The relationship between electrospray ionization behavior and cytotoxic activity of [MI(P)4]+-type complexes (M = Cu, Ag and Au; P = tertiary phosphine)

RATIONALE: To try to find a correlation between the antiproliferative activity of a series of [M-I(P)(4)](+) complexes (M=Cu, Ag and Au; P=tertiary phosphine) and their stability at micromolar concentration under mass spectrometric conditions. METHODS: [M-I(P)(4)](+) complexes were investigated by positive ion electrospray ionization mass spectrometry with multiple collisional experiments using an ion trap mass spectrometer. RESULTS: The displacement of P from native [M-I(P)(4)](+), previously described for the copper derivative, is common for the triad complexes leading to the formation of [M(P)(3)](+) and [M(P)(2)](+) adducts. Further dissociation of [M(P)(2)](+) depends on the nature of the metal (Cu similar to Ag>Au). More labile [Cu(P)(2)](+) and [Ag(P)(2)](+) are more cytotoxic against HCT-15 human colon carcinoma cells compared to less labile [Au(P)(2)](+) species. CONCLUSIONS: The dissociation of P ligand(s) from the [M-I(P)(4)](+) complexes is the driving force for the triggering of the antiproliferative activity. The more favored is the displacement of P from the [M(P)(2)](+) active form, the more favored is in turn the possibility for the metal to interact with biological substrates related to cancer proliferation.