1998 onwards, a span reporting thousands of research articles describes the ever-increasing applicability of Schiff bases and their metallic complexes; this chapter comprehensively examines the literature of the last 20 years. The structural diversity of these molecules made them available for a very wide range of biological and abiological applications. Schiff bases are excellent chelators and due to this unique property have found their place in qualitative and quantitative determination of metals in aqueous media. The structural diversity of metal chelates proved these to be outstanding catalysts and displayed interesting fluorescence effect. Finally, Schiff base moieties have found a unique position during the in vitro and in vivo experiments for drug development against a huge number of biological entities including bacteria, fungi, cancer cells, viruses, parasites, etc.
- electronic and vibrational spectra
Even Hugo Schiff might not know while publishing his research findings as a scientific communication some 155 years ago that these organic compounds would become an independent area of immense interest not only in chemistry but also in other areas of scientific domains including physical, materials, biological, and engineering [1, 2]. Simply, Schiff bases can be defined as the products of chemical reaction of a primary amine with an aldehyde or a ketone under a given set of conditions. Structurally, oxygen of the carbonyl functionality (C═O) in an aldehyde and/or a ketone is replaced with nitrogen leading to the formation of imine or azomethine or anilino or azimethine (C═N) functionality with the liberation of a water molecule which is characteristic of Schiff bases . There has been a substantial increase to study the coordination of the Schiff bases to the transition metals as well as main group metals and main group organometallics. The aforementioned metallic derivatives of Schiff bases have shown a rich diversity of structural motifs based upon coordinating ability of the ligand under investigation [4, 5, 6, 7].
Schiff bases and their metallic derivatives have got outstanding applicability in biological systems acting as antibacterial, antifungal, antiviral, antitubercular, antitumor, insecticidal, bacteriostatic, in vitro cytotoxic, anti-inflammatory, analgesic, and antipyretic agents [8, 9, 10, 11, 12, 13, 14, 15].
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 . 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 . 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 . 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 . Schiff base ZnO complexes have been investigated as semiconductors by fabricating field-effect transistors to electronic performance . Azo dye-based Schiff bases have been reported efficient chemosensors for detection and quantification of S2− ions . Photovoltaic characteristics of pyridine Schiff bases have been reported by illumination-dependent current–voltage measurements in solar cell applications . Nickel Schiff base complexes have been studied for molecular docking experiments and their interaction with β-lactamase . 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 . 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 . Metal–organic coordination polymers are widely used as conducting/semiconducting materials because of their accessible band gap 1–5 eV . 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 .
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 
Aldol-like condensation of aldehyde 
Oxidative synthesis of imines from alcohols and amines 
Addition of organometallic reagents to cyanides 
Reaction of phenols and phenol-ethers with nitriles 
Reaction of metal amides 
Synthesis of ketimines from ketals 
Reaction of olefins and tertiary alcohols with hydrazoic acid 
Conversion of α-amino acids into imines 
Reduction of nitro compounds 
2.1 Isomerization of Schiff bases
Schiff bases tend to isomerize because of the imine group (C=N) to yield two stereoisomers
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
More recently, 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
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
Multinuclear (1H 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 (1H 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;
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 ortho-hydroxyaryl 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 lastly, stabilization is also achieved due to delocalization of electrons in the chelate systems which are defined as resonance-assisted hydrogen bonds (RAHB) .
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 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, 50, 51].
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
Platinum complexes of salicylaldehyde and 2-furaldehyde Schiff base with o- and p-phenylenediamine were screened against
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
Schiff base metal complexes conjugated with oligonucleotides were used to inhibit antitumor effect; zinc fingers are small protein motifs consisting of finger-like 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, 60, 61, 62, 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) .
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 .
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 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,
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 .
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.