Solution equilibrium studies of anticancer ruthenium(II)-η6-p-cymene complexes of pyridinecarboxylic acids

Abstract

Stoichiometry and stability of antitumor ruthenium(II)-η 6 -p-cymene complexes of picolinic acid and its 6-methyl and 6-carboxylic acid derivatives were determined by pHpotentiometry, 1 H NMR spectroscopy and UV/Vis spectrophotometry in aqueous solution in the presence or absence of coordinating chloride ions. The picolinates form exclusively monoligand complexes in which they can coordinate via the bidentate (O,N) mode and a chloride or a water molecule is found at the third binding site of the ruthenium(II)-η 6 -p-cymene moiety depending on the conditions. [Ru(η 6 -p-cymene)(L)(H 2 O/Cl)] species are predominant at physiological pH in all studied cases. Hydrolysis of the aqua complex or the chlorido/hydroxido co-ligand exchange results in the formation of the mixed-hydroxido species [Ru(η 6 -p-cymene)(L)(OH)] in the basic pH range. There is no indication for the decomposition of the mono-ligand complexes during 24 h in the ruthenium(II)-η 6 -pcymene−picolinic acid system between pH 3 and 11; however, a slight dissociation with a low reaction rate was found in the other two systems leading to the appearance of the dinuclear trihydroxido-bridged species [Ru 2 (η 6 -p-cymene) 2 (OH) 3 ] + and free ligands at pH > 10. The replacement of the chlorido by an aqua ligand in [Ru(η 6 -p-cymene)(L)Cl] was also monitored and equilibrium constants for the exchange process were determined.

Solution equilibria and antitumor activities of pentamethylcyclopentadienyl rhodium complexes of picolinic acid and deferiprone

“…The Rh(III) center exhibits a pseudo-octahedral geometry ("piano-stool"), and the Cp* moiety occupies facially three coordination sites, while the and angles between the metal center and the donor atoms were found in the same range as reported for related structures [28]. Proton dissociation equilibria of the studied ligands dhp and pic are well known in the literature [40][41][42], and pK a values determined by pH-potentiometry (see table 2) are in reasonably good agreement with data reported under identical conditions as used in this study [43,44] with the exception of dhp (at I = 0.20 M (KNO 3 )) where no data were available. [22,45].…”

“…On the other hand not only the competition of the metal ion with protons for the ligand but that of the ligand with the hydroxide for the metal ion has to be taken into consideration, which becomes more pronounced at higher and higher pH values. Overall stability constants of the analogous complexes formed in the Ru(II)(h 6 -pcymene) -dhp / pic / maltol systems are also available in the literature [41,44]. Log  values of the Ru(II)(h 6 -p-cymene) complexes formed with dhp and maltol are higher compared to those of RhCp* species, although the picolinate complexes show reverse tendency.…”

Comparative equilibrium and structural studies of new pentamethylcyclopentadienyl rhodium complexes bearing (O,N) donor bidentate ligands

“…Proton dissociation constants of the ligands 6-Mepic, 2-QA and 3-iQA were determined by pH-potentiometry and 1 H NMR spectroscopy ( Table 1), and are in reasonably good agreement with data acquired under similar conditions reported in literature [41,42]. The proton dissociation constant can be attributed to the deprotonation of the quinolinium (NH + ) group.…”

[(η6-p-cymene)Ru(H2O)3]2+ binding capability of aminohydroxamates — A solution and solid state study

“…Earlier studies mostly dealt with the design, synthesis, characterization and biological test of these [(η 6 -arene)Ru(XY)Z] type (arene = benzene(derivative), XY = chelating, Z = monodentate ligand) complexes. [6][7][8][9][10] Recent years research focusing on their solution behaviour or the interaction with various high [11][12][13][14][15][16][17] or low molecular mass [18][19][20][21][22][23][24][25][26][27][28][29] biomolecules is also in progress.…”