A new Co^II complex of diniconazole: synthesis, crystal structure and anti­fungal activity

\ Heterocyclic ligands have attracted much inter­est as versatile ligands with a variety of coordination modes with transition metal centres (Galani et al., 2014; Vimal Kumar & Radhakrishnan, 2011; Coropceanu et al., 2014; Wang, Chen et al., 2012; Wang, Zhang et al., 2012). In particular, 1,2,4-triazole derivatives and their metal complexes have been studied extensively in recent years (Naik et al., 2011; Wang, Chen et al., 2012; Wang, Zhang et al., 2012; Wang et al., 2014; Liu, He et al., 2009; Liu, Lu & Yan, 2009), mainly because of their unique structures and their potential applications in optical (Manjunatha et al., 2013 ), electrical (Luo et al., 2013; Matesanz et al., 2004), and biological and anti­microbial areas (Tabatabaee et al., 2013; Xiong et al., 2014; Singh et al., 2012).

Diniconazole [systematic name: (E)-(RS)-1-(2,4-di­chloro­phenyl)-4,4-di­methyl-2-(1H-1,2,\ 4-triazol-1-yl)pent-1-en-3-ol, denoted L], as a broad-spectrum systemic triazole fungicide, was successfully developed by the Japanese Sumitomo Chemical Company in 1984, and has also been used as an effective plant growth regulator (Sumitomo, 1984). It inhibits de­methyl­ation of fungal ergosterol biosynthesis, resulting in the death of fungi, especially for ascomycetes and basidiomycetes, such as Powdery mildew, Rust, Smut fungus, Venturia, and so on (Zhao et al., 2008; Zhang et al., 2005). However, the extensive use and single-acting mechanism of diniconazole have led to a rapid selection of resistance strains. In addition, basic studies of the metal complexes of diniconazole are still rare (Nie et al., 2012; Gao et al., 2001). Given the limitations of the current diniconazole and the aim to possibly improve its properties and potential applications, in this present work, the title complex, [Co(L)₄(H₂O)₂](NO₃)₂.2H₂O, (1), has been synthesized from cobalt nitrate and diniconazole. We have determined the crystal structure of (1) and have compared the anti­fungal activities of coordination complex (1) with that of diniconazole. The microbial results show that the anti­fungal activities of the metal coordination compound were improved for Botryosphaeria ribis and Botryosphaeria berengriana compared to those of the conventional triazole fungicide diniconazole.

Diniconazole was acquired from commercial sources and was used after repeated recrystallizations. All other reagents were of reagent grade and were used as received. Elemental analysis was performed on a Vario EL III elemental analyzer. The IR spectrum was measured using a EQUINX 55 with a KBr presser bit.

Co(NO₃)₂.6H₂O (0.2910 g, 1 mmol) in ethanol (5 ml) was added dropwise to a solution of diniconazole (0.6524 g, 2 mmol) in ethanol (10 ml) under stirring for 4 h at room temperature. The resulting solution was filtered and the filtrate was left undisturbed at room temperature. Red block-shaped crystals suitable for X-ray analysis were obtained by slow evaporation afetr 12 d.

Crystal data, data collection and structure refinement details are summarized in Table 1. H atoms bonded to C atoms and hy­droxy O atoms were placed at calculated positions and refined using a riding-model approximation, with C—H = 0.95–1.00 Å and O—H = 0.84 Å, and with U_iso(H) = 1.5U_eq(C) for methyl and hy­droxy H atoms, and 1.2U_eq(C) for all other H atoms. H atoms bonded to water O atoms were located in difference Fourier maps and treated as riding atoms, with O—H = 0.8252–0.8597 Å and U_iso(H) = 1.5U_eq(O).

The anti­fungal activities of complex (1) and the ligand diniconazole were evaluated by the mycelial growth rate method (Saetae & Suntornsuk, 2010; Devappa et al., 2012) against the selected phytopathogens Botryosphaeria ribis, (I), Gibberella nicotiancola, (II), Botryosphaeria berengriana, (III), and Alternariasolani, (IV), which were provided by Shaanxi Microbiology Institute, China. Sterilized potato dextrose agar (PDA) was cooled to 323 K and mixed with these target compounds to obtain four concentrations (0.5, 1, 2 and 4 µg l^-1) immediately before pouring into the petri plates (7.5 cm in diameter). The prepared phytopathogens were inoculated in each well of 8 mm diameter (made with a borer), and then the fungi strains were cultured at 301 K for 72 h in the incubator. Petri plates inoculated with the fungal strains without compounds were also incubated as control. Each experiment was performed in triplicate. The diameter of the fungal colonies on PDA plates was measured after 72 h. The percentage inhibition of mycelial growth was calculated using the following formula:

% inhibition of mycelia growth = (dc - dt)/dc × 100,

where dc is average diameter of fungal colony in control set and dt is the average diameter fungal colony in experimental sets. The EC₅₀ values were calculated through the EXCEL program (Liu, He et al., 2009; Liu, Lu & Yan, 2009).

In the crystal structure of complex (1) (Fig. 1), each molecule consists of one Co^II cation, four coordinated diniconazole ligands, two coordinated water molecules, two free nitrate counter-anions and two additional lattice water molecules. Each Co^II centre exhibits a six-coordinated o­cta­hedral geometry. The axial positions are occupied by atoms O3W and O3Wⁱ from two coordinated water (see Table 2 for symmetry code). The equatorial positions are occupied by atoms N1, N1ⁱ, N4 and N4ⁱ atoms of four triazole rings . The Co—O/N bond lengths (Table 2) are all consistent with corresponding bond lengths found in the literature (Gökçe et al., 2015; Adach et al., 2015).

As shown in Table 3 and Fig. 2, there are two kinds of hydrogen bonds in the crystal structure. The hy­droxy O2 atom acts as a hydrogen-bond donor to nitrate atoms O4, O6 and N7 and as a hydrogen-bond acceptor to water atom O7W of the same asymmetric unit. Hy­droxy O1 atom also acts as a hydrogen-bond donor to nitrate atoms O5ⁱ, O6ⁱ and N7ⁱ (Table 3). The O3W atom takes part in three inter­molecular hydrogen bonds, viz. O3W—H2W···O7Wⁱ, O3W—H1W···O7Wⁱⁱⁱ and O3W—H2W···O6ⁱⁱⁱ (Table 3). Meanwhile, the O7W atom of lattice water takes part in one inter­molecular hydrogen bond, viz. O7W—H3W···O1ⁱⁱ (Table 3). The inter­molecular hydrogen bonds contribute to the formation of a one-dimensional chain in the crystal structure. Furthermore, the one-dimensional chains are connected by van der Waals forces and electrostatic inter­actions, giving rise to the three-dimensional framework (Fig. 3).

According to the anti­fungal screening data (Table 4), metal complex (1) shows enhanced inhibitory effects on the selected plant pathogenic fungi than diniconazole against the two fungi Botryosphaeria ribis, (I), and Botryosphaeria berengriana, (III). Especially, the title complex has the best inhibitory activity for (III) with an EC₅₀ value of 0.0031 mg l^-1. And for the fungi (I), the EC₅₀ value of complex (1) is 1.397 mg l^-1. However, the inhibitory activities of complex (1) are lower than those of diniconazole for selected plant pathogenic fungi Gibberella nicotiancola, (II), and Alternariasolani, (IV), with EC₅₀ values of 0.4438 and 0.4655 mg l^-1, respectively. In general, the title complex has the higher selectivity of anti­fungal activities for the fungi (I) and (III) but lower selectivity for the fungi (II) and (IV).

In summary, we have synthesized a new Co^II complex using diniconazole as a ligand and characterized it by elemental analysis, IR spectroscopy and single-crystal analysis techniques. The crystal structure analysis shows that Co^II adopts an o­cta­hedral geometry, coordinated by two water O atoms and by four N atoms from diniconazole ligands. There are also two free nitrate anions and two lattice water molecules in the crystal molecule. The anti­fungal activities of complex (1) were enhanced for Botryosphaeria ribis and Botryosphaeria berengriana, but reduced for Gibberella nicotiancola and Alternariasolani compared to the activities of the parent diniconazole.