Bülent Dede

Novel homo- and hetero-nuclear copper(II) complexes of tetradentate Schiff bases: Synthesis, characterization, solvent-extraction and catalase-like activity studies

Twelve homo- and hetero-nuclear copper(II) complexes of tetradentate Schiff base ligands containing N(4) donor sets have been prepared by employing several steps. The characterization and nature of bonding of the complexes have been deduced from elemental analysis, FT-IR, molar conductivity, magnetic moment measurements and thermal analysis. The three Schiff base ligands were further identified using (1)H and (13)C NMR spectra. All copper(II) complexes are 1:2 electrolytes as shown by their molar conductivities (Lambda(M)) in DMF and paramagnetic. The subnormal magnetic moment values of the di- and tri-nuclear complexes explained by a very strong anti-ferromagnetic interaction. The extraction ability of the ligands has been examined by the liquid-liquid extraction of selected transition metal (Mn(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Pb(2+), Cd(2+), Hg(2+)) cations. The ligands show strong binding ability toward copper(II) ion. Furthermore the homo- and hetero-nuclear copper(II) complexes were each tested for their ability to catalyse the disproportionation of hydrogen peroxide in the presence of the added base imidazole.

A Schiff base derivative for effective treatment of diethylnitrosamine-induced liver cancer in vivo.

Hepatocellular carcinoma is one of the most prevalent cancers, with a high morbidity rate, even in developed countries. In the present study, the curative effect of the Schiff base (SB) heterodinuclear copper(II)Mn(II) complex on diethylnitrosamine (DEN)-induced liver carcinoma was investigated. Hepatocarcinoma was initiated by an injection of DEN and promoted by phenobarbital (0.05%) in the diet. In addition, the potential nephrotoxicity of SB was evaluated in a cisplatin-induced nephrotoxicity model. Rats were administered the SB complex (1 and 2 mg/kg body weight/day) for 24 weeks, and cancer progression was investigated by macroscopic, histopathological, and western blot examinations. The administration of SB decreased the incidence and the number of hepatic nodules in a dose-dependent manner by regulating inflammation response and the apoptotic pathway. Western blot analyses from the livers of rats treated with SB after DEN induction showed significantly enhanced Bax and caspase-3 levels, with a marked decrease in the levels of Bcl-2, NF-&kgr;B p65 and cyclooxygenase (COX)-2. Results from the nephrotoxicity study showed that, whereas cisplatin increased serum urea nitrogen and creatinine levels, no increase in serum biochemical parameters was detected in SB-treated animals. Moreover, protein levels of NF-E2-related factor-2 (Nrf2) and heme oxygenase-1 were lower, whereas nuclear factor-&kgr;B (NF-&kgr;B p65) and activator protein-1 levels were higher in the kidneys of cisplatin-treated animals compared with that of the SB groups. Therefore, the SB complex could be an alternative chemotherapeutic option for liver cancer treatment once its safety in clinical applications has been examined.

Preparation and analytical application of the novel Hg(II)-selective membrane electrodes based on oxime compounds.

Novel Hg(II)-selective poly(vinyl) chloride (PVC) membrane electrodes based on oxime compounds of (4-(4-methylphenylaminoisonitrosoacetyl)biphenyl, I1; 4-(4-clorophenylaminoisonitrosoacetyl)biphenyl, I2; N,N-bis[1-(4-phenylphenyl)-2-hydroxyimino-2-(4-chloroaniline)-1-ethylidene]-diethylenetriamine, I3 and N,N-bis[1-(4-phenylphenyl)-2-hydroxyimino-2-(4-chloroaniline)-1-ethylidene]- 1,3-propanediamine), I4 were developed. Effects of the species and ratios of ionophore, plasticizer, PVC and lipophilic additive on the potentiometric response of electrodes were investigated in order to determine the electrode specifications. Overall results revealed that the optimum membrane composition was: 4% ionophore, 64% plasticizer (o-NPOE), 31% PVC, and 1% lipophilic additive (NaTPB). Obtained results showed that the electrodes have detection limit of 1.76×10(-6), 1.68×10(-6), 2.35×10(-6) and 2.44×10(-6) and have linear responses of 34.2, 33.4, 35.9 and 37.6 mV/pHg(2+) for a wide concentration range of Hg(II) ions. According to durability studies, the electrodes can be used for approximately 1 month without any considerable divergence in potential values. Analytical applications of the electrodes were performed and it was found that developed electrodes can successfully be used as indicator electrodes for the potentiometric titration of Hg(II) ion with EDTA solution.

The course of spinal tuberculosis (Pott disease): results of the multinational, multicentre Backbone-2 study

We aimed to describe clinical, laboratory, diagnostic and therapeutic features of spinal tuberculosis (ST), also known as Pott disease. A total of 314 patients with ST from 35 centres in Turkey, Egypt, Albania and Greece were included. Median duration from initial symptoms to the time of diagnosis was 78 days. The most common complications presented before diagnosis were abscesses (69%), neurologic deficits (40%), spinal instability (21%) and spinal deformity (16%). Lumbar (56%), thoracic (49%) and thoracolumbar (13%) vertebrae were the most commonly involved sites of infection. Although 51% of the patients had multiple levels of vertebral involvement, 8% had noncontiguous involvement of multiple vertebral bodies. The causative agent was identified in 41% of cases. Histopathologic examination was performed in 200 patients (64%), and 74% were consistent with tuberculosis. Medical treatment alone was implemented in 103 patients (33%), while 211 patients (67%) underwent diagnostic and/or therapeutic surgical intervention. Ten percent of the patients required more than one surgical intervention. Mortality occurred in 7 patients (2%), and 77 (25%) developed sequelae. The distribution of the posttreatment sequelae were as follows: 11% kyphosis, 6% Gibbus deformity, 5% scoliosis, 5% paraparesis, 5% paraplegia and 4% loss of sensation. Older age, presence of neurologic deficit and spinal deformity were predictors of unfavourable outcome. ST results in significant morbidity as a result of its insidious course and delayed diagnosis because of diagnostic and therapeutic challenges. ST should be considered in the differential diagnosis of patients with vertebral osteomyelitis, especially in tuberculosis-endemic regions. Early establishment of definitive aetiologic diagnosis and appropriate treatment are of paramount importance to prevent development of sequelae.

Synthesis, structure, and solvent-extraction properties of tridentate oxime ligands and their cobalt(II), nickel(II), copper(II), zinc(II) complexes

Synthesis of four different types of ligands Ar[COC(NOH)R]n (Ar = biphenyl, n = 1, HL1; Ar = biphenyl, n = 2, H2L2; Ar = diphenylmethane, n = 1, HL3; Ar = diphenylmethane, n = 2, H2L4; R = furfurylamine in all ligands) and their dinuclear Co2+, Ni2+, Cu2+, and Zn2+ complexes is reported herein. These compounds were characterized by elemental analysis, ICP-OES, FT-IR spectra, and magnetic susceptibility measurements. The ligands were further characterized by 1H NMR. The results suggest that dinuclear complexes of HL1 and HL3 have a metal to ligand mole ratio of 2: 2 and dinuclear complexes H2L2 and H2L4 have a metal to ligand mole ratio of 2: 1. Square pyramidal or octahedral structures are proposed for complexes of oxime ligands. Furthermore, extraction abilities of the four ligands were also evaluated in chloroform using selected transition metal picrates such as Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, Hg2+, Pb2+. The ligands show strong binding ability towards Hg2+ and Cu2+ ions.

Poloxamer P85 increases anticancer activity of Schiff base against prostate cancer in vitro and in vivo

Prostate cancer is the second most common cancer among men and the leading cause of death after lung cancer. Development of hormone-refractory disease is a crucial step for prostate cancer progression for which an effective treatment option is currently unavailable. Therefore, there is a need for new agents that can efficiently target cancer cells, decrease tumor growth, and thereby extend the survival of patients in late-stage castration-resistant prostate cancer. In the current study, a novel heterodinuclear copper(II)Mn(II) Schiff base complex combined with P85 was used to evaluate anticancer activity against prostate cancer in vitro and in vivo. Cell proliferation and cytotoxicity were evaluated by cell viability, gene, and protein expression assays in vitro. Results showed that the heterodinuclear copper(II)Mn(II) complex–P85 combination decreased cell proliferation by upregulating the apoptotic gene expressions and blocking the cell proliferation-related pathways. Tramp-C1-injected C57/B16 mice were used to mimic a prostate cancer model. Treatment combination of Schiff base complex and P85 significantly enhanced the cellular uptake of chemicals (by blocking the drug transporters and increased life time), suppressed tumor growth, and decreased tumor volume steadily over the course of the experiments. Overall, heterodinuclear copper(II)Mn(II) complex–P85 showed remarkable anticancer activity against prostate cancer in in vitro and in vivo.

MONO-, TRINUCLEAR NICKEL(II) AND COPPER(II) DIOXIME COMPLEXES: SYNTHESIS, CHARACTERIZATION, CATECHOLASE AND CATALASE-LIKE ACTIVITIES, DNA CLEAVAGE STUDIES

The synthesis and molecular structures of six new mono- and trinuclear complexes [M1L 2 {M2(phen)} 2 ](ClO 4 ) 2 [phen = 1,10-phenanthroline, H 2 L = dioxime ligand, M1, M2 =Ni(II) and Cu(II)] of the ligand, 4-(4-methylphenylamino)biphenylglyoxime are reported. Structural assignments are supported by a combination of FT-IR, elemental analyses, ICP-OES, magnetic susceptibility and molar conductivity studies. Furthermore these complexes were each tested for their ability to catalyze the oxidation of catechol substrates to quinone with dioxygen at 25oC and disproportionation of hydrogen peroxide in the presence of the added base imidazole. The catalytic results indicated that the heterotrinuclear Cu(II)Ni(II)Cu(II) complex (5) shows greater catecholase activity. On the other hand the trinuclear complexes display efficiency in disproportion reactions of hydrogen peroxide producing water and dioxygen in catalase-like activity and homotrinuclear Cu(II) (6) complex is more active towards catalytic decomposition of hydrogen peroxide. The interaction between these compounds with DNA has also been investigated by agarose gel electrophoresis, the trinuclear copper(II) complexes (5, 6) with H 2 O 2 as a cooxidant exhibited the strongest cleaving activity.

Synthesis of (2-hydroxo-5-chlorophenylaminoisonitrosoacetyl)phenyl ligands and their complexes: Spectral, thermal and solvent-extraction studies

Four different types of new ligands Ar[COC(NOH)R]n (Ar=biphenyl, n = 1 H2L1; Ar=biphenyl, n = 2 H4L2; Ar=diphenylmethane, n = 1 H2L3; Ar=diphenylmethane, n = 2 H4L4; R=2-amino-4-chlorophenol in all ligands) have been obtained from 1 equivalent of chloroketooximes Ar[COC(NOH)Cl]n (HL1-H2L4) and 1 equivalent of 2-amino-4-chlorophenol (for H2L1 and H2L3) or 2 equivalent of 2-amino-4-chlorophenol (for H4L2 and H4L4). (Mononuclear or binuclear cobalt(II), nickel(II), copper(II) and zinc(II) complexes were synthesized with these ligands.) These compounds have been characterized by elemental analyses, AAS, infra-red spectra and magnetic susceptibility measurements. The ligands have been further characterized by 1H NMR. The results suggest that the dinuclear complexes of H2L1 and H2L3 have a metal:ligand ratio of 1:2; the mononuclear complexes of H4L2 and H4L4 have a metal:ligand ratio of 1:1 and dinuclear complexes H4L2 and H4L4 have a metal:ligand ratio of 2:1. The binding properties of the ligands towards selected transition metal ions (MnII, CoII, NiII, CuII, ZnII, PbII, CdII, HgII) have been established by extraction experiments. The ligands show strong binding ability towards mercury(II) ion. In addition, the thermal decomposition of some complexes is studied in nitrogen atmosphere.

Anticancer activity of Schiff base–Poloxamer P85 combination against kidney cancer

AbstractPurposeRenal cell carcinoma (RCC) accounts for approximately 80% of the primary renal cancers, and current treatment strategies are not sufficient to provide a certain solution. Since there are not many treatment options, interest in discovery of alternative drugs has increased. MethodsIn the current study, anticancer activity of a novel heterodinuclear Cu(II)–Mn(II) complex (Schiff base—SB) in combination with poly(ethylene oxide) and poly(propylene oxide) block copolymer (pluronic) P85 was tested against RCC. Cell viability, apoptosis and gene expression analysis were conducted in vitro by using Renca cells. ResultsThe results revealed that the SB–P85 combination decreased cell proliferation by increasing the apoptotic gene expressions and apoptosis. Renca-injected BALB/c mice were used to mimic early stage of RCC model. Treatment with SB–P85 combination suppressed tumor formation and growth compared to baseline.ConclusionOverall, SB–P85 showed promising anticancer activity against RCC in vitro and in vivo.

Synthesis, characterization and electrochemical behavior of a new diimine-dioxime compound and its application in developing Hg(II)-selective membrane electrode

In this work, a new diimine-dioxime compound (N,N′-bis[1-biphenyl-2-hydroxyimino-2-(4-chloroanilino)-1-ethylidene]-1,4-phenylenediamine) was synthesized and characterized by a combination of elemental analyses, FT-IR, 1H- and 13C-NMR spectra. The extraction ability of the new compound has been examined in chloroform by using several transition metal picrates such as Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Pb(II), Cd(II) and Hg(II). It has been observed that diimine-dioxime compound shows a high affinity to Hg(II) ion. The electrochemical measurements of the compound were performed by cyclic voltammetry in acetonitrile solution at room temperature, and two irreversible oxidation waves were observed. A Hg(II)-selective electrode based on the diimine-dioxime compound has been developed. The electrode showed linear responses with Nernstian slopes of 33 ± 1 mV per decade over a wide concentration range (1.0 × 10−2–8.0 × 10−6 M). The limit of detection was 2.4 × 10−6 M. The electrode has a response time about 10–15 s and it did not show a considerable divergence in its potential response over a period of 1 month. The proposed electrode revealed selectivity towards Hg(II) ion in the presence of various cations. The electrode could be used over a wide pH range of 4.0–9.0. The electrode can be successfully used as an indicator electrode for potentiometric titration of Hg(II) with EDTA.