Supramolecular Assembly of Benzimidazole Derivatives and Applications

*Ana Beloqui*

#### **Abstract**

Herein, we focus on the chemical and physical properties of benzimidazole and its derivatives used for the synthesis of supramolecular materials. The design and modification of benzimidazole opens the scope of the diversity of structures (different sizes and morphologies) that can be built. The synthesized materials include not only small coordination complexes but also isolated crystals, metal-organic frameworks, metal-coordination polymers, smart nanocontainers, and more advanced macrostructures such as microflowers and nanowires. These supramolecular structures are based on noncovalent interactions, mostly on metal coordination chemistry and π-π stacking interactions. Moreover, the same molecule, due to its chemical structure, can undergo both sorts of interactions in order to induce the self-assembly into supramolecular materials. In this process, as it is shown in this chapter, the conditions used for the assembly determine the final structure and morphology of the fabricated macromolecule. Finally, we show most recent applications of these materials in the field of sensing, photoluminescence, fuel cell, and fabrication of new nanostructures.

**Keywords:** self-assembly, supramolecular interactions, metal-imidazole coordination, π-π stacking interactions

#### **1. Introduction**

Benzimidazole and its derivatives are mostly known by their role in therapeutic drugs and by their pharmacological activities, for example, antimicrobial, analgesic, and anti-inflammatory [1]. Moreover, they are part of essential biomolecules as vitamin B12 [2]. Thus, the biological activity of benzimidazole and its derivatives is unquestionable. However, there is a growing research interest in using benzimidazole derivatives for their assembly into supramolecular structures for technological applications. This implies the formation of well-defined complex bond through noncovalent interactions. In this regard, the interest on benzimidazole molecule is twofold (**Figure 1**). On the one hand, benzimidazole is a popular N-donor ligand that is often used in coordination chemistry, meaning that it can through metal- or small-molecule coordination to the assembly of molecules. Indeed, the imidazole ring is commonly found as part of essential components of biological products,

#### **Figure 1.**

*The physicochemical nature of benzimidazole allows the assembly through different chemistries such as hydrophobic interactions (mainly through the benzyl group) and small-molecule coordination (mainly through the imidazole ring). Benzimidazole derivatives (different "R") will lead to the synthesis of assemblies of diverse composition and thus morphology and properties.*


**205**

rized in **Table 1**.

*Supramolecular Assembly of Benzimidazole Derivatives and Applications*

acid

Hydrogen bonding 40-(6-(Benzimidazolethio)

benzoate

pyridine

*Examples of materials synthesized through supramolecular assembly of benzimidazole derivatives.*

1,1′-(1,4-butanediyl) bis(benzimidazole)

1,1-(1,4-Butanediyl) bis-1*H*-benzimidazole

4-(1*H*-Benzimidazole-2-yl)-benzoic

Covalent (Tris)imidazole Cu sensor [22]

hexoxy)-biphenyl-4-yl 4-(alkoxy)

2,6-bis(1′-methylbenzimidazolyl)

**Assembly Ligand Application Reference**

Thermostable polymers

Integration in functional devices

Liquid crystals for electronic conduction

Self-healing material [24]

di-Benzimidazole Nanocontainers [21]

Electrochemistry [19]

[18]

[20]

[23]

such as histidine (in proteins), purine, histamine, and nucleic acids. In the specific case of proteins, it is common to find the imidazole ring in coordination with metal cations, which are essential for their biological function. On the other hand, the benzyl ring of the benzimidazole can undergo physical interactions (hydrophobic, π-π interactions) with other planar benzyl groups or hydrophobic moieties. Moreover, the controlled intra- and intermolecular π-π interactions can lead the

Supramolecular assemblies are emergent structures basically driven by physical interactions [3]. It consists in a controlled multilevel organization process, from the assembly of discrete elementary molecular units via noncovalent interaction, to the further assembly of those into complex functional structures. The interaction forces operate under entropic constraints, looking for energy minimization. Selected organic and/or inorganic molecules can determine the chemical and structural composition of the eventually formed material. Therefore, this is a versatile methodology for the fabrication of nano-microstructures of defined size, morphology, and properties. In this chapter, we show different approaches that are currently utilized for the controlled assembly of benzimidazole and its derivatives for the formation of large and ordered structures. Derivatives of imidazole are specifically designed for the assembly into structures with diverse size and morphology [4]. We will go through the methodologies that allow the fabrication of isolated crystals, metal-coordinated polymers, metal-organic frameworks, helical structures, smart nanocontainers, and advanced structures such as microflowers or nanowires. Moreover, benzimidazole can be combined with biological macromolecules (proteins, nucleic acid) to trigger their assembly. Finally, we show that benzimidazole derivatives, besides the key role they have shown in the self-assembly of macromolecules, are used in a reasonably broad range of technological applications such as sensing, photoluminescence, fuel cell, and fabrication of new nanostructures. A list of examples in which benzimidazole molecule is used for the assembly into supramolecular structures are summa-

*DOI: http://dx.doi.org/10.5772/intechopen.85333*

Metal coordination,

Metal coordination, Cd(II), Zn(II)

Metal coordination-Pd(II)-anion binding

Metal coordination,

Zn(II)

Hydrophobic interactions

Co(II)

**Type of material**

Helical coordination polymers

Selfassembled polymer

Metal-organic macrocycles

Conjugates of calix-6-arenes

Coordination polymer

Liquid polymers

**Table 1.**

Macrocycles and large structures

supramolecular assembly into large structures.


*Supramolecular Assembly of Benzimidazole Derivatives and Applications DOI: http://dx.doi.org/10.5772/intechopen.85333*

#### **Table 1.**

*Chemistry and Applications of Benzimidazole and its Derivatives*

**Assembly Ligand Application Reference**

N,N′-bisoctadecyl-2-(1*H*benzimidazole-2-carbonyl)-L-

*The physicochemical nature of benzimidazole allows the assembly through different chemistries such as hydrophobic interactions (mainly through the benzyl group) and small-molecule coordination (mainly through the imidazole ring). Benzimidazole derivatives (different "R") will lead to the synthesis of assemblies of diverse* 

2-Pyridin-4-yl-1*H*-benzoimidazole

1*H*-benzimidazole-5-carboxylic

Tris(benzimidazole-2-ylmethyl)

1,3-Bis(5,6-dimethylbenzimidazole)

1,4-Bis(5,6-dimethylbenzimidazole)

1,6-bis(5,6-dimethylbenzimidazole)

3-(1*H*-benzoim-dazol-2-yl)

propanonic acid

1,1-(1,4-Butanediyl) bis-1*H*-benzimidazole

1,1′-(1,5-Pentanediyl) bis-1*H*-benzimidazole

glutamic amide

acid

amine

propane

butane

hexane

2,6-Bis(benzimidazol-2′-yl)pyridine Nanocontainer for

N-methylbenzimidazole Tautomer switch [7]

1-Benzylamonium Photoluminiscence [9]

2-Pyridin-3-yl-1*H*-benzoimidazole Photoluminiscence [10]

2-Heptadecylbenzimidazole Dye adsorption [11]

small molecules

Chiral materials, photoluminiscence

Fluorescence [12]

Photoluminescence [13]

Adsorbent materials [14]

— [15]

— [16]

Photoluminescence [17]

[4–6]

[8]

**204**

**Type of material**

**Figure 1.**

Coordination polymer

Metal-organic crystals

Metal-organic frameworks

Metal-organic frameworksmetalogel

Coordination polymer

Metal-organic frameworks

Coordination polymer

Coordination polymer

Coordination polymer

Coordination polymer

Metalogel Metal-metal,

Macrocycles Anion binding

hydrophobic interactions

*composition and thus morphology and properties.*

coordination

Metal coordination, Ag(I), Cu(II), lanthanides (III), hydrophobic interaction

Metal coordination, Cu(II), Zn(II)

Metal coordination,

Metal coordination,

Metal coordination,

Metal coordination,

Metal coordination, lanthanides (III)

Metal coordination, Zn(II) and Cd(II)

Metal coordination,

Metal coordination,

Cd(II)

Ag(I)

Cd(II)

Cd(II)

Co(II)

Cd(II)

*Examples of materials synthesized through supramolecular assembly of benzimidazole derivatives.*

such as histidine (in proteins), purine, histamine, and nucleic acids. In the specific case of proteins, it is common to find the imidazole ring in coordination with metal cations, which are essential for their biological function. On the other hand, the benzyl ring of the benzimidazole can undergo physical interactions (hydrophobic, π-π interactions) with other planar benzyl groups or hydrophobic moieties. Moreover, the controlled intra- and intermolecular π-π interactions can lead the supramolecular assembly into large structures.

Supramolecular assemblies are emergent structures basically driven by physical interactions [3]. It consists in a controlled multilevel organization process, from the assembly of discrete elementary molecular units via noncovalent interaction, to the further assembly of those into complex functional structures. The interaction forces operate under entropic constraints, looking for energy minimization. Selected organic and/or inorganic molecules can determine the chemical and structural composition of the eventually formed material. Therefore, this is a versatile methodology for the fabrication of nano-microstructures of defined size, morphology, and properties.

In this chapter, we show different approaches that are currently utilized for the controlled assembly of benzimidazole and its derivatives for the formation of large and ordered structures. Derivatives of imidazole are specifically designed for the assembly into structures with diverse size and morphology [4]. We will go through the methodologies that allow the fabrication of isolated crystals, metal-coordinated polymers, metal-organic frameworks, helical structures, smart nanocontainers, and advanced structures such as microflowers or nanowires. Moreover, benzimidazole can be combined with biological macromolecules (proteins, nucleic acid) to trigger their assembly. Finally, we show that benzimidazole derivatives, besides the key role they have shown in the self-assembly of macromolecules, are used in a reasonably broad range of technological applications such as sensing, photoluminescence, fuel cell, and fabrication of new nanostructures. A list of examples in which benzimidazole molecule is used for the assembly into supramolecular structures are summarized in **Table 1**.

#### **2. Supramolecular self-assembly through coordination chemistry**

The combination of organic and inorganic compounds to raise supramolecular structures is an on-growing research field. This approach broadens the applications and the nature of the morphologies and chemistries that can be applied for. Of particular importance is the assembly of metal (inorganic)-organic structures based on coordination chemistry. A good design of the ligands and metal cations and the selection of the appropriate synthesis method can lead to the formation of welldefined crystals, frameworks, or polymers as it is discussed below. Furthermore, the anion binding chemistry is another field of application of coordination chemistry. Small molecules such as anions coordinate to ligands to form stable complexes with interesting properties.

In this section, we focus on the ability of the imidazole ring to coordinate to small molecules such as anions and metal ions for the formation of discrete complexes and large supramolecular structures.

#### **2.1 Supramolecular assembly with small molecules**

The field of the coordination chemistry compiles a broad range of interactions, from classical Werner transition metal complexes, clusters, and organometallics, to host-guest complexes and supramolecular complexes (e.g., crown ethers or cryptands) [25]. Usually, in most of the examples found in the literature, benzimidazole derivatives are coordinated through metal-cation interaction. However, the anion binding chemistry has an important impact within the coordination chemistry field and, as it is going to be shown below, in the formation of discrete complexes and large supramolecular assemblies with benzimidazole derivatives.

Anionic species are generally larger than metal cations and thus might require greater size of the ligands. Moreover, the coordination of anions is usually saturated and therefore they only interact with ligands via weak forces, that is, hydrogen bonding and van der Waals interactions. Additionally, the relatively narrow pH window in which many anions exist determines the stability of the synthesized complexes. Anions play significant roles in biology, as receptors or cofactors, and in a broad number of applications such as sensing, crystal engineering, transmembrane transport, or anion-based catalysis [26].

Imidazole and benzimidazole derivatives have been used as ligands in anion binding-coordinated complex formation. In the case of imidazole molecule, both the nitrogen atoms within the imidazole ring are both covalently bond to sp3 hybridized carbon atoms. In these systems, the positively charged imidazolium group works as a hydrogen bond donor, interacting with the coordinated anion through a combination of hydrogen bonding and electrostatic interactions [7]. Furthermore, when using benzimidazole units, those can be employed as NH hydrogen bond donors and, in this case, a tautomerism process may affect the nature of the hydrogen bond presented to an anionic guest. As example, the N-methylbenzimidazole-based ligands selectively interact with the dihydrogen phosphate ion, acting as both a hydrogen bond donor and acceptor. Hence, several receptors containing benzimidazole derivatives have been reported as colorimetric, fluorescent, and electrochemically active sensors (**Table 1**).

#### **2.2 Supramolecular assembly with metal cations**

As a component of vitamin 1benzimidazole moiety exhibits good coordination ability with various transitional metal ions, such as Mn(II), Fe(II), Co(II), Ni(II), Cd(II), Hg(II), Pd(II), Cu(II), Zn(II), Ag(I), and Pb(II). In addition, it has

**207**

*Supramolecular Assembly of Benzimidazole Derivatives and Applications*

in their functionality, for example, catalysis in enzymes.

been shown to coordinate with rare earth metal ions (lanthanides) [8]. The metal coordination of the imidazole ring is used in nature for the hierarchical assembly of biopolymers, for example, mussel byssus or worm jaws, and metalloproteins, in which the metal cations can not only show a structural function, but also contribute

The metal coordination chemistry is an advantageous and widely used approach

The aforementioned advantages of metal coordination have been exploited to arrange small organic ligands into well-defined assemblies, organized arrays, that is, metal-organic frameworks (MOFs) and polymers. These materials have found applications in the host-guest chemistry, sensing, storage/separation, and catalysis.

Benzimidazole unit has been used for the formation of complexes using a very simple synthesis approach [27]. The assemblage into well-defined crystals is driven through the spontaneous metal coordination assembly at room temperature. As example, the combination of CuCl2·6H2O salt in a mixture of water/MeOH solution with benzimidazole in a molar ratio of 1:4 [9, 28] derives into the formation of dark blue crystals that consisted in a complex with formula [Cu(bim)4Cl2]·2H2O. Similar results are obtained by mixing ZnCl2 in a DMF solution for the synthesis of crystals

Nevertheless, most of the cases require the derivatization of the benzimidazole

unit to allow its assembly into larger arrays, frameworks, and polymers as it is

The exploration of metal-organic frameworks (MOFs) has received much attention because of their well-defined architectures and wide range of potential applications in different fields. The assembly of transition metal cations such as Zn(II) and Cd(II) with multidentate nitrogen-containing ligands has produced various MOFs with fascinating structures and luminescent and catalytic properties [10, 11, 29]. The selection of chelating or bridging organic linkers often favors a structure-specific assembly, guiding the eventual morphology of the formed macromolecule. The factors that govern the formation of such complexes are complicated and include not only the nature of the metal ions and the ligand structure but also anion-directed interactions, hydrogen bonds, van der Wall forces, and

The design and prediction of MOFs with potential properties is still a challenge to date [12]. Usually, the synthesis of MOFs starts from stiff bridging ligands via relatively strong dative bonds. Nevertheless, it has been proven that the contribution of hydrogen-bonded interactions leads to highly stable and porous architectures. Thus, of extreme importance is the design of ligands that can eventually undergo

Benzimidazole derivatives have been used for the synthesis Cd-based MOFs.

Cd-containing structures, both discrete assemblies and infinite molecular

for assembly. The metal-ligand bonds are usually stronger that anion binding coordination; they are highly directional and kinetically labile. This means that, from one side, the symmetry and stereochemical preference is usually imposed by the metal cation and that this process is governed by a thermodynamic control, which is usually dependent on pH variations. Finally, metal ions bring along their intrinsic reactivity (as Lewis acidity, redox reactivity), which can be transferred to

*DOI: http://dx.doi.org/10.5772/intechopen.85333*

the assembled material.

of [Zn(bim)2Cl2]·3H2O.

*2.2.2 Synthesis of metal-organic frameworks*

employed reaction conditions.

stabilization interactions.

explained below.

*2.2.1 Metal-organic macrocycles*

#### *Supramolecular Assembly of Benzimidazole Derivatives and Applications DOI: http://dx.doi.org/10.5772/intechopen.85333*

been shown to coordinate with rare earth metal ions (lanthanides) [8]. The metal coordination of the imidazole ring is used in nature for the hierarchical assembly of biopolymers, for example, mussel byssus or worm jaws, and metalloproteins, in which the metal cations can not only show a structural function, but also contribute in their functionality, for example, catalysis in enzymes.

The metal coordination chemistry is an advantageous and widely used approach for assembly. The metal-ligand bonds are usually stronger that anion binding coordination; they are highly directional and kinetically labile. This means that, from one side, the symmetry and stereochemical preference is usually imposed by the metal cation and that this process is governed by a thermodynamic control, which is usually dependent on pH variations. Finally, metal ions bring along their intrinsic reactivity (as Lewis acidity, redox reactivity), which can be transferred to the assembled material.

The aforementioned advantages of metal coordination have been exploited to arrange small organic ligands into well-defined assemblies, organized arrays, that is, metal-organic frameworks (MOFs) and polymers. These materials have found applications in the host-guest chemistry, sensing, storage/separation, and catalysis.

#### *2.2.1 Metal-organic macrocycles*

*Chemistry and Applications of Benzimidazole and its Derivatives*

interesting properties.

plexes and large supramolecular structures.

brane transport, or anion-based catalysis [26].

fluorescent, and electrochemically active sensors (**Table 1**).

**2.2 Supramolecular assembly with metal cations**

**2.1 Supramolecular assembly with small molecules**

**2. Supramolecular self-assembly through coordination chemistry**

The combination of organic and inorganic compounds to raise supramolecular structures is an on-growing research field. This approach broadens the applications and the nature of the morphologies and chemistries that can be applied for. Of particular importance is the assembly of metal (inorganic)-organic structures based on coordination chemistry. A good design of the ligands and metal cations and the selection of the appropriate synthesis method can lead to the formation of welldefined crystals, frameworks, or polymers as it is discussed below. Furthermore, the anion binding chemistry is another field of application of coordination chemistry. Small molecules such as anions coordinate to ligands to form stable complexes with

In this section, we focus on the ability of the imidazole ring to coordinate to small molecules such as anions and metal ions for the formation of discrete com-

The field of the coordination chemistry compiles a broad range of interactions, from classical Werner transition metal complexes, clusters, and organometallics, to host-guest complexes and supramolecular complexes (e.g., crown ethers or cryptands) [25]. Usually, in most of the examples found in the literature, benzimidazole derivatives are coordinated through metal-cation interaction. However, the anion binding chemistry has an important impact within the coordination chemistry field and, as it is going to be shown below, in the formation of discrete complexes and large supramolecular assemblies with benzimidazole derivatives. Anionic species are generally larger than metal cations and thus might require greater size of the ligands. Moreover, the coordination of anions is usually saturated and therefore they only interact with ligands via weak forces, that is, hydrogen bonding and van der Waals interactions. Additionally, the relatively narrow pH window in which many anions exist determines the stability of the synthesized complexes. Anions play significant roles in biology, as receptors or cofactors, and in a broad number of applications such as sensing, crystal engineering, transmem-

Imidazole and benzimidazole derivatives have been used as ligands in anion binding-coordinated complex formation. In the case of imidazole molecule, both the nitrogen atoms within the imidazole ring are both covalently bond to sp3 hybridized carbon atoms. In these systems, the positively charged imidazolium group works as a hydrogen bond donor, interacting with the coordinated anion through a combination of hydrogen bonding and electrostatic interactions [7]. Furthermore, when using benzimidazole units, those can be employed as NH hydrogen bond donors and, in this case, a tautomerism process may affect the nature of the hydrogen bond presented to an anionic guest. As example, the N-methylbenzimidazole-based ligands selectively interact with the dihydrogen phosphate ion, acting as both a hydrogen bond donor and acceptor. Hence, several receptors containing benzimidazole derivatives have been reported as colorimetric,

As a component of vitamin 1benzimidazole moiety exhibits good coordination ability with various transitional metal ions, such as Mn(II), Fe(II), Co(II), Ni(II), Cd(II), Hg(II), Pd(II), Cu(II), Zn(II), Ag(I), and Pb(II). In addition, it has

**206**

Benzimidazole unit has been used for the formation of complexes using a very simple synthesis approach [27]. The assemblage into well-defined crystals is driven through the spontaneous metal coordination assembly at room temperature. As example, the combination of CuCl2·6H2O salt in a mixture of water/MeOH solution with benzimidazole in a molar ratio of 1:4 [9, 28] derives into the formation of dark blue crystals that consisted in a complex with formula [Cu(bim)4Cl2]·2H2O. Similar results are obtained by mixing ZnCl2 in a DMF solution for the synthesis of crystals of [Zn(bim)2Cl2]·3H2O.

Nevertheless, most of the cases require the derivatization of the benzimidazole unit to allow its assembly into larger arrays, frameworks, and polymers as it is explained below.

#### *2.2.2 Synthesis of metal-organic frameworks*

The exploration of metal-organic frameworks (MOFs) has received much attention because of their well-defined architectures and wide range of potential applications in different fields. The assembly of transition metal cations such as Zn(II) and Cd(II) with multidentate nitrogen-containing ligands has produced various MOFs with fascinating structures and luminescent and catalytic properties [10, 11, 29]. The selection of chelating or bridging organic linkers often favors a structure-specific assembly, guiding the eventual morphology of the formed macromolecule. The factors that govern the formation of such complexes are complicated and include not only the nature of the metal ions and the ligand structure but also anion-directed interactions, hydrogen bonds, van der Wall forces, and employed reaction conditions.

The design and prediction of MOFs with potential properties is still a challenge to date [12]. Usually, the synthesis of MOFs starts from stiff bridging ligands via relatively strong dative bonds. Nevertheless, it has been proven that the contribution of hydrogen-bonded interactions leads to highly stable and porous architectures. Thus, of extreme importance is the design of ligands that can eventually undergo stabilization interactions.

Benzimidazole derivatives have been used for the synthesis Cd-based MOFs. Cd-containing structures, both discrete assemblies and infinite molecular

frameworks, have been released from and characterized due to their useful properties in catalysis, luminescent materials, NLO materials, phase transformation, and host-guest chemistry. The use of 1,1′-(1,5-pentanediyl)bis-1*H*-benzimidazole as ligand formed a supramolecular structure that showed photoluminescence properties, which could be modulated by the influence of different counterions [13]. This points out the influence of anions in the arrangement of the coordination molecules and thus the final structure of the macromolecules.

Changing from transition metals to lanthanides leads to new applications and properties. The benzimidazole derivative (tris(benzimidazole-2-ylmethyl)amine, ntb) has been utilized as ligand for the synthesis of lanthanide (Ln: Nd3+, Eu3+, Gd3+, and Er3+) coordination monomers ([ln(ntb)(NO3)3]) that are further assembled via hydrogen bonding into three-dimensional (3D) frameworks [14]. Synthesis and crystallization conditions controlled the eventual morphology of the materials for each lanthanide used (monoclinic, hexagonal and cubic crystals). The Eu3+ and Nd3+ derivatives showed solid-state photoluminiscence in the near-infrared and visible region. In this case, the use of benzimidazole derivatives for the synthesis of porous coordination frameworks is advantageous for the supraorganization of structures through hydrogen-bonded frameworks, which is known to provide highly stable porous structures.

#### *2.2.3 Fabrication of metal coordination polymers*

There is a strong controversy on the use of the terms metal-organic frameworks and metal coordination polymers to assign the arrangement of an array of ligands through noncovalent coordination using metal cations [30]. As the term, metalorganic framework is very much appropriate to use for three-dimensional networks, the formation of one-dimensional and two-dimensional extended structures such as layers is named metal coordination polymers.

As the structures of coordination polymers are strongly influenced by the organic ligands and metal ions [15, 16, 31], it is important to choose suitable ligands and metal ions under appropriate synthetic conditions in order to synthesize coordination complexes with interesting structures. The flexibility of the ligand is a key parameter to direct the assembly into polymers instead of frameworks [17].

In this field, the synthesis of flexible divergent ligands is preferred. As example, the introduction of butane moieties to benzimidazole units provides the required flexibility for the fabrication of metal-coordinated polymers using Co(II). Hence, the ligand 1,1′-(1,4-butanediyl)bis(benzimidazole) (L) can be used for the fabrication of Co polymers (L1, [CoL2(H2O)2](NO3)2·8H2O; and L2, [CoL(H2O)2(CH3CO2)2]H2O) Those polymers were obtained from the same ligand just varying slightly the synthesis conditions [18]. This variation leads to different composition and morphology for each of the polymers. While L1 forms infinite networks, the coordination of Co(II) in L2 leads to the formation of an infinite zigzag two-dimensional polymeric structure. Furthermore, same ligand L in presence of Cd(II) ions led to the fabrication of one-dimensional helical chain polymeric structures [19].

The assembly of these structures usually is sensitive to pH values and the protonation states of the ligands, as in the case of carboxylates and nitrogen donor groups. In order to have a better understanding of the effect of the pH value on the aromatic nitrogen-donor ligands, Li et al. [12] studied the reaction system using the benzimidazole derivative H2bic (1*H*-benzimidazole-5-carboxylic acid) as ligand. In this case, they used Cd(II) for the assembly of the metal-coordinated polymer. The assembly was performed at different pH values, leading to different morphologies and compositions of the polymer. Hence, at pH 5.0, a two-dimensional

**209**

bic molecules.

*Supramolecular Assembly of Benzimidazole Derivatives and Applications*

supramolecular assembly consisting in stacked one-dimensional chains was obtained. However, when the pH was raised to 6.5, a rhombus network structure was obtained. Finally, at a pH of 7.2, a three-dimensional architecture based on

**3. Supramolecular self-assembly through π-π stacking interactions**

reported in the fabrication of protein nanoflowers and nanosponges [32, 33].

The design of stimuli-responsive materials is a growing research field. These materials are capable of altering their chemical and/or physical properties upon exposure to an external stimulus, such as temperature, humidity, light, or pH. Thus, they have been applied to biomedical applications as drug delivery vectors or as

The ability of benzimidazole to coordinate metal cations can be used for the detection and study of metal cations in smart biodevices and organic nanocages. Here, we show two examples, benzimidazole conjugates of cyclodextrin and calix-6 arene, in which benzimidazole units are coupled to arranged molecules that can act as containers of small molecules, releasing those molecules under specific stimuli.

Cyclodextrins (β-CD) are cyclic biomacromolecules typically containing six to eight glucose subunits bound through α-1,4 glycosidic bonds. They show toroid-like structures, with two external rims, one larger and the other smaller, that expose the secondary and primary hydroxyl groups of the glucose subunits, respectively. Importantly, the interior of the toroid is hydrophobic, being able to host hydropho-

**4. Benzimidazole conjugates as smart nanocontainers**

degradable biocompatible containers.

**4.1 Cyclodextrin conjugates**

As aforementioned, coordination chemistry is not the only noncovalent interaction used for the assembly of supramolecular structures. Indeed, nanostructures can be formed through interactions such as hydrogen bond, pi-pi stacking, metal coordination, or electrostatic interactions. In the specific case of benzimidazole derivatives, the heteroaromatic benzimidazole moiety introduces both pi-pi attacking and coordination unit. Benzimidazole derivatives have shown gelification and formation of structures in absence of metal cations or anions and completely different structures in presence of metal cations [8, 20]. As example, N,N′-bisocyadecyl-2-(1*H*-benzimidazle-2-carbonyl)-l-glutamic amide, BzLG) ligand was assembled through a supramolecular gelation method named low-molecular-weight organogels (LMWGs) in various organic solvents or in water. Once the gel is formed, the solvent is removed and nanostructures can be obtained with relatively uniform structures and large quantity. BzLG gelifies in several organic solvents, including cyclohexane, toluene, acetonitrile, ethanol, and dimethyl formamide. Obtained structures relied upon the solvent used in the gelification process: from nanotubes in dimethyl formamide and acetone to nanofibers in acetonitrile and cyclohexane. When BzLG was used to coordinate with transitional metal ions and lanthanide ions, completely different structures were obtained. Nanotube flowers were obtained upon addition of Eu(NO3)3 and Tb(NO3)3, while in the case of Cu(NO3)2, microflower structures were observed. The latter structures were very similar to the nanoflower structures formed from bovine serum albumin (BSA) in phosphate buffer and Cu(SO4)2 metal salt

*DOI: http://dx.doi.org/10.5772/intechopen.85333*

binuclear cadmium units was retrieved.

*Chemistry and Applications of Benzimidazole and its Derivatives*

and thus the final structure of the macromolecules.

highly stable porous structures.

*2.2.3 Fabrication of metal coordination polymers*

such as layers is named metal coordination polymers.

frameworks, have been released from and characterized due to their useful properties in catalysis, luminescent materials, NLO materials, phase transformation, and host-guest chemistry. The use of 1,1′-(1,5-pentanediyl)bis-1*H*-benzimidazole as ligand formed a supramolecular structure that showed photoluminescence properties, which could be modulated by the influence of different counterions [13]. This points out the influence of anions in the arrangement of the coordination molecules

Changing from transition metals to lanthanides leads to new applications and properties. The benzimidazole derivative (tris(benzimidazole-2-ylmethyl)amine, ntb) has been utilized as ligand for the synthesis of lanthanide (Ln: Nd3+, Eu3+, Gd3+, and Er3+) coordination monomers ([ln(ntb)(NO3)3]) that are further assembled via hydrogen bonding into three-dimensional (3D) frameworks [14]. Synthesis and crystallization conditions controlled the eventual morphology of the materials for each lanthanide used (monoclinic, hexagonal and cubic crystals). The Eu3+ and Nd3+ derivatives showed solid-state photoluminiscence in the near-infrared and visible region. In this case, the use of benzimidazole derivatives for the synthesis of porous coordination frameworks is advantageous for the supraorganization of structures through hydrogen-bonded frameworks, which is known to provide

There is a strong controversy on the use of the terms metal-organic frameworks and metal coordination polymers to assign the arrangement of an array of ligands through noncovalent coordination using metal cations [30]. As the term, metalorganic framework is very much appropriate to use for three-dimensional networks, the formation of one-dimensional and two-dimensional extended structures

As the structures of coordination polymers are strongly influenced by the organic ligands and metal ions [15, 16, 31], it is important to choose suitable ligands and metal ions under appropriate synthetic conditions in order to synthesize coordination complexes with interesting structures. The flexibility of the ligand is a key parameter to direct the assembly into polymers instead of frameworks [17]. In this field, the synthesis of flexible divergent ligands is preferred. As example, the introduction of butane moieties to benzimidazole units provides the required flexibility for the fabrication of metal-coordinated polymers using Co(II). Hence, the ligand 1,1′-(1,4-butanediyl)bis(benzimidazole) (L) can be used for the fabrication of Co polymers (L1, [CoL2(H2O)2](NO3)2·8H2O; and L2, [CoL(H2O)2(CH3CO2)2]H2O) Those polymers were obtained from the same ligand just varying slightly the synthesis conditions [18]. This variation leads to different composition and morphology for each of the polymers. While L1 forms infinite networks, the coordination of Co(II) in L2 leads to the formation of an infinite zigzag two-dimensional polymeric structure. Furthermore, same ligand L in presence of Cd(II) ions led to the fabrication of one-dimensional helical chain polymeric

The assembly of these structures usually is sensitive to pH values and the protonation states of the ligands, as in the case of carboxylates and nitrogen donor groups. In order to have a better understanding of the effect of the pH value on the aromatic nitrogen-donor ligands, Li et al. [12] studied the reaction system using the benzimidazole derivative H2bic (1*H*-benzimidazole-5-carboxylic acid) as ligand. In this case, they used Cd(II) for the assembly of the metal-coordinated polymer. The assembly was performed at different pH values, leading to different morphologies and compositions of the polymer. Hence, at pH 5.0, a two-dimensional

**208**

structures [19].

supramolecular assembly consisting in stacked one-dimensional chains was obtained. However, when the pH was raised to 6.5, a rhombus network structure was obtained. Finally, at a pH of 7.2, a three-dimensional architecture based on binuclear cadmium units was retrieved.

## **3. Supramolecular self-assembly through π-π stacking interactions**

As aforementioned, coordination chemistry is not the only noncovalent interaction used for the assembly of supramolecular structures. Indeed, nanostructures can be formed through interactions such as hydrogen bond, pi-pi stacking, metal coordination, or electrostatic interactions. In the specific case of benzimidazole derivatives, the heteroaromatic benzimidazole moiety introduces both pi-pi attacking and coordination unit. Benzimidazole derivatives have shown gelification and formation of structures in absence of metal cations or anions and completely different structures in presence of metal cations [8, 20]. As example, N,N′-bisocyadecyl-2-(1*H*-benzimidazle-2-carbonyl)-l-glutamic amide, BzLG) ligand was assembled through a supramolecular gelation method named low-molecular-weight organogels (LMWGs) in various organic solvents or in water. Once the gel is formed, the solvent is removed and nanostructures can be obtained with relatively uniform structures and large quantity. BzLG gelifies in several organic solvents, including cyclohexane, toluene, acetonitrile, ethanol, and dimethyl formamide. Obtained structures relied upon the solvent used in the gelification process: from nanotubes in dimethyl formamide and acetone to nanofibers in acetonitrile and cyclohexane.

When BzLG was used to coordinate with transitional metal ions and lanthanide ions, completely different structures were obtained. Nanotube flowers were obtained upon addition of Eu(NO3)3 and Tb(NO3)3, while in the case of Cu(NO3)2, microflower structures were observed. The latter structures were very similar to the nanoflower structures formed from bovine serum albumin (BSA) in phosphate buffer and Cu(SO4)2 metal salt reported in the fabrication of protein nanoflowers and nanosponges [32, 33].

#### **4. Benzimidazole conjugates as smart nanocontainers**

The design of stimuli-responsive materials is a growing research field. These materials are capable of altering their chemical and/or physical properties upon exposure to an external stimulus, such as temperature, humidity, light, or pH. Thus, they have been applied to biomedical applications as drug delivery vectors or as degradable biocompatible containers.

The ability of benzimidazole to coordinate metal cations can be used for the detection and study of metal cations in smart biodevices and organic nanocages. Here, we show two examples, benzimidazole conjugates of cyclodextrin and calix-6 arene, in which benzimidazole units are coupled to arranged molecules that can act as containers of small molecules, releasing those molecules under specific stimuli.

#### **4.1 Cyclodextrin conjugates**

Cyclodextrins (β-CD) are cyclic biomacromolecules typically containing six to eight glucose subunits bound through α-1,4 glycosidic bonds. They show toroid-like structures, with two external rims, one larger and the other smaller, that expose the secondary and primary hydroxyl groups of the glucose subunits, respectively. Importantly, the interior of the toroid is hydrophobic, being able to host hydrophobic molecules.

The chemical nature of benzimidazole makes it a good ligand to interact with cyclodextrin (β-CD) oligomers through hydrophobic interactions. Moreover, the physicochemical properties of benzimidazole molecules can be altered with the pH [34]. Therefore, under neutral pH condition, benzimidazole interacts with the inner part of the β-CD, blocking the diffusion through the macromolecule. As the pH is lowered, the dissociation constant between benzimidazole and β-CD decreases and benzimidazole is released to the medium. Using this approach, β-CD pH-responsive nanovalves have been fabricated: as the pH decreases, the external rings are opened, and the cargo release occurs. More complex structures were designed for sensing glucose or lactose using this system [35, 36].

#### *4.1.1 Assembly into cyclodextrin-like architectures*

The versatility and the high ability of benzimidazole derivatives to assemble are here demonstrated [4–6]. Through the controlled coordination to metal cations, that is, Pd(II), it is possible to self-assemble macrocyclic containers that mimic β-CD [21]. Moreover, these nanocontainers have the ability to bind anion guests and induce the transformation in the morphology and compositional unit of the nanocontainer. The hydrogen bonding between the inner surface of the macrocycles and the bound guests induced the fit—transformation properties of the assembled material, as observed in nature. Hence, the in situ anion-adaptative self-assembly gives rise to PdnL2n species for n:3, 6, 7. As example, Sun et al. demonstrated the assembly of BzIbased ligands using square-planar palladium(II) ions into well-defined hydrogenbonding pockets that will find applications in molecular sensing and catalysis.

#### **4.2 Calix-6-arene conjugates**

The benefits of the combination of benzimidazole molecules with nanocontainer scaffolds are also evidenced in this example in which benzimidazole is attached to calix-6-arenes [22]. Calix-6-arenes are organic macrocycles composed of (derivatives of) phenol subunits. Due to its hydrophobic cavity, they can be used to host smaller hydrophobic molecules or ions. They have been extensively used as a molecular platform to host catalytic units.

In benzimidazole-calixarene conjugates, the benzimidazole moieties are localized hanging out from the small rim of the macrocycle, pointing toward the environment. The coordination of metal cations to the imidazole ring of the benzimidazole molecule mimics the hydrophobic environment of the copper site in proteins and enzymes [37, 38]. The coordination of metal cations, that is, Cu(II), triggers a detectable modification in the structure of the conjugate, therefore being this a very sensitive method for the detection of metal ions.

#### **5. Recent applications of assembled materials and new perspectives**

As aforementioned, the assembly of benzimidazole and its derivatives has been utilized for the fabrication of stable materials with applications in several fields [39–42], some of them collected in **Table 1**: sensor fabrication [22], drug delivery systems [35], fuel cell design, biomedicine [43], conductivity in liquid crystals [23], or the fabrication of nanostructures [17].

Additionally, new applications of benzimidazole-derived materials are being raised. Thanks to the intrinsic properties of polymeric structures and the optical properties of some of the macroassemblies described above (luminescence, phosphorescence, or fluorescence), there is a growing interest in using these structures

**211**

**Author details**

**Acknowledgements**

of Gipuzkoa Fellows program.

**6. Conclusions**

Ana Beloqui

provided the original work is properly cited.

CIC nanoGUNE, Donostia-San Sebastian, Spain

\*Address all correspondence to: a.beloqui@nanogune.eu

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

*Supramolecular Assembly of Benzimidazole Derivatives and Applications*

application in data recording and security protection [44].

as healable and/or writable materials. These polymeric assemblies respond to external stimuli, for example, heat, presence of ions, with the surface rearrangement, and entanglement of the chains. The use of benzimidazole moieties in these systems, thanks to their chromophore rings, allows the use of an optical irradiation to heal the material [24]. Moreover, the ability of these polymers to bind and interact with different anions shows that their optical properties are used for advanced

In this chapter, we show the use of benzimidazole and its derivatives as important ligands that are currently being used for their supramolecular assembly into large structures with interesting properties and applications. Due to the physicochemical properties of benzimidazole, different chemistries and interactions can guide the assembly into very stable materials. Among them, the metal coordination to the imidazole ring seems to be the most exploited one for the formation of metal macromolecules, metal coordination polymers, and metal-organic frameworks. The selected benzimidazole derivatives and metal cation, together with the utilized synthesis conditions, will lead to the formation of materials with very diverse size and morphology. Thus, the establishment of a solid knowledge on the prediction of the assembled structures would contribute to the advancement of material science with strong strategic implications for the on-demand synthesis of smart responsive materials. However, in spite of the large efforts that are being done, currently there is no method to predict the composition and structure of the eventually synthesized materials.

This project has received funding from the Spanish Ministry of Economy and Competitiveness (MINECO) and FEDER funds in the frame of "Plan Nacional— Retos para la Sociedad" call with the grant reference MAT2017-88808-R. This work was performed under the Maria de Maeztu Units of Excellence Programme—MDM-2016-0618. A.B. thanks Diputación de Guipúzcoa for current funding in the frame

*DOI: http://dx.doi.org/10.5772/intechopen.85333*

*Supramolecular Assembly of Benzimidazole Derivatives and Applications DOI: http://dx.doi.org/10.5772/intechopen.85333*

as healable and/or writable materials. These polymeric assemblies respond to external stimuli, for example, heat, presence of ions, with the surface rearrangement, and entanglement of the chains. The use of benzimidazole moieties in these systems, thanks to their chromophore rings, allows the use of an optical irradiation to heal the material [24]. Moreover, the ability of these polymers to bind and interact with different anions shows that their optical properties are used for advanced application in data recording and security protection [44].

#### **6. Conclusions**

*Chemistry and Applications of Benzimidazole and its Derivatives*

glucose or lactose using this system [35, 36].

**4.2 Calix-6-arene conjugates**

molecular platform to host catalytic units.

or the fabrication of nanostructures [17].

this a very sensitive method for the detection of metal ions.

*4.1.1 Assembly into cyclodextrin-like architectures*

The chemical nature of benzimidazole makes it a good ligand to interact with cyclodextrin (β-CD) oligomers through hydrophobic interactions. Moreover, the physicochemical properties of benzimidazole molecules can be altered with the pH [34]. Therefore, under neutral pH condition, benzimidazole interacts with the inner part of the β-CD, blocking the diffusion through the macromolecule. As the pH is lowered, the dissociation constant between benzimidazole and β-CD decreases and benzimidazole is released to the medium. Using this approach, β-CD pH-responsive nanovalves have been fabricated: as the pH decreases, the external rings are opened, and the cargo release occurs. More complex structures were designed for sensing

The versatility and the high ability of benzimidazole derivatives to assemble are here demonstrated [4–6]. Through the controlled coordination to metal cations, that is, Pd(II), it is possible to self-assemble macrocyclic containers that mimic β-CD [21]. Moreover, these nanocontainers have the ability to bind anion guests and induce the transformation in the morphology and compositional unit of the nanocontainer. The hydrogen bonding between the inner surface of the macrocycles and the bound guests induced the fit—transformation properties of the assembled material, as observed in nature. Hence, the in situ anion-adaptative self-assembly gives rise to PdnL2n species for n:3, 6, 7. As example, Sun et al. demonstrated the assembly of BzIbased ligands using square-planar palladium(II) ions into well-defined hydrogenbonding pockets that will find applications in molecular sensing and catalysis.

The benefits of the combination of benzimidazole molecules with nanocontainer scaffolds are also evidenced in this example in which benzimidazole is attached to calix-6-arenes [22]. Calix-6-arenes are organic macrocycles composed of (derivatives of) phenol subunits. Due to its hydrophobic cavity, they can be used to host smaller hydrophobic molecules or ions. They have been extensively used as a

In benzimidazole-calixarene conjugates, the benzimidazole moieties are localized hanging out from the small rim of the macrocycle, pointing toward the environment. The coordination of metal cations to the imidazole ring of the benzimidazole molecule mimics the hydrophobic environment of the copper site in proteins and enzymes [37, 38]. The coordination of metal cations, that is, Cu(II), triggers a detectable modification in the structure of the conjugate, therefore being

**5. Recent applications of assembled materials and new perspectives**

As aforementioned, the assembly of benzimidazole and its derivatives has been utilized for the fabrication of stable materials with applications in several fields [39–42], some of them collected in **Table 1**: sensor fabrication [22], drug delivery systems [35], fuel cell design, biomedicine [43], conductivity in liquid crystals [23],

Additionally, new applications of benzimidazole-derived materials are being raised. Thanks to the intrinsic properties of polymeric structures and the optical properties of some of the macroassemblies described above (luminescence, phosphorescence, or fluorescence), there is a growing interest in using these structures

**210**

In this chapter, we show the use of benzimidazole and its derivatives as important ligands that are currently being used for their supramolecular assembly into large structures with interesting properties and applications. Due to the physicochemical properties of benzimidazole, different chemistries and interactions can guide the assembly into very stable materials. Among them, the metal coordination to the imidazole ring seems to be the most exploited one for the formation of metal macromolecules, metal coordination polymers, and metal-organic frameworks. The selected benzimidazole derivatives and metal cation, together with the utilized synthesis conditions, will lead to the formation of materials with very diverse size and morphology. Thus, the establishment of a solid knowledge on the prediction of the assembled structures would contribute to the advancement of material science with strong strategic implications for the on-demand synthesis of smart responsive materials. However, in spite of the large efforts that are being done, currently there is no method to predict the composition and structure of the eventually synthesized materials.

#### **Acknowledgements**

This project has received funding from the Spanish Ministry of Economy and Competitiveness (MINECO) and FEDER funds in the frame of "Plan Nacional— Retos para la Sociedad" call with the grant reference MAT2017-88808-R. This work was performed under the Maria de Maeztu Units of Excellence Programme—MDM-2016-0618. A.B. thanks Diputación de Guipúzcoa for current funding in the frame of Gipuzkoa Fellows program.

#### **Author details**

Ana Beloqui CIC nanoGUNE, Donostia-San Sebastian, Spain

\*Address all correspondence to: a.beloqui@nanogune.eu

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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[14] Jiang JJ, Pan M, Liu JM, Wang W, Su CY. Assembly of robust and porous hydrogen-bonded coordination frameworks: Isomorphism, polymorphism, and selective adsorption. Inorganic Chemistry. 2010;**49**(21): 10166-10173. DOI: 10.1021/ic1014384

[15] Li XY, Peng YQ, Li J, Fu WW, Liu Y, Li YM. Assembly of ZnII and CdII coordination polymers with different dimensionalities based on the semi-flexible 3-(1*H*-benzimidazol-2-yl)propanoic acid ligand. Acta Crystallographica Section E: Crystallographic Communications. 2018;**74**(1):28-33. DOI: 10.1107/ S2056989017017534

[16] Wang XL, Hou LL, Zhang JW, Liu GC, Mu B, Lin HY. Two different dimensional bbbm-based cobalt(II) coordination polymers tuned by benzenedicarboxylates: Assembly, structures and properties. Inorganica Chim Acta. 2013;**397**:88-93. DOI: 10.1016/j.ica.2012.11.024

[17] Jiao CH, He CH, Geng JC, Cui GH. Syntheses, structures, and photoluminescence of three cadmium(II) coordination polymers with flexible bis(benzimidazole) ligands. Journal of Coordination Chemistry. 2012;**65**(16):2852-2861. DOI: 10.1080/00958972.2012.706283

[18] Agarwal RA, Aijaz A, Ahmad M, Sañudo EC, Xu Q, Bharadwaj PK. Two new coordination polymers with Co(II) and Mn(II): Selective gas adsorption and magnetic studies. Crystal Growth & Design. 2012;**12**(6):2999-3005. DOI: 10.1021/cg300217v

[19] Liu S, Yang Y, Qi Y, Meng X, Hou H. New Cd(II), Zn(II) helical coordination polymers constructed from hybrid ligands 4-ferrocenylbutyrate and 1,1-(1,4-butanediyl)bis-1*H*benzimidazole. Journal of Molecular Structure. 2010;**975**(1-3):154-159. DOI: 10.1016/j.molstruc.2010.04.013

[20] Wang X, Zeng F, Ma Z, Jiang Y, Han Q, Wang B. Self-assembly of benzimidazole-ended nano hyperbranched polyester and its Host-guest response. Materials Letters. 2016;**173**:191-194. DOI: 10.1016/j. matlet.2016.01.129

[21] Zhang T, Zhou LP, Guo XQ, Cai LX, Sun QF. Adaptive self-assembly and induced-fit transformations of anionbinding metal-organic macrocycles. Nature Communications. 2017;**8**:15898. DOI: 10.1038/ncomms15898

[22] Izzet G, Akdas H, Hucher N, Giorgi M, Prangé T, Reinaud O. Supramolecular assemblies with calix-6-arenes and copper ions: From dinuclear to trinuclear linear arrangements of hydroxo—Cu(II) complexes. Inorganic Chemistry. 2006;**45**(3):1069-1077. DOI: 10.1021/ ic051221e

[23] Tan S, Wei B, Liang T, Yang X, Wu Y. Anhydrous proton conduction in liquid crystals containing benzimidazole moieties. RSC Advances. 2016;**6**(40):34038-34042. DOI: 10.1039/ C6RA03375J

[24] Burnworth M, Tang L, Kumpfer JR, Duncan AJ, Beyer FL, Fiore GL, et al. Optically healable supramolecular polymers. Nature. 2011;**472**(7343): 334-337. DOI: 10.1038/nature09963

[25] Bowman-James K. Alfred Werner revisited: The coordination chemistry of anions. Accounts of Chemical Research. 2005;**38**(8):671-678. DOI: 10.1021/ ar040071t

**212**

*Chemistry and Applications of Benzimidazole and its Derivatives*

receptors: Tautomeric switching and selectivity. Organic & Biomolecular Chemistry. 2012;**10**(30):5909-5915. DOI:

[8] Zhou X, Jin Q, Zhang L, Shen Z, Jiang L, Liu M. Self-assembly of hierarchical chiral nanostructures based on metal-benzimidazole interactions: Chiral nanofibers, nanotubes, and microtubular flowers. Small. 2016;**12**(34):4743-4752. DOI: 10.1002/

[9] Bibi S, Mohammad S, Manan NSA, Ahmad J, Kamboh MA, Khor SM, et al. Synthesis,

and electrochemical studies of novel mononuclear Cu(II) and Zn(II) complexes with the 1-benzylimidazolium ligand. Journal of Molecular Structure. 2017;**1141**:31-38. DOI: 10.1016/j.

[10] Wang JH, Tang GM, Qin TX, Wang YT, Cui YZ, Ng SW. Structural and luminescent properties of a series of Cd(II) pyridyl benzimidazole complexes that exhibit extended three-dimensional hydrogen bonded networks. Journal of Coordination Chemistry. 2017;**70**(7):11189. DOI: 10.1080/00958972.2017.1299143

[11] Zhang YM, You XM, Yao H, Guo Y, Zhang P, Shi BB, et al. A silver-induced metal-organic gel based on biscarboxyl-

[12] Guo Z, Cao R, Li X, Yuan D, Bi W, Zhu X, et al. A series of cadmium(II) coordination polymers synthesized at different pH values. European Journal of Inorganic Chemistry. 2007;**5**:742-748.

functionalised benzimidazole derivative: Stimuli responsive and dye sorption. Supramolecular Chemistry. 2014;**26**(1):39-47. DOI: 10.1080/10610278.2013.822968

DOI: 10.1002/ejic.200600844

molstruc.2017.03.072

characterization, photoluminescence,

10.1039/ c1ob06800h

smll.201600842

[1] Boiani M, González M. Imidazole and benzimidazole derivatives as chemotherapeutic agents. Mini Reviews in Medicinal Chemistry. 2005;**5**(4): 409-424. DOI: 10.2174/1389557053

[2] Weissbach H, Barker HA. Isolation and properties of B12 coenzymes containing benzimidazole or

dimethylbenzimidazole. Proceedings of the National Academy of Sciences of the United States of America. 1959;**45**(4): 521-525. DOI: 10.1073/pnas.45.4.521

dynamics. Proceedings of the National Academy of Sciences. 2002;**99**(8):

[4] Jiang B, Zhang J, Zheng W, Chen LJ, Yin GQ, Wang YX, et al. Construction of alkynylplatinum(II) bzimpyfunctionalized metallacycles and their hierarchical self-assembly behavior in solution promoted by Pt···Pt and π–π interactions. Chemistry—A European Journal. 2016;**22**(41):14664-14671. DOI:

[3] Davis AV, Yeh RM, Raymond KN. Supramolecular assembly

4793-4796. DOI: 10.1073/

10.1002/chem.201601682

[5] Datta S, Saha ML, Stang PJ. Hierarchical assemblies of supramolecular coordination complexes. Accounts of Chemical Research. 2018;**51**(9):2047-2063. DOI:

10.1021/acs.accounts.8b00233

[6] Zhang Y, Zhou Q-F, Huo G-F, Yin G-Q, Zhao X-L, Jiang B, et al. Hierarchical self-assembly of an alkynylplatinum(ll) bzimpyfunctionalized metallacage via Pt···Pt and π–π interactions. Inorganic

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*Chemistry and Applications of Benzimidazole and its Derivatives*

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[34] Yi S, Zheng J, Lv P, Zhang D, Zheng X, Zhang Y, et al. Controlled drug release from cyclodextrin-gated mesoporous silica nanoparticles based on switchable host-guest interactions. Bioconjugate Chemistry. 2018;**29**(9):2884-2891. DOI: 10.1021/acs.

[35] Díez P, Sánchez A, Gamella M, Martínez-Ruíz P, Aznar E, De La Torre C, et al. Toward the design of smart delivery systems controlled by integrated enzyme-based biocomputing ensembles. Journal of the American Chemical Society. 2014;**136**(25): 9116-9123. DOI: 10.1021/ja503578b

[36] Llopis-Lorente A, Díez P, de la Torre C, Sánchez A, Sancenón F, Aznar E, et al. Enzyme-controlled nanodevice for acetylcholine-triggered cargo delivery based on janus Au–mesoporous silica nanoparticles. Chemistry—A European Journal. 2017;**23**(18):4276-4281. DOI:

[37] Holm RH, Kennepohl P, Solomon EI. Preface: Bioinorganic enzymology. Chemical Reviews. 1996;**96**(7): 2237-2238. DOI: 10.1021/cr9604144

[38] Lewis EA, Tolman WB. Reactivity of dioxygen-copper systems. Chemical Reviews. 2004;**104**(2):1047-1076. DOI:

[39] Ricco R, Pfeiffer C, Sumida K, Sumby CJ, Falcaro P, Furukawa S, et al. Emerging applications of metalorganic frameworks. CrystEngComm. 2016;**18**(35):6532-6542. DOI: 10.1039/

10.1002/chem.201700603

10.1021/cr020633r

c6ce01030j

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bioconjchem.8b00416

adfm.201803115

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[27] Shaker SA, Khaledi H, Cheah SC, Ali HM. New Mn(II), Ni(II), Cd(II), Pb(II) complexes with 2-methylbenzimidazole and other ligands. Synthesis, spectroscopic characterization, crystal structure, magnetic susceptibility and biological activity studies. Arabian Journal of Chemistry. 2016;**9**:S1943-S1950. DOI:

10.1016/j.arabjc.2012.06.013

[28] Pettinari C, Marchetti F, Cingolani A, Troyanov SI, Drozdov A. Ligation properties of N-substituted imidazoles: Synthesis, spectroscopic and structural investigation, and behaviour in solution of zinc(II) and cadmium(II) complexes. Polyhedron. 1998;**17**(10):1677-1691. DOI: 10.1016/S0277-5387(97)00455-5

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Supramolecular metallopolymers:

2018;**57**(46):14992-15001. DOI: 10.1002/

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## *Edited by Maria Marinescu*

Finding new strategies for synthesizing benzimidazole derivatives and functionalizing the benzimidazole core has proved to be important due to the compound's various applications in medicine, chemistry, and other areas. The multitude of benzimidazole derivatives marketed as drugs has led to intensive research in the field for the discovery of new biologically active structures. The general applications of benzimidazole derivatives in materials chemistry, electronics, technology, dyes, pigments, and agriculture open up new research horizons.

This book guides the rational design of benzimidazole derivatives synthesis with certain applications. Chapters cover such topics as therapeutic use of benzimidazole in conditions like diabetes, viruses, and parasitic diseases; X-ray crystal structure of selected benzimidazole derivatives; benzimidazole compounds for cancer therapy; and others.

Published in London, UK © 2019 IntechOpen © vsanderson / iStock

Chemistry and Applications of Benzimidazole and its Derivatives

Chemistry and Applications

of Benzimidazole and its

Derivatives

*Edited by Maria Marinescu*