**2. Synthesis of Schiff bases and derivatives**

The following routes are commonly adopted to prepare Schiff bases and their metallic derivatives:

• Reaction of aldehydes/ketones with primary amines under acidic/basic conditions [30]

**85**

**Figure 1.**

*Mechanisms of photoisomerization of azobenzenes.*

of one *sp*<sup>2</sup>

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

• Reaction of olefins and tertiary alcohols with hydrazoic acid [37]

Schiff bases tend to isomerize because of the imine group (C=N) to yield two stereoisomers *E* and *Z* (or *cis* and *trans*) isomers, and the formation of these stereoisomers can be controlled either kinetically or thermodynamically. Azobenzenes—common organic dyes—have been studied extensively owing to their potential applications in materials, medical, molecular switches, and other devices. Azobenzenes are photosensitive materials which undergo rapid reverse photoisomerization from the more stable *E* isomer to the less stable *Z* isomer. The exact mechanism of the *cis-trans* isomerization is not clear yet even after several decades of research. Reverse photoisomerization largely depends on the synthetic conditions like polarity of the medium; viscosity of the solvent used; and molecular substitutions on the azobenzene skeleton as these have very dramatic effects on the

In the literature, two possible mechanisms can be seen for the reversible photoisomerization of azobenzenes. First, the "inversion mechanism" (**Figure 1A**), proceeds via a linear transition state in which the N=N double bond remains undamaged, whereas the "rotation mechanism" (**Figure 1B**) occurs via a twisted transition state in which the N=N π-bond is broken. Extending the discussion, the trans form gets photoexcited, and an electron is excited from its ground state S0 orbital to its first or second singlet-excited state S1 or S2, retaining its spin under an n-π\* or a π-π\* excitation, respectively. Azo groups (N=N) photoisomerize via two distinct mechanisms: the π-π\* transition with an out-of-plane rotation mechanism in which the N=N π bond is ruptured heterolytically or the n-π\* electronic transition with an inversion

hybridized nitrogen atom through a *sp* hybridized linear transition state in

which the double bond is retained. The rate of inversion isomerization is relatively

spectra of the molecules and the kinetics of isomerization [40].

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

• Reduction of nitro compounds [39]

**2.1 Isomerization of Schiff bases**

• Conversion of α-amino acids into imines [38]


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


#### **2.1 Isomerization of Schiff bases**

*Stability and Applications of Coordination Compounds*

**2. Synthesis of Schiff bases and derivatives**

• Aldol-like condensation of aldehyde [31]

• Synthesis of ketimines from ketals [36]

• Reaction of metal amides [35]

metallic derivatives:

conditions [30]

The following routes are commonly adopted to prepare Schiff bases and their

• Reaction of aldehydes/ketones with primary amines under acidic/basic

• Oxidative synthesis of imines from alcohols and amines [32]

• Addition of organometallic reagents to cyanides [33] • Reaction of phenols and phenol-ethers with nitriles [34]

analgesic, and antipyretic agents [8–15].

antitumor, insecticidal, bacteriostatic, in vitro cytotoxic, anti-inflammatory,

On the other hand, abiological applications of Schiff bases and their metallic derivatives are also very diverse, for example, in polymer chemistry, mechanochemical treatment often leads to the destruction of polymer under investigation, while very recently, the concept of mechanochemical polymerization has seen remarkable improvements which was initially reported with limited success [16]. Schiff base reaction is responsible for visual process in animals; the process starts with excitation of retinaldehyde leading to the formation of Schiff linkage with lysine and change in the membrane electrical potential with eventual transmission of signal to brain [17]. Schiff bases have been exploited very efficiently to monitor hazardous materials in the environment; for example, Cr3+ and organophosphates in the environmental samples were recognized, quantified, and removed with high accuracy and precision [18]. Electroanalytical techniques are very helpful for studying laboratory, clinical, and environmental samples as these are versatile and economical; Schiff bases have been known as ionophores and when fabricated with organic polymers can be transformed into membranes as ion-selective potentiometric sensors [19]. Schiff base ZnO complexes have been investigated as semiconductors by fabricating field-effect transistors to electronic performance [20]. Azo dye-based Schiff bases have been reported efficient chemosensors for detection and quantification of S2<sup>−</sup> ions [21]. Photovoltaic characteristics of pyridine Schiff bases have been reported by illumination-dependent current–voltage measurements in solar cell applications [22]. Nickel Schiff base complexes have been studied for molecular docking experiments and their interaction with β-lactamase [23]. Schiff bases have successfully employed in vitro as well as in vivo for probing real-time sensing and analysis of Al3+ in a variety of diseases in human beings [24]. Polymeric Schiff bases strongly influence the electrochemical properties of the fuel cells and subsequent modification leading to an improved maximum power density in comparison to standard materials [25]. Metal–organic coordination polymers are widely used as conducting/semiconducting materials because of their accessible band gap 1–5 eV [26]. Schiff base palladium complexes immobilized on the mesoporous materials have been used as a heterogeneous catalyst for the Heck-Mizoroki coupling reaction and exhibited excellent catalytic activities for a wide range of alkenes [27, 28]. Schiff bases derived from cyclohexanediamine exhibited unusual structures, and these chiral molecules exhibited interesting photoluminescent properties [29].

**84**

Schiff bases tend to isomerize because of the imine group (C=N) to yield two stereoisomers *E* and *Z* (or *cis* and *trans*) isomers, and the formation of these stereoisomers can be controlled either kinetically or thermodynamically. Azobenzenes—common organic dyes—have been studied extensively owing to their potential applications in materials, medical, molecular switches, and other devices. Azobenzenes are photosensitive materials which undergo rapid reverse photoisomerization from the more stable *E* isomer to the less stable *Z* isomer. The exact mechanism of the *cis-trans* isomerization is not clear yet even after several decades of research. Reverse photoisomerization largely depends on the synthetic conditions like polarity of the medium; viscosity of the solvent used; and molecular substitutions on the azobenzene skeleton as these have very dramatic effects on the spectra of the molecules and the kinetics of isomerization [40].

In the literature, two possible mechanisms can be seen for the reversible photoisomerization of azobenzenes. First, the "inversion mechanism" (**Figure 1A**), proceeds via a linear transition state in which the N=N double bond remains undamaged, whereas the "rotation mechanism" (**Figure 1B**) occurs via a twisted transition state in which the N=N π-bond is broken. Extending the discussion, the trans form gets photoexcited, and an electron is excited from its ground state S0 orbital to its first or second singlet-excited state S1 or S2, retaining its spin under an n-π\* or a π-π\* excitation, respectively. Azo groups (N=N) photoisomerize via two distinct mechanisms: the π-π\* transition with an out-of-plane rotation mechanism in which the N=N π bond is ruptured heterolytically or the n-π\* electronic transition with an inversion of one *sp*<sup>2</sup> hybridized nitrogen atom through a *sp* hybridized linear transition state in which the double bond is retained. The rate of inversion isomerization is relatively

**Figure 1.** *Mechanisms of photoisomerization of azobenzenes.*

rapid and mostly independent of the medium's polarity or the nature of substituents on the azobenzene, but the rate for the rotation mechanism increases rapidly with increasing solvent polarity. During the photochemical studies of the unique properties of azobenzenes, considering the polarity of solvent effect of six different solvents, namely, cyclohexane, toluene, benzene, tetrahydrofuran, acetone, and 3-pentanol, on the kinetics of the *cis*-*trans* isomerization of 4-anilino-4′-nitroazobenzene using a camera flash and a UV–Vis spectrophotometer. The data obtained revealed that the rate of *cis*-*trans* interconversion is solvent dependent, while solvent polarity has no effect on the rate of isomerization going through inversion mechanism. This strong relationship between rate of reactions and polarity of solvent pointed to an intermediate transition state that is considerably more polar than the *cis* conformation. The increase in polarity of solvent resulted in an obvious decrease in the activation energy, entropy, enthalpy, and Gibbs free energy of activation for the *cis*-*trans* isomerization process, while structural changes and nature of substituents also played an important role in the isomerization mechanisms of azobenzenes [41].

More recently, thermal *cis*-*trans* isomerization with detailed spectral and kinetic data of 4-aminoazobenzene has been examined in a range of solvents of with varying polarities. Interestingly, unlike azobenzene, the rate of thermal isomerization of 4-aminoazobenzene is highly dependent on solvent polarity with marked increase in rates in polarity of solvents when compared to nonpolar solvents. Moreover, inversion is the preferred pathway in *cis*-*trans* thermal isomerization in a nonpolar medium; but, under polar conditions, the isomerization adopted a rotational behavior. The same study concluded that kinetics and the mechanism of thermal isomerization is controlled by the polarity of the medium [42–44].

Recently, effect of fluorine atom as substituent at either side of the double bond has also been thoroughly examined in a thermodynamic and kinetic perspective of *cis*-*trans* isomerization reactions. The work also comprehensively explained *cis effect* produced by cis-oriented fluorine atoms on opposite ends of the double bond. This substitution resulted in the fluorine-*cis* (*Z*) isomer being lower in energy than the *trans* contrary to conventional wisdom, in which steric interaction between *cis* substituents lead to *trans* isomer lower in energy. The following is a summary of the results. For CF3CF=CHF, the enthalpy of isomerization was measured from the equilibrium constant data as a function of temperature, and it was observed that the *Z* (*cis*) isomer was of lower energy than the *E* (*trans*) isomer, and "cis effect" of fluorine was very pronounced. In another case, *E* (*trans*) isomer was lower in energy than the *Z* (*cis*) because of the destabilizing steric interaction of the two relatively large groups. The measurement of the steric interaction between the CF3 groups in the case of *Z*-CF3CH=CHCF3 allowed a better interpretation of the measured *E*(*trans*) to *Z*(*cis*) enthalpy of isomerization than that already reported for CF3CF=CFCF3. The absolute rate constant of 2-butene's *cis* to *trans* isomerization is also reported; the activation energies of the *E* isomers when compared with that of *E*-2-butene showed that the uncoupling energy of the π-bond decreased with fluorine substitution across the double bond [45].

#### **3. Spectroscopic properties of Schiff bases**

UV–Visible spectroscopy is a very useful analytical tool for studying the spectral properties of Schiff bases generally obtained as mixture of geometrical isomers, their sensitivity to the solvent properties, effect of substitution, pH, ambient temperature, etc. Absorbance spectra are generally recorded in the range of 300–450 nm; and the spectra are strongly solvent dependent and the corresponding *E* or *Z* isomer. With isatin Schiff bases under consideration, *Z*(*cis*) isomer appeared at higher wavelengths, that is, of lower energy when compared with *E*(*trans*) at

**87**

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

In the IR spectra, C=N is most commonly reported in the 1690–1640 cm<sup>−</sup><sup>1</sup>

and the corresponding force constant, 10.6 dynes cm<sup>−</sup><sup>1</sup>

Generally, water of crystallization appeared at 3300 cm<sup>−</sup><sup>1</sup>

Multinuclear (1

varying isomeric compositions [47].

use of 1-D (1

as a strong and a sharp band at somewhat lower frequencies than the bands of C=O groups and close to C=C stretching frequencies. Angle strain, steric repulsion, and other complicated local factors and solution concentration and nature of solvent, in neutral solvents, the stretching frequency of C=N is found to be at 1670 cm<sup>−</sup><sup>1</sup>

tor approximation. The frequency is usually lowered in the absence of one or more groups in conjugation with the C=N. Generally, there is no difference between IR and Raman frequencies and between the spectra of pure liquids and solids and their solutions in common organic solvents CCl4 or other not very associative solvents.

NOESY) NMR spectral analyses are helpful to establish absolute configuration of isatin Schiff bases. For example, the chemical shifts were assigned by a combined

NOESY, HSQC, and HMBC). 2-D NOESY experiments were used assess solution conformation of Schiff bases; *E* (*trans*) stereochemistry was assigned as major isomer in DMSO-d*6* solutions. Signals of some protons considerably shifted upfield by approximately 1 ppm relative to the same signals in the parent isatin; in contrast, chemical shifts of the protons present in *Z* (*cis*) isomer showed no difference to those found in parent isatin. Similarly, the same analogy was applied to understand to the electronic influences of substituents like —NO2, and —OH and —OCH3 group showed only the presence of *E* (*trans*) isomer. In contrast, electron-donating groups enhanced the stability of *Z* (*cis*) isomer; these factors affected the physicochemical properties and lead to the differences in biological behaviors because of

H and 13C proton-decoupled and 2-D NMR experiments COSY,

Generally, in physical sciences and especially in chemistry, hydrogen bonding is one of the very important concepts for the deciding properties of the new materials. Intramolecular hydrogen bonds in ortho-hydroxyaryl Schiff bases, in orthohydroxyaryl ketones and amides, and in proton sponges and related compounds could be considered as classical objects for the investigation. The geometric and spectroscopic characteristics of the H-bonds that are typical for H-bonds are of medium strength, that is, it is shortened XY contact, elongated XH, directionality trend, change in frequency, and shielding and de-shielding. One of the most prominent aspects is the possibility of delocalization of proton leading to tautomers; and the existence of tautomer's equilibrium depends on room temperature, nature of solvent, and substitution. Proton delocalization is also observed due to the formation of stronger intramolecular H-bonds with larger proton potentials and due to thermally fluctuating media; either of these phenomena cause influence on the geometry of H-bond. Tautomeric equilibria changed with the change in the intrinsic geometry and spectroscopic properties of contributing tautomers, which further complicated the analysis of the experimental data. Computational work often provides the necessary insight via adiabatic and nonadiabatic PES calculations; and

H and 13C) and multidimensional (HSQC, HMBC, COSY, and

region

, is in the harmonic oscilla-

plus range [46].

,

lower wavelengths (higher energy); solvent-dependent electron density transfer was also observed, and the role of the position of substituent affected the appearance of frequency bands. Excited state was stabilized with a directional π-conjugative electron density shift in the molecule which might be a consequence of the longrange transmission of substituent effects, which supports the larger polarization of carbonyl group and thereby enhancing H-bonding capability of carbonyl oxygen and separation of electronic charges. Solvent affects are very complex phenomena, and the absorbance maxima altered inconsistently with respect to solvent and the position/type of the substituent(s) and geometrical features. In addition, other molecular properties like dipole moments, difference of electronegativity, partial charges, and chemical reactivity also significantly affected electronic spectra [46].

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

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

lower wavelengths (higher energy); solvent-dependent electron density transfer was also observed, and the role of the position of substituent affected the appearance of frequency bands. Excited state was stabilized with a directional π-conjugative electron density shift in the molecule which might be a consequence of the longrange transmission of substituent effects, which supports the larger polarization of carbonyl group and thereby enhancing H-bonding capability of carbonyl oxygen and separation of electronic charges. Solvent affects are very complex phenomena, and the absorbance maxima altered inconsistently with respect to solvent and the position/type of the substituent(s) and geometrical features. In addition, other molecular properties like dipole moments, difference of electronegativity, partial charges, and chemical reactivity also significantly affected electronic spectra [46]. In the IR spectra, C=N is most commonly reported in the 1690–1640 cm<sup>−</sup><sup>1</sup> region as a strong and a sharp band at somewhat lower frequencies than the bands of C=O groups and close to C=C stretching frequencies. Angle strain, steric repulsion, and other complicated local factors and solution concentration and nature of solvent, in neutral solvents, the stretching frequency of C=N is found to be at 1670 cm<sup>−</sup><sup>1</sup> , and the corresponding force constant, 10.6 dynes cm<sup>−</sup><sup>1</sup> , is in the harmonic oscillator approximation. The frequency is usually lowered in the absence of one or more groups in conjugation with the C=N. Generally, there is no difference between IR and Raman frequencies and between the spectra of pure liquids and solids and their solutions in common organic solvents CCl4 or other not very associative solvents. Generally, water of crystallization appeared at 3300 cm<sup>−</sup><sup>1</sup> plus range [46].

Multinuclear (1 H and 13C) and multidimensional (HSQC, HMBC, COSY, and NOESY) NMR spectral analyses are helpful to establish absolute configuration of isatin Schiff bases. For example, the chemical shifts were assigned by a combined use of 1-D (1 H and 13C proton-decoupled and 2-D NMR experiments COSY, NOESY, HSQC, and HMBC). 2-D NOESY experiments were used assess solution conformation of Schiff bases; *E* (*trans*) stereochemistry was assigned as major isomer in DMSO-d*6* solutions. Signals of some protons considerably shifted upfield by approximately 1 ppm relative to the same signals in the parent isatin; in contrast, chemical shifts of the protons present in *Z* (*cis*) isomer showed no difference to those found in parent isatin. Similarly, the same analogy was applied to understand to the electronic influences of substituents like —NO2, and —OH and —OCH3 group showed only the presence of *E* (*trans*) isomer. In contrast, electron-donating groups enhanced the stability of *Z* (*cis*) isomer; these factors affected the physicochemical properties and lead to the differences in biological behaviors because of varying isomeric compositions [47].

Generally, in physical sciences and especially in chemistry, hydrogen bonding is one of the very important concepts for the deciding properties of the new materials. Intramolecular hydrogen bonds in ortho-hydroxyaryl Schiff bases, in orthohydroxyaryl ketones and amides, and in proton sponges and related compounds could be considered as classical objects for the investigation. The geometric and spectroscopic characteristics of the H-bonds that are typical for H-bonds are of medium strength, that is, it is shortened XY contact, elongated XH, directionality trend, change in frequency, and shielding and de-shielding. One of the most prominent aspects is the possibility of delocalization of proton leading to tautomers; and the existence of tautomer's equilibrium depends on room temperature, nature of solvent, and substitution. Proton delocalization is also observed due to the formation of stronger intramolecular H-bonds with larger proton potentials and due to thermally fluctuating media; either of these phenomena cause influence on the geometry of H-bond. Tautomeric equilibria changed with the change in the intrinsic geometry and spectroscopic properties of contributing tautomers, which further complicated the analysis of the experimental data. Computational work often provides the necessary insight via adiabatic and nonadiabatic PES calculations; and

*Stability and Applications of Coordination Compounds*

role in the isomerization mechanisms of azobenzenes [41].

isomerization is controlled by the polarity of the medium [42–44].

fluorine substitution across the double bond [45].

**3. Spectroscopic properties of Schiff bases**

rapid and mostly independent of the medium's polarity or the nature of substituents on the azobenzene, but the rate for the rotation mechanism increases rapidly with increasing solvent polarity. During the photochemical studies of the unique properties of azobenzenes, considering the polarity of solvent effect of six different solvents, namely, cyclohexane, toluene, benzene, tetrahydrofuran, acetone, and 3-pentanol, on the kinetics of the *cis*-*trans* isomerization of 4-anilino-4′-nitroazobenzene using a camera flash and a UV–Vis spectrophotometer. The data obtained revealed that the rate of *cis*-*trans* interconversion is solvent dependent, while solvent polarity has no effect on the rate of isomerization going through inversion mechanism. This strong relationship between rate of reactions and polarity of solvent pointed to an intermediate transition state that is considerably more polar than the *cis* conformation. The increase in polarity of solvent resulted in an obvious decrease in the activation energy, entropy, enthalpy, and Gibbs free energy of activation for the *cis*-*trans* isomerization process, while structural changes and nature of substituents also played an important

More recently, thermal *cis*-*trans* isomerization with detailed spectral and kinetic data of 4-aminoazobenzene has been examined in a range of solvents of with varying polarities. Interestingly, unlike azobenzene, the rate of thermal isomerization of 4-aminoazobenzene is highly dependent on solvent polarity with marked increase in rates in polarity of solvents when compared to nonpolar solvents. Moreover, inversion is the preferred pathway in *cis*-*trans* thermal isomerization in a nonpolar medium; but, under polar conditions, the isomerization adopted a rotational behavior. The same study concluded that kinetics and the mechanism of thermal

Recently, effect of fluorine atom as substituent at either side of the double bond has also been thoroughly examined in a thermodynamic and kinetic perspective of *cis*-*trans* isomerization reactions. The work also comprehensively explained *cis effect* produced by cis-oriented fluorine atoms on opposite ends of the double bond. This substitution resulted in the fluorine-*cis* (*Z*) isomer being lower in energy than the *trans* contrary to conventional wisdom, in which steric interaction between *cis* substituents lead to *trans* isomer lower in energy. The following is a summary of the results. For CF3CF=CHF, the enthalpy of isomerization was measured from the equilibrium constant data as a function of temperature, and it was observed that the *Z* (*cis*) isomer was of lower energy than the *E* (*trans*) isomer, and "cis effect" of fluorine was very pronounced. In another case, *E* (*trans*) isomer was lower in energy than the *Z* (*cis*) because of the destabilizing steric interaction of the two relatively large groups. The measurement of the steric interaction between the CF3 groups in the case of *Z*-CF3CH=CHCF3 allowed a better interpretation of the measured *E*(*trans*) to *Z*(*cis*) enthalpy of isomerization than that already reported for CF3CF=CFCF3. The absolute rate constant of 2-butene's *cis* to *trans* isomerization is also reported; the activation energies of the *E* isomers when compared with that of *E*-2-butene showed that the uncoupling energy of the π-bond decreased with

UV–Visible spectroscopy is a very useful analytical tool for studying the spectral properties of Schiff bases generally obtained as mixture of geometrical isomers, their sensitivity to the solvent properties, effect of substitution, pH, ambient temperature, etc. Absorbance spectra are generally recorded in the range of

300–450 nm; and the spectra are strongly solvent dependent and the corresponding *E* or *Z* isomer. With isatin Schiff bases under consideration, *Z*(*cis*) isomer appeared at higher wavelengths, that is, of lower energy when compared with *E*(*trans*) at

**86**

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

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

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

#### **Figure 2.**

*Epoxidation of olefin using a polyhedral oligomeric silsesquioxane (POSS)-bridged oxo-molybdenum Schiff base complex [49–51].*

**89**

**Figure 3.**

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

bond coupling of carbonyl groups and nitro alkanes to generate organic intermediate natural products, drugs, and dyes. Schiff base Cu complex exhibited a very high enantioselectivity but limited to 2-nitrobenzaldehyde; also, Cu complexes of iminopyridines catalyzed reactions of nitromethane with aliphatic and aromatic aldehydes. Cu complexes of salen Schiff bases improved the chiral induction of Henry's reaction (yield: 95%); the m- and p-substituted benzaldehydes required

**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

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

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

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

lower temperatures and inert conditions [49–51].

the lipoic membrane (**Figure 3**) [53–55].

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

the treatment of infections caused by any of these strains [52].

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

bond coupling of carbonyl groups and nitro alkanes to generate organic intermediate natural products, drugs, and dyes. Schiff base Cu complex exhibited a very high enantioselectivity but limited to 2-nitrobenzaldehyde; also, Cu complexes of iminopyridines catalyzed reactions of nitromethane with aliphatic and aromatic aldehydes. Cu complexes of salen Schiff bases improved the chiral induction of Henry's reaction (yield: 95%); the m- and p-substituted benzaldehydes required lower temperatures and inert conditions [49–51].
