.2 ) ( 223-255

519.38

2

9.04

12.13

16.55

( 11.13)

[Zn(OX) (L)]

525.82

white

216-220

12.43

17.18

( 11.93) )

Molecular Weight =M.wt (OX =C2O4) De. = decomposition . OX) (L)= C21H24 N4O8(

All the synthesized complexes were found to be non-hygroscopic solids and varying colors and completely soluble in water and dimethyl sulfoxide whereas insoluble in ethanol, chloroform, methanol, acetone and other solvents used. See table (3-9).

65

Chapter Three


Table (3-9) The solubility of the ( L- Metal -Oxalte) complexes in different solvents Compound

H2 O

DMF DMSO MeOH

EtOH Acetone Chloroform

[Cr (OX) (L)]Cl

+

–

+

–

–

–

–

[Co(OX) (L )]

+

+

+

–

–

–

–

[Ni(OX)(L)]

+

+

+

–

+

–

–

[Cu(OX) (L)]

+

–

+

–

–

–

–

[Zn(OX) (L)]

+

+

+

–

–

–

–

(+) Soluble and (–) Insoluble The observed molar conductance values (Λ m) were measured in DMSO (10−3M )solution) at room temperature for [M (L) (C2O4)] complexes lie in the (16.55- 25.88) Ω-1 cm2 mol-1 range . It is obvious from these data that the complexes are nonelectrolytes . (Λm) = 37.88 Ω-1 cm2 mol-1 for [Cr (OX) (L)]Cl electrolytes types 1:1 [57,64 ], see table (3-10).

66

Chapter Three


Table (3-10) Molar Conductivity )Ω−1cm2mol−1 ) in some solvents[57] Electrolyte Type

Non No.

solvent Electrolyte

1:1

1:2

1:3

1:4

120

240

360

480

35-45

70-90

120

 160

1

Water

0

2

Ethanol

0-20

3

Nitromethane

0-20

75-95

150-180

220-260

290-330

4

Methyl cyanide

0-30

120-160

220-300

340-420

 500

0-35

65-90

130-170

200-240

 300

0-20

30-40

70-80

-

-

5

6

Dimethyl formamide Dimethyl sulfoxide

3.7. FT-IR spectra of [Cr (OX) (L)]Cl (1), [Co (OX) (L)] (2), [Ni(OX) (L)] (3),[Cu(OX)2(L)] (4), and [Zn(OX)2(L)](5) complexes: In order to determine the coordination sites (binding modes) of the ligands in the complexes. FT-IR- spectra of the

ligands were compared with the

spectra of the complexes and other related complexes in references [58-60,77,78] The relevant vibration bands of the free ligands and their complexes were recorded in KBr disc in the region 400–4000 cm−1. The assignment of the characteristic bands (FT-IR) spectrum of the free ligand (L), figure (3-5), and (3-6 ), are summarized in Table (3-5) and (3-11) respectively. The characteristic frequencies of the (1),(2),(3),(4), and (5) complexes are given in table (3-12). The vibrational mode assignments of the metal complexes were supported by comparison with the vibrational frequencies of 67

Chapter Three


the free ligand and other related compounds. [58,79] The FT-IR spectrum of the free ligand L exhibits a sharp band at 1658 cm−1 ascribed to υ(C=N-). On complexation this band was shifted to lower frequency for all complexes except for Cu(II)complex appeared in the range (1642–1656) cm-1, indicating coordination the (-C=N→ M) ion. The st, vib (υ) at (1682) cm-1 is ascribed to υ (C=O) group, this band has been shifted to lower frequencies at [1678 , 1674, 1686, 1678, and 1674] cm-1 for complexes {(1), (2), (3), (4), and (5), showing that the coordination is through the oxygen atom (C=O) group in acetyl. [63,64] Because υ (C=O) group is free from coupling with other modes and is not secluded y the outshoot of other vibrations.

In the lower frequencies region new weak bands observed at (408-453), (437-540) cm−1 and (513-555) cm−1 have been ascribed to the υ(M-N), and υ(M–O) vibrations, respectively [23 ,93-96]. v(C-N)of conjugated cyclic system of the ligand is lowered in cheleate . Accordingly, one can deduce that the primary ligand (L) binds the metal ion as fourdentate fashion (NNNO) donors while the (oxalate anoin ) binds the (M) ion as mono dentate donors via oxygen atom. [61, 62] figures (3-28) to (3-34.).

68

Chapter Three


The spectrum of the oxalic acid in solution is dominated b y υ (C=O) stretching at( 1735) cm-1 and υ (C-OH) stretching at (1227) cm-1. [63, 64] Table (3-11) Infrared spectrum data (wave number ύ) cm-1 for the (H2OX) υOHComp./ound

(H2O)

H2OX

3132vs

υ (C=O)

1735

C-OH

ν(C-C)ali

1227

Figure (3-11) FT-IR spectrum of oxalic acid(H2C2O4)

69

Chapter Three


Figure (3- 12 ). FT-IR spectrum of [Cr (OX) (L)]Cl complex

Figure (3-13). FT-IR spectrum of [Co (OX) (L)] complex

70

Chapter Three


Figure (3- 14 ) FT-IR spectrum of [Ni (OX) (L)] complex

Figure (3- 15 ) FT-IR spectrum of [Cu (OX) (L)] complex

71

Chapter Three


Figure (3-16 ) FT-IR spectrum of [Zn (OX) (L)] complex

72

73

5) Zn

4) Cu

amine

3) Ni

Primary

3408

3406

3390

3217

3339

3321

3305

* br

1130

1130

1130

s

2956, 2870

s

2956, 2668

s

2958, 2870

Vs

2933, 2872

2955, 2868

3344

Stretch

vs

Symmetric

* br

1128

1130

1674

1678

1666

l

1678

1643

vs

1648

s

1643

* br

1668

1643

m

1504

1504

s

1531

1508

1500

m

1263

1263

1265

1265

1265

m

-

1242

1238

1242

1238

1238

acid

2) Co

υ CH3

m

υ (C-O) str

3321

ν (-OCH3)

1258

m

542

w

513

m

532

m

524

526w

-

682

484m

506

437

536m

472m

524w

480m

505w

457m

-

υ (M-N)

3344

and

3465

Asymmetric

1504

459

483

455

459

459

-

υ (M-O)

1) Cr

H-C-H

vs

υ(C=O)

br

(-C=N-)

1658

υs

1682

arom.

2924, 2602

υ(C=C)

1126

aliph.

3344

υ(C-C)

3448

υ (M-N)

L

Oxalic

ounds

Comp

Table (3-12) Infrared spectral data(ύ) cm-1 for the mixed -ligand (L-M-OX) complexes.

Chapter Three Results and Discussion

υ(C-H)

aliph

υ(N-H)

Chapter Three


3.8. The ultra violet visible spectra and magnetic measurements for the complexes: The electronic absorption bands for the complexes are due to: 1. Absorption bands due to the ligand. 2. Charge transfer (CT) transitions between metal (M) and ligand (L).see Figure (3-17)

M

hv

L

CT (M

M+

L-

M

L)

CT (L

hv

L M)

Figure (3-17) Types of Charge transfer (CT)

74

M-

L+

Chapter Three


Ligands (L) possess (σ, σ*, π, π*, and nonbonding (n)) molecular orbitals. If the ligand orbitals (L) are full, CT may occur from ( L) to the empty or partially filled metal (M) d-orbitals.

3. Ion pair. 4. d – d transitions at low energy. The d–d transitions are forbidden due to (Laporte law Forbidden), which is appeared at lower energy with low intensity, and appeared in the visible region. The (Orgel- and Tanabe-Sugano) diagrams are now universally used for the interpretation of the spectra of transition metal complexes. In the electronic spectral studies the ligand field9 (LF )parameters such as 10 Dq =splitting energy, B =Racah's interelectronic repulsion parameter and

β =nephelauxetic ratio . have been determined by using the following relationships

75

Chapter Three


Free ion

(Cm-1) (B')

Mn+2

960

Cr+3

1027

Co+2

971

Ni+2

1030

Cu+2

1240

β order for donor atom as : Electronic transitions occur between split d’ levels of the central atom giving rise to so the called d-d or ligand field spectra. The spectral region where these spans occur the near IR, visible and U.V. region ,see table(1-13).

Table (1-13): spectral region (unite)

(Ultraviolet)-Uv-

(Visible)-Vis-

(Near infrared) –NIR-

cm-1

50,000 to 26300

26300 to12800

12800 to 5000

nm

200 to 380

380 to 780

780 to 2000

76

Chapter Three


3.8.1. The ultra violet visible spectra and magnetic measurements(eff) for the mixedligand metal complexes [Cr (OX) (L)]Cl (1), [Co(OX) (L)] (2), [Ni(OX)( (L)] (3), [Cu(OX)2(L)] (4), and [Zn(OX)2(L)] (5)

complexes

The (eff) values and absorption data for complexes are presented in

(3-14).. The(eff) values for [Cr(III)= 3.52 , Co(II) = 4.86 Ni(II) =2.24 and Cu(II) =1.98]BM , respectively, which suggest an octahedral geometry.[35,41,42] .The Zn(II) complex is diamagnetic.

77

Chapter Three


Table (3-14) Electronic spectral data of the mixedligand [L-M- OX ]complexes

Comp.

H2C2O4= OX L [Cr (OX) (L)]Cl

λ nm

Є max mol-1

υ'cm-1

Assignments

(BM)

.L.cm-1

262

166

38167

π → π*

312

1141

28490

n→π*

281

2166

35587

π → π*

-

-

277

2433

425

452

36101

4A →4T (P) 2g 1g

509

250

23529

4A →4T 2g 1g

401

19646

604

eff

Charge transfer

4A 2g

→4T2g

3.52

ν3

ν2

ν1

16556

[Co(OX) (L )]

[Ni(OX)(L)]

[Cu(OX) (L)]

[Zn(OX) (L)]

279

2438

35847

521

124

19011

672

366

14880

826

39

12106

2437

34847

419

.166

23866

628

70

13923

778

81

12853

279

281

2267

859

22

281

1810

35587

Charge transfer 4T1g(F)

→ 4T2g(P) ν3

4T1g(F)

→ 4A2g(F) ν2

4T1g(F)

→ 4T2g(F) ν1

Charge transfer 3

(F)

3

(F)

3

(p)

A2g → T1g 3

(F)

4.86

2.24

( ν3)

A2g → T1g (2)

3

A2g(F) →3T2g(f) υ1

Charge transfer 2

1.98

2

Eg → T2g

35587

78

C.T

Diamag.

Chapter Three


3.8.2. [Cr(L)( OX)]Cl The assignment of the electronic spectral bands, their positions, and the spectral parameters for Cr(III) d3 (Term

4

F) agree with data reported by several research

workers [74 - 76]. The first high intense peak at 277 nm (36101cm-1) is due to the charge transfer transition and shows other three bands at 425nm(23529 cm-1), 509nm(19646 cm-1), and 604nm(16556 cm-1) (table 3-14) which are assignable to ( 4A2g→4T1g (ν3 ), 4

A2g→4T1g (ν2) and (4A2g →4T2g ( ν1) respectively[,70,74].

υ = [1/λ (nm)] (1 x 10000000) cm-1 ΔE = Δo =10 Dq =16556 cm-1 We can use the other energy units for the absorption which may be obtained following conversion factors as following : 1 cm-1 = 1.24 x 10-4 eV = 0.01196 kJ/mol ΔE = Δo =16556 x1.24 x 10-4 = 2.0529 eV ΔE = Δo =16556 x0.01196=198.009 kJ/mol The spectral parameters of the Cr(III) complex are as follows [77,80] : 1/2 ratio is 0.842, Dq = 16556cm-1, The 2/1 ratio is 1.186, which is in the usual range reported for an octahedral Cr(III) complexes [77, 78].

Figure (3-18) .Electronic spectrum of [Cr(OX) (L)] complex 79

Chapter Three


3.8.1.2. [Co(OX) (L] The (U.V-Vis) Co(II) d7 (Term 4F) spectrum, exhibits four peaks, Figure (319), the first peak at (279nm) (35842cm-1) which is assignable (CT )transition . The electronic absorption spectrum showed (3) absorption bands (d-d) transitions as shown in table (3-13) at (526nm)(19011)cm-1 at (672nm)(14880)cm-1, and (826nm)(12106cm-1.), which are considered as , [4T1g(F) → 4T2g(P) υ3 , 4T1g(F) → 4A2g(F) υ2 and 4T1g(F) →4T2g(F) υ1.] respectively, The 10 Dq = 12106 cm-1 ,υ1 / υ2 = 0.81, υ2 / υ1=1.22 which is in the usual range reported for an (Oh) , Co (II) complexes are as follows [93]

Figure (3-19) Electronic spectrum of [Co(OX) (L)] complex

80

Chapter Three


3.8.1.3. [Ni(OX) (L)] The (U.V-Vis) Ni(II) d8 spectrum, exhibits four peaks, Figure (3-39), the first peak at (279nm) (35842cm-1)which is assignable to charge transfer transition .The electronic absorption spectrum showed three absorption bands (d-d) transitions as shown in table (3-13) at

(419nm)(23866)cm

at

(628nm)(15923)cm-1, and

(778nm)(12853cm-1.), which are considered as , [3A2g(F) → 3T1g(F) ( ν3) , 3A g(F) 2

→3T1g(p) (2) and 3A2g(F) →3T2g(f) υ1] respectively .

The (10 Dq = 2853cm-1) ,(υ1 / υ2 = 0.80), (υ2 / υ1=1.23) which is in the usual range reported for an octahedral Ni(II) complexes are as follows [93]

Figure (3-20) Electronic spectrum of [Ni (OX) (L)] complex

81

Chapter Three


3.8.1.4. [Cu(OX) (L)] This complex shows two bands at (859 nm) 11641 cm-1 and (281 nm) 11641 cm-1, assignable to 2Eg →2T2g, charge transfer (CT) respectively [69-77]. The high energy bands spreading in (32051-36630) cm-1 range are owing to ligand to metal charge transfer. (LMCT) (Lever, 1984) [77]. These results reveal the distorted octahedral geometry for a such complex. figure (3-41) [77-79,108].

Figure (3-21) Electronic spectrum of [Cu (OX) (L)]complex

82

Chapter Three


3.8.1.5. [Zn (OX) (L)] The electronic spectra of d10 [Zn(II), complex was diamagnetic and their electronic spectrum exhibited band at (281nm) 35587cm-1, ascribed to the LM (charge transfer), which are compatible with these complexes having octahedral structures (Taghreed et al[52-54 ] and (Bharti et al., 2013)[18] were reported for such complexes.

Figure(3-22).Electronic spectrum[Zn(OX)(L)]

3.9. The Proposed molecular structure for studying complexes Studying complexes on bases of the above analysis, spectral observations suggested the octahedral geometry for the [M(II) = Co(II) , Ni(II) ,Cu(II) and Zn(II)] complexes which exhibit coordination number six and may be formulated as [Cr (L)(OX)]Cl and [M (L)(OX)] for M(II). The general structure of the complexes is 3D which is shown in figure (345) and (3-46) respectively. It was found that (OX-) interacts with all of these 83

Chapter Three


metal ions and coordinates in a bidentate fashion through two oxygene atoms to Cr and M(II) ions and Schiff base (L) interacts with all of these metal ions in the anionic form and coordinates in acting as a neutral tetradentate (NNNO) ligand.

Figure (3-23) 3D molecular modeling proposed [Cr(L)(OX)]Cl complex

Figure (3-24) 3D molecular modeling proposed [M(L)(OX)] complexes M= Co(II), Ni(II) and Cu(II) and Zn(II)

84

Chapter Three


3.10. Characterization of (TMA- M-Oxalic acid) complexes. Generally, the complexes were prepared by reacting the respective metal salts with the ligands using 1:1:2 mole ratio, i.e., one mole of Trimethoprim , one mole of metal chloride, and two moles of potassium oxalate. The synthesis of mixed ligand Metal complexes may be represented according to the following proposed general equation: 2H2Ox + 4KOH → 2K2OX + 4H2O MCl2 .nH2O + 2K2OX + MAT→ K2[M(OX)2(TMA)(H2O)]+ nH2O + 2KCl and CrCl3 .6H2O + 2K2OX + TMA→K [Cr(TMA)( OX)2]+ 6H2O +3KCl where; H2OX = Oxalic Acid= H2 C2O4 = (primary ligand). OX -2 = Oxalate anion = C2O4 -2 TMA = Trimethoprim (secondary ligand). M=Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) The formula weights and some physicochemical characteristics are given in (Table 3-15) it was found that all the complexes were non-hygroscopic, stable at room temperature. The solubility of the prepared complexes was studied in various solvents. All complexes are soluble in water and (DMSO) and (DMF), while insoluble in common solvents, see table (3-16). (AAS) analysis of the complexes was carried out by the direct method which gave metal percentage (M% ) in each complex [65].The calculated and experimental values of M% are in fair agreement. These results are very supportive of the proposed formulae of the prepared complexes. The observed molar conductance values measured in DMSO (10 −3M solution) at room temperature table (3-15) lie in the )49-89) Ω-1 cm2 mol-1 range , It is obvious from these data that the complexes are electrolytes types 85

Chapter Three


1:2 for all complexes and type 1:1 for K [Cr(TMA)( OX)2] complex. See table (3-10) [64].

Table (3-15) Some physical properties and atomic absorption results of the (L-M-Ox) complexes

Comp.

K [Cr(OX)2(TMA)(H2O)]

Color

Dark

M.WT g/mol

M%

/De.

Calculate

ºC

(found)

285

9.04

49

De.

(10.12)

(127)

215 De.

10.19

89

(10.45)

(240)

223-255

10.85

81

De.

(11.29)

(240)

216

9.45

78

(11.01)

(240)

10.15

78

(10.11)

(240)

10.41

76

(11.19)

(239)

575.47

green

616.97

K2[Mn(OX)2(TMA)(H2O)]

K2[Co (OX)2(TMA)(H2O)]

K2[Ni(OX)2(TMA)(H2O]

pink

Light-

620.97

621.26

green

K2[Cu(OX)2(TMA)(H2O)]

Light

626.12

253-255

green

K2[Zn(OX)2(TMA)(H2O)]

Off

627.95

Λm

M.P.

216-220

white

TMA = C14H18N4O3 , .(OX) = (C2O4) . De. = decomposition

86

(ohm-1.cm2.mol-1) in DMSO 10-3M. in (H2O)

Chapter Three


Table (3-16) The Solubility of the ) OX - Metal - TMA) complexes in different solvents Compexes

H2 O

DMF

DMSO

MeOH

EtOH

Acetone

K [Cr(OX)2(TMA)(H2O)]

+

–

+

–

–

–

K2[Mn(OX)2(TMA)(H2O)]

+

–

+

–

–

–

K2[Co (OX)2(TMA)(H2O)]

+

–

+

–

–

–

K2[Ni(OX)2(TMA)(H2O]

+

–

+

–

–

–

K2[Cu(OX)2(TMA)(H2O)]

+

–

+

–

–

–

K2[Zn(OX)2(TMA)(H2O)]

+

–

+

–

–

–

(+) Soluble , (–) Insoluble

3.10,1. FT-IR spectra of K [Cr(OX)2(TMA) (H2O)] (1),

K2[Mn(OX)2(TMA) (H2O)] (2), K2[Co (OX)2(TMA)(H2O)] (3), K2[Ni(OX)2(TMA) (H2O] (4), K2[Cu(OX)2(TMA) (H2O)] (5), and K2[Zn(OX)2(TMA) (H2O)](6) complexes: The assignment of the characteristic bands (FT-IR) spectra of the ligand (L), and (OX), are summarized in Tables[ (3-5) and (3-11)],. The important IR peaks of the complexes are given in Table (3-17) and as shown in Figures (3-25) to (3-30). In free ligand (H2C2O4) has 2 dissociable carboxylate protons (-Coo- and identification of peak strong and sharp bands at 3132 cm-1 which is affected by the outshoot of (H……. O) hydrogen bonds [36]. The peaks

ligand around

(1635-1593)cm-1 shifted to the region 1636-1697 cm-1 for all the complexes are ascribed to [ν(C=N) pyrimidine nitrogen] group present in complexes . may be explained on the basis of drift of the (IP) lone pair electron density from the heteroatom(N:) towards the (M) atom [26].The beaks observed around[ (149487

Chapter Three


1504) cm-1 and (2854-3100) cm-1] were ascribed to ν(C=C) and ν(C-H) aromatic stretching, respectively. In the present case, the bands of weak intensity observed in the regions (435501)cm-1 and(424-650) cm-1 can be ascribed to ν(M- O) and ν(M- N), respectively. [36 ,75] In their paper, they have reported a peak at 1535-1560 cm-1 for (amine NH2) in complexes.The ν (C= O) stretching in oxalic acid H 2C2O4 (-COOH) peak at (1519-1404) cm-1 and strong band at (1230cm-1)has been ascribed to ν(C-O str)of acid . In the complexes, the ν (C= O) is shifted to higher frequencies. In the complexes studies of ν (CO) finde

good information about the bonding

andstructure of carbonyl chelates . [36] broad peaks appear at range ( 3417-3456) cm-1, sharp peak at(725–775) cm1

assignable to ( hydroxtl -OH )stretching, and rocking vibrations respectively

indicating the outshoot of coordinated (water H2O) molecules in the complexes [12,75]

88

υOH-(H2O)

89 br 3421vs

3417vs-

3456vs

3286vs

3182

3259vs

3187

3228v

3294br

3116

3251vs

3186

3232vs

1647s

1651s

1654

1651vs

1697s

1635s

1130

1126

1130

1131

1134

m

1149

s

1126v

1639s

1635s

1597

1635vs

1635vs

1635vs

-

1330

1400

1330

1435 vs

1435 vs

1400w

-

220

221

221

219

212

214

227

- υas COO

br

K2[Zn(OX)2(TMA)A(H2O)] 3441vs-

K2 [Cu(OX)2(TMA)(H2O)]

K2 [Ni (OX)2(TMA)(H2O)]

K2 [Co(OX)2(TMA)(H2O)]

ν (N-H) sym

K2 [Mn(OX)2(TMA)(H2O)] 3425vs

ν (N-H) sym

-

1494

1504

1504

1504

1504

1504s

1502s

1492

1338

1234

w

1242

1276

1273

1249

1234v

s

1230v

748

744

775

752

748

725

-

-

474

513

451

489

443

470

451

466

435

501

-

-

459

542 493

424

621

528

482w

543

-

-

ν M-O

K[Cr(OX)2(TMA)A(H2O)] 3425vs

nitrogen

1593

Pyrimidine

3116vs

ν (C=N)

1635vs

ν (-OCH 3)

3317vs

of Oxalic acid

3468vs

ν (-CO)asym

TMA

of Oxalic acid

br

ν (-CO)sym

1404vs

υas COO-

1519vs-

arom.

-

υ(C=C)

-

)(C-O) str (OX

-

ν M-OH2

3132vs

ν M-N

Oxalic acid

Compounds

Table (3-17) infrared spectral data (wave number ύ) cm-1 for the mixedligand (L- METAL –OX]complexes. Chapter Three Results and Discussion

υ

Chapter Three


Figure (3-25) FT-IR spectrum of K [Cr(OX)2(TMA) (H2O)]complex

Figure (3-26). FT-IR spectrum of K2[ Mn (OX)2(TMA) (H2O)]complex 90

Chapter Three


Figure (3-27) . FT-IR spectrum of K [Co (OX)2(TMA) (H2O)] complex

Figure (3-28). FT-IR spectrum of K2[Ni (OX)2(TMA) (H2O)]complex

91

Chapter Three


Figure (3-29). FT-IR spectrum of K2[Cu (OX)2(TMA) (H2O)]complex

Figure (3-30) . FT-IR spectrum of K2[Zn(OX)2(TMA) (H2O)]complex

92

Chapter Three


3.10.2. The ultra violet visible spectra and magnetic measurements(eff) for the mixed ligand complexes : K [Cr (OX)2(TMA) (H2O)](1), K2[Mn(OX)2(TMA) (H2O)] (2), K2[Co (OX)2(TMA) (H2O)] (3), K2[Ni(OX)2(TMA) (H2O] (4), K2[Cu(OX)2(TMA) (H2O)] (5), and K2[Zn(OX)2(TMA) (H2O)] (6) : The values (eff) and electronic spectra data are presented in table (3-18). The(eff) values for [Cr(III) = 5.71, Mn= 5.60 ,Co(II) = 5.08 Ni(II) =2.85 and Cu(II) =1.7] BM , respectively, which suggest an octahedral geometry.[35,41,42] .The Zn(II) complex is diamagnetic. The electronic spectra of all the compounds solutions under study were recorded in 10 - 3 M in ( DMSO) at room temperature .The Uv- spectra of the {(TM A) and(oxalic acid )} as to that mentioned in paragraphs (2.5.8).

93

Chapter Three


Table (3-18) Electronic spectral data of the mixedligand (TMA - M-OX) metal complexes

Comp.

K [Cr (OX 4)2(TMA) (H2O)]

K2[Mn(OX)2(TMA) (H2O)]

K2[Co (OX)2(TMA) (H2O)]

K2[Ni(OX)2(TMA) (H2O]

K2[Cu(OX)2(TMA) (H2O)]

K2[Zn(OX)2(TMA) (H2O)]

λ nm

Є max mol-1

υ'cm-1

Assignments

(BM)

.L.cm-1

277

81

36101

Charge transfer

386

62

25906

4

574

43

17421

842

76

11876

255

127

39215

550

5

18181

6

785

6

12738

6

69

39682

532

18

18796

834

15

11990

252

757

39682

Charge transfer

292

41

43246

3

403

87

24813

655

55

1526

275

1915

36363

613

118

15847

294

7

34013

252

eff

94

5.71

A2g→4T1g(P) ν3 4

A2g→4T1g ν2 4

A2g →4T2g ν1

Charge transfer

5.60

A1g→4T1g(G) A1g→4T2g(G)

Charge transfer

5.08

4

T1g(F) →4T2g(p)

4

T1g(F)→4T1g(f) 2.85

A2g(F) → 3T1g(F) (3)

3

A2g(F) →3T1g(p) (2)

3

A2g(F) →3T2g(f) υ1

Charge transfer

1.7

2

Eg →2T2g

C.T

Diamag.

Chapter Three


3.10.2. 1- K [Cr (OX)2(TMA) (H2O)] The magnetic moment table (3-18) of the Cr (III) d3 (Term

4

F) complex is

5.71 B.M. the assignment of the electronic spectral bands, their positions, and the spectral parameters for Cr(III)agree with data reported by several research workers [77, 78, 79]. The first high intense peak at 277 nm (36101cm-1) is due to the (C.T) transition and show other three bands at 386 nm(25906 cm-1) , 574nm (17421 cm-1), and 842nm (11876 cm-1) (table 3-22) which are assignable to ( 4

A2g→4T1g (ν3 ), 4A2g→4T1g (ν2) and (

A2g →4T2g ( ν1) respectively[80]. B =740

4

cm-1, β=0.79 cm-1. Convert {λ(nm)} into wavenumbers { υ ( cm-1)} as following relationship : υ = [1/λ (nm)] (1 x 10000000) cm-1 From the information given, the ratios : ν2 / ν1 = 17421 / 11876 = 1.466 ν1 / ν2= 11876 /17421= 0.86 Using Figure (3-54) for a d3 system {receiving of the graph to find the Therefore for ν1 (first transition) =11876cm-1. Δo = ν1 = [1/λ (nm)] (1 x 107) cm-1 (Convert to wavenumbers) 107(nm/cm)/( 11876 nm)= 8420 cm-1 this electronic transition occurs between ( 4A2g and 4T2g )states ΔE = Δo =10 Dq We can use the other energy units for the absorption which may be obtained following conversion factors as following : 1 cm-1 = 1.24 x 10-4 eV = 0.01196 kJ/mol ΔE = Δo =11876 x1.24 x 10-4 = 1.4726 eV ΔE = Δo =11876 x0.01196=142.036 kJ/mol

95

Chapter Three


Figure (3-31) Electronic spectrum of K [Cr (OX)2(TMA) (H2O)]

3.10.2. 2- K2 [Mn (OX)2(TMA) (H2O)] The (U.V-Vis) spectrum of Mn exhibits three peaks as shown in table (3-18) the first high intense peak at (255 nm) (38022 cm-1 is due to (C.T), second, and third absorption speak (d-d) transitions at (11990 and 18796 cm-1 which are consistent with υ2 and υ3 respectively. These transitions may be assigned as: 6 A1g→4T1g(G) and 6A1g→4T2g(G) .µeff value equals to 5.60B.M, which suggests octahedral geometry around the central metal ion [77].

96

Chapter Three


Figure (3-32).Electronic Spectrum of K[Mn (OX)2(TMA)(H2O)]

3.10.2. 3- K2 [Co (OX)2(TMA) (H2O)] The electronic absorption spectrum showed three absorption peaks The first high intense peaks at (252 nm)( 39682 cm-1) is due to the charge transfer transition and two absorption bands (d-d) transitions at (11990 and 18796 cm-1 which are considered as υ2 and υ3 respectively. These transitions may be assigned as: 4T1g→4A2g(f) υ2 and 4T1g→T1g(p) υ3 .[77]

97

Chapter Three


Figure (3-33) Electronic spectrum of K2[Co (OX)2(TMA) (H2O)]

3.10.2. 4- K2 [Ni (OX)2(TMA) (H2O)] The (U.V-Vis) spectrum for [K2[Ni (OX)2(TMA) (H2O)] exhibits four peaks, the first two peaks at (252nm) (39682 cm-1 ) and (292nm) (34482 cm-1 ) are due to the ( L.f ) and (C.T) transitions respectively . Two weak peaks at (403 nm) (11627 cm-1) and (655 nm) (28196 cm-1) 860(11627 cm-1 ) ascribed to (d–d) transition including {3A2g(F) → 3T1g(F) (3) and 3A2g(F) →3T1g(p) (2), and 3

A2g(F) →3T2g(f) υ1 }respectively. The complex exhibits a value of µeff =

2.85B.M, which suggests octahedral geometry around the central metal ion.. The spectral parameters of the Ni(II) complex are as follows [77,80] : 1/2 ratio is 0.637, Dq = 11627cm-1, The 2/1 ratio is 1.56, which is in the usual range reported for an octahedral Ni(II)complexes

98

Chapter Three


Figure (3-34) . Electronic spectrum of K2[Ni(OX)2(TMA) (H2O]]

3.10.2. 5- K2 [Cu (OX)2(TMA) (H2O)] The K2[Cu(OX)2(TMA) (H2O)]complex shows bands at (275 nm) 36363 cm-1 is ascribed to symmetry forbidden ligand - metal charge transfer (L → CT ) and a low intensity band at (613nm) 15847 cm-1 is ascribed to 2Eg →2T2g. Also, µef value (1.7 B.M.) for the Cu (II)..These bands are characteristic in position and width appear to be in the (Oh)geometry with dx2-y2 ground state Cu (II) complexes [75] .

99

Chapter Three


Figure (3-35).Electronic spectrum of K2 [Cu(OX)2(TMA) (H2O)]

3.10.2. 6-The K2[Zn(OX)2(TMA) (H2O)] The K2[Zn(OX)2(TMA) (H2O)] complex showed diamagnetic properties as expected from (d10)electronic configuration and exhibited only one band at 294nm (34013 cm-1 )which was ascribed to M → ligand (CT)..

Figure ( 3-36). Electronic spectrum of K2[Zn(OX)2(TMA) (H2O)] 100

Chapter Three


3.11. The proposed molecular structure for studying complexes Studying complexes on bases of the above analysis, spectral observations suggested the octahedral geometry for all complexes which exhibit coordination number six and may be formulated as K2 [M (OX)2(TMA) (H2O)] and K [Cr (OX)2(TMA) (H2O)] The general structure of the complexes is 3D which is shown in figure (3-45). It was found that(OX-2) interacts with all of these metal ions as a dianionic bidentate fashion through (two oxygene ) atoms to Cr and M(II) ions as figure and while (TMA) coordinates as neutral mondentate through pyrimidine (N) group.

Figure (3-37)3D molecular modeling proposed [M(OX)2(TMA) (H2O)]complexes M= Mn(II), Co(II), Ni(II), Cu(II) ,Zn(II), n=2 M=Cr(III) , n =1

3D Figure (3-38) structure of the oxalate anion (OX -2)

101

Chapter Four

Biological activity

4. Biological activity 4.1. Introduction Biological activity spectrum of a compound represents the biochemical vs, physiological and pharmacological effects [83] of activity of known have high activities such as antibacterial [84], anti-inflammatory [85], antifungal [86]and anti-HIV [87, 88] antipyretic [89]and antitumor [84]

Agents produced by microorganisms can inhibit or kill other microorganisms. Antibiotics are (non-protein) low molecular weight (M.Wt) molecules produced as secondary metabolites, because microorganisms that live in the soil . The mechanisms of action of antimicrobial drugs can be discussed under inhibition of [ cell wall synthesis , cell membrane function, protein synthesis and DNA synthesis]. [85-86]

4.2. Material and equipment's: [84,90]. (1) Nutrient agar medium. (2) Macferr land tube (3) Cork borer (4) Autoclave (5) Refrigerator petri dish (6) Distilled water (7) DMSO as (solvent and control)

102

Chapter Four

Biological activity

4.3. Principle of antimicrobial susceptibility test Disk diffusion method is very simple, it requires commercial disks used to determine the antibiotic sensitivity in which disks impregnated with various antibiotics are placed on the surface of an agar plate that has been inoculated with the organism (Figure 4-1). After incubation at 37°C for 24 hours, during which time the antibiotic diffuses outward from the disk, the diameter of the zone of inhibition (ZI) is determined. The size of the zone of inhibition is compared with control to determine the sensitivity of the organism to the compounds.[ 87-90] zone width has to be measured and compared against a reference standard which contains measurement ranges and their equivalent qualitative categories of susceptible, intermediately susceptible or resistant. any samples since the (ZI) interpretation chart is as follows: Resistant: 1-10mm or less Intermediate : [13–15] Susceptible: 17 mm or more see Figure (4-1) The test solution (3×10 -3 M) was prepared by dissolving the compounds in DMSO and the well was filled with the test solution using micropipette. The results of the tested samples in this study was compared with the control (DMSO).

103

Chapter Four

Biological activity

Figure (4-1). Antibiotic sensitivity testing

4.4. Types of pathogenic bacteria and bacterial infections in this study: 4.4.1. Escherichia coli: (Gram- negative) Commonly abbreviated E.coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of blooded organisms. E. coli bacteria cause severe anemia or kidney failure, can cause urinary tract infections or other infections which can lead to death .

Figure (4-2) .Escherichia coli

104

Chapter Four

Biological activity

4.4.2. Enterobacter cloacae : (Gram- negative) It is a member of the normal gut flora of many humans and is not usually a primary pathogen.[88, 91] It is sometimes associated with urinary tract and respiratory tract infections.

Figure (4-3). Enterobacter cloacae

4.4. 3. Staphylococcus S.P :( Gram-positive ) Ball or oval shaped, this type of bacteria is regarded as the main type of non– pathogenic staphylococcus bacteria which is characterized by the formation of thrombinogen enzyme and this is regarded as a main feature for this type of bacteria [90]. It also affects skin and causes skin wound and skin necrosis and later on pus discharge. This may progress to cause bacteria in blood and lymph system, figure (4-5). [88,89].

Figure (4-4) :(a) S. aureuscells and (b) skin infection by S. aureus.

105

Chapter Four

Biological activity

4.4.4. Bacillus subtilis (Gram-positive) Rod-shaped , is often called (a soil organism), aerobic , high risk known to cause disease in severely patients, allowing it to tolerate extreme environmental conditions. [90,91].

Figure (4-5) . Bacillus subtilis

4.5. Results and Discussion: 4.5.1. The biological effect of the prepared compounds: The in vitro antibacterial activity was carried against 4 hold cultures of pathogenic bacteria like gram (+) and gram (-) at 37oC. In order to ensure that no effect of solvent on bacteria, a control test was performed with DMSO and found inactive in culture medium.A set of solution (0.01 M) of compounds of the synthesized [90,91]. Schiff base and their complexes ,and mixed ligand were studied by the zone of inhibition (ZI) technique. Antibacterial activities were evaluated by measuring inhibition zone diameters (IZ) and compared with the standard DMSO(as control) Biological activities. In the present chapter, the antibacterial activities of the synthesized ligands and complexes have been screened against gram four bacteria namely :( Esherichia Coli ,Enterobacter Cloacae , Staphylococcus aureus and Bacillus Subtili]. 106

Chapter Four

Biological activity

4.5.2. Anti bacterial activities of the Schiff base metal-mixed ligands complexes A comparative study of ligands and their metal complexes listed in Table (41), Chart (4-1) reveals that the synthesized mixed ligands complexes have been tested against growth of Esherichia Coli ,Enterobacter Cloacae , Staphylococcus aureus

and Bacillus Subtili].

1- Generally the antibacterial activities were in the following order; [Cr(C2O4) (L]Cl >SL(Schiff base ligand) > K2[Ni(C2O4)2(L)] > [Cu(C2O4) (L] ≈ [Co(C2O4) (L] > [Zn(C2O4) (L] > C2O4-2 = (DMSO) This means that complexes

significantly affects the antimicrobial act of the

organic ligand. figures [ (4-5) to (4-8)] 2- The antibacterial activity (ZI) of all the complexes >> Oxalic acid ≈ (DMSO) 3- (DMSO) used as solvent and a negative control as it did not show any activity against bacteria, ≈ Oxalic acid 4- All tests lacked anti bacterial activity against Enterobacter cloacae. 5- All complexes tests were have anti bacterial activity against [Esherichia Coli , Staphylococcus aureus and Bacillus Subtili].

107

test bacteria

Chapter Four

Biological activity

Table (4-1) The antibacterial activity (IZ mm) data of Set Schiff base metal-mixed ligands complexes Compounds

Staphylococcus

Bacillus

Enterobacter

Esherichia

aureus

subtilis

cloacae

Coli

(Gram+)

(Gram+)

(Gram -)

(Gram - )

4

4

5

5

H2C2O4= H2OX

4

5

L

21

48

[Cr(C2O4)(L)]Cl

23

49

[Co(C2O4)(L)]

23

46

[Ni(C2O4)(L)]

22

39

[Cu(C2O4)(L)]

21

43

[Zn(C2O4)(L)]

16

41

Control (DMSO)

6 4 4 4 4 4 4

4 25 25 22 25 27 24

The results show that the nature of the (M(II),Cr(III) ion in complexes play significant roles in the (ZI)activity.[93-94] Also (L) structure by the presence of (C═N) group which is significant in the mechanism reactions in biological reaction and that ligands with (N )and (O)donor systems might inhibit enzyme production, and possibly (π-electron )delocalization through the whole (chelate ring) system thus include through coordination. .[95-97]

108

Chapter Four

Biological activity

Figure(4-6).Effects of compounds on Bacillus Subtitis

109

Chapter Four

Biological activity

Figure (4-7) .Effects of compounds on Enterobacter cloacae

110

Chapter Four

Biological activity

Figure (4-8). Effects of compounds on Esherichia coli

111

Chapter Four

Biological activity

Figure (4-9) . Effects of compounds on Staphylococeus aureus

112

Chapter Four

Biological activity

49

48

50

46

45

43

41

39 27

25

25

24

22

4

Staphylococcus aureus

4

4

23

23

22

21 16

40 35

25

4

Bacillus subtilis

4

4

21 4 6

5

5 4

5 4

Enterobacter cloacae

4

30 25 20 15 10 5 0

Esherichia Coli

Chart (4-1). Biological effect of the set1_ Schiff base metal-mixed ligands complexes

113

Chapter Four

Biological activity

4.5.3. Anti bacterial activities of the metal-mixed ligands complexes A comparative study of ligands and their metal complexes listed in Table (42), Chart (4-2) reveal that the synthesized mixed ligands complexes have been tested against growth of same bacteria in section 4.7.1. 1- The rate of inhibition diameter was varied according to the variation in the ligands type and bacteria type. [97].Generally the antibacterial activities were in the following order; TMA > K2[Ni(C2O4)2(TMA) (H2O] >k2[Co(OX)2(TMA)(H2O)] > K2[Cu (C2O4)2(TMA) (H2O)] >K2[Zn(OX)2(TMA)(H2O)]=K2[Mn(OX)2(TMA)(H2O)]> K [Cr(OX)2(TMA)(H2O)]=C2O4-2=Control (DMSO) 2- TMA it is significant antimicrobial activities [53,94] 3- All complexes are significant antimicrobial activities for (gram +) more Than (gram - ) Table (4-2) :The antibacterial activity (IZ mm) data of metal-mixed ligands complexes, Esherichia Coli

Enterobacter

Bacillus

Staphylococcus

cloacae

subtilis

aureus

Control (DMSO)

5

4

4

5

H2C2O4= H2OX

5

5

4

4

)TMA)

37

5

58

29

K [Cr (C2O4)2(TMA) (H2O)]

5

5

4

4

K2[Mn(C2O4)2(TMA) (H2O)]

5

5

22

4

K2[Co(C2O4)2(TMA) (H2O)]

5

5

33

4

K2[Ni(C2O4)2(TMA) (H2O]

5

5

44

4

K2[Cu(C2O4)2(TMA) (H2O)]

5

5

33

15

K2[Zn(C2O4)2(TMA) (H2O)]

5

5

23

4

Compounds ( ligands and M-comp.)

114

Chapter Four

Biological activity

60 50 40 30 20 10 0

Enterobacter cloacae Bacillus subtilis Gram-positive Staphylococcus aureus Grampositive Esherichia Coli Gram-negative

Chart (4-2). Set 2 metal-mixed ligands complexes

115

Chapter Four

Biological activity

Figure (4-10) . Effects of compounds on Enterobacter cloacae

Figure (4-11) . Effects of compounds on Esherichia Coli

116

Chapter Four

Biological activity

Figure (4-12) .Effects of compounds on Staphylococcusaureus

Figure (4-13). Effects of compounds on Bacillus

117

References References [1] Farrelln., Metal Complexes as Drugs and Chemotherapeutic Agents.Comprehensive Coordination Chemistry II, (2003), (1thed.), Elsevier Ltd. [2] Rafique S.,Idrees M.,Nasim A.,Akbar H.and Atha A.: Biotechnol Mol. Biol. Rev. (2010); 5(2), 38-45. [3] Christodoulou, C. V.; Ferry, D. R.; Fyfe, D. W.; Young, A.; Doran, J.; Sheehan, T. M.; Eliopoulos, A.; Hale, K.; Baumgart, J.; Sass, G.; Kerr, D. J. Clin. Oncol. (1998) ; 16, 2761–2769. [4] Harding, M. M.; Mokdsi, G.; Lucas, W. Inorg. Chem. (1998); 37, 2432–2437. 234. Sun, H.; Li, H.; Weir, R. A.; Sadler, P. J. Angew Chem., Int. Ed. Engl. (1998) ; 37, 1577–1579. [5]Reynolds J. E. F. Ed., Martindale The Extra Pharmacopoeia, 31 st The Royal Pharmaceutical Society; London, (1996) ;Martindales Pharmacopeia. [6] Edwards, E.I; Epton , R; Marr, G. J.Orgnometal .Chem.(1975); 85 , 23. [7] Gray H. B., Proc. Natl. Acad. Sci. USA ,( 2003); 100, 3563. [8] Leo Di, Berrettin D., and Renzo F, C. J. Chem. Soc. Dalton Trans., (1998); 1, 1993-2000. [9 Saud Ai- Resayes, J. Saudi Chem, Soc.; (2001), 5 (2). 205-210. [10] Tella, A.C;Obaleye, M.O and Akolade, E.O. J. Middle- East Scientific Research, (2011);7(3),260-265. [11]Zahid Chohan, H.And Maimoon F.Jaffer, J. Metal Based Drugs, (2000) ,7,( 5), 265-269. [12] Marija Z, Iztok T and Peter B. Turk J Biol. (2001); 74,61-74. [13] Taghreed. H. Al-Noor, Ahmed.T.AL- Jeboori,Manhal. Reemon. J. Advances in Physics Theories and Applications,( 2013 );18(1), 1-8. 118

References [14] Saravanan,J. and Mohen, S., J. Asian. Chem., (2003);15, 67. [15] Jeewoth, K.W.,Li,W.H., Minu, G.B.,Ghooroboo, D. and Babooram, KJ. Synthesis

Reaction

Inorganic Metal Organic Chemistry., (2000) ;

30, 1023. [16] Mohamed G., Zayed M.A., Abdallah S.M.J Mol Struct,(2010);979, 62–71. [17] El-Sherif A.A., Eldebss,T.M.A. J.Spectrochim Acta, (2011) ; 79A. 1803–1814. [18] Bharti

Jaina B. K., Suman Malikb, Neha Sharmaa and Shrikant

Sharma Pelagia Research Library Der Chemica Sinica, (2013); 4(5),40-45 [19]Farzana Nazir, Iftikhar Hussain Bukhari, Muhammad Arif, Muhammad Riaz, Syed Ali Raza Naqvi, Tanveer Hussain Bokhari, Muhammad Asghar Jamal, J. International Current Pharmaceutical Research (2013);5,( 3), 40-47. [20] Taghreed. H. Al-Noor, Ahmed. T.AL- Jeboori, Manhel. Reemon J. Chemical and Pharmaceutical Research, (2014) ;6(4): 1225-1231. [21]X.-Jia Hong, X. Liu, J.B. Zhang, X. Wu, C.-Ling Lin, Y.-Jun Ou, J . Cryst Eng Comm, 16 (2014) , 7926–7932. [22] Hanaa Hameed Haddad American Journal of Analytical Chemistry, (2016) ; 7, 446-451. [23]Aliakbar Dehno Khalajia, Salar Hafez Gorana, Sepideh Mehrania, Karla Fejfarovab, Michal Dusekb , J.Iranian Chemical Communication (2017) ;5,186-19 [24] Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names (2013)(Blue Book) Cambridge:The Royal Society of Chemistry. (2014). 415, 745. 119

References [25]Leiserowitz L and Nader F, J.Acta Crystallogr.(1977);B33, 2719. [26]Thomas Steiner, J. Acta Crystallogr. (2001); B57, 103 . [27]Ramanadham, M.; Jakkal, V.; Chidambaram, R. Federation

of

European Biochemical Societies Lett. (1993); 323, 203− 206. [28] Jack Y. Lu, Michael A. Lawandy, and Jing Li . J.Inorg. Chem. (1999) ; 38, 2695-2704. [29] Warad I, Eftaiha A , Nuri M, Ahmad I, Husein A Assal M,. J. Mater. Environ. Sci. (2013); 4 (4): 542-557. [30] Wai-Yin Sun R, Lung Ma D, Lai-Ming E, Ming Che W. The Royal Society of Chemistry (2007) ; 4884– 4892. [31] Abd El-Wahab, Z H, Mashaly, M M, Salman A A, El-Shetary, B A, and Faheim, A A, Spectrochim. Acta, (2004) ;Part A, 60, 2861 [32] Emina M. Mrkalić,a Ratomir M. Jelić,b Olivera R. Klisurićc and Zoran D. Matović, Dalton Transactions,View Article Online.The Royal Society of Chemistry (2014). [33] Chainok Kittipong, a Phailyn Khemthong,b Filip Kielarb and Yan Zhou , Acta Cryst. (2016) ; 2,(1), 87–91. [34] Quan-Liang Chen, J. International New Technology and Research , (2016) , 40-43. [35] Albrecht,M.;Schmid, S.; De Groot, M.; Weis, P.; Fröhlich, R. J. Chem. Comm. (2003) ; 2526–2527. [36] Cotton,F. Albert; Wilkinson, Geoffrey; Murillo, Carlos A.; Bochmann, Manfred(1999), Advanced Inorganic Chemistry (6thed.), New York: WileyInterscience, [37]Charles, R. G. J.. Inorg. Synth. (1963) ; 7, 183–184. [38]Snider, B. B. (2004) ; Encyclopedia of Reagents for Organic Synthesis. New York, NY: J. Wiley & Sons . [39] Seco, M. J. Chem. Ed. (1989) ; 9, 779-780. 120

References [40] Döhring, A.; Goddard, R.; Jolly, P. W.; Krüger, C.; Polyakov, V. R. Inorg. Chem. (2007) ;36 (2), 177–183. [41] Wenzel, T.J.;Ciak, J.M.; Encyclopedia of Reagents for Organic Synthesis, (2004) ; John Wiley & Sons, Ltd. [42] Isakova V. G., Baidina I. A., Morozova N. B.,Igumenov I. K. J.Polyhedron (2000) ; 19, 1097–1103. [43] Bhalla, G.; Oxgaard, J.; Goddard, W. A.; Periana, Roy A J, Organometallics. . (2005) , 24: 5499–5502 [44] Rudolph, G.; Henry, M. C. J. Inorg . Synth. (1967) ;10, 74–77 [45] Sadeek S. A. and Refat M. S. , J.; Korean Chemical Society (2006) ; 50, No. (2 ),107-115. [46]Adnan dib J.; Chem.Tech Research , (2013) ; 5, (1), 204-211. [47]Gajendra Kumara, Shoma Devi, And Rajeev Johari, E-Journal of Chemistry (2012) ;9(4), 2255-2260 [48]Santhi and Radhakrishnan Namboori, Int J Chem Tech Res, (2013) ; 5 (4) 1750–1755 [49] Huovinen, P J.Clinical Infectious Diseases. (2001). 32 (11): 1608–14. [50] Adedibu C. Tella and Joshua A. Obaleye , J. International . Biological. Chemecal. Sciences . (2010) ; 4(6) , 2181-2191. [51] Omoruyi G. Idemudia, Peter A. Ajibade and Anthony I. Okoh J.African Biotechnology( 2012) ; 11(39), 9323-9329, [52]Taghreed. H. Al-Noor , Lekaa K. Abdul Karim; J., Chemistry and Materials Research ,( 2015),7(3) ,32-39. [53]Taghreed. H. Al-Noor , Lekaa K. Abdul Karim , J., Chemistry and Materials Research. ( 2015) ;7(5),82-91. [54] Taghreed. H. Al-Noor , Lekaa K. Abdul Karim , ,( 2016), J. TOFIQ Medical Sciences, (2016) ; 3, ( 2), 64-75 121

References [55] Lawal A., Ayanwale P. A. , Obaleye J. A. , Rajee A. O. , Babamale H. F.

Lawal M. J. International Chemical, Material and Environmental

Research( 2017) ; 4 (1): 97-101 [56]Vogel AIA "Text Book of Quantitative Inorganic Analysis " 2nd Ed. (Longman, London), (1978); 694. [57] Geary, W. J., J. Coord. Chem. Rev.(1971); 7, 81-122. [58]Dutta R.L.and Syamal A., "Elements of Magnatochemistry",(1996) ; 2nd Ed., East west press, New Delhi. [59]Silverstein R.M., Bassler G.C. and Morrill T.C., “Spectrometric Identification of Organic Compounds”, (1981);4th Ed., John Wiley and Sons, New York, U.S.A, 3-40. [60] Pavia D.L.,Lampman G.M. and Kriz G.S., “Introduction to Spectroscopy: A Guide For Students Of Organic Chemistry”, Saunders College Publishing, Orlando, Florida, U.S.A., (1979); 225-287. [61] Taghreed. H. Al-Noor ,Amer. J. Jarad , Abaas Obaid Hussein, J.Chemistry and Materials Research, (2014), 6 (3), 20-30. [62] Abbas Obaid Hussein"Synthesis,Characterization And Antibacterial Activities of Mixed Ligands Complexes of Some β- Lactam Antibiotic Drugs" A Dissertation Submitted to collage of education for pure sciences Ibn Al Haitham of Baghdad University in partial fulfillment of the requirements for the degree of doctorate of science in chemistry,( 2014). [63] Axe, K., & Persson, P. (2001). Cosmochim. Acta 65, 4481-4492, 0016-7037. [64] Taghreed H. Al-Noor a, Nisreen H. Karam a, Faeza H. Ghanim a, Alia S. Kindeel a, Ammar H. Al-Dujaili, Inorganica Chimica Acta 466 (2017) 612–617 . 122

References [65] Nakamoto K.” Infrared and Raman Spectra of Inorganic and Coordination Compounds., John Wiley and Sons Inc., New York. (1997); 5th Ed [66]Bellamy L J( 1975) ; The infrared spectra of complex molecules 3rd edn (London: Chapman and Hall) [67] Tayyari S.F., Milani-nejad F., J. Spectrochimica Acta (2000) ; Part A 56, 2679–2691 [68] Ogoshi H., Nakamoto K., J. Chem. Phys. (1966) ; 45 ,3113. [69] Schiering D.W., Katon J.E., J. Appl. Spectrosc. (1986) ,40, 1049. [70] Seliskar C.J., Hoffmann R.E., J. Mol. Spectrosc. (1982) ,96 ,146. [71] Olsson D., Wendt O.F., J. Organomet. Chem.,( 2009); 694, 3112. [72] Marcus, R. A. J. Annual Review of Physical Chemistry 15.1 (1964) ; 155-96. [73] Rehmanen,Visa, Nicolai V. Tkachenko, Hiroshi Imahori, Shunichi Fukuzumi, and Helge Lemmetyinen. J. Spectrochimica Acta Part (2001) ;A 57, 2229-244. [74] Simons WW. ;The Sadtler Handbook of Proton NMR Spectra, Sadtler Re-search Laboratories , Philadelphia, Sadtlerk,(1978). [75] Muhammad Ameen, Gilani S.R., Amina Naseer, Ishrat Shoukat and S.D. Ali, J. Bull. Chem. Soc. Ethiop. (2015) ; 29(3), 399-406. [76] Sangwan V., Singh D.P. J. Iranian Chemical Communication, 5 (2017) ; 345-351 [77] Lever A.B.P. “Inorganic Electronic Spectroscopy“, Elsevier Science Publishers, (1984); 2nd Ed., Amsterdam. 161. [78] Sakakibara Y, Okutsu S, Enokida T, Tani T;. J. Applied Physics Letters, (1999); 74(18): 2587. 123

References [79] Demirezen N., Tarınç D., Polat D., Ceşme M., Gölcü A., Tümer M., J. Spectrochim Acta A Mol. Biomol. Spectrosc., (2012) , 94, 243-255. [80] Simo B., Perello L., Ortiz R., Castineiras A., Latorre J.,Canton E., J. Inorg. Biochem., (2000).81(4), 275-283. [81] Vikas Sangwan, Dharam Pal Singh, J. Iranian Chemical communication, (2017) 5,345-351. [82] William K., (1991) ;. Organic spectroscopy (3rd Ed.), Macmillan Education Ltd, London, 49-54, 60-75. [83] Chohan ZH,. J. Appl, Organomet Chem., (2006)., 20: 112-116. [84] Vernekar J.V.,Tanksale A. M., Ghatge M. S. and Deshpande V. V, J. Biochem. Biophy. Res. Commu. (2001); 285,1018-1024 . [85] Yao Y., Du J., Bai B., Wang C. and Qian Z.; J. Tianran Chanwu Yanjiu Yu Kaifa, (2006) ;18, 751-755 . [86] Lu F Y., Su, F. Zhang and J. Li; J. Zhongcaoyao, (2008); 39, 15801583 . [87] Li , F. Yu, P. Li, M. Wang, H. Bai S.and Chen, H.; Wuji. Yixu. Xueb. (2009); 18,271-273 . [88] Awetz J.,Melnick, And Delbrgs A,(2007).“Medical icrobiology” 4th Ed McGraw Hil-USA. [89] Barry, A.L,"The Antimicrobic Susceptibility test principle and practices", 4th Ed, New York. [90] Philip D.Lister, Daniel J.Welter, and Nancy D. Hanson, J. Clin Microbial Rev., (2009); 22(4), 582–610. [91] Medline (1991) On the safety of Bacillus subtilis and B. amyloliquefaciens: a review. Appl. Microbiol. Biotechnol. 36:1–4.

124

References [92] McQueary, CN; Kirkup, BC; Si, Y; Barlow, M; Actis, LA; Craft, DW; Zurawski, DV.. Journal of microbiology (Seoul, Korea) June (2012); 50 (3), 434–43 [93] Smith, J. Ame. Med. Asso. (1964) ;187, 142-143. [94] Vaghasia Y, Nair R, Soni M, Baluja S, Chanda S., J. Serb Chem Soc (2004);69, 991-998. [95] Tweedy BG.. Phytopathology (1964); 55: 910- 914. [96] Balan A. M., Ashok R. F., Vasanthi M., Prabu R., A. Paulraj, J. Int. Life Sci. Pharma Rev. (2013) ; 3, 67. [97] Al Zoubi W., Al-Hamdani A. A., Kaseem M., J.Appl. Organometal. Chem.(2016) ; 30, 810.

125

‫الخالصة‬

‫تناول العمل المقدم بهذه الرسالة تحضير وتشخيص‪:‬‬ ‫‪ (A‬الليكاند قاعدة شف )‪: ( L‬‬

‫‪(Z)-4-((4-amino-5-(3,4,5-trimethoxybenzyl)Pyrimidin -2-yl)imino)pentan-2-one‬‬ ‫مشتق من مضاد حيوي مختار الترايمثمبريم )‪ Trimethopri (TMA‬مع اسيتايل اسيتون ‪acetylacetone‬‬

‫)‪ (aac‬متضمن (‪ )N,O‬كذرات واهبة من نوع )‪(N.N.N & O‬‬ ‫تم تشخيص الليكاند )‪ (L‬باستعمال طيف (‪ ( 1H-NMR‬و(‪ )13C-NMR‬أطياف األشعة تحت الحمراء‬ ‫‪ FT-IR‬وفوق البنفسجية المرئية ‪، U.V–Vis -‬التحليل الدقيق للعناصر)‪ ، (C.H.N.S‬درجة االنصهار‬ ‫وكما تم رسم الشكل المقترح لليكاند باستعمال البرنامج الكيميائي الجاهز كيم اوفيس ‪Cs Chem 3D Ultra‬‬ ‫)‪،program package (2015‬وكما مبين في الشكل االتي الثالثي االبعاد ‪ 3D‬لليكاند‪:‬‬

‫‪ (B‬تحضير المعقدات المختلطة الليكاند‬ ‫كليكاند ثانوي‬

‫‪)1‬استعمال قاعدة شف )‪ (L‬كليكاند اولي مع حامض االوكزاليك ) ‪(H2OX= H2C2O4‬‬ ‫مع االيونات )‪ M(II‬و)‪:Cr (III‬‬ ‫‪ )2‬استعمال الترايمثمبريم )‪ (TMA‬كليكاند اولي مع حامض االوكزاليك كليكاند ثانوي مع االيونات )‪M(II‬‬ ‫و)‪ Cr (III‬وكما في الجدول االتي‪:‬‬

‫‪Compositions‬‬

‫‪Secondary ligand‬‬

‫])‪[M (Ox) (L‬‬ ‫)‪M= Co(II), Ni(II),Cu(II),Zn(II‬‬ ‫‪& [Cr (Ox) (L)]Cl‬‬ ‫‪K2[M (Ox)2(TMA) (H2O) ] .‬‬ ‫)‪M=Mn(II), Co(II), Ni(II),Cu(II),Zn(II‬‬ ‫‪& K [Cr (Ox)2(TMA)].‬‬

‫‪Oxalic acid‬‬

‫‪H2Ox= H2C2O4‬‬ ‫‪Oxalic acid‬‬

‫‪Primary ligand‬‬ ‫‪L‬‬ ‫‪Schiff base‬‬

‫‪C19H24N4O4‬‬ ‫‪Trimethoprim‬‬ ‫‪TMA‬‬ ‫‪C14H18N4O3‬‬

‫المعقدات المحضرة مسحوق صلب درست من النواحي اآلتية‪:‬‬ ‫التوصيلية الموالرية‪ ،‬الدراسات الطيفية (األشعة تحت الحمراء‪ ،‬فوق البنفسجية– المرئية و مطيافية‬ ‫االمتصاص الذري) فضال عن قياس الحساسية المغناطيسية مع استعمال البرنامج الكيميائي ‪Chem‬‬ ‫)‪ Office– Cs. chem– 3D pro 2015‬في رسم اشكال المعقدات‪.‬‬ ‫قيم العزوم المغناطيسية واألطياف االلكترونية لجميع المعقدات دلت على أن جميع المعقدات لها بنية ثماني‬ ‫السطوح‪.‬كما تم اختبار الفعالية البايولوجية المضادة للبكتريا لليكاند الحر مع المعقدات المحضرة بقياس‬ ‫منطقة التثبيط )‪. (ZI‬‬

‫وزارة التعليم العالي والبحث العلمي‬ ‫جامعة بغداد ‪-‬كلية التربية للعلوم الصرفة ‪ /‬أبن الهيثم‬ ‫قسم الكيمياء‬

‫تحضير‪،‬تشخيص ودراسة الفعالية البكتيرية لمعقدات قاعدة شف جديدة‬ ‫مع بعض االيونات الفلزية‬ ‫رسالة مقدمة الى‬ ‫مجلس كلية التربية للعلوم الصرفة – أبن الهيثم – جامعة بغداد‬ ‫وهي جزء من متطلبات نيل درجة الماجستير في علوم الكيمياء‬ ‫من قبل‬ ‫غسان ثابت شنين‬ ‫بكالوريوس علوم كيمياء –‪ -2002‬جامعة بغداد‬ ‫بأشراف‬ ‫ا‪.‬د‪ .‬تغريد هاشم النور‬

‫‪ 2017‬م‬

‫‪ 1439‬ه‬