Synthesis, Characterization, and Cytotoxic Activity of Novel Potentially pH-Sensitive Nonclassical Platinum(II) Complexes Featuring 1,3-Dihydroxyacetone Oxime Ligands

Yulia Scaffidi-Domianello, Anton Legin, Michael Jakupec, Vladimir Arion, Vadim Yu Kukushkin, Mathea Sophia Galanski (Korresp. Autor*in), Bernhard Keppler

Veröffentlichungen: Beitrag in FachzeitschriftArtikelPeer Reviewed

Abstract

The reaction of 1,3-dihydroxyacetone oxime with diam(m)minediaquaplatinum(H) under basic conditions produced zwitterionic diam(m)mine(3-hydroxy-2-(oxidoimino)propan-1-olato-kappa(2)N,O)platinum(II) complexes featuring the N,O-chelating ligand. Upon reaction with hydrochloric acid, it was possible to isolate either the singly protonated species still exhibiting the intact N,O-chelate or the open-chain chlorido complex All complexes were characterized in detail with multinuclear ((1)H, (13)C, and (195)Pt) NMR spectroscopy, ESI mass spectrometry, and in one case X-ray diffraction. Cytotoxicity was investigated in three human cancer cell lines (CH1, SW480, and A549). The obtained IC(50) values are in the medium or even low micromolar range, remarkable for platinum complexes having N(3)O or N(3)Cl coordination spheres. To study the solution behavior of the prepared complexes at physiologically relevant proton concentrations, time-dependent (1)H NMR measurements were performed for the ethane-1,2-diamine-containing series at pH values of 7.4, 6.0, and exemplarily 5.0. While the zwitterionic complex proved to be stable at both pH 7.4 and 6.0, the protonated species were deprotonated at pH 7.4, tending toward ring opening in slightly acidic environments, as characteristic for many solid tumors. Finally, the open-chain form stayed intact at pH 6.0, being completely converted into its chelated analogue at pH 7.4. A pH-dependent evaluation of antiproliferative effects of the two latter complexes at pH 7.4 and pH 6.0 revealed an activation under slightly acidic conditions, which might be of interest for further in vivo studies.
OriginalspracheEnglisch
Seiten (von - bis)10673-10681
Seitenumfang9
FachzeitschriftInorganic Chemistry
Jahrgang50
Ausgabenummer21
PublikationsstatusVeröffentlicht - 2011

ÖFOS 2012

  • 104003 Anorganische Chemie

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