Dichlorobis(2-phenylazopyridine)ruthenium(ii) complexes: characterisation, spectroscopic and structural properties of four isomers

Abstract

The didentate ligand 2-phenylazopyridine (azpy) can -in theory -give rise to five different isomeric complexes of the type [Ru(azpy) 2 Cl 2 ], of which three have been known since 1980. The molecular structures of the cisdichlorobis(2-phenylazopyridine) ruthenium() complexes α-[Ru(azpy) 2 Cl 2 ] and β-[Ru(azpy) 2 Cl 2 ] (in which the coordinating pyridine nitrogen atoms are in mutually trans and cis positions, respectively, whilst the azo nitrogen atoms are in mutually cis positions) were unambiguously determined in the early 1980s. The third isomer, γ-[Ru(azpy) 2 Cl 2 ], has for two decades, erroneously, been assumed to be the all-trans isomer. In a recent communication we have proven that for this γ isomer the chloride ions are indeed in a trans geometry, but the pyridine nitrogen and azo nitrogen atoms of the two azpy ligands are in mutually cis geometries. In this paper the isolation of a fourth isomer is presented, the hitherto unknown δ-[Ru(azpy) 2 Cl 2 ]. The isomeric structure of δ-[Ru(azpy) 2 Cl 2 ] has been determined by 1 H-NMR spectroscopy and single-crystal X-ray diffraction analysis, and is the all-trans isomer. The bis(azpy)-ruthenium() isomers are of interest because of the pronounced cytotoxicity they exhibit against tumour cell lines and could be very useful in the search for structure-activity relationships of antitumour-active ruthenium complexes, as among the isomers there is a significant difference in activity. It is of paramount importance to have a good understanding of the structural and spectroscopic properties of these complexes, which in this paper are compared and discussed, with a particular emphasis on 1D and 2D 1 H NMR spectroscopies.

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]

“…In both syntheses, the presence of small amounts of d isomer has been reported, in 5% and 20% yield, respectively [11]. Interestingly, the d isomer has not been detected by NMR in the crude product obtained after the synthesis of c-[Ru(mazpy) 2 Cl 2 ] from RuCl 3 and mazpy in methanol.…”

“…The isomer (with coordinating pairs of Cl ligands cis, Npy atoms cis and Nazo nitrogen atoms trans) is not formed under normal conditions [12], and moreover, as it will isomerize to another isomer under physiological temperatures, it is not suitable for a study of structural and biological properties. The d isomer of [Ru(azpy) 2 Cl 2 ] (d indicates the coordinating pairs Cl, Npy and Nazo trans, trans, trans) is formed as a side product in the synthesis of c-[Ru(azpy) 2 Cl 2 ], and it has recently been fully characterized [11]. The c isomer of [Ru(azpy) 2 Cl 2 ] has been shown to be kinetically the most favoured isomer, and it is found as the main product in the synthesis of the crude mixture of isomers starting from RuCl 3 AExH 2 O in methanol [9], as well as from cis-[Ru(dmso) 4 Cl 2 ] in acetone [10].…”

“…In a recent publication, the use of 2D NOESY NMR spectroscopy was proven to be useful in determining the isomeric structure of the isomers of [Ru(azpy) 2 Cl 2 ] complexes [11]. 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.…”

“…As a thorough structural characterization of the parent complexes a, b, c and d-[Ru(azpy) 2 Cl 2 ] has recently been reported [11], we will focus now on the differences in structural aspects caused by the added methyl group. Moreover, by adding new data on the effects on tumour cell proliferation of these methylated azpy complexes, we will reconsider the cytotoxic activity of [RuL 2 Cl 2 ] complexes (L=azpy, tazpy and mazpy).…”

“…The fourth newly discovered so-called delta isomer has been reported to be the all-trans isomer, and a thorough characterization of the four isomers, i.e. a, b, c and d-[Ru(azpy) 2 Cl 2 ] is now available [11]. The synthesis of the fifth isomer, -[Ru(azpy) 2 Cl 2 ] (Cl and Npy atoms cis, Nazo atoms trans), has been mentioned in the literature, but no clear NMR characterization and/or X-ray structure determination has been reported, and the configuration was proven only by spectrophotometric data [12].…”