Studies of the interaction between bis(dithiocarbamato)copper(II) complexes with nitric oxide in aqueous solution and biological applications

Three new bis(dithiocarbamato)copper(II) complexes have been prepared and characterized by elemental analysis, UV–Vis, and IR spectroscopy: bis(4-piperidonedithiocarbamato)copper(II), [Cu(Pdtc)2]2 (1), bis(piperidinedithiocarbamato)copper(II), [Cu(Ppdtc)2]2 (2), and bis[(2-piperidinecarboxy)dithiocarbamato]copper(II), Cu(Ppidtc)2 (3). The crystal structures of the complexes 1 and 2 have been determined using X-ray diffraction methods and they are dimeric. The coordination sphere of copper(II) ions is described as a distorted square-pyramid: the axial Cu–S bond distances 2.7 and 2.8 Å for 1 and 2, respectively, are longer than the equatorial Cu–S ones (2.3 Å). Complexes 1 and 2 are not soluble in water. In contrast, 3 is water soluble. The interaction of 3, the previously prepared bis[N-(dithiocarboxy)sarcosine]copper(II), Cu(Sdtc)2 (4), and bis[(dicarboxymethyl)dithiocarbamato]copper(II), Cu(Idadtc)2 (5), with nitric oxide in aqueous solution at pH 7.4 and 20 °C was spectrophotometrically studied and the experimental data were analysed by means of the spefo-letagrop and hyperquad programs, respectively. The stability constants of the complexes CuL2(NO) and CuL2(NO)2 [L = dithiocarbamate] were determined. The interaction of 1 and 2 with nitric oxide was theoretically studied by molecular mechanics methods. Complexes 3, 4 and 5 and the previously studied bis[(dihydroxyethyl)dithiocarbamato]copper(II), Cu(Deadtc)2 (6), decrease the NO produced in vitro either by sodium nitroprusside (NPS) or by cultured murine macrophages J774 stimulated with lipopolysaccharide (LPS) and interferon-γ (IFNγ). Inducible nitric oxide synthase (iNOS) activity was determined by measuring the stable NO end product, nitrite, using a colorimetric assay.

Graphical abstractThree new bis di(thiocarbamato)copper(II) complexes, CuL2, have been prepared and characterized. The interaction of three CuL2 complexes soluble in water with nitric oxide at pH 7.4 and 20 °C was spectrophotometrically studied, and the stability constants of the complexes CuL2(NO) and CuL2(NO)2 were determined. These CuL2 complexes decrease the NO produced by NPS and cultured murine macrophages J774.Figure optionsDownload full-size imageDownload as PowerPoint slide