SYNTHESIS CHARACTERIZATION AND ANTIMICROBIAL ACTIVITY OF SCHIFF BASE DERIVED FROM P-CHLOROANILINE AND P-HYDROXYBENZALDEHYDE AND ITS COPPER (II) COMPLEX.

 

Schiff base reaction was investigated by Hugo Schiff from last 155 years ago, and these compounds are still having attention from scientists and researchers due to their applications in different fields. Schiff base compounds are prepared from the reaction of a primary amine with the carbonyl group of aldehyde (RHC=O) or ketone (R2C=O). Schiff bases have a functional group carbon-nitrogen double bond (-C=N-) called azomethine or imine, this imine group is very important for complex reaction and gives an important application in biological activity. The Schiff base mechanism is nucleophilic addition reaction throw the carbonyl group (C=O). The nucleophile is the primary amine which is reacts with the aliphatic or aromatic aldehyde or ketone to give an intermediate compound called carbinolamine. This intermediate compound was loses water molecule by hydrolyses process with acidic or basic media as a catalyst. Schiff bases metal complex are widely used in medicine for treating multiple viral diseases due to their transition metal complexes, which is play a key role in several areas, including, antibacterial, antifungal, anticancer, and anti-inflammatory, as well as these organometallic materials, were used as a catalyst in many reactions such as Aldo reaction, polymerization reaction, oxidation reaction, and others. Currently, Schiff base complexes have effective scavengers of reactive oxygen species, which is act as antioxidant compound. These compounds are decrease the free radicals in the human body, which is causes various disorders and disease. The metal ions are responsible for the operation of enzymes system in the human body. Many Schiff bases complexes were used to synthesis medication compounds and this is because the reactive interacting of the Schiff base ligand with the metal ion and become more effective if compared with the free metal Schiff bases. The objective of this paper is the present of biological activity of the Schiff base complexes and ligand against the bacterial and fungal.

Schiff base complexes have continued to play the role of one of the most important stereo chemical models in transition metal coordination chemistry due to their structural versatility associated with various applications (V.T. K., et al., 2006). In analytical chemistry, Schiff bases are prepared by the reaction of aldehydes with amines. They can act as multidentate ligands with transition metals and show many applications (A. Lennartson., et al., 2007). Schiff bases are azomethine (-C=N-) groups in chemical compounds. They are formed by mixing a primary amine and an aldehyde or ketone (Shrivastava & Shrivastava, 2016). Since the German scientist Hugo Schiff exploited amines to synthesize different "metallo-imines" in 1864, a variety of forms of the condensation products of amines and aldehydes or ketones, such as RCH=NR' where R and R' are alkyl and/or aryl substituents, have gained prominence. Schiff bases, anils, imines, and azomethines are alternative names for them (Mangamamba et al., 2014)

Because of their facile production and high metal binding capabilities, Schiff bases have been employed for the synthesis of metal complexes. They are often bi-, tri-, or tetra-dentate ligands capable of generating extremely stable complexes with transition metals (Arulmurugan et al., 2010).

Schiff base reactions are important in organic synthesis for generating carbon-nitrogen bonds. Their corresponding metal complexes have developed greatly, comprising a wide spectrum of organometallic compounds as well as other components of bio-inorganic chemistry (Sha et al., 2017). 

Schiff bases are vital compounds having broad biological and commercial uses, including antibacterial, antifungal, antiviral, anticancer, and anti-inflammatory properties (Zemede et al., 2015).

Researchers have continued to be interested in the chemistry of copper complexes with Schiff base ligands having oxygen and nitrogen as donor atoms. These ligands have been actively explored due to their broad potential uses in catalysis, electrochemistry, and biological systems, and are known to coordinate to copper atoms in diverse ways under different reaction circumstances (Zemede et al., 2015).

Because of the growth of antibiotic-resistant bacteria and the need for viable alternatives, the discovery of novel compounds with antimicrobial characteristics has gained a lot of interest in recent years. Because of their diverse chemical structures and coordination skills with metal ions, Schiff bases, a family of organic compounds, have demonstrated potential antibacterial qualities. 

Researchers are particularly interested in the Schiff bases produced from 4-hydroxybenzaldehyde and 4-chloroaniline due to their potential therapeutic uses. These compounds' structural variability and simplicity of synthesis bring up a wide range of potential for generating novel bioactive molecules (Benson et al., 2015).

The initial materials for the formation of Schiff bases are commonly 4-hydroxybenzaldehyde and 4-chloroaniline.The phenolic hydroxyl group in 4-hydroxybenzaldehyde makes it a good substrate for the synthesis of Schiff bases, on the other hand, its a primary aromatic amine that may readily create the needed Schiff base by condensation with 4-hydroxybenzaldehyde.

The coordination of the ligand to a central metal ion is necessary for the production of Schiff base ligands and their metal complexes. The ligand's chemical and physical characteristics shift as a result of this coordination, including enhanced biological activity. In addition, the metal ion acts as a site for coordination with other ligands, resulting in the development of coordination complexes.

      Fig 1. General Reaction Scheme of Schiff Base.    

Schiff bases are compounds formed by the condensation of a primary amine and an aldehyde or ketone. The resultant compound, R1R2C=NR3 is called a Schiff base, where R1 is an aryl group, R2 is a hydrogen atom and R3 is either an alkyl or aryl group. Schiff bases that contain aryl substituents are substantially more stable and readily synthesised while those which contain alkyl substituents are relatively unstable (Hine and Yeh, 1967).

Schiff bases are generally bidentate, tridentate, tetradentate or polydentate ligands capable of forming very stable complexes with transition metals. They can only act as coordinating ligands if they bear a functional group, usually hydroxyl, sufficiently near the site of condensation in such a way that a four, five or six membered ring can be formed when reacting with a metal ion.

 

Schiff bases derived from aromatic amines and aromatic aldehydes have a wide variety of applications in many fields, e.g, biological, inorganic and analytical chemistry. (Cimerman et al.,2000). Applications of many new analytical devices require the presence of organic reagents as essential compounds of the measuring system.

Transition metal complexes with Schiff bases have expanded enormously and embraced wide and diversified subjects comprising vast areas of organo-metallic compounds and various aspects of bio coordination chemistry (Anacona et al., 1999). The design and synthesis of symmetrical Schiff bases derived from the 1:2 step wise condensation of carbonyl compounds, with alkyl or aryl diamines and a wide range of aldehyde or ketone functionalities, as well as their metal (II) complexes have been of interest due to their preparative accessibility, structural variability and tunable electronic properties allowing t○ carry out systematic reactivity studies based ancillary ligand modifications (Trujille et.al., 2008). In recent years much effort has been put in synthesis and characterization of mono- and bi-nuclear transition metal complexes (Trujillo et.al., 2008)

Schiff bases are used in optical and electrochemical sensors, as well as in various chromatographic methods to enable detection of enhanced selectivity and sensitivity (Valcarcel et.al.,2016) Among the organic reagents actually used, Schiff bases possess excellent characteristics, structural similarities with natural biological substances, relatively simple preparation procedures and the synthetic flexibility that enables design of suitable structural properties (Patai 1970). Schiff bases are widely applicable in analytical determination, using variation in their spectroscopic characteristics following Changes in pH and solvent (Metzler et.al., 1980). Schiff bases play important roles in coordination chemistry as they easily form stable complexes with most transition metal ions (Clarke et.al., 1998). In organic synthesis, Schiff base reactions are useful in making carbon-nitrogen bonds.

Many biologically important Schiff bases have been reported in the literature possessing antimicrobial, antibacterial, antifungal, anti-inflammatory, anticonvulsant, anti-tumour and anti HIV activities (Schmid 1996). Another important role of Schiff base structure is in transamination (Schmid 1996).

Transamination reactions are catalyzed by a class of enzymes called transaminases. Transaminases are found in mitochondria and cytosal of eukaryotie cells. Schiff base formation is also involved in the chemistry of vision, where the reaction occurs between the aldehydes function of 11-cis-retinal and amino group of the protein (opsin) (Carry 1992). The biosynthesis of porphyrin, for which glycine is a precursor, is another important pathway, which involves the intermediate formation of Schiff base between keto group of one molecule of ɠ-aminol evulinic acid and ɛ-amino group of lysine residue of an enzyme (Carry 1992).

Schiff base ligands may contain a variety of substituent with different electron-donating or electron-withdrawing groups and therefore may have interesting chemical properties. They have attracted particular interest due to their biological activities (Shapiro 1998). For example,, acting as radio pharmaceuticals for cancer targeting (Singh 1999), They have also been used as model systems for biological macromolecules (Singh 1999). Besides the biological activity, solid-state thermochromism and photochromism are an another characteristic of these compounds leading to their application in various areas of materials science such as the control and measurement of radiation intensity, display systems and optical memory devices (Joudis and Mavridis, 2004).

Schiff bases derived from the salicylaldehydes with two or more donor atoms are well known as polydentate ligands, coordinating in deprotonated of neutral forms (Kaim 1987). The ability of metal ions to control the oxidation potentials of organic molecule by complexation has a significant role in biological electron transfer processes, molecular electronics and also in catalysis (Kaim 1987). Schiff bases are used as corrosion inhibitor e.g. fluorinated Schiff base derived from 3,4-difluorobenzaldehyde and 4,4’-benzidine were used as inhibitor in steel (Kaim 1987).

The metallo elements which are present in trace and ultra-trace quantities play vital roles at the molecular level in a living system. In a healthy body, of an adult, the trace and ultra-trace elements weigh less than 10 grams in total but life depends upon these elements for more than this figure (Das, 1990). The transition metal ions are responsible for the proper functioning of different enzymes. If their concentration exceeds a certain level, then their toxic effects are evident.

It has been found that the activity of the bio-metals is attained through the formation of complexes and the thermodynamic and kinetic properties of the complexes govern the mode of biological action. Sometimes, the permeability, i.e., lipophilicity of drugs increased through the formation of chelates in vivo and the drug action is significantly increased due to much more effective penetration of the drug into the site of action. The knowledge of drug action in vivo is extremely important in designing more potential drugs.

The preparation and study of inorganic compounds containing biologically important ligands is made easier because certain metal ions are active in many biological processes. The fact that copper, together with magnesium, calcium, iron, zinc, cobalt, chromium, vanadium and manganese are essential metallic elements and exhibit great biological activity when associated with certain metal-protein complexes, participating in oxygen transport, electronic transfer reactions or the storage of ions has created enormous interest in the study of these systems containing these metals (Karlin and Zubieta, 1983).

Transition elements (also known as transition metals) are elements that show variable valency and a strong tendency to form coordination compounds and have partially filled d-orbitals. Many of their compounds are coloured.  According to IUPAC, transition elements are element having a d- subshell that is partially filled with electrons, or an element that has the ability to form stable cations with an incompletely filled d orbital. They exhibit unique properties that make them essential in various industrial, chemical, and biological processes which include.

These unique properties make them play a significant role in various aspects of chemistry, physics, and technology due to their unique electronic and chemical properties.

Ligands are molecules or ions that donate a pair of electrons to the central atom or ion to form a coordination compound. When a ligand binds to its respective receptor, the shape and activity of the ligand is altered to initiate several types of cellular responses. Common examples of ligands include water (H2O), ammonia (NH3), chloride ion (Cl-), and ethylenediamine (en).

A coordination compound is a chemical compound consisting of a central atom or ion, called the central metal or central ion, surrounded by other atoms or molecules called ligands held together by forces that are dependent on specific properties of particular atomic structures.

The interaction between the central atom and the ligands is usually through coordinate covalent bonds, where the ligands donate a pair of electrons to the central atom leads to the formation of a complex.

The scope of his project is limited to the synthesis, characterization, and antimicrobial activity evaluation of the Schiff base derived from P-hydroxybenzaldehyde and 4-chloroaniline and its copper(II) complex. The antimicrobial activity will be evaluated against a selected range of microorganisms commonly encountered in medical and clinical settings. However, this study does not include detailed studies on the mechanism of action of the synthesized compounds or their toxicity profiles. These aspects may be investigated and addressed in future studies.

The increasing incidence of bacteria resistance especially in developing countries, such as Nigeria has become alarming hence the need to develop efficient antibacterial agents to face the challenge of resistant bacteria. Schiff bases are reported to possess a lot of biological activities such as anticancer, plant growth, insecticidal, antidepressant antibacterial, anti-inflammatory, antimicrobial and anti-tuberculosis. Due to such significant biological activities and the use of conventional method which is efficient in synthesizing Schiff base, which made scientists interested in synthesizing Schiff base. This work is an attempt to explore possibilities of developing a new and effective antibacterial agents.

The synthesis and characterization of Schiff base ligands and their metal complexes have attracted significant interest due to their potential applications in various fields, including medicine, agriculture and industry. The use of Schiff base ligands and their metal complexes as antimicrobial agents is particularly important due to the increasing prevalence of antibiotic-resistant bacteria and fungi. The investigation of the antimicrobial activity of the synthesized Schiff base and its copper(II) complex can potentially lead to the discovery of new and effective antimicrobial agents. With the growing concern of antibiotic resistance, the development of alternative antimicrobial compounds is crucial to combat infectious diseases.

The problem addressed in the study "Synthesis, Characterization, and Antimicrobial Activity of Schiff Base Derived from p-chloroaniline and p-hydroxybenzaldehyde and its copper(II) complex" revolves around the need to explore and evaluate the antimicrobial potential of the synthesized Schiff base and its copper(II) complex. The study seeks to address the increasing prevalence of antibiotic-resistant pathogens poses a significant threat to public health. Traditional antimicrobial agents are becoming less effective, emphasizing the urgent need to explore new compounds with antimicrobial properties.

The main aim of this research work is to synthesize a copper (II) complex with Schiff base ligand derived from p-chloroaniline and p-hydroxybenzaldehyde  

1. To synthesize the Schiff base derived from p-chloroaniline and p-hydroxybenzaldehyde. 

2. To synthesize the copper(II) complex of the Schiff base derived from p-chloroaniline and p-hydroxybenzaldehyde.

3. To characterize the Schiff base and the synthesized compounds using IR spectroscopic techniques, solubility, anti-microbial activity. 

4. To evaluate the antimicrobial activity of the synthesized compounds against selected bacteria.