Crystal structure, DNA interaction, and antiproliferative activity of the cobalt(II) complex of demethylcantharate and imidazole

Abstract

A new cobalt(II) complex, [Co(C₃H₄N₂)(C₈H₈O₅)(H₂O)₂]·2H₂O, of demethylcantharate(7-oxabicyclo[2,2,1]heptane-2,3-dicarboxylate, C₈H₈O₅) with imidazole has been synthesized from cobalt chloride, demethylcantharidin (NCTD) and imidazole. The complex was characterized by elemental analysis, IR, and X-ray single crystal diffraction. The complex crystallized in the monoclinic crystal system and P2₁/m space group with a = 0.634790(10) nm, b = 0.963030(10) nm, c = 1.221770(10) nm, α = 90°, β = 95.9700(10)°, γ = 90°, V = 0.742844(15) nm³, M_r  = 383.22, D_c  = 1.713 g cm⁻³, Z = 2, F(0 0 0) = 398, μ = 1.206 mm⁻¹, the final R = 0.0291, and wR = 0.0837 [I > 2σ(I )]. The interaction of the complex with deoxyribonucleic acid (DNA) was studied by electronic absorption spectra, fluorescence spectra, and viscosity measurements, which indicate that the complex binds to calf thymus DNA through a partially intercalative mode. The binding constant K _b for the complex was 2.62 × 10⁴ L mol⁻¹. The antiproliferation activity test showed that the complex has high antiproliferative ability against human hepatoma cells SMMC7721 (with IC₅₀ being 42.8 ± 0.9 µmol L⁻¹) and human lung cancer cells A549 (with IC₅₀ being 65.1 ± 3.2 µmol L⁻¹). The inhibition rates of the complex are much higher than those of NCTD.

Keywords:

• Demethylcantharidin
• Cobalt(II) complex
• Crystal structure
• DNA binding
• Antiproliferative activity

Acknowledgments

Financial support from Natural Science Foundation of Zhejiang Province (grant no. Y407301) is gratefully acknowledged.