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 I 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 angstrom for 1 and 2, respectively, are longer than the equatorial Cu-S ones (2.3 angstrom). Complexes I and 2 are not soluble in water. In contrast, 3 is water soluble. The interaction of 31 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 degrees 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-gamma (IFN gamma). Inducible nitric oxide synthase (iNOS) activity was determined by measuring the stable NO end product, nitrite, using a colorimetric assay. (c) 2006 Elsevier Ltd. All rights reserved.