In vitro and in vivo biological activity screening of Ru(III) complexes involving 6-benzylaminopurine derivatives with higher pro-apoptotic activity than NAMI-A

A series of novel octahedral ruthenium(III) complexes involving 6-benzylaminopurine (L) derivatives as N-donor ligands has been prepared by the reaction of [(DMSO)₂H][trans-RuCl₄(DMSO)₂] with the corresponding L derivative. The complexes 1-12 have the general compositions trans-[RuCl₄(DMSO)(n-Cl-LH)] ⋅ xSol (1-3), trans-[RuCl₄(DMSO)(n-Br-LH)] · xSol (4-6), trans-[RuCl₄(DMSO)(n-OMe-LH)] · xSol (7-9) and trans-[RuCl₄(DMSO)(n-OH-LH)] · xSol (10-12); n = 2, 3, and 4, x = 0-1.5; and Sol = H₂O, DMSO, EtOH and/or (Me)₂CO. The complexes have been thoroughly characterized by elemental analysis, UV-visible, FTIR, Raman, and EPR spectroscopy, ES + (positive ionization electrospray) mass spectrometry, thermal analysis, cyclic voltammetry, magnetic and conductivity measurements. The X-ray molecular structure of trans-[RuCl₄(DMSO)(3-Br-LH)] ⋅ (Me)₂CO (5) revealed the distorted octahedral coordination in the vicinity of the central atom, and also confirmed that the 3-Br-L ligand is present as the N3-protonated N7-H tautomer and is coordinated to Ru(III) through the N9 atom of the purine moiety. The tested complexes have been found to be in vitro non-cytotoxic against K562, G361, HOS and MCF7 human cancer cell lines with IC₅₀ > 100 μM in contrast to the moderate results regarding the antiradical activity with IC₅₀ ≈ 10^− 3 M. On the contrary, in vivo antitumor activity screening showed that the prepared Ru(III) complexes possess higher pro-apoptotic activity than NAMI-A. The reduction of Ru(III) to Ru(II) and Ru(II)-species formation in tumor tissues was confirmed by means of a simple method of detection and visualization of intracellular Ru(II) by fluorescence microscopy. The originality of this method is based on the preparation of a Ru(II)-bipyridine complex in situ.     

Inhibition of endonuclease cleavage and DNA replication of E. coli plasmid by the antitumor rhodium(II) complex

Binding effect of the antitumor complex rhodium(II) acetate [Rh(2)(O(2)CCH(3))(4)] (Rh1) to the plasmid pUC19 DNA has been studied under different molar ratio of Rh1 compound to base pair of pUC19 DNA (R(f)) and reaction time. The Rh1 binding inhibited the activity of restriction enzyme. The binding effect was monitored using gel electrophoresis. The results indicate that at least one Rh1 binds with the recognition sequence and the binding has no preference between A-T and G-C pairs. At high value of R(f)=100, ICP-MS (Inductively Coupled Plasma Mass Spectrometry) measurement confirmed that 46% of Rh1 binds to DNA. PCR amplification of the DNA was also inhibited by the Rh1 binding. The transformation experiment using Escherichia coli suggested that the cell growth was inhibited after binding the Rh1 to the plasmid. These results indicated that DNA synthesis could be inhibited both in vitro and in vivo by the Rh(2)(O(2)CCH(3))(4) binding.     

Formation and stabilization of five-coordinate iron(II) verdoheme analogues by axial weakly coordinating anion ligation. X-ray crystal structures of [(OEOPFe)2O](X)2 (X = AsF6, SbF6)

The effect of weakly coordinating anions, , as axial ligands on the formation and coordination chemistry of verdoheme analogues have been examined. Two new five-coordinate and stable iron(II) verdoheme analogues, [OEOPFe^IIX], where OEOP is the monoanion of octaethyloxoporphyrin and X = AsF₆ and SbF₆, have been isolated. The compounds have been characterized by different spectroscopic methods as well as elemental analysis. ¹H NMR spectroscopy and magnetic moment measurements show that the [OEOPFe^IIX] are paramagnetic and iron is five-coordinate. Exposure of dichloromethane solutions of [OEOPFe^IIX] (X = AsF₆ (2), SbF₆ (3)) to dioxygen result in their transformation into the μ-oxo bridged compounds, [(OEOPFe)₂O](X)₂ (X = AsF₆ (4), SbF₆ (5)). The structures of 4 and 5 have been determined by X-ray diffraction analysis, both are structurally similar with a P2₁/c space group in the monoclinic crystal system.