ABSTRACT
Eight metal(II) amino acids complexes in aqueous basic solution, [CuL2], [CuL12], [CoL2], [CoL1], [ZnL2], [ZnL12], [NiL2], and [NiL12] with L=L-methionine and L1=L-leucine were synthesized and analyzed by gravimetric analyses, molar conductivity measurements, magnetic susceptibility measurements, powder X-ray diffraction analysis, UV-Vis and IR spectroscopies.Molar conductivity measurements showed that the complexes are non-electrolytic, suggesting a metal-ligand ratio of 1:2 for the complexes, with respect to the amino acids. Solubility studies indicated DMSO as the most suitable solvent for dissolving the compounds;hence, all solvent bound analyses were carried out in DMSO. The IR spectra showed that the amino acids acted as bidentate ligands with coordination involving the carboxyl oxygen and the nitrogen of the amino group. Electronic spectra and magnetic susceptibility measurements suggested a square planar geometry for Cu(II), tetrahedral for both Zn(II) and Ni(II) complexes, and octahedral for those of Co(II). Magnetic susceptibility studies also revealed that the complexes of Cu, Co and Ni are paramagnetic while those of Zn are diamagnetic. The result also suggested L-methionine and L-leucine to be weak field ligands as they formed high spin complexes with Co(II) ion ([CoL] = 6.0 BM, [CoL1] = 5.10 BM) and tetrahedral complexes with Ni(II) ion.Gravimetric analyses showed that the complexes of Cu, Co and Zn contain one mole of water of crystallization while those of Ni contain two moles.Powder XRD studies suggested that the amino acid complexes are crystalline in nature and that they possibly crystallized in monoclinic fashion. The agar diffusion antimicrobial studies revealed that the amino acids are biologically active with their metal complexes showing significantly enhanced activity against the studied microbial strains in comparison to the free ligands.
TABLE OF CONTENTS
Contents Page
Cover page i
Fly leaf ii
Title page iii
Declaration iv
Certification v
Dedication vi
Acknowledgement vii
Table of Content viii
List of Tables xiii
List of Figures xiv
List of Appendices xv
Abbreviations xvi
Abstractxviii
CHAPTER ONE1
1.0 INTRODUCTION 1
1.1 Transition Metals 1
1.2Methionine 2
1.3 Leucine 2
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1.4 Transition Metal Complexes 3
1.5 Statement of Research Problem 3
1.6 Justification of the Research 4
1.7 Aim and Objectives of the Research 5
CHAPTER TWO 6
2.0 LITERATURE REVIEW 6
2.1 Biological Importance of Cobalt 6
2.2 Biological Importance of Copper 6
2.3 Biological Importance of Zinc 7
2.4 Biological Importance of Nickel 8
2.5 Amino Acids 8
2.5.1 Essential amino acids 9
2.5.2 Non-essential amino acids 10
2.5.3 Biological importance of amino acids 10
2.6 Transition Metal Complexes with Amino Acids11
2.7 Biological Importance of Coordination Complexes of Amino Acids 11
CHAPTER THREE17
3.0 MATERIALS AND METHODS 17
3.1 Materials 17
3.2 Methods18
3.2.1 Synthesis of metal(II) methionine complexes 18
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3.2.2 Synthesis of metal(II) leucine complexes 18
3.3 Characterization 19
3.3.1 Melting point analysis 19
3.3.2 Solubility test 19
3.3.3 Molar conductivity 20
3.3.4 Magnetic susceptibility 20
3.3.5 Determination of water of hydration in the complex compounds 21
3.3.6 Metal content analysis 21
3.3.7 Infra-red spectroscopy 22
3.3.8 UV-Vis spectroscopy 22
3.3.9 Powder x-ray diffraction 22
3.4 Antimicrobial Screening 23
3.4.1 Minimum inhibition concentration 24
3.4.2 Minimum bactericidal concentration/minimum fungicidal concentration 25
CHAPTER FOUR 26
4.0 RESULTS 26
4.1 Physical Properties 26
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4.2 Solubility Studies 26
4.3 Spectroscopic Analyses 26
4.4 Magnetic and Conductivity Measurements 31
4.5 Gravimetric Analyses 31
4.6 X-ray Diffraction Studies 31
4.7 Antimicrobial Studies 31
4.7.1 Zone of inhibition 31
4.7.2 Minimum inhibition concentration 39
4.7.3 Minimum bactericidal concentration/minimum fungicidal concentration 39
CHAPTER FIVE46
5.0DISCUSSION46
5.1 Physical Properties of Metal(II) Complexes 46
5.2 Solubility 47
5.3 Infra-red Spectroscopic Analysis 47
5.4 UV-Vis Spectroscopy 50
5.5 Magnetic Susceptibility Measurements 51
5.6 Molar Conductivity Measurement 53
5.7 Metal Content Analysis 54
5.8 Hydration Water Analysis 54
5.9 Powder X-ray Diffraction Studies 54
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5.10 Antimicrobial Screening 60
CHAPTER SIX64
6.0SUMMARY, CONCLUSION AND RECOMMENDATION64
6.1 Summary and Conclusion64
6.2 Recommendation 65
REFERENCES 66
APPENDICES 77
CHAPTER ONE
1.0 INTRODUCTION
Metals perform quite a number of functions in human body. Hemoglobin carries oxygen to vital areas of the body by binding it to the iron atom contained within it. Metal ions such as zinc provides the structural framework for the zinc fingers that regulate the function of genes in the nuclei of cells (O’Shea, 2004). Minerals containing calcium are the basis of bones which are the framework of the human body. Metals such as zinc, copper, iron and manganese are incorporated into catalytic processeswhich facilitate a number of chemical reactions needed for life (Da Silva and Williams, 1991).
The ability of metals to lose electrons to form positively charged ions allow them to play important roles in biological systems. Whereas metal ions are electrophilic, most biological molecules such as protein and DNA are electron rich. The attraction of these opposing forces lead to interaction between metal ions and biological molecules (O’Shea, 2004). Metal ions have been reported to improve, or induce the activity of biologically important moieties (Sadler and Guo, 1998) and that of some known drugs such as paracetamol, sulfamethoxazole and aspirin (Agbaje et al., 2014; Osowale, 2017).
1.1 Transition Metals A transition metal isone thatcontains a partially filled dor fsub-shellin elemental state or one of its important oxidation states (Petrucci et al., 2002; Rayner-Canham and Overtone, 2006). Several transition elements are important to the chemistry of living systems, the most familiar examples being iron, cobalt, copper, zinc, nickel, and molybdenum. Iron is by far the most widespread and important transition metal that has a function in living
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systems; proteins containing iron participate in two main processes, these are; oxygen transport and electron transfer (oxidation–reduction) reactions (Sundberg and Martin, 1974; Vallee and Auld, 1993).
The chemistry of transition metal complexes is well known. However, the evaluation of their antimicrobial activities has continued to attract more and more attention (Pierpont and Lange, 2007; Patil et al., 2011; Pllana-Zeqiri et al., 2012). This is because bacteria can cause foodborne diseases and other infections that affect our lives; therefore, there has been a growing effort towards synthesizing new antimicrobial agents. Coordination complexes of transition metals have been widely studied for their antimicrobial activities (Faundez et al., 2004).Efforts to understand the function of transition metals in biological systems have led to the growth of the field of bioinorganic chemistry (Farrel et al., 2003). 1.2 Methionine
Methionine, with molecular formula C5H11NO2S (Fig.1.1a)is one of the amino acids containing sulphur (Nelson et al., 2005).It helps to prevent disorders of the hair, skin and nails, in lowering the cholesterol levels by increasing the liver’s production of lecithin and reduces fat build-up in the liver and body (Cao et al., 2000). It is known that methionine presents antioxidant properties in several models of oxidative stress. It has been shown that it acts as a powerful endogenous antioxidant agent, leading to the reduction of lipid peroxidation in membranes (Gill and Tuteje, 2010).
1.3 Leucine
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Leucine, an amino acid with molecular formula C6H13NO2 (Fig. 1.1b) is a major component of the subunits in ferritin, astacin, and other “buffer” proteins (Nelson et al., 2005). It is used in the liver, adipose tissue, and muscle tissue. Adipose and muscle tissue use leucine in the formation of sterols. Combined leucine use in these two tissues is seven times greater than in the liver (Rosenthal and Farkas, 1974). Leucine is rapidly taken up into the brain where astrocytes convert it into α-ketoisocaproate via transamination of α-ketoglutarate to glutamate (Yudkoff, 2005).
Figure 1.1: Structures of methionine (a) and leucine(b)
1.4 Transition Metal Complexes
These consist of a central transition metal atom or ion, called the coordination center, and a surrounding array of bound molecules or ions known as ligands or complexing agents. Transition metal complexes play very important roles in biological systems (Rayner-Canham and Overtone, 2006; Noro et al., 2009).
1.5Statement of the Problem
Many of the current antimicrobial agents that are used in therapy are either becoming resistant or have adverse side effects (Agbaje et al., 2014). This hasled to continued search for new antimicrobial compounds, including coordination complexes of biologically
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important molecules (Farrell et al.,2003).The medicinal uses and applications of metals and metal complexes are of increasing clinical and commercial importance. The field of inorganic chemistry in medicine has been divided into two main categories: firstly, ligands as drugs which target metal ions in some form, whether free or protein-bound; and secondly, metal-based drugs and imaging agents where the central metal ion is usually the key feature of the mechanism of action (Reynold and Martidale, 1996; Farrel et al., 2003).The use of chelating agents in the treatment of Wilson’s disease is a good example of how medical problems due to free metal ion toxicity beenarrested by chelating agents (Sarkar, 1999).Continued research aimed at developing metal-based drugs which perhaps work by different mode of action and therefore arrest the challenge of resistance, is therefore, a way forward (Agbaje et al., 2014).
1.6Justification of the Research
There have been some reports of antimicrobial activity of certain metal complexes of amino acids. However, there is little information on coordination compounds of methionine. Literature studies showed that there is scanty information on the structure of M(II) coordination compounds of methionine and leucine in solid and aqueous phase as those reported have often been poorly characterized with such analytical tools as X-ray diffraction, molar conductivity, magnetic susceptibility and metal content analysis often ignored (Asemave et al., 2015; Vilhena et al.,2017). The biological activity of some bio-important moieties have been reportedly induced or elated on coordination with transition metal ions (Sadlers et al., 2007; Agbaje et al., 2014; Osowale, 2017).
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In spite of the interesting biological features exhibited by methionine and leucine, their coordination complexes with transition metals have not been well studied (Hakimi and Aliabadi, 2012) and this has ledtothe neglect in exploring their potential antimicrobial activity.It will rather be a step forward to synthesize and study the biological activities of complexes of such ligands with other similar biologically important metal ions as well in ordertoadd to the already existing body of knowledge available on such complexes. The reported widespread applications of amino acids and their coordination compounds, therefore, informed our interest in the synthesis ofneutral metal(II) complexes of L-methionine and L-leucine with the aim of obtaining alternative antimicrobial therapeutic agents to arrest the challenge of drug resistance.The current study is thus focused on synthesizing amino acid complexes of some metal(II) and characterizing them using XRD, magnetic susceptibility and molar conductivity in addition to other already used methods, and evaluating their biological potency against some pathogenic bacteria and fungi. 1.7 Aim and Objectives of the Research
The aim of this work is to synthesize and characterizeamino acid complexes of Cu(II), Co(II), Zn(II) and Ni(II), and evaluate their microbial potential.
To achieve this aim, the following objectives were set:
(a) To synthesize Cu(II), Co(II) Zn(II) and Ni(II) complexes of L-methionine and L-leucine.
(b) To characterize the amino acid complexes through spectrophotometric (UV, FT-IR and X Ray Diffraction) and classical methods(magnetic susceptibility measurements, molar conductivity and gravimetric analyses).
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(c) To investigate the antibacterial and antifungal potential of the synthesize complexes on some fungi and bacteria.
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