SYNTHESIS AND CHARACTERIZATION OF METRONIDAZOLE (FLAGYL) DRUG – METAL COMPLEXES OF NICKEL (II), MANGANESE (II), COPPER (II) AND IRON (II) IONS

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TABLE OF CONTENTS

TITLE PAGE                                                                                     i

CERTIFICATION                                                                              ii

DEDICATION                                                                                   iii

ACKNOWLEDGEMENT                                                                   iv

TABLE OF CONTENT                                                                      v

ABSTRACT                                                                                       vii

1.0    CHAPTER ONE

1.1    Introduction                                                                           1

1.2    Antibiotic : Classification and side effect.                             2

1.2.1  Classification of Antibiotics                                                  2

1.2.2   Side effect of Antibiotic                                                        3

1.3      Flagyl (Metronidazole)                                                          4

1.3.1   Mechanism of action                                                            4

1.3.2   Resistance                                                                            5

1.3.3   Spectrum Activity of metronidazole.                                   5

1.3.4   Pharmacokinetic of Metronidazole                                     6

1.3.5   Toxicity of Metronidazole                                                     6

1.3.6    Half-life of Metronidazole                                                   7

1.3.7    Topical Administering of Metronidazole                            7

1.4       Metal Complexes                                                                 8

1.5       Properties of Ligands                                                8

1.6       Properties of Nickel, Biological importance and Toxicity.          9

1.7       Properties of Iron, Biological importance and Toxicity     10

1.8       Properties of Cobalt, Biological importance and Toxicity 10

1.9       Properties of Manganese, Biological importance and Toxicity  11

1.10     Aim of the project                                                                12

2.0 CHAPTER TWO

2.0 Apparatus, reagents and experiments                                    13

2.1 Flagyl Fe(ii) complex formation                                                15

2.3 Flagyl Co(ii) complex formation                                                15

2.3 Flagyl Ni(ii) complex formation                                       16

2.4 Flagyl Mn(ii) complex formation                                               16

2.5 Characterization                                                                       17

2.6 Melting point determination                                                     17

2.7 Atomic Absorption Spectra                                                      18

3.0 CHAPTER THREE

3.1 Result of flagyl Fe(ii) complex formation                                  19

3.2 Result of flagyl Co(ii) complex formation                                 19    

3.3 Result of flagyl Mn(ii) complex formation                                19

3.4 Result of flagyl Ni(ii) complex formation                                  19

3.5 Result of solubility test                                                             20

3.6 Result of melting point determination                                     20

3.7 Result of Atomic Absorption Spectra (AAS)                             21

4.0 CHAPTER FOUR

4.1 Conclusion and Recommendation                                           22

4.2 References                                                                                 23

ABSTRACT

Metronidazole (flagyl) metal complexes were prepared from the reactions of metronidazole (flagyl) and FeS04.7H20, NiCO3.7H2O, MnSO4.7H2O and CoSO4.H2O. The complexes were characterized using physical properties such as melting point determination; solubility and Atomic Absorption spectra (AAS), the result obtained from each property showed that the drug metal complexes were more effective and powerful than the parent drug.

CHAPTER ONE

1.l INTRODUCTION

Antibiotics belong to a class of compounds of biosynthetic or semi-synthetic in nature. Most of them are produced by various species of microorganisms and other living synthetic and are capable in small concentrations of inhibiting the growth of or killing bacteria and other micro-organisms. An extensive review on the metal complexes of various antibiotics was published (1) It includes complexes of tetracycline and bleomycin, valinomycin, beauverian and otherenniatins, gramicidins, nactins, lasalcid, monensin, calcimycinand related antibiotics D-eycloserine and related aminoacids with antibiotics properties and iron-containing antibiotics.

Chlorotetracycline (aureomucin) and oxytetracycline (terramycin) were shown to have high affinity for the cations of heavy metals, the acidity of terracycline towards first row transition metals ions and the corresponding stability constants of the metal complexes have been reported. The stoichiometeries and concentrations of the different metal complexes formed by tetracyclines in vivo could be assessed on a quantitative basis by using high speed.(2) Thiadiazole derivates have been reported to be biologically versatile compounds, possessing anti­viral, anti-bacterial, anti-pyretic, antifungicidal and analgesic activities. Complexes of 4-acetyl-2-(ace- tylamino)-5-dimethyl- 2-l, 3, 4-thiadiazole with cadmium, mercury and first row transition metals have been described.

1.2   ANTIBIOTICS -.CLASSIFICATION AND SIDE EFFECT

An antibiotics are drugs that kills or slow down the growth of bacterial, antibiotics are one class of antimicrobials, a large group which also include anti-viral, anti-fungal and anti-parasitic drug. Antibiotics are chemicals produced by or derived from microorganism (i.e bugs, germs such as bacteria and fungi), the first antibiotics was discovered by Alexander Fleming in 1928 in significant breakthrough for medical science.(3)

Antibiotics are among the most frequently prescribed medications in modern medicine , some antibiotics are bactericidal meaning that they work by killing bacteria ,other antibiotics are bacteriostatic meaning that they work by stopping bacteria multiplying each different type of antibiotics affect different bacteria in different ways for example an antibiotics might inhibit a bacterium ability to turn glucose into energy or it ability to construct its cell wall when this happens the bacterium dies instead of reproducing.

SYNTHESIS AND CHARACTERIZATION OF METRONIDAZOLE (FLAGYL) DRUG – METAL COMPLEXES OF NICKEL (II), MANGANESE (II), COPPER (II) AND IRON (II) IONS