Synthesis, characterization, and cytotoxic activity of N-metallated rhenium(I) pincer complexes with (thio)phosphoryl pendant arms

Abstract ortho-Phosphorylated aniline and its thio analog were used as key precursors for the synthesis of new multidentate ligands based on functionalized monothiooxamides. These compounds readily formed pincer-type complexes in reactions with Re(CO)5Br upon addition of a base. The realization of a tridentate monoanionic coordination of the functionalized monothiooxamide ligands in the resulting complexes through the oxygen or sulfur atom of the ancillary P=X donor group, the nitrogen atom of the deprotonated amide unit, and the sulfur atom of the thioamide moiety was unambiguously confirmed by the multinuclear NMR and IR spectroscopic data as well as X-ray diffraction. Investigation of the cytotoxic properties of these complexes against several human cancer cell lines revealed the high potential of the P(O)-substituted derivative. For comparison, the related complex with the more flexible phosphoryl pendant arm was prepared in an analogous manner and tested for cytotoxic activity. Although this compound also demonstrated remarkable cytotoxic effects on the cancer cell lines explored, it was slightly inferior to its analog with the more rigid phosphorus(V) coordination arm. The cytotoxic properties of the rhenium complexes were shown to be associated mainly with the coordination by Re(I) ions, since the free monothiooxamide ligands almost do not inhibit or even stimulate proliferation of the cancer cells. All this renders the creation of new potential anticancer agents based on Re(I) pincer complexes of functionalized ortho-phosphorylanilides very promising.