Large-bite bis(phosphite) ligand containing mesocyclic thioether moieties: synthesis, reactivity, group 11 (Cu-I, Au-I) metal complexes and anticancer activity studies on a human cervical cancer (HeLa) cell line

Abstract

The large-bite bis(phosphite) ligand [{(-OC10H6(mu-S)C10H6O-)P{mu-(-OC10H6(mu-S)C10H6O-)}-P( -OC10H6(mu-S)C10H6O-)}] ((PP)-P-Lambda) (2) was obtained by the reaction of PCl3 and thiobis(2,2'-naphthol) (1). The stoichiometric reactions of 2 with elemental sulfur and selenium afforded the corresponding chalcogenide derivatives [(E) (PP)-P-Lambda(E)] (3, E = S; 4, E = Se) in good yield. Treatment of two equivalents of [ClAu(SMe2)] with 2 afforded a dinuclear complex [ClAu((PP)-P-Lambda)AuCl] (5), whereas the 1 : 1 reaction with CuI yielded the [((PP)-P-Lambda)CuI] (6) complex. The copper(I) complex 6 on treatment with various pyridyl derivatives, produced mixed-ligand complexes [((PP)-P-Lambda)CuI(NC5H5)] (7), [((PP)-P-Lambda)Cu(2,2'-bpy)]I (8), [((PP)-P-Lambda)Cu(1,10-phen)]I (9) and {[((PP)-P-Lambda)Cu(4,4'-bpy)]I}(infinity) (10). The compounds 2-5 were tested for their cytotoxic activity on the human cervical cancer (HeLa) cell line. Compounds 2 and 3 were found to inhibit proliferation of HeLa cells significantly. These agents also induced apoptotic cell death in cancer cells. Evidence presented in this study indicated that the compounds 2 and 3 activate the tumor suppressor protein p53 in the colon adenocarcinoma (HCT-116) cell line.