The relationship between the electrospray ionization behaviour and biological activity of some phosphino Cu(I) complexes

Abstract

Electrospray ionization mass spectrometry was usefully employed for the characterization of three phosphino copper(I) complexes of medicinal interest. This technique revealed that the original [CuL(4)](+) pro-drugs (L = hydrophilic tertiary phosphine) underwent dissociation with production of coordinative unsaturated [CuL(3)](+) and [CuL(2)](+) species, which represented key intermediates for the activation of potential biological properties. The more favoured was the displacement of the ligands from the [CuL(4)](+) parent complex, the more favoured was in turn the possibility for the metal ion to directly interact with biological substrates, including pharmacological targets related to cancer proliferation. An inverse correlation between the stability and the cytotoxic activity of the three copper(I) complexes investigated has been clearly established.

In vitro antitumour activity of water soluble Cu(I), Ag(I) and Au(I) complexes supported by hydrophilic alkyl phosphine ligands

“…In the case of copper, the nature of the coordinated phosphine determined the degree of dissociation of the [Cu(L) 4 ] + complex and the formation of the likely 'active ingredients' [Cu(L) 2 ] + and [Cu(L)] + . Hence, [Cu(thp) 4 ] + 1 was found to be more cytotoxic than [Cu(PTA) 4 ] + 4 [71]. Speciation studies involving silver and gold complexes are in progress.…”

“…As observed in the ESI(+)MS spectra, none of [M(L) 4 ] + species show the molecular ion peak, but the ESI-MS base peak is consistently ascribed to the [M(L) 2 ] + molecular fragment. At micromolar concentrations, typical of both ESI-MS measurements and in vitro cell culture conditions, the easy formation of [Cu(L) 2 ] + and [Cu(L)] + species was found to be the key factor for controlling the biological activity of the native [Cu(L) 4 ] + species [71]. In the case of copper, the nature of the coordinated phosphine determined the degree of dissociation of the [Cu(L) 4 ] + complex and the formation of the likely 'active ingredients' [Cu(L) 2 ] + and [Cu(L)] + .…”

Homoleptic phosphino copper(i) complexes with in vitro and in vivo dual cytotoxic and anti-angiogenic activity

“…10 -5 M). 32 The difficulty of growing crystals of complexes 2 and 3 suitable for X-ray diffraction studies and the lack of unambiguous NMR and MS data confirming the [Cu(P)4] + assembly prompted us to investigate the molecular structure at the Cu site in the representative [Cu(DAPTA)4]BF4, 2 by X-Ray Absorption spectroscopy (XAS). XANES spectra of Cu complexes displayed a typical feature in the rising part of the XAS spectrum which is assigned to the 1s-4p electronic transition.…”

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

“…In agreement with this suggestion, ESI-MS experiments showed that the chelate complex (1) retains its tetracoordination at the high dilutions required by in vitro and MS experiments (10 −5 -10 −6 mol L −1 ), while the complexes containing monodentate phosphines, (2) and (3), are partially dissociated. 12,15 Therefore, the nature and stability of the species of these Cu(I)-based compounds seems to be of fundamental importance for their biological activity. In this work, solution equilibria for the formation of Cu(I) and Ag(I) complexes with the phosphine 1,3,5 triaza-7-phosphadamantane (PTA, Scheme 1) are reported.…”