Copper(II) complexes of fused ring selenosemicarbazones: Synthesis, structure elucidation, biological activity and molecular modeling

Abstract

Reaction of copper(II) acetate with cyclohexanoneselenosemicarbazone (Hcysesc), 5-chloro isatinselenosemicarbazone (5-ClHIstsesc), 1-methyl isatinselenosemicarbazone (1-MeHIstsesc), 3-indole selenosemicarbazone (3HInsesc), 3-acetylindole selenosemicarbazone (3-AcHInsesc and 2-naphthaldehyde selenosemicarbazone (2Hnaphsesc) in 1:2 (M: L) molar ratio yielded complexes of stiochiometry, [Cu(L)2] 1-6 (L = cysesc 1; 5-ClIstsesc 2; 1-MeIstsesc 3; 3-Insesc 4; 3-AcInsesc 5; 2-naphsesc 6). All the complexes are characterized by IR, Mass and ESR spectroscopy. Two well defined g values (g

and g perpendicular to) in ESR spectrum of complexes 1-4, 6 indicate axial symmetry, whereas symmetry around copper(II) metal in complex 5 is confirmed by three different g values (g1, 2.095; g2, 2.15; g3, 2.26), which supports rhombic distortion. The value of g

obtained is greater than g perpendicular to, which is greater than ge, in 1-4, 6 is in well agreement in dx2-y2 ground term of square planar geometry. The value of empirical factor f for complexes 1-4, 6 lies in the range, 102-135 cm indicating a square planar geometry with small distortion, where as in complex 5 value (f = 146 cm) is in conformity of tetrahedral geometry with larger distortion. All the compounds (selenosemicabazones and their complexes) are tested for DPPH radical scavenging, ABTS radical scavenging, FRAP ferric reducing and CUPRAC cupric reducing antioxidant capacity assay and all the compounds have shown good antioxidant capacity in general. Best results are obtained for H1L with FRAP, 6.75 +/- 0.01 mu g TE/ml and CUPRAC, 9.52 +/- 0.07 mu g TE/ml. All the compounds are also tested for their anti-tubercular activity against M. tuberculosis H37RV strain ATCC27294. Ligands, H1L, H3L, H6L and complex 6 have shown highest anti-TB activity (MIC = 1.6 mu g/ml) which is similar to the standard drugs (Isoniazid, Ethambutol). anti-TB activity of H2L and H5L (MIC = 12.5 mu g/ml and 25 mu g/ml) increased on complexation with copper(II) (MIC = 1.6 mu g/ml, 2; 12.5 mu g/ml, 6). Experimental results are supported by molecular modeling studies, where a considerable intermolecular interaction of these compounds with the active site of amino acid of enoyl reductase from M. tuberculosis has been observed with minimum binding energy -6.2, -7.3, -7.7, -7.4, -7.2, -8.7 Kcal/mol for H1L, H2L, H3L, H4L, H5L, and H6L and -7.2, -9.4, -8.6, -9.3, -9.9, and -10.6 Kcal/ mol for copper complexes 1, 2, 3, 4, 5 and 6 exhibited respectively.