**5. Biological significance of Schiff bases and their metallic derivatives**

The progress of biological inorganic chemistry has seen a marked interest in Schiff base complexes, as many of these complexes may be considered as models for biologically important species. Co, Ni, Fe, Zn, and UO2 Schiff base complexes of 2-thiophene displayed good antibacterial activity against *E. coli*, *P. aeruginosa*, and *S. pyogenes*; these complexes also inhibited the growth of Gram-positive bacterial strains *S. pyogenes* and *P. aeruginosa*. This unique property could be applied safely in the treatment of infections caused by any of these strains [52].

Platinum complexes of salicylaldehyde and 2-furaldehyde Schiff base with oand p-phenylenediamine were screened against *E. coli*, *B. subtilis*, *P. aeruginosa*, and *S. aureus*; the data proved the complexes were more potent than the parent Schiff bases. Complexes of Schiff bases derived from sulfametrole and varelaldehyde were screened against *E. coli* and *S. aureus*, and it was observed to have a significant effect on *E. coli*. Membrane of Gram-negative bacteria contains lipopolysaccharides; the reported Schiff bases and their metallic complexes could combine with these lipoic layers to enhance the membrane permeability of the Gram-negative bacteria. Lipophilicity is an important factor that controls the antibacterial activity as lipophilic cell membrane favored the passage of only lipid soluble materials; and this increase in lipophilic nature enhances the penetration of Schiff bases and their metallic complexes into the lipid membranes and seizing the growth of the organism. Schiff bases and their metallic derivatives are more toxic on *S. aureus* than on *E. coli*; it may be due to the SOH, OCH3, and CH3CH2CH groups, interacting with the lipoic membrane (**Figure 3**) [53–55].

Cu, Ni, and Co complexes of 3-(2-hydroxy-3-ethoxybenzylideneamino)-5-methyl isoxazole and 3-(2-hydroxy-5-nitroben-zylidene amino)-5-methyl isoxazole Schiff bases were screened against *Aspergillus niger* and *Rhizoctonia solani*, and it was found that the activity increased upon coordination. The enhanced antifungal activity of the metal chelates can be explained based on chelation theory, which considers the overlapping of orbitals of each metallic ion with the ligand orbitals. Increased activity results in enhancement in the lipophilicities of the complexes due to delocalization of

**Figure 3.** *Antibacterial activity and DNA interaction of Schiff bases [54, 55].*

*Stability and Applications of Coordination Compounds*

**4. Schiff base metallic derivatives as catalysts**

lastly, stabilization is also achieved due to delocalization of electrons in the chelate systems which are defined as resonance-assisted hydrogen bonds (RAHB) [48].

Schiff bases are easily supported on polymers and loaded with different metallic ions to check their catalytic action; and these polymer-supported catalysts are consistent in drastic reaction conditions like moisture and high temperature reactions. A careful survey of literature reveals that during the past two decades, several reports were seen on the synthesis of polymer-supported Schiff base complexes catalysts. Transition metal Schiff base complexes are well-recognized homogeneous catalysts for various organic transformations with high homogeneity, good reproducibility, selectivity, and excellent catalytic activity to catalyze reactions under routine conditions. But there are certain drawbacks associated with these catalysts like corrosion, contamination of products, and separation of the catalysts. To address these challenges, heterogeneous catalysis is a good alternative approach; and there are two steps to achieve this task, that is, dispersing metallic ions on porous solid supports categorized as solid supported liquid phase catalyst (SLPC), and second step is the easy separation of the supported species from reaction mixture by filtration. Polystyrene is a well worked out cost-effective support, easily available, mechanically robust, chemically inert, and facile functionalization. When compared with the other supports like alumina or silica, the polymer-supported catalysts furnish the polymer chain flexibility for better microenvironment. Cobalt Schiff base complexes-functionalized polystyrene were effective and excellent catalysts in resolution of racemic mixtures. For the epoxidation of alkenes, early transition metal complexes proved excellent catalysts in combination H2O2; similarly, vanadium Schiff base complexes have been considered as versatile catalyst for oxidation of olefins, allylic alcohols, aromatic compounds, sulfides, and alcohols. There has always been a great need for high-quality pharmaceuticals, insecticides, and perfumes which significantly lead to develop enantioselective catalysts for epoxidation of olefins (**Figure 2**). More recently, chirally modified Li and Mg t-butyl peroxides have been used successfully in the epoxidation of electron deficient olefins. Henry's reaction also known as nitroaldol reaction is carbon–carbon

*Epoxidation of olefin using a polyhedral oligomeric silsesquioxane (POSS)-bridged oxo-molybdenum Schiff* 

**88**

**Figure 2.**

*base complex [49–51].*

π-electrons in the chelate ring; it is also reported that increased lipophilicity leads to breakdown of the permeability barrier of the cell. Cu complexes proved to be more active, which may be attributed to higher stability constant than the other complexes [56–58].

Schiff base metal complexes conjugated with oligonucleotides were used to inhibit antitumor effect; zinc fingers are small protein motifs consisting of fingerlike projections with a Zn2+ ion in each lump typically coordinated to two histidines and two cysteinic moieties. Binding with DNA takes place via classical (C2H2)-type zinc finger which regulates metathesis making these exciting targets for cancer therapy, especially breast, lung, liver, and brain cancers. The transition metal ions coordinated to Schiff bases have a very high affinity toward amino acid residues such as histidine and cysteine; their interaction with Zn fingers can, therefore, result in displacing Zn2+ from the Zn-finger and prohibiting the DNA binding with transcription factor. Co3+ Schiff base complexes were also attempted and showed greater specificity toward transcription factor inhibition than either of the precursors, that is, oligonucleotide and/or Co3+ complex, and Co3+ complex was required in >100-fold concentration for transcription factor inhibition, and the interaction with the protein was also non-specific [59–63].

Vaccination is a preemptive strategy to counter viral attacks like polio, small pox, chicken pox, etc. Viral attacks are a life-threatening situation for patients with compromised immunity, and a prompt treatment is required. To counter this, therapeutic options for viral infections are limited as antiviral agents in clinical practice are not yet completely effective, due to viral mutation against the drugs, and in addition, they also present several side effects. 1-amino-3-hydroxyguanidine salicylaldehyde Schiff bases are being considered as a good platform for the design of new and effective antiviral agents against mouse hepatitis with 50% growth inhibition at very low concentrations. Recently, abacavir-derived series of new Schiff bases prodrugs have been reported to use to treat human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) under the trade name Ziagen (GlaxoSmithKline) [64].

Recently, researchers have focused work in search of metal-based antioxidants to identify the compounds having the potential in scavenging free radicals relevant to diseases associated with oxidative damage caused by reactive oxygen species. Synthetic antioxidants are widely used as effective and low-cost than natural antioxidants. Schiff base metallic derivatives have been reported as effective scavengers of reactive oxygen species acting as antioxidants [65].

#### **6. Schiff base sensors**

Sensor may be defined as system capable of detecting changes in its surroundings and transferring the information obtained to computer processor. During the past two decades, researchers have shown an increasing interest to develop new molecules/materials for the sensing of chemical species present in the environment. For example, inorganic anions and cations have a very huge impact on biological systems and the environment; these ions affect a wide range of chemical and biological processes in terms of toxicity to environment as well as human health. All the discussed points account for the aforesaid growth in the demand for ion-selective sensors. Anion sensors development is a very challenging task in comparison to cations as anions are larger in size, geometrically very diverse, and more importantly pH dependent. Chemosensors are abiotic molecules which have the selective and reversible binding ability with the analyte; azo Schiff bases have been reported as fluoride chemosensors. On the hand, Schiff base fluorescent sensors are becoming

**91**

*Schiff Bases and Their Metallic Derivatives: Highly Versatile Molecules with Biological…*

first choice as they exhibit high sensitivity even at very low concentration of analyte under consideration. In analytical chemistry, electrochemical methods are based on two fundamental parts, namely, *receptor*, and second is *transducer*, either performing transformation of the chemical information. The first does it into a form of energy, and second transforms the chemical information into a useful signal, respectively. Recently, azo Schiff bases chemosensors have been studied to show high selectivity and sensitivity for the detection of Hg2+, Cd2+, and fluoride ions in the presence of competing cations/anions; these chemosensors can be utilized in DMSO by both selective coloration and change in the absorption spectra with a more prominent

Energy demand is a daunting challenge confronting the world as the quality of life depends largely on the availability of energy as we have burnt major part of fossil fuels. Renewable energy sources like solar light and wind generate larger amounts of energy and could potentially solve our immediate energy demands. Transformation of light into electric power in photovoltaic cells and subsequently light generation are two important interconnected phenomena which focus considerable interest to the researchers. Schiff base Zn2+ and Pt2+ complexes and organometallic compounds can produce, transform, and utilize energy due to their unique electronic setup which can be easily modified varying their chemical structure to develop a suitable material to fit an energy application. Remarkable work has been reported on salicylaldimine Schiff bases complexes with divalent Cu, Ni, Co, Zn, Mn, Fe, and Pt capable of being tailored into materials of applications in photo-

The corresponding author on behalf of all the co-authors exclusively declares

that there is/are no conflict(s) of interest(s) among authors to be declared.

color change that is observable to the naked eye (**Figure 4**) [66, 67].

*DOI: http://dx.doi.org/10.5772/intechopen.80799*

*Fluoride ion sensing by Schiff bases [66].*

**Figure 4.**

**7. Schiff base energy applications**

physics and optoelectronics [68].

**Conflict of interest**

*Schiff Bases and Their Metallic Derivatives: Highly Versatile Molecules with Biological… DOI: http://dx.doi.org/10.5772/intechopen.80799*

**Figure 4.** *Fluoride ion sensing by Schiff bases [66].*

*Stability and Applications of Coordination Compounds*

with the protein was also non-specific [59–63].

name Ziagen (GlaxoSmithKline) [64].

**6. Schiff base sensors**

of reactive oxygen species acting as antioxidants [65].

[56–58].

π-electrons in the chelate ring; it is also reported that increased lipophilicity leads to breakdown of the permeability barrier of the cell. Cu complexes proved to be more active, which may be attributed to higher stability constant than the other complexes

Schiff base metal complexes conjugated with oligonucleotides were used to inhibit antitumor effect; zinc fingers are small protein motifs consisting of fingerlike projections with a Zn2+ ion in each lump typically coordinated to two histidines and two cysteinic moieties. Binding with DNA takes place via classical (C2H2)-type zinc finger which regulates metathesis making these exciting targets for cancer therapy, especially breast, lung, liver, and brain cancers. The transition metal ions coordinated to Schiff bases have a very high affinity toward amino acid residues such as histidine and cysteine; their interaction with Zn fingers can, therefore, result in displacing Zn2+ from the Zn-finger and prohibiting the DNA binding with transcription factor. Co3+ Schiff base complexes were also attempted and showed greater specificity toward transcription factor inhibition than either of the precursors, that is, oligonucleotide and/or Co3+ complex, and Co3+ complex was required in >100-fold concentration for transcription factor inhibition, and the interaction

Vaccination is a preemptive strategy to counter viral attacks like polio, small pox, chicken pox, etc. Viral attacks are a life-threatening situation for patients with compromised immunity, and a prompt treatment is required. To counter this, therapeutic options for viral infections are limited as antiviral agents in clinical practice are not yet completely effective, due to viral mutation against the drugs, and in addition, they also present several side effects. 1-amino-3-hydroxyguanidine salicylaldehyde Schiff bases are being considered as a good platform for the design of new and effective antiviral agents against mouse hepatitis with 50% growth inhibition at very low concentrations. Recently, abacavir-derived series of new Schiff bases prodrugs have been reported to use to treat human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) under the trade

Recently, researchers have focused work in search of metal-based antioxidants to identify the compounds having the potential in scavenging free radicals relevant to diseases associated with oxidative damage caused by reactive oxygen species. Synthetic antioxidants are widely used as effective and low-cost than natural antioxidants. Schiff base metallic derivatives have been reported as effective scavengers

Sensor may be defined as system capable of detecting changes in its surroundings and transferring the information obtained to computer processor. During the past two decades, researchers have shown an increasing interest to develop new molecules/materials for the sensing of chemical species present in the environment. For example, inorganic anions and cations have a very huge impact on biological systems and the environment; these ions affect a wide range of chemical and biological processes in terms of toxicity to environment as well as human health. All the discussed points account for the aforesaid growth in the demand for ion-selective sensors. Anion sensors development is a very challenging task in comparison to cations as anions are larger in size, geometrically very diverse, and more importantly pH dependent. Chemosensors are abiotic molecules which have the selective and reversible binding ability with the analyte; azo Schiff bases have been reported as fluoride chemosensors. On the hand, Schiff base fluorescent sensors are becoming

**90**

first choice as they exhibit high sensitivity even at very low concentration of analyte under consideration. In analytical chemistry, electrochemical methods are based on two fundamental parts, namely, *receptor*, and second is *transducer*, either performing transformation of the chemical information. The first does it into a form of energy, and second transforms the chemical information into a useful signal, respectively. Recently, azo Schiff bases chemosensors have been studied to show high selectivity and sensitivity for the detection of Hg2+, Cd2+, and fluoride ions in the presence of competing cations/anions; these chemosensors can be utilized in DMSO by both selective coloration and change in the absorption spectra with a more prominent color change that is observable to the naked eye (**Figure 4**) [66, 67].

## **7. Schiff base energy applications**

Energy demand is a daunting challenge confronting the world as the quality of life depends largely on the availability of energy as we have burnt major part of fossil fuels. Renewable energy sources like solar light and wind generate larger amounts of energy and could potentially solve our immediate energy demands. Transformation of light into electric power in photovoltaic cells and subsequently light generation are two important interconnected phenomena which focus considerable interest to the researchers. Schiff base Zn2+ and Pt2+ complexes and organometallic compounds can produce, transform, and utilize energy due to their unique electronic setup which can be easily modified varying their chemical structure to develop a suitable material to fit an energy application. Remarkable work has been reported on salicylaldimine Schiff bases complexes with divalent Cu, Ni, Co, Zn, Mn, Fe, and Pt capable of being tailored into materials of applications in photophysics and optoelectronics [68].

### **Conflict of interest**

The corresponding author on behalf of all the co-authors exclusively declares that there is/are no conflict(s) of interest(s) among authors to be declared.

*Stability and Applications of Coordination Compounds*
