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.