Significant Aspects of Heterocyclic Schiff Bases and Their Metal Complexes

Abstract

Schiff bases are useful precursors for the synthesis of vital pharmaceutical and biochemical compounds due to their multifunctional transformations through different processes. Indeed, the heterocyclic Schiff bases have played a unique role in coordination chemistry owing to their wide-ranging potential bio-applications, such as anticancer, antibacterial, antifungal, etc. The exploration of novel heterocyclic Schiff bases and their metal complexes has certainly been progressing because of their proven usefulness as attractive key structures for the development not only in the field of biology but also in the field of catalysis, sensing, corrosion inhibitors, etc. The unusual characteristics of heterocyclic Schiff bases have resulted in many scopes, making significant advances from both the fundamental and applied perspectives.

1. Introduction

The discovery of Schiff base, more than one and a half century ago, has significantly stimulated chemical research, and has provided a crucial impetus for founding as well as rapidly expanding the domain of coordination chemistry that has persisted at a quick pace until now. Over the decades of intensive research, the Schiff base unit has been distinguished as a great versatile plinth for ligand design and complex synthesis in order to have their wonderful applications not only in the therapeutic but also in the catalysis and other fields. Schiff base ligands hold a privileged rank in the sphere of metal-ligand complex chemistry due to their characteristic advantage in synthesis. In fact, the Schiff base is a unique class of compounds that basically contain at least a moiety of imine (azomethine, −CH〓N− and ketimine, >C〓N−), generated by the condensation reactions between active carbonyl groups either from aldehyde or from ketone and primary amine compounds, wherein the nitrogen atom is bonded to an alkyl or aryl group (Figure 1) [1]. Thus, the common structural feature of Schiff bases is an imine group. Imine nitrogen is sp² hybridized and does contain a lone pair of electrons providing considerable biological and chemical significances. The mechanism of Schiff base generation involves the attack of lone pair of electrons present on the nitrogen in primary amine (nucleophile) at the carbonyl carbon (electrophilic site) forming a tetrahedral intermediate. Subsequently, this process liberates water molecule and produces the imine group, irrespective of the methods or routes employed.

Figure 1.

A typical reaction scheme showing the generation of Schiff base.

Schiff bases involving heterocyclic rings show several advantages due to the presence of more donor atoms, such as nitrogen (N), oxygen (O), and sulfur (S), and exhibit a vital role in coordination chemistry. However, among various heterocyclic molecules, nitrogen containing heterocycles have emerged as essential entities in the realm of medicinal chemistry. For instance, the benzimidazole and its derivatives represent groups of imperative chromophores with desirable medicinal properties and have dragged lots of attention in modern drug discovery [2, 3, 4]. As reported, the Schiff bases with benzimidazole moiety are extremely sensitive toward many human pathogens and microbial agents. Properties like antioxidant, antitumor, analgesic, anti-inflammatory, anticancer, and inhibitory are also their key functions [5]. Indole-derived Schiff bases have demonstrated extensive biological properties with anticancer, antitumor, and antimicrobial activities [6]. Such wide applications of heterocyclic Schiff bases (HSBs) are obviously rooted in the exclusive combination of the properties of the heterocyclic moiety, which exhibits a high degree of chemical stability but is amenable to several synthetic modifications.

One of the best abilities of almost all Schiff bases is to form strong complexes with metal ions. The formation of complex takes place owing to the coordination of donor atoms (mostly N, O, and S) through their unshared pair of electrons to the valence shell of metal ion, which in turn serves for alteration of electronic and steric surrounding of the metal center. Unlike reactive ligands, coordinated Schiff bases generally do not undergo irreversible transformations while modulating the reactivity of the metal ion at the core of the complex, and hence, these are called auxiliary ligands. Literature shows that Schiff base-derived metal complexes have played a promising role as drugs. The phenomenal pharmacological properties of HSBs have encouraged Schiff base complexation to a different level. HSB complexes have striking biological activities that include anticancer, antibacterial, antifungal, antimalarial, anti-inflammatory, antiproliferative, and antipyretic [7]. In addition, there are so many HSB complexes that exhibit excellent catalytic activity due to their exceptional stabilities. These versatile applications of HSBs and their metal complexes are undoubtedly attributed to their remarkable structural features, and some of the important applications have been discussed in this chapter.

2. Types of heterocyclic Schiff bases

The rewarding properties of Schiff bases are not restricted to a common integral feature of imine bond, rather they include the type of substituents present on its either side. The properties of Schiff bases can significantly be enhanced by modifying structurally with numerous scaffolds such as heterocyclic and substituted heterocyclic compounds on either or both sides of the imine unit. Although the conventional classification of Schiff base ligands is inherently dedicated to their denticities, here we have categorized HSBs into three types, such as Type-I, Type-II, and Type-III, depending on the presence of heterocyclic moiety(ies) around imine bond (Figure 2).

Figure 2.

Schematic representation of types of HSBs.

These HSBs could be obtained by different combinations of active carbonyls (aldehydes/ketones) with primary amines. For example, condensing heterocyclic carbonyl with non-heterocyclic amine or non-heterocyclic carbonyl with heterocyclic amine or heterocyclic carbonyl with heterocyclic amine offers Type-I, Type-II, and Type-III HSBs, respectively, or it could be achieved by the modifications of non-heterocyclic Schiff bases with the incorporation of heterocycle(s). The discussion pertaining to this chapter will purely be focused on the HSBs and related metal complexes containing at least one heterocyclic unit on either side of the imine group. Quite a few structural representations of HSBs (1–15) and some of their complexes (16–24) are shown in Figure 3.

Figure 3.

Some examples of different types of HSBs 1–15 and complexes 16–24.

3. Applications of heterocyclic Schiff bases and related complexes

Over the last decades, HSBs and their metal complexes find applications in versatile fields, such as biology, catalysis, and other industrial sectors. The goal of this chapter is to put forth a critical evaluation of these compounds taking into account current trends, the adaptability of Schiff bases with different heterocyclic moieties, and potential future research dimensions. Here, the applications of HSBs and their related metal complexes have been emphasized mostly on three crucial aspects, namely, anticancer activity, antimicrobial activity, and catalytic activity. Apart from this, a miscellaneous application section has been incorporated which basically provides a glimpse of other applicational diversities of HSBs or HSB-derived metal complexes.

3.1 Anticancer activity

Cancer is considered one of the lethal diseases after the cardiovascular disease. This is caused owing to the abnormal and uncontrolled cell growth. Continuous studies in the last few decades and development of pertinent drugs have raised hope to curb the cancer. It has been observed that indole containing alkaloids, such as vinblastine, vincristine, vinorelbine, and vindesine, are used as anticancer agents, due to their ability to interact with various receptors. However, several Schiff bases that contain indole moiety(ies) are explored to possess the properties of anticancer against different types of cancer cells. Ghaidan et al. synthesized a series of HSBs (25–27) containing indole units (Figure 4), and these bases were found to be very effective for the inhibition of AMJ13 breast cancer cells while bringing no damage to normal cell growth [8]. Among these, dimethyl-substituted Schiff base 27 exhibits better activity even at its lesser dose of 10 μg/mL, inhibiting 60% after 72 h of exposure, and giving a scope for the researchers to reconsider it as an anticancer drug.

Figure 4.

Indole-derived HSBs.

The ability of indole-based Schiff bases as active anticancer agents has been exploited by Trivedi et al. while they synthesized quite a few numbers of 3-substituted indole Schiff base derivatives consuming N-substituted indole-3-carboxaldehyde and substituted hydrazide (Figure 5) [9]. The anticancer activities of these compounds were tested against the A549 cell line (lung cancer) using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and showed moderate to excellent anticancer activity in comparison to the Osimertinib, a commercially available anticancer drug to treat lung cancer. Interestingly, the presence of furan ring in the Schiff base has produced better and remarkable results over other derivatives along with Osimertinib [9]. Thus, substituting suitable heterocycles for the R-group generates improved results than those obtained with non-heterocycles, signifying the importance of the heterocycles in the development of anticancer drugs.

Figure 5.

Structure of indole-based Schiff base derivatives with various ‘R’ substituents.

Indole-3-carbaldehyde thiosemicarbazone-derived palladium complexes 28–34 (Figure 6) were synthesized by Haribabu et al. [10]. The anticancer activities of these metal complexes were evaluated against HepG2, A549, and MCF7 cell lines using MTT assay, and were found to have good activity against HepG2 cells. However, the complexes 31 and 32 exhibit potential cell killing. Al-Shemary et al. have found the possible anticancer activities of triazole-derived Schiff base and its transition metal complexes (Co, Ni, Cu, and Zn) against quite a few human cancerous cell lines, such as HepG2 liver cancer, HCT116 colorectal cancer, A549 lung carcinoma, and MCF-7 breast cancer cell lines, taking doxorubicin as the standard [11]. Of all complexes, when compared to untreated, the Zn(II) complex displayed significant activity for inhibiting the growth of HepG2, HCT116, A549, and MCF7 cell lines by a factor of 88, 70, 75, and 70, respectively. Numerous studies have been conducted in an effort to find out the improved anticancer activities of HSBs containing varied heterocycles and their several metal complexes [12, 13, 14, 15, 16, 17, 18].

Figure 6.

Structure of indole-3-carbaldehyde thiosemicarbazone-derived palladium complexes.

A series of Cu(II) complexes were obtained from N-alkyl-substituted benzimidazole-based Schiff bases and investigated for their anticancer activities against lung (A-549), breast (MDA-MB-231), and cervical (HeLa) cancer cell lines [19]. In vitro cytotoxicity results revealed that the complexes act as effective drug candidates against these cancer cell lines in contrast to the usually used cisplatin. A typical series of Ruthenium(II) (Ru(II)) arene HSB complexes were synthesized and assessed for their anticancer activities [20]. These complexes exhibited significant cytotoxic effects on several cancer cell lines, relying on their structure and the presence of diverse hydrophobic moieties. Furthermore, the condensation reaction between 3-(2-aminoethylamino)quinoxalin-2(1H)-one and o-vanillin resulted in the formation of quinoxalinedione-tethered Schiff base ligand, and this ligand was reacted with different metal ions, such as Cu(II), Ni(II), Co(II), and Zn(II), to form respective metal chelate complexes [21]. Upon evaluation of their anticancer properties against a human cervical cancer cell line (HeLa), it was revealed that the metal chelates perform as potential anticancer agents compared to their ligand systems.

3.2 Antimicrobial activity

The possibility of increasing mortality due to infectious diseases arises when the bacteria have multiple resistances to antibiotics. Since most of the bacteria have already adopted the situation that an antibacterial drug generates within the body, the effectiveness of the drugs against bacteria has relatively gone down. As a result, the research and development of more effective novel antibacterial drugs are undoubtedly an urgent therapeutic need [22]. In this context, Schiff base compounds have emerged as promising antibacterial agents, and their antimicrobial properties could be enhanced by metal complexations. The reason for the improved efficacy of metal complexes can be described with the help of Overtone’s concept and Tweedy’s chelation theory [23, 24]. According to Overtone’s concept of cell permeability, the lipid membrane of the cell basically favors the passage of merely the lipid soluble constituents as liposolubility is a significant factor, which controls the activity. On chelation, the polarity of the metal ion gets reduced largely through the delocalization of electrons over chelate ring and the partial sharing of positive charge upon metal ion with donor groups, thereby enhancing the lipophilicity of the complexes. Thus, the increased lipophilicity helps metal complex to enter into the lipid membrane easily (a schematic representation is given in Figure 7) and restricts further multiplication of microorganisms by blocking metal-binding sites of concerned enzymes [25, 26].

Figure 7.

Schematic representation of easy passage of metal complexes into the bacterial lipid membrane after enhanced lipophilicity of metal complexes upon chelation.

Shanty et al. synthesized a series of HSBs and investigated their antibacterial activities against Salmonella typhi, Bacillus coagulans, Bacillus pumilus, Escherichia coli, Bacillus circulans, Pseudomonas, Clostridium, and Klebsiella pneumoniae [27]. All compounds exhibited low to moderate cytotoxic effect, except in the case of Escherichia coli. Singh et al. prepared a variety of Zn(II) complexes (35–46) (Figure 8) with HSBs derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole and 2-hydroxyacetophenone/benzaldehyde/indoline-2,3-dione components [28]. They measured the antimicrobial properties of these compounds against bacteria (Bacillus subtilis and Escherichia coli) and fungi (Colletotrichum falcatum, Aspergillus niger, Fusarium oxysporum, and Curvularia pallescens). While antibacterial activity was measured in three respects (percentage growth inhibition, minimum inhibitory concentration, and zone of inhibition), the antifungal activity was measured only in terms of percentage growth inhibition. It revealed that, in contrast to corresponding Schiff bases, their Zn(II) complexes exhibit significantly higher antimicrobial activities. They also observed that both antibacterial and antifungal activities are enhanced with increasing chelation. The 2-chloro-substituted compounds display more activity than other substituted compounds. The compound 44 was found to be more active against all bacteria and fungi, possibly due to the presence of an additional heterocyclic ring (indoline-2,3-dione). Thus, the structure-property relationship of the ligands revealed that the additional indoline-2,3-dione ring significantly increases the pharmacological potency of Zn(II) complex 44 making it more active against both bacteria. In particular, the zone of inhibition measurement corresponding to Bacillus subtilis revealed that complex 44 has almost same zone (19 mm) of the standard drug streptomycin (20 mm) [28].

Figure 8.

Zn(II) complexes (35–46) with HSBs derived from 2-hydrazino-5-[substituted phenyl]-1,3,4-thiadiazole and benzaldehyde/2-hydroxyacetophenone/indoline-2,3-dione.

With an aim to explore the impact of ligand chelation with metal atoms, Karekal et al. synthesized a biologically dynamic HSB 47 from the reaction of 5-chloro-3-phenyl-1H-indole-2-carboxyhydrazide with 3-formyl-2-hydroxy-1H-quinoline, and the obtained Schiff base was complexed with Cu(II), Co(II), Ni(II), Zn(II), Cd(II), and Hg(II) ions with their proper characterizations (Figure 9) [29]. Antibacterial and antifungal properties of these complexes 48–53 were studied by checking their minimum inhibitory concentration (MIC). The MIC values were found to be in the ranges of 12.50–75 μg mL⁻¹ and 12.50–50 μg mL⁻¹ for bacterial and fungal species, respectively. The antimicrobial activity of the HSB 47 is enhanced upon complexation with metal ions mostly Cu(II), Co(II), and Ni(II), and establishing themselves essential for the growth-inhibitor effect [29].

Figure 9.

Structure of hydrazone-type ligand 47 and its bioactive metal complexes 48–53.

Heterocyclic Schiff bases (HSBs) derived from 3-amino-2-methyl-4(3H)-quinazolinone and substituted aldehydes were combined with Pd(II) ions to get novel mononuclear Pd(II) complexes. All the ligands and their Pd(II) complexes were found to exhibit promising activity against the bacterial species, such as B. subtilis, Staphylococcus aureus, and E. coli [30]. Triazole-derived different HSB ligands 54–56 (Figure 10) were synthesized by the condensation reaction of 3-amino-1H-1,2,4-triazole with pyrrole-2-carboxaldehyde, 4-bromothiophene-2-carboxaldehyde, and 5-iodo-2-hydroxybenzaldehyde, respectively. All these ligands were reacted with Co(II), Ni(II), Cu(II), and Zn(II) ions to generate corresponding metal complexes 57–68 (Figure 10) [31]. The ligands showed varying degrees of inhibitory effects, with 54 displaying considerable activity (66% inhibition as determined by MIC). However, upon antimicrobial evaluation against four different Gram-negative, i.e., E. coli, Shigella sonnei, Pseudomonas aeruginosa, and Salmonella typhi, and two Gram-positive, i.e., B. subtilis and S. aureus bacterial species, metal complexes 58, 62, 64, 66, 67, and 68 showed effectual activity (54–82%) against all experimental bacterial strains [31]. In addition, the agar-well diffusion method was used to realize the antifungal activity of metal complexes against fungal species, i.e., Candida albicans, Trichophyton longifusus, Microsporum canis, Aspergillus flavus, Fusarium solani, and Candida glabrata [31]. The metal complexes showed significant activity, as evidenced by their higher zones of inhibition with respect to their parent ligands. In particular, the complex 58 exhibited effective activity with 73% inhibition against C. glabrata.

Figure 10.

Molecular structures of triazole-derived HSBs 54–56 and their metal complexes 57–68.

Ali et al. synthesized a number of chitosan-based Schiff bases by reacting different heterocyclic compounds, namely, 1,3-dimethyl-2,4,6-trioxohexahydropyrimidine-5-carbaldehyde, 3-acetyl-2H-chromen-2-one, 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, and 4-oxo-4H-chromene-3-carbaldehyde, with chitosan using two different approaches, namely, ultrasound and thermal [32]. These Schiff bases display thermal stability more than pure chitosan. While testing their antimicrobial activities against Gram-positive (S. aureus and Enterococcus faecalis) and Gram-negative (E. coli and Salmonella typhimurium bacteria, it showed an interesting fact that the Schiff base obtained through ultrasound method exhibited a greater degree of antimicrobial activity over the Schiff base produced through the thermal approach. The in vitro antimicrobial properties of the heteroleptic metal complexes containing HSB moiety were also studied by Casanova et al. [33]. Antimicrobial studies of metal (Cd and Ni) complexes display significantly higher selectivity against common Gram-positive bacteria.

3.3 Catalytic activity

Schiff bases act as potential catalysts for various organic and inorganic transformations with enhanced yields and product selectivity. The unique aspects, such as facile synthesis, structural diversity, and thermal stability, have made Schiff base ligands as well as their metal complexes more suitable for catalytic applications even in the high temperature processes, for which these ligands are extensively studied. Zhang et al. explored the ring-opening polymerization of ε-caprolactone to polycaprolactone using neodymium complex as single component catalyst that contains an aromatic HSB containing thiazole unit (Figure 11). The conversion of ε-caprolactone monomer was found to be as high as 94% after being polymerized for 1 hour. As investigated, the polymerization of ε-caprolactone is accompanied by a coordination anionic mechanism that involves ring opening via acyl-oxygen bond cleavage [34].

Figure 11.

Ring-opening polymerization of ε-caprolactone using HSB neodymium complex as catalyst.

One of the important reactions that find excessive applications in chemical industry is the hydrogenation of aromatic compounds. In particular, the conversion of benzene to cyclohexene is of great value in the industry, because the cyclohexene is used as a precursor for the formation of adipic acid and caprolactam, and both are found to have been used as intermediates in the synthesis of Nylon 6 and Nylon 66 [35, 36]. In contrast to simple olefins, the catalytic reduction of benzene requires more severe conditions. Arun et al. prepared two HSB metal complexes 69 and 70, and both the complexes were shown to be catalytically excellent toward the hydrogenation of benzene (Figure 12) [37]. Compared to 69, the catalyst 70 gives a higher conversion rate under identical experimental conditions. Interestingly, the catalyst 70 is more selective toward cyclohexane, while the catalyst 69 is more selective for cyclohexene.

Figure 12.

Hydrogenation of benzene using HSB metal complexes as catalyst.

A unique class of ligands, which revolutionized the field of homogeneous catalysis, is N-heterocyclic carbene (NHC). This is because, NHCs are very good σ-donor ligands and have proven to be good stabilizing ligands to a wide variety of metal ions. These ligands serve as reliable alternatives to traditional ligands, namely, amines and phosphines [38]. Exploiting the unique electron-donating properties of NHC, Abubakar et al. synthesized a trinuclear Ni(II) complex that contains a NHC functionalized Schiff base. This particular complex was found to have excellent catalytic property in the transfer hydrogenation reaction of a range of aromatic and aliphatic ketones (Figure 13), at a very low catalyst concentration of 0.1 mol% [38]. As revealed, there were quantitative conversions of aromatic ketones to corresponding alcohols in the presence of isopropyl alcohol, and these values were found to be similar to the values obtained by means of a more expensive Ru-complex catalyst containing no heterocyclic moieties at a concentration of 0.25 mol% [39].

Figure 13.

Catalytic transfer hydrogenation of ketones to corresponding alcohols.

It has been observed that half-sandwich Ru-complexes play an important role as catalysts in the synthesis of valuable organic compounds. In particular, half-sandwich Ru-complexes containing HSB ligands with oxygen-nitrogen donor centers effectively catalyze the transfer hydrogenation of a wide range of ketones. Several half-sandwich Ru-complexes (71–76) bearing HSB ligands, which in turn are being used as catalysts for transfer hydrogenation of ketones, are shown in Figure 14 [40, 41].

Figure 14.

Molecular structures of half-sandwich Ru-complexes 71–76 bearing HSB ligands.

The compound p-aminophenol is quite useful and has industrial importance due to its extensive applications in different fields, such as making antipyretic and analgesic drugs, corrosion inhibitors, hair-dyeing agents, photographic developers, and anticorrosion lubricants [42]. Recently, two Ni(II) complexes with a pyrazole-based HSB ligand have been reported by Mandal et al. [43], and both the complexes were found to be remarkably capable of converting p-nitrophenol to p-aminophenol in the presence of sodium borohydride as reducing agent. Santa Barbara Amorphous No. 15 (SBA-15) is an interesting mesoporous silica material, and it exhibits promising catalytic activity for wider applications having unique properties of highly ordered mesopores, thick wall, hydrothermal stability, large surface area, and enormous pore volumes [44]. Since it lacks functionality, heteroatoms and organic functional groups can be introduced, either by direct or by post-synthesis methods to modify its functionality, thereby enhancing the catalytic activity [45]. In view of this, Yari et al. prepared SBA-15-supported cobalt complex as a novel heterogeneous nanocatalyst comprising N–O chelating HSB ligand [46]. Initially, they synthesized HSB by reacting pyridoxal 5′-phosphate or PLP (biologically active form of vitamin B₆) with 3-(aminopropyl)-triethoxysilane, and complexed with Co(II) ion, which on subsequent grafting to SBA-15 afforded Co(II)-PLP-HSB/SBA-15 nanocatalyst. This particular nanocatalyst is suitable for the synthesis of several benzothiazole heterocycles (77–92) by the cyclo-condensation of aryl-aldehydes with 2-aminothiophenol having yields good to excellent under green conditions [46]. The catalyst is active, stable, and can be reused without leaching of metal ions into the reaction medium (Figure 15).

Figure 15.

Preparation of benzothiazole heterocycles using Co(II)-PLP-HSB/SBA-15 nanocatalyst.

3.4 Miscellaneous applications

In addition to the applications mentioned at earlier sections, HSBs and their related metal complexes also find their uses in other fields, and a few instances are described here in brief. By and large, the most extensively used forms of energy derived from nonrenewable sources include coal, natural gas, and petroleum, and in fact, these sources of energy become key factors of environmental pollution creating an unhealthy atmosphere for natural habitats. In such a scenario, it is crucial to find alternate eco-friendly sources of energy which will be capable of producing adequate power to meet the world’s energy crisis. Thus, solar energy is considered one of the sensible choices, and for this, solar cell or photovoltaic cell acts as a unique device that converts sun’s light energy into electrical energy. Researchers have been continuously putting their utmost effort to improve the efficiency of a solar cell, and the use of HSB compounds has played a great role in this regard. For example, Chen et al. synthesized polymeric HSB with thiophene units, and the polymer was employed as an active layer for polymer solar cell devices. The conductivity of polymers was substantially improved under natural light condition, indicating the possession of photoelectric conversion efficiency with a potential in conjugated polymer photovoltaic materials [47]. Quinoline-derived Schiff base and its chromium complex were synthesized by Salman et al., and both were used to make nano-films on Si layer via drop casting technique [48]. The accrued efficiency of the fabricated inorganic silicon solar cell was found to be higher than that of the organic solar cell. Similarly, the pyrazole-derived HSB ligand and its nickel complex were utilized to make the thin films for improving the solar cell efficiency [49]. Interestingly, the asymmetric fluorescence benzimidazole complexes were obtained from the half-condensed asymmetrical HSB ligand, [N¹-((quinoline-2-yl) methylene) N²-(H-(quinoline-2-yl) methylenehydroxy)o-phenylenediamine], by means of a metal(II)-induced method [50]. These complexes were used as cosensitizers in dye-sensitized solar cell to enhance its performance.

Benzanthrone is a polycyclic aromatic hydrocarbon and its derivatives find multiple useful applications in the chemical industry. Orlova et al. synthesized novel benzanthrone azomethines by condensing 3-aminobenzanthrone with a series of heterocyclic aldehydes [51]. The obtained benzanthrone derivatives were reduced to corresponding thermally stable amines with higher luminescence efficiency. These compounds absorb light at 420–525 nm with quite large Stokes shifts and emit at 500–660 nm. Pertinent results suggested that the emission is sensitive to the polarity of solvent exhibiting negative fluorosolvatochromism for azomethines and positive fluorosolvatochromism for reduced azomethines [51]. The high fluorescence in the red region intensifies the possibilities of practical application of the prepared amines that are promising as luminescent dyes.

Corrosion inhibitors are very indispensable for protecting metals from destructive chemical reactions that occurred in the presence of moisture, humidity, and acidic conditions [52, 53]. Generally, inhibitors possessing increased basicity centers, such as N, O, and S, unsaturated bonds, and planar-conjugated aromatic compounds are endorsed as active corrosion inhibitors [54, 55]. Because of the presence of the imine bond, the use of Schiff bases as corrosion inhibitors in metals and alloys has been the major motivation [56, 57]. Boulechfar et al. synthesized 2-furaldehyde semicarbazone HSB metal complexes of Mn(II), Co(II), and Zn(II), and the corrosion inhibitions of these complexes against the XC38 carbon steel were evaluated in 1 M hydrochloric acid (HCl) [58]. Among these complexes, Mn-complex was found to have the highest inhibitory effect at around 91%. These findings are highly important in demonstrating the effectiveness of the HSB-based metallic complex inhibitors in protecting the surfaces of metals, storage tanks, pipelines, and other industrial equipment that are exposed to corrosive environs. The incorporation of these inhibitors into various materials such as paint and plastics will enhance their resistance to corrosion significantly. Recently, the dipeptide HSBs synthesized by S. Satpati et al. [59] have been found to possess excellent anticorrosion properties. These compounds exhibit outstanding efficiency in preventing corrosion of mild steel.

The development of chemosensors for selective sensing of analytes continues to be one of the most essential research areas of supramolecular chemistry. A chemosensor is a molecule whose interaction with the analyte produces a detectable change or signal. A series of studies have revealed that colorimetric and fluorescent chemosensors are of crucial molecules for sensing ionic or neutral species through changes in color or fluorescence. Krishna et al. in 2019 synthesized a number of isatin-based HSBs as colorimetric chemosensors [60]. Out of many analytes such as AsO₂⁻, Hg²⁺, Mn²⁺, Fe²⁺, Co²⁺, Ni²⁺, Zn²⁺, Al³⁺, Pb²⁺, Ag⁺, Cd²⁺, Cr³⁺, Ca²⁺, Na⁺, Mg²⁺, K⁺, and Cu²⁺ that were subjected to detection, the chemosensors selectively detected the arsenite and Hg²⁺ ions only through color change visible to the naked eye [60]. Because of the facile and selective detection of both toxic ions, the strategy could be extended to both industrial applications and the environmental monitoring against hazardous metal ions. Moreover, the HSB comprising indole-triazole motif provides a platform for effective binding unit to recognize a variety of cations and anions, and serves as well-known fluorescence chemosensors [16]. In 2018, Singh et al. synthesized indole-triazole HSB as chemosensor for the selective sensing of Ni²⁺ and Cu²⁺ ions over a wide range of metal ions [61]. Novel triazole-coumarin HSB, a fluorescent chemosensor, was prepared by Wang et al. [62] and this particular chemosensor was found to be suitable for selective sensing of Cu²⁺ ions. Furthermore, the bis(phenyl)fluorene and carbazole appended dipodal HSBs were synthesized and evaluated as efficient fluorescent chemosensors for detection of Sn²⁺ ions [63]. The study revealed that both nitrogen atoms in the two imine groups of HSB might lead to electron transfer to vacant orbitals of Sn²⁺, resulting in C〓N isomerization quenching. The fluorescence quantum yield of dipodal HSB-Sn²⁺ chelation was found to be 17.4% with an outstanding photostability under excitation at 320 nm.

Hence, the structural diversities and inherent chemical properties of HSB-based molecules provide scopes for numerous utilities in different segments. Without limiting their applications in the above-mentioned zones, these molecules too exhibit some foremost activities in the field of antimalarial, antiviral, anti-inflammatory, antioxidant, and anti-obesity that have been documented in the literature [16, 64, 65, 66]. In the contemporary period, the pharmacological applications of HSB-related compounds have excellent potential and are widely used within the pharmaceutical sector.

4. Conclusions

The unique features of HSBs and their coordination complexes with several transition metal ions offer a significant prospect for the design of novel drug molecules against a variety of cancer cell lines as well as active pathogens. Certainly, the HSB ligands have good biological properties, and the ability of heteroatoms in HSBs to form chelate complexes with pharmacologically important metal ions corresponding to cobalt, nickel, copper, and zinc is an extra advantage to their pharmacophore properties. The enhanced activity of complexes can rationally be credited to a cluster of factors, such as the occurrence of chelation, reduced polarity of metal ions, increased lipophilicity, accessibility of suitable heteroatom(s) in HSB ligand, and geometry of the complexes. The HSBs that contain N, O, and S heteroatoms owned better cytotoxicity against microbial strains and their activities have still been nurtured radically after metalation. Moreover, the chemical and thermal stabilities of HSB complexes make them efficient catalysts for a wide range of important organic transformation reactions that include ring-opening polymerization, hydrogenation of benzene, transfer hydrogenation of ketones, cyclo-condensation of aryl-aldehydes with 2-aminothiophenol, etc. The study can further be stimulated by exploiting the chemistry of uranyl complexes corresponding to their extensive HSB ligands for the catalytic and therapeutic studies due to their intriguing structural diversities along with an unprecedented complex core. The inexorable research activity focused on Schiff base compounds and their prevalent applications can be expected to continue, even in the future to yield more attractive results in terms of both novelty and function. The insights provided in this chapter can help researchers to rationally design novel HSB derivatives as well as pertinent metal complexes for suitable applications in multiple domains.