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

Reactions between the cationic triangular metallaprism [(p-cymene)(6)Ru(6)(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 aqueous solution at pD 7 using NMR spectroscopy and electrospray ionisation mass spectrometry. Coordination to the imidazole nitrogen atom of His or to the basic NH/NH(2) groups in Arg and Lys slowly displaces the dhnq and tpt ligands from the (p-cymene)Ru units, and subsequently additional 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)(6)Ru(6)(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 week of incubation. Solutions of [1](6+) are also able to catalyse oxidation 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 oxidation of Cys and ascorbic acid is not complete, and the formation of intermediate adducts could be evidenced. On the other hand, the oxidation of GSH remains fast and is completed after only 12 h. Oxidation 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-soluble organometallic cages.