Proapoptotic activity in vitro of two novel ruthenium(II) complexes with flavanone-based ligands that overcome cisplatin resistance in human bladder carcinoma cells

In this study we examined their proapoptotic activity of cis-dichloridobis(3-imino-2-methoxyflavanone)ruthenium(II)3H₂O (1) and cis-dichloridobis(3-imino-2-ethoxyflavanone)ruthenium(II)2H₂O (2) towards human bladder carcinoma cell line EJ and its cisplatin resistant subline EJcisR. On the basis of the experiments we carried out, it may be concluded, that: CDDP (cis-diamminedichloridoplatinum) resistance of EJcisR cells is probably based on partial loss of apoptotic pathway activating caspase-8 and increased resistance to DNA strand breaks and/or alkali-labile sites. Increased glutathione levels, as well as activity of P-gp transporter seems to be not relevant in this case. The proapoptotic activity of the ruthenium compounds is higher than that of cisplatin. Higher proapoptotic activity of 1 and 2 when compared to CDDP may be due to the presence of large, lipophilic flavanone-based ligands that may facilitate their trans-membrane transport and their redox activity. 1 and 2 induce apoptosis apparently in more than one way. Although caspase-8 activation and DNA strand breaks and/or alkali-labile sites are caused by the compounds, their ability to cause the oxidative stress in the cells may also participate in apoptosis induction.     

Unusual hexamers and infinite water chains trapped in the complexes of 2-(4-pyridyl)benzimidazole

Unusual hexamers and water chains have been observed in the complexes of (HPyBIm)⁺(Hterephate)⁻(PyBIm) · 4H₂O (1) and [Ag₂(PyBIm)₂(μ₂-SO₄)] · 4H₂O (2), respectively (PyBIm = 2-(4-pyridyl)benzimidazole). In 1, a chair-shaped hexamer (not water hexamer) formed by the water molecules and carboxylate groups as well as one-dimensional water chain are being observed. While in 2, a water hexamer-shaped as parallelogram is obtained; more interestingly, the parallelogram-shaped water hexamers are further aggregated into tape like infinite water chain via hydrogen-bonding interactions.     

ortho-Carom-N bond fusion in aniline associated with electrophilic chlorination reactions at ruthenium(III) coordinated acetylacetonates

In an unusual reaction of [Ru^III(acac)₂(CH₃CN)₂](ClO₄) ([1], acac = acetylacetonate) and aniline (Ph-NH₂), resulted in the formation of ortho-semidine due to dimerisation of aniline via oxidative ortho-C_arom-N bond formation reaction. This oxidation reaction is associated with stepwise chlorination of coordinated acac ligands at the γ-carbon atom resulting in the formation of [Ru^III(acac)₂L⁻] [2a], [Ru^III(Cl-acac)(acac)L⁻] [2b], [Ru^III(acac)(Cl-acac)L⁻] [2c] and [Ru^III(Cl-acac)₂L⁻] [2d] (L⁻ = N-phenyl-ortho-semiquinonediimine) complexes, respectively. These have been characterized by ¹H NMR, UV-Vis-NIR, ESI-MS and cyclic voltammetry studies. Single crystal X-ray structures of 2c and 2d are reported. Crystallographic structural bond parameters of 2c and 2d revealed bond length equalization of C-C, C-O and M-O bonds. It has been shown that perchlorate () counter anion, present in the starting ruthenium complex, acts as the oxidizing agent in bringing about oxidation of Ph-NH₂ to ortho-semidine. The chloronium ions, produced in situ, chlorinate the coordinated acac ligands at the γ-carbon atom. Such electrophilic substitution of coordinated acac ligands indicates that the Ru-acac metallacycles in the reference compounds are aromatic. The complexes showed an intense and featureless band centered near 520 nm, and a structured band near 275 nm. These displayed one reversible cathodic response in the range, −1.1 to −0.8 V and one reversible anodic response between 0.4 and 0.6 V versus the Saturated Calomel reference Electrode, SCE. The response at the anodic potential is due to oxidation of the coordinated ligand L, while the reversible response at cathodic potential is due to reduction of the metal center.     

Molecular and electronic structures of new iron complexes containing N,S-coordinated o-iminothionebenzosemiquinonate(1-) π radical ligands: An experimental and density functional theoretical study

Two new o-aminothiophenol type ligands have been synthesized, namely 1,3-propanediamine-N,N′-bis(benzenethiol), H₄(¹L), and 1,2-bis(2-mercapto-3,5-di-tert-butylaniline)ethane, H₄(²L). The reactions of these ligands with FeBr₂ in dry acetonitrile in the presence and absence of air (and other oxidants such as iodine) afforded seven new complexes which were characterized by single-crystal X-ray crystallography and Mössbauer spectroscopy (as well as EPR- and UV-Vis spectroscopies). Their magnetochemistry has been studied and their electronic structures have been established and verified by broken symmetry (BS) density functional theoretical (DFT) calculations using the B3LYP functional. The ligands are redox-active and the o-iminothiophenolate(2-)-o-iminothiobenzosemiquinonate(1-) oxidation levels are chemically readily accessible. The complexes characterized comprise the dimers [Fe^III(¹L)]₂ (S_T = 0) (1); [Fe^III(²L)]₂ (S_T = 0) (2), and the mononuclear, five coordinate species: [Fe^III(¹L)I] (S_T = ¹/₂) (3); [Fe^III(²L)I] (S_T = ¹/₂) (4); [Fe^II(¹L){P(CH₃)₃}] (S_T = 0) (5); [Fe^II(²L){P(C₆H₅)₃}] (S_T = 0) (6), and [Fe^III(²)(^tpy)] (S_T = 1) (7). (^tBupy) represents 4-tert-butylpyridine and (²)³⁻ is the π radical trianion of the one-electron reduced (²L_gma)²⁻ which in turn is the oxidized form of (²L)⁴⁻ (−4H⁺, −2e).