Synthesis, characterization, electrochemical behavior and in vitro protein tyrosine kinase inhibitory activity of the cymene-halogenobenzohydroxamato [Ru(η6-cymene)(bha)Cl] complexes

Abstract

The ruthenium(II)-cymene complexes [Ru(eta(6)-cymene)(bha)Cl] with substituted halogenobenzohydroxamato (bha) ligands (substituents = 4-F, 4-Cl, 4-Br, 2,4-F-2, 3,4-F-2, 2,5-F-2, 2,6-F-2) have been synthesized and characterized by elemental analysis, IR, H-1 NMR, C-13 NMR, cyclic voltammetry and controlled-potential electrolysis, and density functional theory (DFT) studies. The compositions of their frontier molecular orbitals (MOs) were established by DFT calculations, and the oxidation and reduction potentials are shown to follow the orders of the estimated vertical ionization potential and electron affinity, respectively. The electrochemical E-L Lever parameter is estimated for the first time for the various bha ligands, which can thus be ordered according to their electron-donor character. All complexes exhibit very strong protein tyrosine kinase (PTK) inhibitory activity, even much higher than that of genistein, the clinically used PTK inhibitory drug. The complex containing the 2,4-difluorobenzohydroxamato ligand is the most active one, and the dependences of the PTK activity of the complexes and of their redox potentials on the ring substituents are discussed.

One and Multiple Bonds Interatomic Spin-Spin Coupling inη6-Cymene Ru(II) of 3,5-Dimethyl-, 3,5-Dicarboxylic-, and 5-Phenyl-pyrazole Derivatives

“…The graphical representation of selected spin-spin interactions in the complexes is shown in Figure 3 and the details of all their spin-spin are shown in Table 5. In many of the experimental characterisations of derivatives of 6 -cymene Ru(II) complexes, the values of the spin-spin 3 J(Hc⋅ ⋅ ⋅ Hc) of benzene ring are often presented as part of their characterisation and have been reported in the literature to have experimental ranges of 6-8 [38,39], 6 [40,41], 5.7-6.2 [42], 6.4 [43], and 6.02-6.56 [44] which agree with our computed ranges of 6.124 in 1a to 7.151 in 6. The changes in the spin-spin coupling of the complexes as corresponding effect of the type of the monodentate, bidentate, and tridentate ligands and hydrolysis of the complexes are examined.…”