SYNTHESIS CHARACTERIZATION AND BIOLOGICAL STUDIES OF DOMPERIDONE AND ITS COMPLEXES WITH SOME TRANSITION METAL IONS

Title of Thesis:

SYNTHESIS CHARACTERIZATION AND BIOLOGICAL STUDIES OF DOMPERIDONE AND ITS COMPLEXES WITH SOME TRANSITION METAL IONS

ABSTRACT

The complexes of Cu(II), Co(II), Ni(II), Fe(II) and Ag(I) have been synthesized with domperidone. The structural features of complexes have been determined by elemental analysis, conductance measurement, UV/VIS and infrared spectroscopy. IR studies revealed that the domperidone coordinate with metal ions through nitrogen and oxygen(C =O). The complexes of Cu(II), Fe(II), and Ni(II) were assigned square planar geometry while Co(II) and Ag(II) were assigned octahedral geometry. High value of conductance of Cu(II), Fe(II), and Ni(II) supports their electrolytic nature and low value of conductance of Co(II) and Ag(II) supports their non – electrolytic nature. The ligand and complexes were checked for their antibacterial activity against three bacterial strains Escherichia coli, Staphylococcus aruseus, Pseudomonas aeurogionaby. Disc diffusion method was adopted for antibacterial activity. The antibacterial activities of the metal complexes were found to be more as compared to parent drug.

Introduction

COORDINATION COMPOUNDS OR METAL COMPLEXES

                                The compounds in which a small number of molecule or ions called ligand surround a central metal atom or ion. Each ligand shares a pair of its electrons with the metal. The metal-ligand bond often represented as M ←: L is an example of a coordinate covalent bond in which both the electrons come from one atom [1a].

HISTORY

                   One of the earliest recorded co–ordination compound is Prussian blue       KCNFe(CN)₂ Fe (CN)₃ an artist color, made by accident when animal wastes and sodium carbonate were strongly heated in an organic container.

                                         Other long known compounds are potassium ferrocyanide (1753) K₂PtCl₆ (1760 – 1765), [Co (NH₃)₆] Cl₃ (1798). The first era of rapid activity in this field began in 1798 when Tassaert isolated orange crystals of CoCl₃.6NH₃ by allowing a mixture of CoCl₂ and aqueous ammonia to stand in air. He puzzled over the fact that two stable compounds would combine to form a new product with properties entirely different from the compounds it obtained. It was Alfred Werner who gave the theory of “primary and secondary valencies”. He suggested that primary valencies are those used in attaching the coordinating groups (e.g. ammonia molecules). Further he showed that the factor that determining the chemical behaviour of co-ordination compounds was not the “primary” valencies but number of “secondary” valencies.

TYPES OF COMPLEXES

                There are three types of complexes ^[2] :

·         Neutral complexes

·         Cationic complexes

·         Anionic complexes

(i) Neutral complexes:

                      Those complexes in which there is no positive or negative charge on square bracket are called “neutral complexes”.

e.g. [Ni (CO)₄], [Ni (NH₃)₂(CN)₂]

  

(ii) Cationic Complexes:

                   Those complexes in which there is positive charge overall on square bracket is called “cationic complexes”.

e.g. [Ag (NH₃)₂]⁺, [Ni (H₂O)₆]⁺², [Fe (NH₃)₆]⁺³                           

(iii) Anionic Complexes:

                    Those complexes in which there is negative charge overall on square bracket is called “anionic complexes”.

e.g. [Ni (CN)₄]^-2, [PtCl₄]^-2, [Fe (CO)₄]^-2

Ligand

           An atom or group of atoms which can donate a pair of electrons to central metal atom or ion is called ligand.

Types of ligands:

                There are three types of ligands. i.e:

v  Neutral ligands

v  Cationic ligand

v  Anionic ligand

(i) Neutral ligands:

                 That ligand which does not contain any charge is called “neutral ligand”. e.g. NH₃, H₂O, CO, NO.

(ii) Cationic ligands:

                 Those ligands which contain positive charge are called “cationic ligands”.   e.g. NO⁺, NH₂N⁺H₃(hydrazinium).

(iii) Anionic ligands:

                 Those ligands which contain negative charge are called “anionic ligand”.

Coordination sphere:

                 The region or space around central metal atom or ion in a complex in which ligands are located is called coordination sphere. Coordination sphere is denoted by

square bracket “[]”.

  

Coordination Number:

 The number of bond made by ligand to the central metal atom or ion in the complex is the coordination number. The coordination number of d-block elements is 2-12 and for f-block elements 2-14 and most common coordination numbers are 2, 4 and 6.

Formation of Metal Complex:

               The formation of a complex ion may be considered to be an example of Lewis acid-base reaction. Ligand is a Lewis base (electron pair donor) and metal ion is a Lewis acid (electron pair acceptor). For example, in the reaction between cupric ion (Cu²⁺) and ammonia molecule; the Cu²⁺ act as a Lewis acid and each NH₃ molecule act as a Lewis base and contribute both of its lone- pair electrons to the formation of a coordinate covalent bond which bonds the Nitrogen to the Cu²⁺ ion. The resulting [Cu (NH₃)₄]²⁺  complex (a deep blue colour solution), therefore, described as consist of four ammonia molecules in coordination to central Cu²⁺ ion and thus the coordination number of Cu²⁺in this complex is 4.^[3]

STABILITY OF METAL COMPLEXES:

                    Stability of metal complexes depends on the following factors;

(i)   Nature of metal

(ii)  Nature of ligand

(iii) Geometry of complex

                         These are discussed below.

(i) Nature of metal:

The central atom or ion form complexes of different stabilities with various ligands which further depend on charge, size, element configuration and polarizability of metal.

               The most stable complexes made up of oppositely charged ions and more over, that the greater the charge on the ion and smaller the size of the ions, greater should be the stability. Small ions are favoured because their centers can be closer together.

(ii) Nature of ligand:

              The ligand may also affect the stability of complex. The nature of ligand depend upon,

1. charge and size
2. base strength
3. crystal field splitting
4. chelate effect
5. steric effect.

(iii) Geometry of complexes

              Structure of complexes may also affect the stability of complex. Five membered ring with all single bonds are more stable than six membered rings, however six membered ring with alternate single and double bonds are more stable.[4]

(iv) Chelate Complexes:

                   Many ligands can bond simultaneously through more than one donor atoms and are called polydentate ligands. When polydentate ligands are attached to central metal atom or ion is called chelate complex or chelate. This process is called chelation.[5]

Effect of Chelation on Stability of Complexes:

                  The stability of metal complex is greater than that of analogous known metal complex, it means that the formation of chelate, gives extra stability to the complex, for example,

                             [Ni (NH₃)₆]⁺²< [Ni (en)_3]⁺² < [Ni (EDTA)]^-2

 The more extensive is the chelation, more stable is the complex.

                            

                   The chelate effect depends upon the entropy effect. The chelate effect also depends upon the enthalpy. Both entropy and enthalpy effect reinforce each other in stability of a complex. 

CLASSIFICATION OF POLYDENTATE LIGANDS

         Poly or multidentate ligands are classified as

Monodentate ligand:

  Ligands which can donate one electron pair. E.g.

                          CH₃-NH₂

                                    methyl amine

Bidentate ligand:

     Which donate two electron pairs to the central metal atom or ion. E.g.

                   NH_2-CH₂-CH₂-NH₂

                               ethylene diamine

Tridentate ligand:

       Ligand which can donate three electron pairs to the central metal atom or ion.

e.g.

                  H₂N_-CH₂-CH₂-NH-CH2-CH₂-NH₂  

                             diethylene triamine

Quadridentates ligand:

        Ligands which can donate four electron pairs to the central atom or ion.

 E.g  NH_2-CH₂-CH₂-NH-CH₂-CH₂-NH-CH₂-CH₂-NH₂

                     Triethylene tetramine

Quin quadric dentate ligand:

        Ligands which can donate five electron pairs to the central metal atom or ion.

e.g.                                         

       NH_2-CH₂-CH₂-NH-CH₂-CH₂-NH-CH₂-CH₂-NH-CH₂-CH₂-NH₂

                                 Tetraethylene pentamine

Hexa dentate ligand:

          Ligand which can donate six electron pairs to the central metal atom or ion.e.g.

                                   HOOCCH₂                                                                                       CH₂COOH

                                                                   ..                      ..

                                                                  NH-CH₂-CH₂-NH 

                                   HOOCCH₂                                                                                         CH₂COOH

         

                                                Ethylene diamine tetracetic acid (EDTA)                                 

USES OF COORDINATION COMPOUNDS

               A brief survey of some of the uses of coordination compounds includes [6].

1. Dyes and Pigments:

             Coordination compounds have been used from earliest times as dyes and pigments, for example madder dye which is red, was used by the ancient Greeks and others. It is a complex of Hydroxyanthraquinone. A more modern example is the pigment copper phtalocyanine, which is blue.

2. Analytical Chemistry:

              In analytical chemistry it is used for;  

a)      Colour Tests: Since many complexes are highly coloured they can be used as calorimetric reagents e.g. formation of red 2, 2-bipyridyl and 1, 10-phenanthroline complexes as a test for Fe²⁺ .

b)      Gravimetric Analysis:gravimetric methods are those that involve the production, isolation and weighing of a solid to determine the amount of a material in a sample. Perhaps the example of this method most often cited, although not complexometric, is the precipitation of AgCl (s) in the determination of the percentage of silver and/or chloride in a substance. One of the most common complexometric gravimetric procedures involves the use of a bidentate chelating agent, dimethylglyoximate (dmgH-), to determine nickel. e.g. Ni (DMG)₂            

                                                   Another common gravimetric procedure involves the    

      determination of aluminium with a chelating agent known as 8-hydroxyquinoline

       (Sometimes called 8- quinolinol or oxime). E.g. Al (oxime)₃ [1b] 

c)      Complexometric Titration and Masking Agents: An example of this is the use of EDTA in the volumetric determination of a wide variety of metal ions in solution, e.g. Zn²⁺, Pb²⁺, Ca²⁺, Co²⁺, Ni²⁺, Cu²⁺, etc. by careful adjustment of pH and using suitable indicators, mixtures of metals can be analyzed, e.g. Bi³⁺ in the presence of  Pb²⁺(see laboratory manual). Alternatively, EDTA may be used as masking agent to remove a metal ion which would interfere with the analysis of a second metal ion present.

3. Sequestering Agents:

                 Related to their use as masking agents is the use of ligands for “sequestering” i.e. for the effective removal of objectionable ions from solution in industrial processing, e.g. EDTA is used to “soften” water. The addition of EDTA to water is used in boilers etc. to prevent “scaling” or build up of insoluble calcium salts.

4. Extraction of Metals:

                  Some times certain metals can be leached from their ores by formation of stable complexes e.g. Ag and Au as complexes of cyanide ion.

5. Bio – Inorganic Chemistry:

                   Naturally occurring complexes include haemoglobin, chlorophyll, and vitamin B₁₂.

1. Therapeutic Chelating Agents for Heavy Metals

                    EDTA and other complexing agents have been used for the elimination of harmful radioactive and other toxic elements from the body. (e.g. Pb²⁺). In these cases a soluble metal chelate is formed.

        b.Chemo-therapy

                       An example of this is the use of cis-platin (cis-Pt (NH₃)₂Cl₂) as an    anti-tumor drug.

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Introduction

Literature Review

Experimental Work

Results and Discussion

References