Complex formation of antitumor active dirhodium(II) acetate with small molecules of biological interest

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Dirhodium(II) acetate, consisting of Rh2(CH3COO)4 complexes, is a compound with significant antitumor activities and limited side effects. Although the antitumor studies are mostly focused on its interaction with DNA, the mechanism is not recognized yet. In addition to DNA, other biological molecules such as amino acids can interact with this complex. In this dissertation the interaction of Rh2(CH3COO)4 with the amino acids cysteine, methionine and imidazole, which is the side chain of the amino acid histidine, have been investigated using different spectroscopic techniques including EXAFS, multinuclear NMR, IR, ESI-MS and UV-Vis spectroscopy. A pink solid complex Rh2(CH3COO)4(lm)2 was formed from the reaction of Rh2(CH3COO)4 and imidazole (Im) in the mole ratio 1 :2, where the imidazole ligands were coordinated through the axial positions of the Rhi(CH3COO)4 complex with the Rh­N bond distance 2.25 ± 0.02 A. In a freshly prepared aqueous solution of Rh2(CH3COO)4 and methionine (Met) in the mole ratio 1:2, axial coordination of methionine ligands occurs m Rhi(CH3COO)4(Met)1.2 complexes, with the average bond distances of 2.03 ± 0.02 A, 2.47 ± 0.04 A and 2.40 ± 0.02 A for the Rh-O, Rh-S and Rh-Rh bonds, respectively. Replacement of acetate in equatorial sites with methionine takes place over a period of 2 - 4 weeks, when the solution is saturated with methionine. The composition of the complexes gradually changes from Rhi(CH3COO)4(S-Meth to [Rh2(CH3COO)4.n(S,O­Met)n](CH3COO)n (n = 2 - 4), with peaks at 4685 ppm and 4616 ppm in the 103Rh NMR spectrum, more shielded than the resonance 8 (103Rh) = 7476.2 ppm for the hydrated Rhi(CH3COO)4(H2Oh complex, with water molecules as axial ligands. An EXAFS spectrum measured after 10 months of Rh2(CH3COO)4 dissolved in saturated methionine solution gives the average bond distances 2.03, 2.29 and 2.55 ± 0.02 A for the Rh-O, Rh­S and Rh-Rh bonds, respectively, assuming [Rh2(CH3COO)4_n(Met)n] (n = 2 - 4) species. The shorter Rh-Sand longer Rh-Rh distances, relative to those of Rhi(CH3COO)4(Met)1_2, confirm the equatorial coordination of the methionine ligands. By dissolving Rh2(CH3COO)4 in ethanethiol a Rh2(CH3COO)4(EtSHh complex is formed, with Rh-Rh and Rh-S bond distances of 2.41 ± 0.02 A and 2.53 ± 0.02 A. The UV-Vis spectra of Rh2(CH3COO)4 dissolved in water, ethanethiol, saturated methionine solution and 0.1 M / 1.0 M imidazole solutions show peak maxima at Amax = 588, 556, 537 and 521 nm, respectively, which imply that the ligand field strength for these axially coordinated ligands (X) in Rh2(CH3COO)2_4X2 is: X = H2O < EtSH (thiol) < methionine (thioether) < imidazole (Nsp2). Ethanethiol has a single functional group (-SH), and in its reaction with Rhi(CH3COO)4, the Rh-Rh bond remains intact. However, the chelating thiol-containing ligands cysteine (H2Cys) and N-acetylcysteine (H2NAC), are capable of breaking the Rh­Rh bond in their reaction with Rhi(CH3COO)4, to form mononuclear and binuclear Rh(III) species, respectively. In the solid [Rh(iii)HCys)(Cys)(H2O)].H2O compound, cysteine coordinates to Rh(III) ion through its thiol, amine and / or carboxylate groups, with average bond distances of Rh-(N/O) 2.17 ± 0.02 A and Rh-S 2.37 ± 0.02 A. In the solid [Rh111i(HNACh(NACh(H2O)4].2H2O compound, the only available coordination sites of N-acetylcysteine are its thiol and carboxylate groups. The oxidation state +3 for the rhodium ions was confirmed by Rh L3-edge XANES and magnetic susceptibility measurements.
Bibliography: p. 148-159
Many pages are in colour.
Niksirat, P. (2012). Complex formation of antitumor active dirhodium(II) acetate with small molecules of biological interest (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from doi:10.11575/PRISM/4890