Interaction of a ruthenium hexacationic prism with amino acids and biological ligands: ESI mass spectrometry and NMR characterization of the reaction products

Reactions between the cationic triangular metallaprism [(p-cymene)6Ru6(tpt)2(dhnq)3]6+ ([1]6+) [tpt is 2,4,6-tri(pyridine-4-yl)-1,3,5-triazine; dhnq is 5,8-dihydroxy-1,4-naphthoquinonato] and Arg, His, Lys, ascorbic acid, lactic acid and glutathione (GSH) have been studied at 37 °C in aq. soln. at pD 7 using NMR spectroscopy and electrospray ionization mass spectrometry. Coordination to the imidazole nitrogen atom of His or to the basic NH/NH2 groups in Arg and Lys slowly displaces the dhnq and tpt ligands from the (p-cymene)Ru units, and subsequently addnl. coordination to the amino and carboxylato groups forms stable N,N,O metallacycles. Compared with our previously reported study with the analogous metallaprism [(p-cymene)6Ru6(tpt)2(dhbq)3]6+ ([2]6+) (dhbq is 2,5-dihydroxy-1,4-benzoquinonato), the larger metallaprism [1]6+ appears to be significantly more stable, and disassembled in the presence of Arg, His and Lys after only 12 h of incubation. Moreover, the reaction with His is not complete, since only 14 % of His reacted after more than 1 wk of incubation. Solns. of [1]6+ are also able to catalyze oxidn. of the thiol group of Cys and GSH to give the corresponding disulfides and of ascorbic acid to give the corresponding dehydroascorbic acid. However, the results are markedly different from those obtained with metallaprism [2]6+: the oxidn. of Cys and ascorbic acid is not complete, and the formation of intermediate adducts could be evidenced. On the other hand, the oxidn. of GSH remains fast and is completed after only 12 h. Oxidn. of GSH to give the corresponding disulfide may explain its higher in vitro anticancer activity as compared with [2]6+. Our results suggest that metallaprism [1]6+ is more robust than [2]6+, may remain intact in the bloodstream and, therefore, may enter cancer cells undamaged, thus confirming the drug delivery potential for such water-sol. organometallic cages. [on SciFinder(R)]