A survey of inter­actions in crystal structures of pyrazine-based compounds

The important role of pyrazine (pz) and its derivatives in fields such as biochemistry and pharmacology, as well as in the study of magnetic properties, is surveyed. Recognition of these properties without extensive investigations into their structural properties is not possible. This review summarizes inter­actions that exist between these organic compounds by themselves in the solid state, as well as those in coordination polymers with metal ions and in polyoxometalate-based hybrids. Complexes based on pyrazine ligands can generate metal–organic framework (MOF) structures that bind polyoxometalates (POMs) through covalent and noncovalent inter­actions. Some biological and magnetic properties involving these compounds are considered and the effect of hydrogen bonding on their supra­molecular architectures is highlighted.

1. Introduction

Pyrazine is a weaker base compared to the other diazines (pyrimidine and pyridazine). These three mol­ecules are rigid compounds which makes them ideal for the construction of metal–organic frameworks (MOFs) (Kumazawa et al., 2003). MOFs are a subclass of coordination polymers with voids of different shapes and sizes whose study has seen rapid growth owing to various inter­esting applications (Rodenas et al., 2015; Huang et al., 2017; So et al., 2015; Bai et al., 2016; Giménez-Marqués et al., 2016; Masih et al., 2018). Whenever construction of MOF structures by covalent bonding has been reported, the importance of noncovalent inter­actions in the MOF architectures has been described infrequently (Manson et al., 2006, 2007, 2009; Manson, Warter et al., 2011). In order to test the ability of hydrogen bonding to create three-dimensional (3D) networks, it is important to prepare complexes with chemically flexible building-block units (such as pyrazine, which ligates easily with various paramagnetic metal ions) and ligands that can engage in very strong hydrogen-bonding inter­actions. Since the hydrogen bonds may link together magnetic centres in an inter­molecular manner, it is inter­esting to understand the relationship between long-range and local structures for magnetic exchange pathways in low-dimensional coordination polymers and in MOFs that are linked by hydrogen-bonding inter­actions (Brown et al., 2007). The functionalization of pyrazine units by electron-withdrawing or -donating groups, such as carboxyl­ate, amine, amide etc., provide opportunities for more inter­actions for the construction of structures with higher dimensions. In this respect, O—H⋯O, O—H⋯N and N—H⋯O hydrogen bonds, due to their strength and directionality, are frequently used to construct crystal structures. Weak hydrogen bonds, such as C—H⋯O and C—H⋯N, can also take part in the connectivity of supra­molecular synthons and should not be discounted (Cockroft & Hunter, 2007; Rebek, 2005; Maurizot et al., 2006; Rosen et al., 2009; Bernstein et al., 1995).

An inter­esting application of MOF structures is to provide a host for polyoxometalate (POM) units which might provide materials with inter­esting redox properties and because there are few high-dimensional structures of POM-based metal–organic frameworks (POMOFs) reported (Zhang et al., 2018; Cheng et al., 2018; Liu et al., 2011), inclusion in this survey seems appropriate.

This review discusses how weak inter­actions between aggregating tectons based on pyrazine and its derivatives, with their varied donor and acceptor sites, induce different supra­molecular assemblies that eventually result in the nucleation of a crystal. We discuss how hydrogen bonding can strengthen the crystal structures of pyrazine derivatives, including instances where the pyrazines are coordinated to metal centres. The investigation of chemical connectivity in the supra­­molecular structures of POM-based hybrids of pyrazine derivatives is inter­esting. By dividing the inter­actions between pyrazine-based MOFs and POM guests into covalent and noncovalent inter­actions, we can obtain knowledge about the directing forces that could be useful for crystal engineering in this class of compounds.

2. Pyrazine derivatives and their available donor–acceptor sites

The emphasis on structural studies of nitro­gen-containing mol­ecules, including pyrazine derivatives, is a result of various efforts that have been made in the synthesis of compounds having potential biological activity. Hence, in this section, the effect of some electron-withdrawing or -donating groups containing O, N, S and halogen atoms on the stability of pyrazine derivatives is investigated. Moreover, how various types of intra- and inter­molecular hydrogen bonding affect the inter­actions between fragments is also analyzed (Etter, 1990). Pyrazine and its methyl­ated derivatives can use H atoms attached to sp²- and sp³-hybridized hydro­carbon groups for C—H⋯N hydrogen bonds and C—H⋯π inter­actions in the crystal packing. It is evident that sp²-hybridized C—H groups have a greater acidity than sp³-hybridized C—H units and it is expected that they should have a greater affinity for N atoms than for a π moiety. This behaviour has been investigated and it is observed that in an excess of any type of C—H donor in combination with pyrazine, tri­methyl­pyrazine or tetra­methyl­pyrazine, C—H⋯N inter­actions are the only ones observed. However, in di­methyl­pyrazine compounds, the stronger donors form C—H⋯N hydrogen bonds and the weaker donors are involved in C—H⋯π inter­actions. In addition, with increasing C—H acidity, the H⋯N distance decreases (Thalladi et al., 2000). Pyridazine, as an isomer of pyrazine, is more basic and forms a layer structure in the crystal with inter­molecular hydrogen bonding that involves four C—H groups of one mol­ecule and the N atoms of adjacent fragments. The final structure is reinforced by π–π inter­actions (Podsiadło et al., 2010). In the following section, the incorporation of O-donor moieties, such as carboxyl­ate fragments, within the pyrazine skeleton and the resultant effect on the final crystal structures is described. Pyrazine N,N′-dioxide can exhibit enol and keto forms, and C—H⋯O hydrogen bonding involving the enol form is stronger than for the keto form. This leads to a planar structure, whereas the keto form exhibits a helical architecture (Näther et al., 2002; Babu & Nangia, 2007). In planar pyrazine-2-carb­oxy­lic acid (2-pzc), one weak intra­molecular hydrogen bond (C3—H3⋯O1) is observed and two inter­molecular C—H⋯O hydrogen bonds with R₂²(7) motifs form zigzag one-dimensional (1D) chains which are coupled via C—H⋯O and π–π inter­actions into the final 3D structure (Fig. 1) (Shi et al., 2006). This crystal structure presents a topology different from that reported previously for the ortho­rhom­bic polymorph (Takusagawa et al., 1974).

Figure 1 The 1D zigzag chains and 2D structure of pyrazine-2-carb­oxy­lic acid formed by O—H⋯N and C—H⋯O hydrogen bonds (dashed lines) between adjacent mol­ecules. Reproduced from Shi et al. (2006) with permission.

The crystal structures of dihydrates of pyrazine-2,3-di­carb­oxy­lic acid (2,3-pzdc) have been reported several times (Ptasiewicz-Bąk & Leciejewicz, 1997a,b, 1998, 2003). The crystal structure of anhydrous pyrazine-2,3-di­carb­oxy­lic acid contains a network of hydrogen bonds that generate a layer assembly with planar pyrazine units (Premkumar et al., 2004). In the 5-methyl­pyrazine-2,3-di­carb­oxy­lic acid crystal structure, inter­molecular O—H⋯N hydrogen bonds form trimeric units that construct a helical assembly through C—H⋯O inter­actions. Inter­estingly, no π–π inter­actions between the layers were found (Babu & Nangia, 2006). Hydrogen bonding in some pyrazine­carb­oxy­lic acid derivatives [Scheme 1; reproduced from Vishweshwar et al. (2004) with permission] have been investigated and longer inter­molecular O(acid)—H⋯O(water) hydrogen bonds were observed in 2, 3 and 4 than in 1, with two reasons given for this. First, due to the stronger hydrogen-bond donor ability of carb­oxy­lic acid compared to water and the presence of more electron-withdrawing groups in 1, the role of σ-bond co-operativity is enhanced. Furthermore, polarization of the water mol­ecules could cause a shortening of the hydrogen bonding in 1. A remarkable result is seen in triacid 5, where the O(acid)—H⋯O(water) hydrogen bonding is shorter than in 1 and is attributed to a stronger polarization-assisted hydrogen bonding in the water mol­ecules in 5 (Vishweshwar et al., 2004).

According to our results presented below, the introduction of N-donor fragments into pyrazine derivatives is expected to provide more stability to the final architectures than for the pyrazine system itself. 2,6-Di­amino-3,5-di­nitro­pyrazine and 2,6-di­amino-3,5-di­nitro­pyrazine 1-oxide take part in extensive intra- and inter­molecular hydrogen-bonding inter­actions which construct two-dimensional (2D) graphite-like sheets (Gilardi & Butcher, 2001a). The presence of dimethyl sul­foxide (DMSO) in the lattice of 2,6-di­amino-3,5-di­nitro­pyrazine, by changing the nature of the inter­action towards weaker C—H⋯O inter­actions, leads to a less compact packing arrangement (Gilardi & Butcher, 2001b). In the 2D network of the 2-amino-3-carb­oxy­pyrazin-1-ium di­hydrogen phosphate salt, O—H⋯O hydrogen bonding creates a double-chain structure of anions. Inter­molecular N—H⋯O and O—H⋯O hydrogen bonds connect cations and anions, with the pyrazinium cation having an intra­molecular N—H⋯O hydrogen bond (Fig. 2) (Berrah et al., 2011).

Figure 2 Schematic representation of the hydrogen bonds in 2-amino-3-carb­oxy­pyrazin-1-ium di­hydrogen phosphate. Reproduced from Berrah et al. (2011) with permission.

Pyrazinamide and its derivatives are a subclass of pyrazine compounds for which many crystal structures have been determined. In these structures, the presence of various donor–acceptor groups, in combination with rigidity (or flexibility) of the mol­ecules, may lead to different architectures. N-(3-Bromo­phen­yl)pyrazine-2-carboxamide, due to its flexibility, can participate in a variety of inter­actions and forms tetra­meric and dimeric polymorphs by halogen or hydrogen bonding (Fig. 3). In polymorph I, in addition to halogen bonding, intra- and inter­molecular hydrogen bonds are found which have comparable bond lengths (Khavasi & Tehrani, 2013).

Figure 3 The tetra­meric halogen/hydrogen-bonded synthon in polymorph I and the dimeric halogen-bonded synthon in polymorph II of N-(3-bromophenyl)pyrazine-2-carboxamide. Reproduced from Khavasi & Tehrani (2013) with permission.

A comparison of the structures of N-(4-halophen­yl)pyrazine-2-carboxamide and N-(5-halo-2-pyridin­yl)pyrazine-2-carboxamide suggests that the intra­molecular N—H⋯N(py) (py is pyridine) hydrogen-bonding inter­action generates better coplanarity between the aromatic rings (Khavasi et al., 2014). In 6-fluoro-3-hy­droxy­pyrazine-2-carboxamide, intra­molecular O—H⋯O hydrogen bonding, in addition to preventing keto–enol tautomerism of the hy­droxy group, forms a six-membered ring motif. Other hydrogen-bond and π–π stacking inter­actions contribute to the stabilization of the network (Shi et al., 2014). N-(Pyrazine-2-carbon­yl)pyrazine-2-carboxamide (Hdpzca) as a symmetric pyrazine imide with various available donor–acceptor sites has the ability to construct 1D, 2D and 3D supra­molecular assemblies. The near planarity of this mol­ecule is the result of a fully conjugated π-system and the bifurcated intra­molecular hydrogen-bonding inter­action between imide atom H3X and pyrazine atoms N1 and N5 [N3⋯N1 = 2.636 (4) Å and N3⋯H3X⋯N1 = 111.9°; N3⋯N5 = 2.631 (4) Å and N3⋯H3X⋯N5 = 111.9°] (Fig. 4) (Cowan et al., 2015).

Figure 4 The structure of the metal-free ligand Hdpzca and its intra­molecular hydrogen bonding. Note the planarity of the entire ligand. Reproduced from Cowan et al. (2015) with permission.

The use of pyrazines with flexible side chains can generate inter­esting structural properties because having atoms such as N, O and S in the substituents increases the reactivity by introducing more sites for inter­molecular inter­actions in the crystal. 1,10-Bis(pyrazinyl-2-carbon­yl)-1,4,7,10-tetra­aza­dec­ane as a soft pyrazine ligand has available donor–acceptor sites and, in the presence of water mol­ecules, acts as a host accommodating a six-membered ring of guest water mol­ecules with four hydrogen bonds via carbonyl and nitro­gen moieties (Shi & Zhang, 2007).

The arrangement of (E)-2-acetyl­pyrazine 4-nitro­phenyl­hydrazone in the crystal is such that in addition to N—H⋯N and C—H⋯O hydrogen bonding, there is π–π stacking between parallel arene [3.413 (14) Å] and pyrazine [3.430 (8) Å] rings that are arranged face-to-face (Shan et al., 2008). In the crystal structures of a series of (pyrazine­carbon­yl)hydrazone monohalobenzaldehyde derivatives, i.e. N₂C₄H₃CONHN=CHC₆H₄X (X = F, Cl or Br), intra­molecular N—H⋯O hydrogen bonding is observed with D⋯A separations ranging from 2.658 (5) Å for X = m-Br to 2.719 (4) Å for X = o-F, which block inter­molecular hydrogen bonding via the N atom of the pyrazine units. In the X = o-Cl structure, in addition to incorporating N—H⋯O hydrogen bonding, a C—H⋯O hydrogen bond is formed between the pyrazine ring and the amide group of a neighbouring mol­ecule. The inter­molecular C—H⋯O hydrogen bonding generates a ribbon-like structure that leads to π-stacking between the layers and the final 3D structure (Baddeley et al., 2009).

Pyrazine-2-carbohydrazides have moderate anti­tuber­cu­losis properties but the methyl­ated pyrazine-2-carbohydrazide derivatives do not. Therefore, comparisons between their structures may help in the understanding of the structure/activity relationships. In (I) [Scheme 2; reproduced from de Souza et al. (2011) with permission], hyperconjugation from the heteroaryl ring to the arene ring through the hydrazine unit has been suggested as the main contributor to the near planarity of type I compounds and this is reinforced by an intra­molecular N—H⋯N hydrogen bond. However, substitution of a methyl group on the N2 atom in the pyrazine-2-carbohydrazide system and the resulting intra­molecular C—H⋯O hydrogen bond between methyl and carbonyl groups changes the conformation so that the mol­ecule is no longer planar overall. It is thus suggested that the anti­tubercular properties of (I) could be attributed to the planarity of the mol­ecules (Fig. 5) (Gomes et al., 2013).

Figure 5 The conformations of N′-[(E)-ar­yl]pyrazine-2-carbohydrazides, where E(1) and E(2) are the trans and cis arrangements of the C=O and N2—CH3 bonds, respectively. Reproduced from Gomes et al. (2013) with permission.

The incorporation of substituents that contain an S atom can play important roles in the stabilization of the crystal structures. The crystal structure of S-methyl 5-methyl­pyrazine-2-carbo­thio­ate and its solid-state inter­actions have been reported (Aubert et al., 2007). This mol­ecule has three types of inter­molecular hydrogen-bonding inter­actions (two C—H⋯N and one C—H⋯O), as well as π-stacking inter­actions that generate the 3D crystal structure. Although the presence of the S atom does not have an important structure-directing effect in the crystal structure of this com­pound, this mol­ecule can act as an inter­mediate in the pre­paration of various compounds of biological inter­est (Aubert et al., 2007). The structures of three thio­(semi)carbazones derived from 2-acetyl­pyrazine segments show various conformations and configurations depending on the arrangements of the mol­ecular components. As there are several available donor–acceptor sites, intra- and inter­molecular hydrogen-bonding networks in the crystal structures can be expected. Indeed, in syn-(1E)-2-acetyl­pyrazine-3-thio­semi­car­bazone (Fig. 6a), the H atom on N4 is involved in three types of inter­actions: (i) intra­molecular hydrogen bonding with N1; (ii) inter­molecular hydrogen bonding with the N atom of the pyrazine ring and the formation of dimers with an R₂²(18) ring pattern; (iii) inter­action with the thio­ureide group of an adjacent mol­ecule. The C—H⋯N(pz) and N2—H⋯S inter­actions connect fragments and lead to the overall 3D structure. In syn-(1E,4Z)-2-acetyl­pyrazine-4-ethyl-3-thio­semi­carbazone (Fig. 6b), the thio­ureide groups inter­act with the pyrazine ring of an adjacent mol­ecule in the mean mol­ecular plane through two adjacent N2—H⋯N(pz) [2.401 (3) Å] and C—H⋯S [2.894 (3) Å] hydrogen bonds, while N4—H⋯N1 is an intra­molecular inter­action. In syn-(1Z)-2-acetyl­pyrazine-4,4-dimethyl-3-thio­semicarbazone, the pyrazine-ring configuration is such that the N atom of the pyrazine ring is syn to the N1—H bond and an intra­molecular hydrogen bond is formed between them. The pyrazine ring also forms C—H⋯S hydrogen bonds generating R₂²(20) graph sets (Fig. 6c) (Venkatraman et al., 2009). In conclusion, the presence of different functional groups in pyrazine-based structures results in the formation of different hydrogen bonds with different strengths that are relevant in crystal engineering.

Figure 6 Displacement ellipsoid plots (50% probability) of three thio­semicarbazones. Reproduced from Venkatraman et al. (2009) with permission.

3. Pyrazine as a potent ligand in coordination polymers

Pillared layer structures are appropriate candidates for the construction of porous 3D networks (Russell et al., 1997). While hydrogen-bonding inter­actions reinforce these structures, it is observed that in the absence of guest fragments, the structures lose their stability. Therefore, introduction of metal centres leads to more stable coordination networks (Zimmerman, 1997). Hence, despite the effective role of metal centres in coordination polymers, hydrogen bonds continue to have a prominent role in increasing the dimensions of the structures. This role was investigated in the crystal structures of complexes containing pyrazine derivatives. Complexes of pyrazine-2,3-di­carb­oxy­lic acid and transition-metal ions (TMs) display various architectures. In the 1:2 complex, monometallic [Ni(2,3-pzdcH)₂(H₂O)₂] units participate in a hydrogen-bonding network and, in addition to strong intra­molecular hydrogen bonding among carboxyl­ate groups [O—H⋯O = 2.408 (2) Å], display hydrogen bonding between coordinated water and neighbouring fragments to form a stable 3D structure. By contrast, [Cu(2,3-pzdcH)₂]_x·2H₂O adopts a chain structure with double-bridging 2,3-pzdc units that are fortified by hydrogen bonding of the lattice water mol­ecules. The monomethyl ester of 2,3-pzdc coordinates differently with Cu cations and this changes the final architecture of the crystal. Here, one O atom and its adjacent N atom chelate in equatorial positions, while an uncoordinated O atom of another ligand occupies an axial position. With the ester groups uncoordinated, only a 2D polymer is generated (Neels et al., 1997). In the case of 1:1 complexes, a 1D linear material is formed in which 2,3-pzdc acts as a tetra­dentate ligand to link to metal centres by coordinating in equatorial sites, with the axial positions occupied by H₂O mol­ecules which participate in the hydrogen-bonding network, leading to a 3D structure (Mao et al., 1996). The use of pz and 2,3-pzdc together resulted in a coordination polymer in which pz as pillared units link sheets of Cu complexes containing tridentate 2,3-pzdc (Kondo et al., 1999). In another coordination polymer of 2,3-pzdc and Cu^II centres, the organic ligand used only three of its six possible donor sites. The N/O donor atoms of the ligand in bidentate mode occupy two equatorial positions on the square-pyramidal Cu ion with the O-donor bridgehead in the axial site forming a 1D polymeric structure. In addition to π–π inter­actions between two adjacent pyrazine rings, hydrogen bonding through coordinated and lattice water mol­ecules generates the 3D structure. A study of the magnetic properties of this compound showed that there are very weak anti­ferromagnetic inter­actions between the Cu centres through the N and O atoms of the 2,3-pzdc unit, with these donor atoms in the basal and apical positions, respectively (Konar et al., 2004). By changing the solvent of the reaction from water to DMSO, despite obtaining the same coordination polymer, the coordination of 2,3-pzdc to the Cu centres occurs as a tridentate ligand with one carboxyl­ate group involved in hydrogen bonding to DMSO (Xiang et al., 2004). With lead(II) halides, 2,3-pzdc forms a 1D double chain coordination polymer with the ligand coordinating in a tetra­dentate manner. Intra- and inter­molecular hydrogen bonding to the ligand O atoms accompanied by Br⁻ bridges generates a 3D network (Fard & Morsali, 2010). The 1D coordination polymer based on the Pb₂Cl₂(2,3-Hpzdc)₂(H₂O)₂ monomer, when submerged in a solution containing Cu^II cations, undergoes cation exchange with preservation of the 1D chain without bridging halides. When solutions containing Hg^II or Co^II cations are used, different products are obtained. In the case of Hg^II, the [Pb₂(2,3-pzdc)₄(H₂O)₂]⁴⁻ dimer is formed with some of the 2,3-pzdc ligands serving to construct 2D layers. It is noteworthy that the Pb—O and Pb—N bond lengths in this complex are shorter than in the starting complex. When Pb₂Cl₂(2,3-Hpzdc)₂(H₂O)₂ is soaked in a Co^II solution, a structural transformation occurs and a 3D network structure based on the Pb₃(2,3-pzdc)₃(H₂O) unit is formed (Wardana et al., 2015). Reaction of pyrazine-2,5-di­carb­oxy­lic acid (2,5-pzdc) with Zn^II salts in di­methyl­formamide (DMF) solution resulted in the 1D coordination polymer [Zn(2,5-pzdc)(DMF)₂]_n (Isaeva et al., 2011).

Metal complexes of pyrazine-2,3,5,6-tetra­carb­oxy­lic acid (pztc) have been studied (Ghosh & Bharadwaj, 2004, 2005, 2006; Ghosh et al., 2006), with the solid-state structures being stabilized by intra- and inter­molecular hydrogen bonding (Fang et al., 2008). Pyrazine­tetra­carb­oxy­lic acid reacted with Cu^II salts in buffer solutions containing different cations generate zigzag chains and also quasilinear polymer structures in which extensive hydrogen-bonding networks stabilized the solid-state structure (Graf et al., 1993). If the above reaction is carried out with added lanthanoid ions, different frameworks result. For example, nine-coordinate Tb^III ions are connected to each other by pztc ligands chelating through two ONO sites to generate a hexa­gonal assembly. On the other hand, with Eu^III cations, the ligand coordinates in mono-, di- and tridentate modes with the inclusion of potassium ions in the solution and only one N and one O atom are left uncoordinated. An inter­molecular hydrogen bond is also observed in [EuK(pztc)(H₂O)₄], whereas in [Tb₂(H₂pztc)₃]·3.5H₂O, there is an inter­molecular O—H⋯O inter­action of 2.395 (6) Å (Thuéry & Masci, 2010).

3-Carbamoylpyrazine-2-carboxyl­ic acid (L₂) acts as a bi­dentate ligand in coordinating to Ni^II ions, forming Ni(L₂)₂(H₂O)₂ in which the amide moiety is uncoordinated and participates in hydrogen bonding with an adjacent mol­ecule, generating a zigzag 1D chain. Additional hydrogen bonding expands this to the 3D structure (Heyn & Dıetzel, 2007). 3-Amino­pyrazine-2-carboxyl­ate as a multidentate ligand could coordinate to transition metals (Fig. 7) and it is observed that in every case the amine groups form intra­molecular N—H⋯O hydrogen bonds to the carboxyl­ate group, while the remaining pyrazine N atom and the amine group participate in hydrogen-bonding inter­actions and construct 2D and 3D supra­molecular architectures (Karmakar et al., 2015; Li & Zhang, 2015; Koleša-Dobravc et al., 2017; Tayebee et al., 2008). It has been shown that vanadium compounds have anti­diabetic effects and complexes of vanadium with bidentate anionic organic ligands have a greater influence than vanadium inorganic moieties. In the two vanadium complexes of 3-aminopyrazine-2-carboxylic acid and 2-pyrazine-2-carb­oxy­lic acid, the central metal atom has distorted octa­hedral geometry, but hydrogen-bonding reinforces the structures with 3D and double-layer networks, respectively. The insulin-like activity of vanadium complexes of 3-aminopyrazine-2-carboxyl­ic acid and pyrazine-2-carb­oxy­lic acid have been compared with VOSO₄ anions. It is observed that these three complexes have similar activities and a bidentate ligand, and also that an amine moiety does not effect the insulin-like activity (Koleša-Dobravc et al., 2017).

Figure 7 Schematic representation of the various coordination modes of 3-amino­pyrazine-2-carboxyl­ate. Reproduced from Karmakar et al. (2015) with permission.

2-Acetyl­pyrazine N⁴-pyridyl­thio­semicarbazone (HL) is a compound with anti­microbial activity whose inter­action with bis­muth(III), a heavy metal with low toxicity, has been studied. Hence, the composition of these two segments can have different effects on the cytotoxicity. In this regard, the [Bi(HL)(NO₃)₃] complex, with unusual eight-coordinated Bi^III centres, has been reported. The results of inhibition studies of some Gram positive and Gram negative bacteria indicated that the IC₅₀ values (compound concentration that produces 50% of cell death) for the complex (1.6 µM) is much lower than for both the mentioned ligands (14.8 µM) and Bi(NO₃)₃·5H₂O (41.6 µM). Thus, its activity is comparable to that of cisplatin (1.2 µM) (Fig. 8) (Zhang, An et al., 2012).

Figure 8 Hydrogen bonds (dashed lines) in [Bi(HL)(NO3)3]. Reproduced from Zhang, An et al. (2012) with permission.

N-[(Z)-Amino­(1,4-diazin-2-yl)methyl­idene]-1,4-diazine-2-car­bohydrazonic acid (PZOAPZ) is a flexible mol­ecule with two pyrazine moieties connected by a chain containing a diazine fragment, as well as amine and hy­droxy functional groups. By coordinating to four metal centres, it forms polynuclear clusters (Thompson et al., 2001). A `locked' structural modification of a dinuclear complex with the tetra­dentate ligand was reported in which three five-membered chelate rings, and also hydrogen bonding between the coordinated water mol­ecules and Br atoms, form a flat arrangement (Fig. 9). These inter­actions generate intra­molecular anti­ferromagnetic inter­actions between the Cu centres through the planar O-atom linkage (Grove et al., 2004).

Figure 9 Structure of [Cu2(PZOAPZ-H)Br3(H2O)2]. Reproduced from Grove et al. (2004) with permission.

3.1. Pyrazine-based MOF structures

Pyrazine as a two N-atom-donor ligand when coordinated to TMs can generate different sizes of multicore MOFs, such as mol­ecular squares, larger coordination polymers, mixed-valence complexes or larger discrete assemblies (Steel & Fitchett, 2008). In the [Ag₂(pz)₃](BF₄)₂ framework, tricoordinated Ag⁺ ions are first linked to the pz ligand to form a 1D zigzag chain, with additional pz linkages connecting the chains to form a 3D framework that has space for the BF₄⁻ anions (Carlucci et al., 1995). A microwave-assisted hydro­thermal synthetic technique, which reduced the reaction time, was used to synthesize a MOF structure based on pyrazine and copper fragments. This crystal structure consists of inter­penetrating ten-membered rings with alternating pyrazine and sulfate groups linking the Cu^II centres. Two coordinated water mol­ecules form short hydrogen bonds to adjacent sulfate rings to construct the 3D framework (Amo-Ochoa et al., 2007). A 2D sheet MOF, i.e. {[Co₂(pztc)(py)₂(H₂O)₄]·4H₂O}_n, provides the perimeter to accommodate infinite chains of cyclic water hexa­mers. Among the many available donor–acceptor sites of pyrazine­tetra­carb­oxy­lic acid, only one carboxyl­ate group was not involved in coordination with the Co ions. Several water mol­ecules involved in hydrogen bonding between themselves and the uncoordinated carboxyl­ate ion, as well as coordination to Co centres, assist in generating the overall structure (Ghosh & Bharadwaj, 2005). Bismuth-based MOFs can be attractive candidates for doping lanthanoid cations into the network due to the similarity in the ionic radii and the preferred coordination spheres of Bi³⁺ and trivalent lanthanoid ions. One example is the in-situ co-doping of lanthanoid ions into the 2D coordination polymer [Bi₂Cl₆(pz)₄] (Heine et al., 2014). Five zinc(II) halide pyrazine coordination compounds were pre­pared and under ligand-poor conditions, a chain-like structure was formed, while in a ligand-rich environment, framework architectures were formed, with bidentate pz ligands occupying equatorial positions and the halides situated in axial positions (Bhosekar et al., 2006).

A partnership of classical covalent and coordination bonds in the construction of MOFs is common, while bifluoride linkers, through strong F—H⋯F bonds can give inter­esting MOF structures. In the 3D {[Cu₂F(HF)(HF₂)(pz)₄][(SbF₆)₂]}_n framework, layers of [Cu(pz)₂]²⁺ cations are connected to each other by the HF₂⁻ linkages with a bond enthalpy of 175 kJ mol⁻¹. Here the hydrogen-bond strength within HF₂⁻ anions [H—F = 1.142 (6) Å and F—H⋯F = 171 (7)°] is comparable to Cu—F and Cu—N coordination bonds (Li et al., 2013). In addition to the HF₂⁻ unit, H₃F₄⁻ ions are observed in the solid state; these are less stable than H₂F₃⁻ or HF₂⁻ segments. While H₃F₄⁻ has the central fluoride ion hydrogen bonded to three additional HF mol­ecules, the resulting 3D structure, i.e. [CuAg(H₃F₄)(pz)₅](SbF₆)₂, was similar to previously reported compounds (Manson et al., 2009).

3-Amino­pyrazine-2-carb­oxy­lic acid is a multicentre ligand and has the ability to establish high-dimensional structures. This bidentate ligand can fill out the coordination spheres of metal ions and have uncoordinated fragments, such as the N atoms of pyrazine and the amine group, available for hydrogen bonding, to organize 3D frameworks with various morphologies (Tayebee et al., 2008; Starosta & Leciejewicz, 2010; Cheng et al., 2009; Gao & Ng, 2010; Deng et al., 2010).

N-(Pyrazine-2-carbon­yl)pyrazine-2-carboxamide forms com­plexes with di- and trivalent metals to construct 3D frameworks with a variety of structures. In the 1:2 complexes [Co^II(dpzca)₂], {[Co^III(dpzca)₂]BF₄}₂·5CH₃CN and [Cu^II(dpzca)₂], two tridentate dpzca ligands occupy all the coordination sites of the approximately octa­hedral metal ions, but the case of [Cu^II(dpzca)(H₂O)₃]₂(SiF₆)·2H₂O is different and a large number of strong hydrogen-bonding inter­actions are observed. Axially coordinated water mol­ecules are involved in hydrogen bonding in bifurcated modes with the O atoms of a neighbouring dpzca ligand to form dimers, and in further hydrogen bonding with axially coordinated water mol­ecules from an adjacent dimer to generate double-stranded chains with water mol­ecules and hexa­fluoro­silicate anions (Cowan et al., 2015).

4. Propagation of magnetic inter­actions through hydrogen bonding

Covalent bonding is generally considered as a necessary link between single-mol­ecule magnets to facilitate inter­actions between them (Sessoli et al., 1993; Inglis et al., 2011). In this regard, pyrazine derivatives can act as a linkage between magnetic metal centres. The role of pyrazine-2,5-di­carboxyl­ate and pyrazine-2,3-di­carboxyl­ate as linker groups is investigated in the spin exchange between paramagnetic metal centres. With either pyrazinedi­carb­oxy­lic acid (pzdc) acting as a bis-bidentate linkage and occupying equatorial positions, the connectivity between metal centres (Mn, Fe, Zn and Cu) is observed. A low magnetic susceptibility of the copper ions is observed when a carboxyl­ate group of the nonplanar 2,3-pzdc ligand acts as a monodentate linkage between the metals (Beobide et al., 2006). Furthermore, the nature of the bridging ligand is key to the properties of the material in the solid state since it dictates the sign and magnitude of the magnetic exchange between the paramagnetic metal ions. In the 2D coordination polymer {[Cu₂(pztc)(py)₂(H₂O)₃]·4H₂O}_n, a very weak coupling between metal centres is observed, as may be expected from the pyrazinetetra­carboxyl­ate linkage with a large Cu⋯Cu distance (Ghosh et al., 2006).

In recent years, noncovalent inter­actions, such as π–π stacking and hydrogen bonding, have been shown to be a new channel for magnetic exchange in supra­molecular chemistry (Fukuroi et al., 2014; Hicks et al., 2001; Atzori et al., 2014; Fitzpatrick et al., 2016). [Fe(HL)₂Cl₄] (L is 2-amino­pyrazine) is a discrete complex having a 2D layer structure formed by halogen bonding between Cl and the N atom of the amine substituent on the pyrazine moiety of an adjacent complex. A 3D noncovalently linked assembly is generated by π–π stacking between pyrazine rings, with a distance of 3.346 (5) Å between them, and an anti­ferromagnetic inter­action between the S = 2 ions was observed (Rusbridge et al., 2018).

Bifluoride (HF₂⁻) and fluoride (F⁻) ligands in copper pyrazine complexes were observed to function as bridging and terminal units through strong hydrogen bonding to connect Cu centres with the suggestion that such compounds may work to stabilize long-range magnetic ordering at low temperature (Brown et al., 2007). F⋯H—O hydrogen bonding (2.612 and 2.597 Å) (Fig. 10) connects the inverted 1D coordination polymer generated from the CuF₂(H₂O)₂(pz) monomer into a quasi-2D lattice whose magnetic properties were studied. The magnitude of the experimental g factor and its reproduction through density functional theory (DFT) calculations proved that the orbitals in the CuF₂O₂ plane generate an anti­ferromagnetic square lattice. Also, a lowering of the temperature affects both the strength of the F⋯H—O hydrogen-bond network and the magnetic ordering (Manson et al., 2008).

Figure 10 Chain packing arrangements of CuF2(H2O)2(pz), viewed along the chain axis. Dashed lines delineate O—H⋯F hydrogen bonds. Reproduced from Manson et al. (2008) with permission.

In further studies, the role of two types of FHF⁻ linkages on the magnitude of the anti­ferromagnetic inter­actions was investigated. For the [Cu(HF₂)₂(pz)]_n coordination polymer, one can conceive of three ways of strengthening spin exchange. One would be through a pyrazine bridge between metal atoms, while the others would be through μ_1,1- or μ_1,3-bridging modes of the HF₂⁻ anion. The results showed that the Cu–pz–Cu path has a weaker spin exchange, whereas a μ_1,1-FHF⁻, by sharing the σ-type orbitals of the F atom with the 3d orbitals of the Cu centre, or a μ_1,3-mode HF₂⁻, which involves spin exchange through π orbitals, has a larger value (Manson, Warter et al., 2011). In addition to the role of the linker in the spin exchange, the arrangement and symmetry of the linker can be of particular importance. Hence by comparison of the [Ni(HF₂)(pz)₂]X (X = PF₆⁻ and SbF₆⁻) coordination polymers it was found that, in spite of similar frameworks, spin exchange through the Ni–FHF–Ni and Ni–pz–Ni pathways differed. Owing to the linear Ni–FHF–Ni linkage and also a higher crystal symmetry that leads to linear Ni–pz–Ni units in the [Ni(HF₂)(pz)₂]SbF₆ framework, this complex has a higher magnetic susceptibility (Manson, Lapidus et al., 2011). The HF₂⁻ unit, as the superexchange pathway, can be actively involved in both the magnetic quantum phase transition and the series of pressure-induced structural distortions which affect the overall magnetic susceptibility (O'Neal et al., 2016).

The Cu(pz)(NO₃)₂ and [Cu(pz)₂(NO₃)]NO₃·H₂O polymers have been considered for investigation of the magnetic property of a quasi-low-dimensional quantum magnet. Although nitrate ions help to increase the dimension of the chain and lattice of Cu(pz)_n through incorporating hydrogen bonding (C—H⋯O inter­actions), for the purposes of determining the feasibility of spin exchange, only the pyrazine linkage and the inter­metallic distances and angles between the Cu centres have been considered (Dos Santos et al., 2016).

The magnetic susceptibility of [CuX(pz)₂]BF₄ (X = Cl or Br), with a distorted octa­hedral coordination of the Cu²⁺ ion by four N atoms of pyrazine and halide linkages, was investigated. It has been shown that the Cu–pz–Cu and Cu–X–Cu pathways have different values for spin exchange between Cu centres (Table 1). In spite of the shorter distance in the inter­layer Cu–X–Cu inter­action compared to that in the intra­layer Cu–pz–Cu inter­action, the mol­ecule exhibits an elongated Jahn–Teller axis along the c axis and the unpaired electron in the d_x²-y² orbital results in a quasi-2D magnetic network through σ-bonding for the Cu⋯N inter­action (Kubus et al., 2018). Consequently, complexes containing pyrazine- and halogen-based ligands, which connect magnetic metal centres through covalent and noncovalent inter­actions, have an effective role in determining the magnetic susceptibility of this class of compounds.

Table 1
Structural and magnetic parameters of compounds with tetra­gonal [Cu(pz)₂]²⁺ layers (T_N the Néel temperature)

Compound	Space group	Distance (Å)		Cu⋯Cu distance (Å)		Pz rotation angle (°)	J∥ (K)	TN (K)
		Cu—N	Cu—X	Cu–pz–Cu	Cu–X–Cu
[CuCl(pz)2]BF4	P4/nbm	2.053	2.865	6.895	5.731	58.8	9.4	3.9
[CuBr(pz)2]BF4	P4/nbm	2.052	2.963	6.894	5.926	55.4	8.9	3.8

5. Role of hydrogen bonding in the stabilization of POM-based hybrids

POMs as anionic clusters have unique properties in various fields, such as biology (Arefian et al., 2017), photophysical systems (Fashapoyeh et al., 2018), magnetism (Clemente-Juan et al., 2012) and catalysis (Liu et al., 2013). Furthermore, their electron-rich surfaces and accessible oxygen groups make them suitable candidates for the construction of two-component (type I) or three-component (type II) hybrids (Mirzaei et al., 2014). Hence, incorporation of POMs into systems containing pz ligands and studies of the inter­actions that connect them could prove fruitful. In many POM-based hybrids, water mol­ecules, whether coordinated to the metal atoms or simply lattice solvent mol­ecules, can affect the dimensions of the structures (Guo et al., 2016; Zhang et al., 2014). It is inter­esting to clarify the roles of hydrogen bonds in POM-based hybrids containing pyrazine derivatives. The α-Keggin ion phospho­dodeca­molybdate creates 3D tunnel structures for the inclusion of pyridazinium, pyrazinium and pyrimidinium ions by electrostatic inter­action, while short inter­actions in [(C₄H₅N₂)₃(PMo₁₂O₄₀)]·nH₂O, containing N—H⋯O, C—H⋯O and O—H⋯O hydrogen bonds, consolidate the architecture of the crystal (Ugalde et al., 1997). In further work, the four-electron reduced [β-PMo₁₂O₄₀]³⁻ anion was reacted with the above cations, and pyridazinium was found to be incorporated by a N—H⋯O hydrogen bond with a ten-membered ring of hydrogen-bonded water mol­ecules that are disposed between polyanion chains of [β-PMo₁₂O₄₀]³⁻ subunits connected by hydrogen-bonding inter­actions. The pyrimidine (pym) units were hydrogen bonded to the water mol­ecules, which formed part of a `waterfall' along the [010] direction with the rest of the water mol­ecules, and were also connected via π-inter­actions with the surface O atoms of the tetra­meric [β-PMo₁₂O₄₀]³⁻ units that adopt a helicoidal arrangement, thereby constructing organic–inorganic hybrids. In a related study, pyrazine units, through participation of both N atoms in hydrogen bonding, create a 3D tunnel network that can accommodate the helicoidal arrangement of [PMo₁₂O₄₀]³⁻ chains and construct 3D reinforced hybrids (Vitoria et al., 2003). The 2-acetyl­pyrazinium ion also exploits N—H⋯O inter­actions in its inter­action with [PW₁₂O₄₀]³⁻ to assemble a hybrid (Liu, 2010). Inter­actions between the do­decyl­pyridazinium (C₁₂pda) cation and the deca­tungstate (W₁₀) anion were investigated. This cation with its long alkyl chain, unlike the pyridazinium cation itself, did not show any π–π stacking or C—H⋯π inter­actions because the arrangement of the organic moieties was such that the heterocyclic portions are located away from each other. Instead, C—H⋯O hydrogen bonds between the hydro­philic head of C₁₂pda and the W₁₀ anion lead to a layer structure (Otobe et al., 2015).

Most of the organic/inorganic salts based on the Anderson–Evans POMs undergo 1D hydrogen-bonding inter­actions with strong N—H⋯O hydrogen bonding. The (Hpym)₂[H₇CrMo₆O₂₄]·2H₂O hybrid shows 1D N—H⋯O hydrogen-bonding inter­actions. Furthermore, protonated polyanions inter­act with uncoordinated N atoms of the cations, while water mol­ecules participate in C—H⋯O hydrogen-bonding inter­actions (Fig. 11) (Singh et al., 2014).

Figure 11 Representation of the (Hpym)2[H7CrMo6O24]·2H2O sheet showing (a) N—H⋯O and C—H⋯O inter­actions, and (b) O—H⋯N inter­actions. Reproduced from Singh et al. (2014) with permission.

Although Anderson–Evans-type clusters link covalently to a discrete [M(pz)₂(H₂O)₂]²⁺ (M = Co, Ni and Zn) complex through corner-sharing forming 1D chains, the uncoordinated N atom of pz, the protonated pyrazine and the water mol­ecules inter­act with the oxygen-rich surface of the {CrMo₆(OH)₆O₁₈}²⁻ polyanion to firmly stabilize the structure. [{Ni(pz)(H₂O)₄}₂{CrMo₆(OH)₆O₁₈}](CH₃COO)₂·6H₂O con­sist of linear chains of {Ni(pz)(H₂O)₄} subunits with amplification of the 2D structure carried out by hydrogen bonding between coordinated water and the POM, and also C—H⋯O inter­actions with the acetate fragments (Singh et al., 2010). The 3D structure of {[M(pz)(H₂O)₄]₂(H₃O)₂[V₁₀O₂₈]} (M = Cu^II and Ni^II) is similar to many coordination polymers containing pyrazine and contains a 1D infinite chain structure, which in this case is connected to the deca­vanadate units by hydrogen bonding (Wang et al., 2008).

Pyrazine-2-carb­oxy­lic acid has various available donor–acceptor sites so that, in addition to coordinating to metal ions, it has potential for hydrogen-bonding inter­actions. In the case below, pyrazine-2-carb­oxy­lic acid is used as an organic linker to form a chain-like coordination polymer. Coordinated water mol­ecules in the Cu(2-pzc)(H₂O)₂ building blocks, in addition to joining chains by hydrogen bonding, link [Mo₈O₂₆]⁴⁻ polyanions via hydrogen bonding into a coordination polymer structure (Zheng et al., 2001). In another report, pyrazine-2-carb­oxy­lic acid, acting as a tridentate ligand, links Ni^II ions to form a 1D zigzag chain that with the [β-Mo₈O₂₆]⁴⁻ anion coordinates to four Ni centres and results in an inorganic–organic hybrid compound (Li, Chen et al., 2014). Pyrazine-2-carb­oxy­lic acid uses three functional groups to coordinate to Cu and Co ions, with subsequent inclusion of the Anderson–Evans cluster {CrMo₆(OH)₇O₁₇}, which acts as a bidentate inorganic linkage and forms a 1D coordination polymer. The presence of water in cavities of the ladder-like sheet, which inter­act with coordinated water and the POM by hydrogen bonding, forms a 3D structure from 2D layers (Singh & Ramanan, 2011). [Na₄(H₂O)₁₄Cu(2,3-pzdc)₂]H[Al(OH)₆Mo₆O₁₈]·5H₂O is a rare 3D organic–inorganic compound in which the decadentate Anderson POM [Al(OH)₆Mo₆O₁₈]³⁻ connects to [Na₄(H₂O)₁₄]⁴⁺ clusters and produces 2D window-like layers. From this is generated a 3D open framework by connection to [Cu(2,3-pzdc)₂]²⁻ complexes (Li et al., 2010). The configuration of POM-containing structures can depend on the type of POM used. Accordingly, two Anderson-type clusters, i.e. [TeMo₆O₂₄]⁶⁻ and [CrMo₆(OH)₅O₁₉]⁴⁻, are used with complexes containing 3-(pyrazin-2-yl)-5-(1H-1,2,4-tri­azol-3-yl)-1,2,4-triazolyl (pytty) and Co^II cations. The product is the first example of a 2D network consisting of a 1D Co–TeMo₆ inorganic chain and a 1D circle-shaped complex of the pytty ligand with adjacent inorganic cations. Finally, C—H⋯O inter­actions between pytty fragments and the POM formed the 3D architecture. Furthermore, C—H⋯O hydrogen bonding between the [Co₂(H₂pytty)₂]⁴⁺ subunit and [CrMo₆(OH)₅O₁₉]⁴⁻ anions increases the dimensions of the hybrid to a 2D network (Bai et al., 2018). In another hybrid, layers of {Cu₄(pztet)₅(Hpztet)(H₂O)₂}³⁺ (pztet is pyrazine­tetra­zole) units consist of hexa- and tetra­coordinated Cu^II ions, while [PMo₁₂O₄₀]³⁻ polyanions occupy axial positions of the Cu^II cations, which have an axially distorted {CuN₄O₂} geometry, to construct a 3D POM-pillared structure (Darling et al., 2013).

A considerable number of flexible N-donor ligands have been used in POM-based metal–organic complexes (Tian et al., 2008; Meng et al., 2009; Wang et al., 2010; Zhang et al., 2011; Taleghani et al., 2016). For example, two flexible bis-pyrazine–bis-amide ligands are reacted with POM and it is seen that noncoordinated [PMo₁₂O₄₀]³⁻ and [SiMo₁₂O₄₀]⁴⁻ anions are trapped at the inter­face between adjacent wave-like chains of {[Cu(L1)]²⁺}_n [L1 is N,N′-(propane-1,3-di­yl)bis­(pyrazine-2-car­boxamide)] cations via C—H⋯O hydro­gen bonds to create a 2D supra­molecular architecture (Fig. 12a). By increasing the carbon chain length, the complex forms 2D {[Cu(L2)]²⁺}_n [L2 = N,N′-(hexane-1,3-di­yl)bis­(pyrazine-2-carboxamide)] layers which connect to the [SiMo₁₂O₄₀]⁴⁻ clusters via hydrogen bonds, thereby increasing the dimension of the supra­molecular structure (Fig. 12b). When the flexible N,N′-(propane-1,3-di­yl)bis­(pyrazine-2-carboxamide) ligand is introduced into the reaction containing smaller POMs, inter­esting structures can be formed. A ribbon-like 1D chain structure, modified by incorporating tridentate [CrMo₆(OH)₆O₁₈]³⁻ Anderson anions as building blocks, involves alternating POMs and Cu^II centres. When the POM building block is [Mo₈O₂₆]⁴⁻, the polyanion creates a bridge between adjacent 1D helical chains to form the 2D {[Cu(L1)(β-Mo₈O₂₆)_0.5(H₂O)₂]·H₂O} network (Wang et al., 2015).

Figure 12 The 2D and 3D supra­molecular structure formed via hydrogen bonds in (a) [Cu2(L1)2(SiMo12O40)(H2O)2]·2H2O and (b) [Cu2(L2)2(SiMo12O40)]·2H2O. Reproduced from Wang et al. (2015) with permission.

In 2012, the first organic–inorganic hybrid based on rare-earth-substituted polyoxometalates (RESPs) with a poly­car­b­oxy­lic acid ligand was reported. Pyrazine-2,3-di­carboxyl­ate acts as a tetra­dentate ligand in the [(α-SiW₁₁O₃₉)RE(H₂O)(2,3-pzdc)]⁷⁻ (RE = Y^III, Dy^III, Yb^III and Lu^III) subunit, connecting discrete RESPs and also Cu(en)₂ fragments (en is ethyl­enedi­amine). One uncoordinated carboxyl­ate group participated in the hydrogen-bonding network that involved the N atoms of en and pyrazine-2,3-di­carboxyl­ate, the surface O atoms of the POM and the coordinated and uncoordinated water mol­ecules organized by intra- and inter­molecular hydrogen bonding to form the 3D supra­molecular architecture (Zhang, Zhao et al., 2012).

6. POMOFs

Numerous investigations (Rangan et al., 2000; Yaghi & Li, 1996; Hennigar et al., 1997; Noro et al., 2000; Tong & Chen, 2000) proved that the nature of the MOFs depends on several factors, such as the type and oxidation state of the metal ion, the steric hindrance of the ligand, the metal-to-ligand ratio and the appropriate template guest mol­ecules. POM clusters usually serve in one of three roles, namely pillar, template and node in POMOFs. Design strategies for the construction of 3D POMOFs recognize some problems: (i) POMs have surface O atoms which provide abundant potential coordination sites to link the transition-metal ions, but the low electron density and large steric hindrance cause them to rarely generate POMOFs; (ii) the size of the MOF is not large enough and it is hard to accommodate the cluster. Furthermore, the selection of the organic ligand which is to be part of the framework organization needs to be effective. Pyrazine ligands may be useful here because of their multiple sites for coordination and hydrogen bonding (Cong et al., 2018). Therefore, in this section, we examine inter­actions that bind POMs in the voids of MOFs, either covalently or not, and the effects of the pyrazine-based ligand and the metal centre in these inter­actions.

6.1. POMOF-based covalent inter­actions

Bowl-like complexes of pz and Cu^I cations were prepared that act as hosts for the [PMo₁₂O₄₀]³⁻ guest in which the Cu—O distance is 2.865 Å (Zhang et al., 2009). (H₄pzdc)₅[(H₂pzdc)₆(pzdc)₂(H₂O)₂Na₆][PW₁₂O₄₀]₄·31H₂O is the first example of a host–guest compound with double-Keggin anions acting as the coordinating template. They are incorporated in a double bowl-like structure [Na₆(H₂pzdc)₆(pzdc)₂]²⁺ by ionic Na—O and Na—N bonds. Inclusion of the [PW₁₂O₄₀]³⁻ template along the [201] direction produced a 2D hybrid architecture. This 2D host–guest framework filled the inter­layer spaces via extensive hydrogen-bonding inter­actions with free H₂pzdc fragments and water mol­ecules, and stabilized the structure (An et al., 2010). In the [Cu(pz)]₃[PW₁₂O₄₀] organic–inorganic hybrid, pyrazine and Cu cations form 1D chains that combine with the 1D inorganic chain generated from Cu cations and O atoms of the POM to form a 3D framework (Yang et al., 2014). In a complex with Ag⁺ ions and pz ligands paired with [SiW₁₂O₄₀]⁴⁻ anions, two deca­nuclear rings linked by pz ligands are formed and tetra­dentate [SiW₁₂O₄₀]⁴⁻ anions are coordinated to four Ag⁺ ions, leading to a twofold inter­penetrating structure (Zhou et al., 2014).

Other POMOFs which have been reported include one with 2-ethyl-3-methyl­pyrazine (2Et,3Me-Pz) ligands linking Cu^I ions to generate a 2D (10,3) sheet with a hexa­gonal window having dimensions 19.691 × 6.659 × 6.659 Å. The inclusion of [SiW₁₂O₄₀]⁴⁻ anions in four-connected linkages surrounded by four Cu–2Et,3Me-Pz chains leads to a 3D framework structure (Fig. 13a). In another compound, the 2,6-di­methyl­pyrazine (2,6-Me₂pz) ligand and Cu^I cations form a 1D zigzag chain which couples with hexa­dentate [SiW₁₂O₄₀]⁴⁻ anions and other Cu atoms to yield a 3D structure (Fig. 13b). Neighbouring 1D chains of the 2,5-di­methyl­pyrazine–Cu (2,5-Me₂pz–Cu) units are connected to tetra­dentate [SiW₁₂O₄₀]⁴⁻ POM anions and generate a (4².6⁴)(4¹.6⁴.8¹) topology (Fig. 13c). When the 2,3,5,6-tetra­methyl­pyrazine (2,3,5,6-Me₄pz) ligand is used in this system, a similar topology results, but the coordination environments of the cations and their packing mode are different (Fig. 13d). Changing the POM to [PMo₁₂O₄₀]³⁻ units, but keeping the rest the same as above, led to changes in the coordination mode and differences in the final structures (Figs. 13e and 13f) (Liu et al., 2011).

Figure 13 Perspective views of (a) the 3D framework in [Cu^I4(2Et,3Me-Pz)5(SiW12O40)], the 2D double layer in (b) [Cu^I4(2,6-Me2Pz)4(SiW12O40)], (c) [Cu^I4(2,5-Me2Pz)4(SiW12O40)(H2O)2], (d) [Cu^I4(pztc)4(SiW12O40)]·H2O and (e) [Cu^I4(2,5-Me2Pz)4(PMo^VI11Mo^VO40)]·1.5H2O, and (f) the 2D layer in [Cu^I3(2,3,5-tmpz)4(PMo12O40)]·H2O (2,3,5-tmpz is 2,3,5-tri­methyl­pyrazine). Reproduced from Liu et al. (2011) with permission.

In the [Cu₅(pz)₆Cl(SiW₁₂O₄₀)] hybrid, a 2D sheet with 6³ topology is formed, with the Keggin units sandwiched between the layers; Cl bridges generate the final 3D structure (Li et al., 2018). However, in [Ag₄(pz)₃(H₂O)₂(SiW₁₂O₄₀)], the Ag^I ions create a 2D layer involving one N atom of pyrazine, two O atoms from two different [SiW₁₂O₄₀]⁴⁻ anions and one water mol­ecule. The Ag(pz) chain is then connected to the Keggin POMs to make the overall 3D framework (Cui et al., 2010). When POM templates are reacted with Cu^I/Ag–pz coordination polymers, [Cu(pz)₆Cl][HPMoMoO₄₀] is pro­duced. The structure consists of two double-layer coordination compounds with hexa­gonal and deca­gonal voids connected to each other by Cl bridges. Inclusion of two types of [PMo₁₂O₄₀]³⁻ anions, that act as bidentate and hexa­dentate units, construct a 3D POM framework. The [Cu₃(pz)₃Cl][Cu₂(pz)₃(H₂O)][PMo₁₂O₄₀] organic–inorganic hybrid has a similar framework to the previous hybrid but differs in some details (Qi et al., 2013). The Ag–pz coordination framework constructs parallelogram-like voids that incorporate [BW₁₂O₄₀]⁵⁻ POMs with eight Ag—O coordination bonds. Use of the [H₂W₁₂O₄₀]⁶⁻ polyanion between 12-node layers of Cu^I–pz subunits through weak Cu⋯O inter­actions gave a 3D POM-based inorganic–organic hybrid (Fig. 14) (Zhu et al., 2011b).

Figure 14 Summary of the formation of three porous coordination polymers templated by different Keggin ions. Reproduced from Zhu et al. (2011b) with permission.

Crystal structures of high-dimensional POMOFs containing monosubstituted Keggin anion chains have been reported less frequently; however, [Cu^II₄Cu^I₂(pzc)₆(HPCuMo₁₁O₃₉)(H₂O)₆]·2H₂O is the first example of a 3D POMOF constructed from monosubstituted Keggin anions and N-heterocyclic carboxyl­ate ligands. The 1D inorganic Keggin chain that is formed by sharing terminal O atoms inter­acts with the 1D metal–organic {[Cu₆(2-pzc)₆]⁴⁺}_n chain in which pyrazine-2-carb­oxy­lic acid acts as a di- and a tridentate ligand coordinated to Cu^I/Cu^II cations (Wang et al., 2014).

When pz and 2,2′-bi­pyridine (2,2′-bipy) mixed ligands were used to construct Wells–Dawson POM-based compounds, Cu^I–pz chains and porous P₂W₁₈–Cu layers are crosslinked over Cu atoms and construct a 3D framework with a (6³)(6²8⁴) topology. The [Cu^II(2,2′-bipy)₂(H₂O)] complex has multiple roles and not only acts as a charge-balance segment, but also as a template in the inorganic pores (Fig. 15) (Zhu et al., 2011a).

Figure 15 Views of (a) the inorganic P2W18–Cu layer with large circular voids and (b) the [Cu^II(2,2′-bipy)2(H2O)]^2+ counter-cations filling the voids. Reproduced from Zhu et al. (2011a) with permission.

6.2. POMOF-based noncovalent inter­actions

Some POMOFs based on pyrazine- and methyl­pyrazine-derived complexes have been reported in which POMs are grafted into 2D voids with noncovalent inter­actions. In the presence of pyrazine or 2,3-di­methyl­pyrazine (2,3-Me₂pz) ligands and Cu^II cations, the frameworks formed have a 4¹8² topology. These three POMOFs, {[Cu(2,3-Me₂pz)(2,5-Me₂pz)_0.5]₄(SiW₁₂O₄₀)(2,5-Me₂pz)}_n, {[Cu(2-Mepz)_1.5]₃(PMo₁₂O₄₀)(H₂O)_3.5}_n and {[Ag(2,3-Me₂pz)_1.5]₄(SiW₁₂O₄₀)}_n, have the same 6³ network. Although it is considered that electrostatic inter­actions hold the structure together, one cannot disregard hydrogen-bond inter­actions between methyl H atoms and the aromatic ring with O atoms on the POM surface. In this manner, H₂O mol­ecules can also take part in the stabilization of these structures. Two H₂O units in {[Cu(pz)_1.5]₄(SiW₁₂O₄₀)·2H₂O}_n coordinated to the Cu^I ion are connected to two [SiW₁₂O₄₀]⁴⁻ subunits by hydrogen bonding (Kong et al., 2006). In the reaction of the [PW₁₂O₄₀]³⁻ polyanion with the Cu^II ion and pz ligand, a Cu₁₂(pz)₁₂ loop-based coordination polymer templated by double-Keggin anions was obtained. A staggered packing of 2D layers leads to a sandwich-type template and decreases the inter­molecular repulsions. Furthermore, C—H⋯O hydrogen-bonding inter­actions between the pyrazine ligands and [PW₁₂O₄₀]³⁻ subunits stabilize the hybrid (Li, Ma et al., 2014). Two different Cu^I/pz frameworks were reported to construct a 3D organic–inorganic hybrid on reaction with [PMo₁₂O₄₀]³⁻ anions. Cu(pz) chains crossed over each other and created cubic-like chambers with dimensions 13.038 × 13.038 × 13.038 Å and, with insertion of [PMo₁₂O₄₀]³⁻ guest anions, formed two types of void (Fig. 16a). In the other framework, with a 2D 4¹8² network, one observes octa­gonal and square voids with dimensions 14.087 × 17.497 Å and 6.826 × 6.929 Å, respectively, with the [PMo₁₂O₄₀]³⁻ clusters occupying the larger void (Fig. 16b). Again, hydrogen bonding, such as C—H⋯O inter­actions, that surround the [PMo₁₂O₄₀]³⁻ units need to be considered (Qi et al., 2013).

Figure 16 Stick/polyhedral view of the 3D structure of (a) [Cu^I(pz)]3[PMo^VI12O40] and (b) [Cu^I(pz)1.5]4[PMo^VMo^VI11O40]·pz·2H2O, along the crystallographic b axis. Reproduced from Qi et al. (2013) with permission.

Most recently, the 3D POMOF [{C_l4Cu₁₀(pz)₁₁}{As₂W₁₈O₆₂}]·1.5H₂O, with a {3.4.5⁶.6⁷}²{3.4⁶.5³}²{3².4².5⁶.6⁵} topology, was reported. The 3D {C_l4Cu₁₀(pz)₁₁} complexes, via coordination of the Cu centre with the N atoms of pyrazine units and chloride bridges, establish two channels which provide void space for the accommodation of classical Wells–Dawson [As₂W₁₈O₆₂]⁶⁻ clusters. The eight coordination sites of the surface O atoms of the [As₂W₁₈O₆₂]⁶⁻ POM are used for connection with Cu ions, while the H atoms of pyrazine are involved in C—H⋯O hydrogen-bonding inter­actions which help to stabilize the structure (Cong et al., 2018).

[Mo₈O₂₆]⁴⁻ and [V₁₀O₂₈H₄]²⁻ anions are included in the coordination polymer containing pyrazine-2-carb­oxy­lic acid and a copper cation. Besides the anions producing 1D zigzag chain-like structures and 2D sheets, respectively, inter­molecular inter­actions between fragments reinforce the final structure. Extensive hydrogen bonding is observed in susceptible sites containing O atoms of the carboxyl­ate and coordinated and lattice water mol­ecules and also oxygen-rich surfaces of the polyanions leading to fortified polymers. However, in the absence of the isopolyanions, only the mononuclear compound Cu(2-pzc)₂(H₂O)₂ was formed (Zheng et al., 2001).

Phenazine (phnz) is a ligand with a short length and it is expected that its MOFs would have small pores. Hence, two types of Lindqvist polyanion are utilized in the [Cu₂(phnz)₃] coordination polymers and it was shown that these POMs [M₆O₁₉] (M = Mo or W) could be placed in the 2D honeycomb voids with 6³ topology and also through C—H⋯O hydrogen-bonding inter­actions with adjacent sheets to form a 3D coordination polymer (Sha et al., 2009). The effect of changes in the organic ligand in POM-based hybrids was investigated. In the presence of phenazine, which acts as a mono- and bidentate bridging ligand, the discrete [Ag₄(phnz)₆(SiW₁₂O₄₀)] cluster was formed, whereas hydrogen bonding (C—H⋯O inter­action between the phnz and POM fragments) and π–π stacking formed the 3D supra­molecular structure. By using pyrazine, which has a smaller steric hindrance, the structure will be different and three types of Ag^I segments are present. There is firstly the wave-like chain consisting of covalently-linked [Ag₂(phnz)(pz)(H₂O)]²⁺ cations with [SiW₁₂O₄₀]⁴⁻ anions and secondly the `S'-like chain formed by hydrogen-bonding inter­actions between the [Ag(phnz)(pz)]⁺ cation and the [SiW₁₂O₄₀]⁴⁻ anion. These two types of chains act together to construct a sheet structure. Finally, the remaining fragment, [Ag₂(phnz)₃]²⁺, is connected to the POM via hydrogen bonding and leads to the final hybrid (Zhu et al., 2010).

7. Conclusion

This review highlights different aspects of the pyrazine ligand and its derivatives for the construction of metal complexes having multinuclear structures. The available donor–acceptor sites of these ligands make them capable of forming intra- and inter­molecular hydrogen bonds which can help to increase the dimension of the structures involved in the construction of coordination polymers and especially MOFs. It was inter­esting that the pyrazine ligand can have a spin-exchange role for inducing magnetic exchange through σ-bonds, particularly in the presence of H-atom-donor groups, such as HF₂⁻, whose hydrogen-bonding inter­actions strengthen spin exchange. Pyrazine ligands can act as bridges to form pillared MOF structures with various pore sizes. Other studies on metal–pyrazine complexes containing POMs in their frameworks demonstrate the role of hydrogen bonding in these supra­molecular architectures.