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

Abstract

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.

Interaction products of cytotoxic Cu(I) complexes with different solvent mixtures: an electrospray ionization mass spectrometry and density functional theory study

“…Complexes 1 and 2 behaved in a similar way under ESI(+)‐MS conditions in water/methanol and in acetonitrile/methanol solutions giving [Cu(P) 2 ] + ‐type and [Cu(P)(MeCN)] + ‐type compounds as predominant species, respectively. Complexes 1 and 2 confirmed the already observed behavior of phosphino Cu(I) complexes to displace phosphine ligands upon dissolution with generation of coordinative unsaturated [Cu(P) 2 ] + species at the micromolar level . Indeed, in the case of complex 1 , DFT calculations (see Fig.…”

“…[Cu(PTA) 4 ][BF 4 ], 1 , and [Cu(thp) 4 ][BF 4 ], 2 , complexes in water/methanol and in water/acetonitrile solutions were preliminary investigated in a previous study under ESI(+)‐MS conditions . In water/methanol solutions, [Cu(PTA) 2 ] + and [Cu(thp) 2 ] + represented the base peaks of the full ESI(+)MS spectra along with low‐abundance peaks (few %) corresponding to [Cu(PTA) 3 ] + and [Cu(thp) 3 ] + species.…”

“…A peculiar physicochemical characteristic of [Cu(P) 4 ] + -type complexes is their property to sequentially displace phosphine ligands at micromolar concentrations (typical of both in vitro assays and ESI-MS studies). [10,11] According to this view, the original, tetrahedral complex [Cu(P) 4 ] + becomes a reactive, coordinative unsaturated [Cu(P) n ] + species (n < 4) that may interact with the surrounding environment populated by an assortment of molecules. The present study aims at the identification of the interaction products generated after dissolution of three representative phosphino [Cu(P) 4 ][BF 4 ] complexes illustrated in Fig.…”

The Important Role of the Nuclearity, Rigidity, and Solubility of Phosphane Ligands in the Biological Activity of Gold(I) Complexes

“…Interestingly, after incubation for 6 hours, a decrease in the fluorescence intensity of the treated cells to the level of the control cells suggests that ligand displacement might have occurred within the cells or that the complex has been cleared (e.g., by efflux transporters). Both effects have been described for gold(I) complexes in colorectal and ovarian carcinoma cells …”

Cu(i) and Ag(i) complex formation with the hydrophilic phosphine 1,3,5-triaza-7-phosphadamantane in different ionic media. How to estimate the effect of a complexing medium

“…65 However, according to our experiments, which has been reported to depend on the instrumental parameters chosen, such as the potential applied to generate the electrospray. 66,67 The same difference could be attributed to an incorrect estimation of log β j,est (Table 4) for the successive Cu-PTA species, used to trace the distribution diagrams in Fig.…”