The relationship between electrospray ionization behavior and cytotoxic activity of [M(I)(P)4](+)-type complexes (M = Cu, Ag and Au; P = tertiary phosphine).
BACKGROUND
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.
CNR Istituto di Chimica Inorganica e delle Superfici, Corso Stati Uniti 4, 35127 Padova, Italy.
Francesco
F
Tisato
Laura
L
Crociani
Marina
M
Porchia
Plinio
P
Di Bernardo
Francesco
F
Endrizzi
Carlo
C
Santini
Roberta
R
Seraglia
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000737:chemistry* / Q000633:toxicity; D006046:Gold / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D010720:Phosphines / Q000737:chemistry* / Q000633:toxicity*; D012834:Silver / Q000737:chemistry* / Q000633:toxicity; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D010720:Phosphines; D012834:Silver; D006046:Gold; D003300:Copper; C044646:phosphine