Synthesis, Characterization, and Crystal Structure of α-[Ru(azpy)₂(NO₃)₂] (azpy = 2-(Phenylazo)pyridine) and the Products of Its Reactions with Guanine Derivatives

Abstract

The synthesis and characterization of alpha-[Ru(azpy)2(NO3)2], 1, are reported (azpy is 2-(phenylazo)pyridine; alpha indicates the isomer in which the coordinating pairs ONO2, N(py), and N(azo) are cis, trans, and cis, respectively). The solid-state structure of 1 has been determined by X-ray crystallography. Crystal data: orthorhombic a = 15.423(5) A, b = 14.034(5) A, c = 10.970(5) A, V = 2374(2) A3, space group P2(1)2(1)2(1) (No. 19), Z = 4, Dcalc = 1.655 g cm-3. The structure refinement converged at R1 = 0.042 and wR2 = 0.118 for 3615 unique reflections and 337 parameters. The octahedral complex shows monodentate coordination of the two nitrate ligands. The Ru-N(azo) bond distances (2.014(4) and 1.960(4) A), slightly shorter than the Ru-N(py) bonds (2.031(4) and 2.059(4) A), agree well with the pi-back-bonding ability of the azo groups. The binding of the DNA-model bases 9-ethylguanine (9egua) and guanosine (guo) to 1 has been studied and compared with previously obtained results for the binding of model bases to the bis(bipyridyl)ruthenium(II) complex. The ligands 9egua and guo appear to form monofunctional adducts, which have been isolated as alpha-[Ru(azpy)2(9egua)Cl]PF6, 2, alpha-[Ru(azpy)2(9egua)(H2O)]-(PF6)2, 3, alpha-[Ru(azpy)2(guo)(H2O)](PF6)2, 4, and alpha-[Ru(azpy)2(guo)Cl]Cl, 5. The orientations of 9egua and guo in these complexes have been determined in detail with the use of 2D NOESY NMR spectroscopy. In 2 and 5, H8 is directly pointed toward the coordinated Cl, whereas, in 3 and 4, H8 is wedged between the pyridine and phenyl rings. The guanine derivatives in the azpy complexes can have more orientations than found for related cis-[Ru(bpy)2Cl2] species. This fluxionality is considered to be important in the binding of the alpha-bis(2-(phenylazo)pyridine)ruthenium(II) complex to DNA. In complex 1, ruthenium is the chiral center and in the binding to guanosine, two diastereoisomers each of adducts 4 and 5 have been clearly identified by NMR spectroscopy.

Structure-dependent in vitro cytotoxicity of the isomeric complexes [Ru(L)2Cl2] (L=o-tolylazopyridine and 4-methyl-2-phenylazopyridine) in comparison to [Ru(azpy)2Cl2]

“…The 2D NOESY NMR data show as most important cross-peaks: an interligand NOE between the H6 resonance and H14 resonance, and an interligand NOE between the H6 and CH 3 resonance. As it is known that in case of the a-Ru(azpy) 2 backbone, an H6-H(o) interligand NOE cross-peak is to be expected [11,36,37], these H6-H14 and H6-CH 3 NOEs confirm the a configuration. The fact that the H6 resonance gives an NOE to both the CH 3 signal, as well as to the H14 resonance, suggests the fast rotation of the phenyl rings in solution, a common feature of a isomeric complexes, despite the presence of the methyl groups.…”

“…The complexes a-and c-[Ru(azpy) 2 Cl 2 ] have a C 2 symmetry, causing the two azpy ligands in each isomer to be identical in NMR. It was proven that the a configuration shows a characteristic (intramolecular) interligand H6-H(o) (H(o)=H10/H14) NOE cross-peak [11,36,37]. 1 Moreover, the averaged interproton H6-H(o) distances from solid-state XRD-data appear to be useful for predicting NOEs in solution [11,36,37].…”

“…It was proven that the a configuration shows a characteristic (intramolecular) interligand H6-H(o) (H(o)=H10/H14) NOE cross-peak [11,36,37]. 1 Moreover, the averaged interproton H6-H(o) distances from solid-state XRD-data appear to be useful for predicting NOEs in solution [11,36,37]. The absence of interligand NOE cross-peaks between the aromatic resonances is characteristic for the c isomer [11].…”

“…The interligand H6-H(o) distance, as shown in the X-ray structure, is on average 4.14 Å , predicting the interligand NOE. Moreover, in asymmetric a-isomeric azpy complexes [37], like a-[Ru(azpy) 2 (9-Egua)(H 2 O)](PF 6 ) 2 or a-[Ru(azpy) 2 Cl(NO 3 )] (unpublished data), the interligand H6-o' and H6'-o (prime denoting the other azpy ligand) are observed and not, for example, the intraligand H6-o NOE.…”

The synthesis, chemical and biological properties of dichlorido(azpy)gold(III) chloride (azpy= 2-(phenylazo)pyridine) and the gold-induced conversion of the azpy ligand to the chloride of the novel tricyclic pyrido[2,1-c][1,2,4]benzotriazin-11-ium cation

“…This asymmetric bidentate ligand coordinates via the pyridine and aza nitrogen atoms, forming a stable 5-membered chelating ring [16,17] which is known to be capable of acting as both r donor and p acceptor.…”