The relationship between electrospray ionization behavior and cytotoxic activity of [M I (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 ~ 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. Copyright © 2013 John Wiley & Sons, Ltd.