Coordination behavior of benzimidazole, 2-substituted benzimidazoles and benzothiazoles, towards transition metal ions

,


Introduction
Benzimidazoles are involved in a great variety of biological processes.13a Therefore, substituted benzimidazoles have attracted the interest of various research groups, especially since it has been reported that the influence of the substitution at the 1, 2 and 5 positions of the benzimidazole ring is very important for their pharmacological effects.][16][17] The biological activity and pharmacological properties of the benzimidazole derivatives, have led us to investigate the coordination behavior of benzimidazole and benzothiazole derivatives towards transition metal ions.Herein, a number of coordination compounds with manganese(II), cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II), mercury(II), chromium(III) and cobalt(III) and polyfunctional benzazole derivatives are discussed.These polyfunctional molecules bear nitrogen, oxygen and sulfur atoms as basic sites for coordination.Bonding occurs through the nitrogen atom in a monodentate form, regardless of the metal ion or the heteroatom (N, S, O) present in the molecule, or in a bidentate mode, giving place to a variety of metal-ligand coordination modes.In some cases, the formation of a six membered ring by inclusion of a metal ion in a planar delocalized system is observed, where the ligand is bonded in a bidentate mode.

Benzimidazole coordination compounds 2.1.1. Halide compounds
Several groups have reported cobalt(II) and zinc(II) coordination compounds showing a similar stoichiometry [M(bz) 2 X 2 ] (M II = Co, Zn; X -= Cl, Br, I).18a-18c In all cases, the geometry adopted by the metal ion is tetrahedral.The compound dichloro-bis(1H-benzimidazole)-cobalt(II), reported Barba-Behrens et.al., is an example is of this type of complexes, where the two chlorine ions (Cl -) and two benzimidazoles are bonded to the metal center through the unprotonated nitrogen, Figure 1.The copper(II) halide complexes, present a different behavior from that of the Co II or Zn II compounds, where the metal ion stabilizes different geometries.In the case of the [Cu(bz) 2 Br 2 ] compound, the Cu II ion adopted a trans-square planar geometry, to minimize the steric hindrance of the benzimidazole molecules.

Carboxylate derivatives compounds
In the past years, it has been of great interest to study the coordination behavior of benzimidazole compounds with a variety of carboxylate derivatives.
The research groups of Xu and Bukowska-Strzyzewska have investigated the chemistry of cobalt(II), nickel(II) and copper(II) coordination compounds containing benzimidazole and carboxylic acids derivatives, as described below.The compounds resulted monomeric, dimeric or polymeric complexes, the number of coordinated benzimidazole molecules to the metal ion varies and also different geometries are stabilized.
Xu et.al. reported the synthesis of monomeric and polymeric coordination compounds with cobalt(II) chloride and malonic acid.In the monomeric compound, the metal ion presented an octahedral geometry with four benzimidazole ligands and one bidentate malonate dianion.23a In the polymeric compound catena-((µ 2 -malonato)-aqua-(1H-benzimidazole)cobalt(II)), the polymeric array was stabilized through the carboxylic groups, where the malonate ligand forms a six-membered chelate, bridging two metal ions, which are in an octahedral geometry, Figure 5a.23b Another example of these compounds is the analogous copper(II) compound, Figure 5b, where the copper(II) atom stabilizes a square-pyramidal geometry.23c In these two compounds, one benzimidazole ligand is coordinated to the metal atoms.Compounds with fumaric and succinic acid, catena-((µ 2 -fumarato-O,O')-diaqua-bis(1Hbenzimidazole-N)-M(II)) (M(II) = cobalt, 25a nickel, 25b copper, 25c ), and catena-((µ 2 -succinato-O,O')-diaqua-bis(1H-benzimidazole-N)-M(II)) (M(II) = cobalt, 25a and copper, 25c ), were obtained from the corresponding acid in alkaline medium.These compounds consist of a polymeric M II complex bridged by fumarato or succinato dianions, each carboxyl group is bonded in a monodentate mode to the metal atom and it is also bonded to a neighboring metal ion through terminal carboxyl groups forming one-dimensional polymeric chains, Figure 7. Adjacent chains are linked via N-H … O hydrogen bonds between benzimidazole and carboxylic groups, as by O-H … O hydrogen bonds between coordinated water molecules and carboxyl groups.A similar copper(II) compound with acetylendicarboxylato was reported by Sieron et.al.The syntheses of the cobalt(II) coordination compounds with terephthalic and isoterephthalic, catena-((µ 2 -terephthalato)-bis(1H-benzimidazole)-cobalt(II)) and catena-((µ 2 -isoterephthalato)-bis(1H-benzimidazole)-cobalt(II)), were carried out under similar conditions to those of the previous complexes.en aromatic hydroxybenzoic acids were reacted with copper(II), different coordination behavior of the metal ion was observed, depending on the OH substitution in the aromatic ring.The salicylate compound, consists of one-dimensional polymeric chains bridged by the salicylate anion, where the copper(II) atom presents a tetragonally distorted octahedral geometry, Figure 10a.28a While 3-hydroxybenzoic acid stabilizes two independent molecules in the unit cell: one of them is a mononuclear compound with the copper(II) atom in a square-planar coordination geometry formed by two benzimidazole molecules and two hydroxylbenzoate anions, stabilizing a trans isomer as observed in the previously described [Cu(bz) 2 Br 2 ], Figure 10b.28b The other molecule is a dimer of the previous one, formed by bridging hydroxybenzoate, where de copper(II) is in a square-pyramidal geometry.When changing from 3-to 4-hydroxylbenzoate anions, the metal atom is located in an inversion center, with a non-regular octahedral geometry, Figure 10c.28c On the other hand, a distorted square planar arrangement is stabilized by the copper(II) ion, in the complex containing 3,5-dihydroxybenzoate ligands, Figure 10d Reedijk and co-workers, reported the compound catena-((tris(µ 2 -pentane-1,5bis(carboxylato)-tetrakis(1H-benzimidazole)-di-copper(II)), Figure 12, where the carboxylate ions are monodentate and in a bridging mode, with pentacoordinated copper(II) ions.Catena-(tris(µ 2 -pentane-1,5-bis(carboxylato))-tetrakis(1H-benzimidazole)-dicopper(II)). 30 Dimeric copper(II) compounds have been obtained with acetate bridges by Bukowska-Strzyzewska 33a and, with methacrylate by Zhou and co-workers.33b The coordination complexes have a dimeric copper arrangement through four carboxylate bridges, while the benzimidazole ligands are coordinated in the axial position, giving place to an octahedral arrangement for each copper(II) ion, Figure 15.

Another example of a polymeric compound is catena-(µ 3 -(3-carboxylatophenoxyacetato-O,O',O'',O''')-(1H-benzimidazole)-copper(II)),
ARKAT USA, Inc.ere are some examples with tridentate ligands that will be discussed in this section.An example of a cobalt(II) coordination compound, with a ligand bearing three oxygen donor atoms, is the oxydiacetate complex, where the tridentate oxydiacetate dianion is bonded to the central metal ion in a facial configuration, and the octahedral Co II coordination sphere is completed by three benzimidazole ligands, as shown in Figure 17a.35a A similar compound with a facial coordination mode is observed in the nickel(II) complex, with L-aspartate, where two oxygen and a nitrogen atoms are bonded to the central metal ion, Figure 17b ARKAT USA, Inc.

Nitrogen monodentate compounds
In this section a series of transition metal compounds with 2-monosubstituted derivatives will be discussed.They all coordinate to the metal ion through N3 of the benzimidazolic nitrogen.Despite of the presence of oxygen atoms as possible coordinating sites towards transition metal ions, both ubz and mbc derivatives behaved as monodentate ligands, bonded through the benzimidazolic nitrogen to the metal atom, as illustrated by the carbamate (mbc) compound, [Co(mbc) 2 Cl 2 ]⋅CH 3 OH, Figure 20.In this complex, the central metal ion acquires a tetrahedral geometry. 37

. 2-(4'-Thiazolyl)benzimidazole. Coordination compounds containing thiabendazole, 2-(4'-thiazolyl)benzimidazole (4tbz), form bis-chelate and tris-chelate compounds, as reported by
Barba-Behrens et.al.In all cases, the ligand coordinates to the metal (cobalt(II), nickel(II), copper(II), zinc(II), cadmium(II) and mercury(II)) through the imidazolic and thiazolic nitrogen atoms; the heterocyclic sulfur does not interact with the metal.The bis-chelate compounds stabilized the cis-isomers, while the tris-chelate complexes gave two types of isomers: the cobalt compound is of C1 symmetry, and the nickel and cadmium complexes are of C3 symmetry, see Figure 23b.For cobalt(II), nickel(II) and copper(II) compounds, a similar interaction with both nitrogen atoms was found, as the M-N bond lengths are within the range, (1.97-2.09Å) Figure 23. 41Copper(II) compounds with thiabendazole have been investigated with different counterions, such as chloride, nitrate and butanedioate.
In [Cu(tbz) 2 Cl]Cl⋅H 2 O⋅EtOH copper(II) is pentacoordinated, with a distorted trigonal bipyramidal geometry, see Figure 24. 42In this context, Muthiah and co-workers reported [Cu(tbz)(NO 3 ) 2 (H 2 O) 2 ], where the copper atom has a distorted octahedral geometry, with one bidentate neutral ligand, two coordinated nitrates (trans), and two H 2 O molecules.are shown in Figure 25.The copper(II) complex is a monomer, with a ligand and two chlorine atoms bonded to the metal ion, in a tetrahedral geometry.While for cadmium(II), a dimeric compound is obtained, where the metal atoms are bridged by two chlorides, each of them bonded to a ligand and a chlorine atom, in a square-pyramidal geometry. 44

. 2-Guanidinobenzimidazole. 2-Guanidinobenzimidazole (2gb
) is a polyfunctional planar molecule with a delocalized π electronic system, five nitrogen atoms that may act as basic centers and five labile N-H bonds.Theoretical calculations were carried out to determine which 2gb isomers may be involved in coordination (see Figure 27), as well as, the structures of the coordination compounds.According to the calculations, tautomer A of 2gb is the most stable species in the solid state, according with its X-ray crystal structure.However, it is important to mention that isomer B-IV yields chelates upon coordination to metal ions. 47 48 In summary, two different types of coordination compounds were found.In the first type, the ligand is bonded to the metal ion in a chelating mode through the imidazolic nitrogen atom, N3 and the guanidino nitrogen atom, N12; which is the case for most of the complexes.The second type of coordination behavior was observed in the cobalt(II) compounds, where the ligand coordinates as monodentate through the imidazolic N3; the structure is tetrahedral, Figure 28. 49ith two chelating 2gb molecules a square-planar geometry was stabilized.On the other hand, for those compounds in which only one ligand is in the coordination sphere, the structure was either tetrahedral (copper and zinc; chloride and bromide) or octahedral (cobalt).Reedijk et al. have also investigated the reactions of 2gb with copper(II), using its triflate and perchlorate salts.The synthesis and characterization of two copper(II) isomers, purple α-Cu(2gb) 2 (CF 3 SO 3 ) 2 and green β-Cu(2gb) 2 (CF 3 SO 3 ) 2 , with different positions of the triflate anions has been reported.In the green compound one of the triflate anions is at a long, semicoordination distance, while in the purple compound the anions are at a much longer distance.50a The crystal structures of these isomers, Figure 29, is also compared with that of the green colored [Cu(2gb) 2 ](ClO 4 ) 2 ⋅H 2 O, 50b and is concluded that they exhibit a similar distorted tetrahedron arrangement around Cu(II), although both green compounds have a dihedral angle of nearly 40°, while that of the purple compound is of 37°.These distortions only occur at the copper(II) compounds and may be related to the electronic properties of the Cu II ion.The X-ray diffraction structure of a Ni II compound, where 2gb is deprotonated and therefore monoanionic, was obtained.Nickel(II) is coordinated to two deprotonated 2gb ligands in a square-planar geometry through the imidazolic N3 and the guanidino N12, see Figure 31 51 The reaction of 2gb with zinc nitrate in hot methanol afforded a crystalline compound in which two 2-guanidinobenzimidazole ligands were coordinated through N3 and N12 atoms to the zinc(II), Figure 32.In this compound 2gb is bonded through the imidazole ring and guanidine group, it id important to mention that both ligands had protons at N1 and N10.The zinc(II) complex was studied by 1 H and 13 C NMR spectroscopy, which confirmed that the presence of a proton at the N atom directly bonded to the benzimidazole induces a shift of the C-2 signal to lower frequencies.Similar structures were obtained by Castillo-Blum and co-workers, when either cobalt(III) or chromium(III) compounds, 52 in both cases, the metal ions are two inert centers toward substitution processes.3 C and 2D NMR spectra together with the X-ray diffraction data for the distorted octahedral [Co(2gb) 3 ] 3+ cation showed that only the mer isomer was obtained, Figure 33.The crystal space group is P 1 therefore, the crystal must contain a racemic mixture of the Λ and ∆ isomers.3.2.1.5 .2-Aminomethylbenzimidazole.Hui-Zhong Kou and co-workers reported complexes of the ligand 2-aminomethylbenzimidazole (2Hamb), with copper(II) and nickel(II).The structure of copper(II) complexes: [Cu(2Hamb) 2 (ClO 4 ) 2 ] and [Cu(2Hamb) 2 (dca) 2 )], where dca = N(CN) 2 is discussed.In both cases 2Hamb behaves as a bidentate ligand; the geometry around each metal ion is octahedral.For [Cu(2Hamb) 2 (ClO 4 ) 2 ], two perchlorate anions occupy the axial positions of a distorted axially elongated octahedron and four nitrogen atoms occupy the equatorial plane in a trans mode, Figure 35a.For [Cu(2Hamb) 2 (dca) 2 )] two amide nitrogen atoms of two dicyanamide anions are situated at the axial sites of an axially elongated octahedron. 56The nickel(II) complex corresponds to [Ni(2Hamb) 2 (2amb)]N(CN) 2 ⋅H 2 O, where the central metal ion is in a distorted octahedral geometry; with three coordinated ligands in a facial mode.Two of the three 2-aminomethylbenzimidazole (2Hamb) ligands are neutral, while the third one is anionic, Figure 35b. 57RKAT USA, Inc.

Concluding Remarks
Coordination compounds containing benzazole derivatives and transition metal ions have attracted the interest of several research groups, partly due to their very interesting chemistry as well as their possible applications.It has been shown that 2-benzimidazole derivatives allow coordination towards metal ions through a variety of sites, with groups bearing nitrogen, oxygen ARKAT USA, Inc. and sulfur atoms coordination occurs through the imidazolic nitrogen atom and also through N, S or O atoms present in the molecule, giving place to a variety of metal-ligand coordination modes.In some compounds the formation of a six membered ring by inclusion of a metal ion gives place to a planar delocalized system, while for other complexes different stereochemistries, geometries, conformers and tautomers are stabilized.
Benzimidazolic coordination compounds containing carboxylates promote the formation of polymeric compounds (catena) by intra and intermolecular interactions, where benzimidazole plays an important role in the stabilization of the structures through π-stacking interactions.These types of compounds show diverse magnetic properties. 18a

2 -
Benzothiazolylaminzole and 2-(2-aminobenzothiazolyl-amino)benzoxazoleo) benzothia.Contreras and co-workers had previously reported heterocyclic systems derived from benzothiazole.Bis-benzothiazolyl amine forms a six membered ring, by inclusion of a metal(II) ion in a planar delocalized system, alternating sp 2 carbon and nitrogen atoms.In all the complexes this ligand is deprotonated and coordinated through N3 and N13, in a bidentate mode.Compounds containing this ligand present different geometries: tetrahedral for cobalt(II), zinc(II) and mercury(II), octahedral and square pyramidal for nickel(II).A related ligand, btz-boz, (2-(2aminobenzothiazolylamino)benzoxazole), was also synthesized by the same group and its coordination chemistry toward metal ions investigated.The nickel(II) compound [Ni(btzboz)(OAc)(MeOH) 2 ] contains one btz-boz bonded to the metal ion, forming a pentacyclic frame, a bidentate acetate, and two trans-methanol molecules completing the hexacoordination, Figure22.40