FT-IR Spectroscopic Investigation of Hofmann Td-Type Complexes of 2-, and 3-Chloropyridine

Hofmann-type modified clathrate hosts containing 2- or 3-chloropyridine molecules attached to metal (II) tetracyanocadmate frame, with a given formula: M(Clpy)₂Cd(CN)₄ where M = Mn, Ni or Cd; Clpy = 2- or 3-chloropyridine, have been synthesised for the first time. Their FT-IR spectra are reported in the 400–4000 cm^-1 region. All the vibrational modes of coordinated Clpy are characterised. The spectral features of the compounds studied are found to be similar to each other indicating that they have analogous structures. The coordination effect on the Clpy modes is analyzed.     

New gold(III) chlorophenyl terpyridine complex: Biomolecular interactions and anticancer activity against human oral squamous cell carcinoma

In this work we synthesized new monofunctional gold(III) complex [Au(Cl-Ph-tpy)Cl]Cl₂ (Cl-Ph-tpy = 4′-[4-chlorophenyl]-2,2′:6′, 2″-terpyridine). This complex was characterized by UV–Vis, NMR, IR, and ESI-MS spectrometry. The kinetic study of the substitution reactions of the Au-Cl-Ph-tpy complex with biomolecules showed that the rate constants depend on the nature of the entering nucleophile. Based on the calculated values of entropy (∆H^≠ > 0) and enthalpy (∆S^≠ < 0) the proposed substitution mechanism is associative. Additionally, the relative stability and thermodynamic properties of Au-Cl-Ph-tpy complex were compared with the analogue Au-tpy complex by the B3LYP/def2-svp method. DNA/BSA binding studies showed that Au-Cl-Ph-tpy complex interacts with CT DNA through the intercalation and moderately quenches the fluorescence of tryptophan residues in serum albumin (BSA). Molecular docking confirmed results obtained by spectroscopic experiments and suggested site I (subdomain IIA) for binding of Au complex to BSA. We demonstrated that the Au chlorophenyl terpyridine complex possessed significant in vitro cytotoxic activity against human oral squamous carcinoma cells (CAL-27), induced apoptosis, inhibited proliferation of CAL-27 cells, and induced cell cycle disturbance. Treatment of CAL-27 cells with the Au complex enhanced expression of cyclin-dependent kinase inhibitors p21 and p27, resulting in cell cycle arrest in the G1 phase, reduced the percentage of CAL-27 cells in S phase and decreased expression of Ki-67. Additionally, Au complex reduced expression of phosphorylated STAT3 and downstream regulated molecules associated with cancer stemness, NANOG, and Sox2 protein.     

Lipophilicity and bio‐mimetic properties determination of phytoestrogens using ultra‐high‐performance liquid chromatography

This paper presents lipophilicity and bio‐mimetic property determination of 15 phytoestrogens, namely biochanin A, daidzein, formononetin, genistein, genistein‐4,7‐dimethylether, prunetin, 3,4,7‐trihydroxyisoflavon, 4,6,7‐trihydroxyisoflavon, 4,6,7‐trimethoxyisoflavon, daidzin, genistin, ononin, sissotrin, coumestrol and coumestrol dimethylether. High‐performance liquid chromatography with fast gradient elution and Caco‐2 cell line were used to determine the physicochemical properties of selected phytoestrogens. Lipophilicity was determined on octadecyl‐sylane stationary phase using pH 2.0 and pH 7.4 buffers. Immobilized artificial membrane chromatography was used for prediction of interaction with biological membranes. Protein binding was measured on human serum albumin and α‐1‐acid‐glycoprotein (AGP) stationary phases. Caco‐2 assay was used as a gold standard for assessing in vitro permeability. The obtained results differentiate phytoestrogens according to their structure where aglycones show significantly higher lipophilicity, immobilized artificial membrane partitioning, AGP binding and Caco‐2 permeability compared with glucosides. However, human serum albumin binding was very high for all investigated compounds. Furthermore, a good correlation between experimentally obtained chromatographic parameters and in silico prediction was obtained for lipophilicity and human serum albumin binding, while the somewhat greater difference was obtained for AGP binding and Caco‐2 permeability.     

The comparison of sample extraction procedures for the determination of cations in soil by IC and ICP-AES

This paper presents the extraction of cations from a soil sample, type ranker on serpentinite, in deionized water, by use of three different extraction techniques. The first extraction technique included the use of a rotary mixer, the second technique involved the use of a microwave digestion system with different extraction temperatures, and the third technique employed an ultrasonic bath with different extraction times. Ion chromatography was used for determining the concentration of Li, Na, K, Ca, Mg and ammonium ions in soil extracts with subsequent determination of concentrations for all cations, except for ammonium ion extraction, conducted by Inductively Coupled Plasma-Atomic Emission Spectrometry. The results of cation extractions showed that microwave assisted extraction was most efficient for the Li, Na, K, Ca, Mg, Co, Mn, Ni, Pb and ammonium ions. Use of a rotary mixer for extraction was most efficient for Cd and Zn ions, while use of ultrasound bath was most efficient for Cr, Cu, Fe and Al ions. Several times higher amount of cations extracted by the most efficient, compared to the second best technique, under optimal conditions, were noticed in the case of: Ca, Mg, Co, Mn, Fe, Al, and Zn ions.     

Simultaneous analysis of mitotane and its main metabolites in human blood and urine samples by SPE-HPLC technique

Adrenocortical carcinoma (ACC) is a rare malignancy with an incompletely understood pathogenesis and a poor prognosis. The adrenalytic activity of mitotane has made it the most important single drug in the treatment of ACC. Unfortunately, the exact mechanism of mitotane action is still unknown. It is believed that mitotane belongs to the class of drugs that require metabolic transformation by cytochrome P450 for therapeutic action; therefore determination of plasma levels of not only mitotane but also its metabolites would help in carrying out the treatment. The objective of this work was to develop and validate an SPE‐HPLC method for simultaneous determination of mitotane and its metabolites in different biological fluids. The sample preparation consisted of a solid‐phase extraction on a Discovery DSC₁₈ cartridge, while analysis of extracts was performed on a Symmetry C₁₈ column. The usefulness of the proposed method was confirmed by analysis of plasma, red cell and urine samples from patient chronically treated with 1.5 g of mitotane. The patient involved in this study had a high plasma concentration of mitotane and none of the investigated metabolites were found. In order to investigate whether the polymorphism of CYP2C9 and CYP2C19 enzymes could be related to the metabolism of mitotane, RT‐PCR analysis was performed. Copyright © 2012 John Wiley & Sons, Ltd.     

In Vitro Evaluation of Antiproliferative Properties of Novel Organotin(IV) Carboxylate Compounds with Propanoic Acid Derivatives on a Panel of Human Cancer Cell Lines

The synthesis of novel triphenyltin(IV) compounds, Ph₃SnLn (n = 1–3), with oxaprozin (3-(4,5-diphenyloxazol-2-yl)propanoic acid), HL1, and the new propanoic acid derivatives 3-(4,5-bis(4-methoxylphenyl)oxazol-2-yl)propanoic acid, HL2, and 3-(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)propanoic acid, HL3, has been performed. The ligands represent commercial drugs or their derivatives and the tin complexes have been characterized by standard analytical methods. The in vitro antiproliferative activity of both ligands and organotin(IV) compounds has been evaluated on the following tumour cell lines: human prostate cancer (PC-3), human colorectal adenocarcinoma (HT-29), breast cancer (MCF-7), and hepatocellular cancer (HepG2), as well as on normal mouse embryonic fibroblast cells (NIH3T3) with the aid of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-12 diphenyltetrazolium bromide) and CV (crystal violet) assays. Contrary to the inactive ligand precursors, all organotin(IV) carboxylates showed very good activity with IC₅₀ values ranging from 0.100 to 0.758 µM. According to the CV assay (IC₅₀ = 0.218 ± 0.025 µM), complex Ph₃SnL1 demonstrated the highest cytotoxicity against the caspase 3 deficient MCF-7 cell line. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated a two-fold lower concentration of tin in MCF-7 cells in comparison to platinum. To investigate the mechanism of action of the compound Ph₃SnL1 on MCF-7 cells, morphological, autophagy and cell cycle analysis, as well as the activation of caspase and ROS/RNS and NO production, has been performed. Results suggest that Ph₃SnL1 induces caspase-independent apoptosis in MCF-7 cells.     

Complex formation reactions of two sterically hindered platinum(II) complexes with some N-bonding ligands

The kinetics of the complex formation reactions of two [(TL ^tBu)PtCl]⁺ and [Pt(tpdm)Cl]⁺ complexes (TL ^tBu = 2,6-bis[(1,3-di-tert-butylimidazolin-2-imino)methyl]pyridine and tpdm = terpyridinedimethane) with N-donor ligands, l-histidine (L-His), inosine (Ino), inosine-5′-monophosphate (5′-IMP) and guanosine-5′-monophosphate (5′-GMP), were studied. All reactions were studied under pseudo-first-order conditions as a function of nucleophile concentration and temperature in aqueous 0.1 M NaClO₄ solution in the presence of 10 mM NaCl using variable-temperature Uv–Vis spectrophotometry. The order of reactivity of the studied ligands is L-His > Ino > 5′-GMP > 5′-IMP. This order of reactivity is in relation to their electronic properties and structures. The mechanism of the substitution reactions is associative in nature as supported by the negative entropy of activation.     

Determination of EDTA by catalytic amperometric and catalytic potentiometric titration at a small constant current

Summary Amperometric and potentiometric methods at a small constant current were developed to follow the course of catalytic titrations. In ammoniacal medium EDTA was determined by titration with 0.1 M copper(II) chloride in the presence of hydrogen peroxide as the indicator. Amounts of 42.26–126.87 mg of EDTA were determined with a maximal average deviation of 0.55 %. The results obtained are in good agreement with those of comparable methods.

---

Bestimmung von ÄDTA mit Hilfe der katalytischen amperometrischen und der katalytischen potentiometrischen Titration bei kleinem konstantem Strom

Zusammenfassung Die amperometrische und die potentiometrische Methode bei kleinem konstantem Strom wurden für die Verfolgung katalytischer Titrationen ausgearbeitet. ÄDTA wurde in Ammoniakmedium mit 0,1 M Kupfer(II)-chlorid in Anwesenheit von Wasserstoffperoxid als Indicator titriert. Mengen von 42,26–126,87 mg ÄDTA wurden mit einer mittleren Abweichung von 0,55% bestimmt. Die Ergebnisse stimmen gut mit denen vergleichbarer Methoden überein.

The authors thank the SIZ for researchs of SAP Vojvodina for the partial financial support of the present work.     

A simple,convenient and expeditious approach to cineol

A convenient two‐step protocol preparation of cineol (1‐isopropyl‐4‐methyl‐7‐oxabicyclo[2,2,1]heptane) from α‐terpineol (p‐menth‐1‐en‐8‐ol) is reported. The phenylselenoetherification of α‐terpineol with PhSeX (X = Cl, Br, I) as a key step is described. α‐Terpineol reacts with PhSeX to form the corresponding phenylselenoether in short reaction time and in quantitative yield. A subsequent reduction with Bu₃SnH to cineol proceeds in high yield (98%) © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:468–470, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20044     

Chemometrically Assisted Development and Validation of LC for Simultaneous Determination of Carbamazepine and Its Impurities Iminostilbene and Iminodibenzyl in Solid Dosage Form

A chemometrical approach was applied to develop a reversed-phase liquid chromatographic method for simultaneous determination of carbamazepine and its impurities iminostilbene and iminodibenzyl in solid dosage form. According to contemporary literature, no method was developed for simultaneous determination of carbamazepine and these impurities by chemometrical approach. The fractional factorial design was used for selection of variables significantly influencing the chromatographic separation of the investigated substances. The investigated variables were: temperature of the column, the percentage of organic modifier, the acetate buffer concentration and pH of water phase. The first three variables were proved to be significant and were optimized by face centered, central composite design. Investigation was performed using C18 XBridge Shield analytical column (50 mm × 4.6 mm i.d., particle size 3.5 µm). The optimal conditions for the separation were established with the mobile phase composition of methanol–10 mM acetate buffer (pH adjusted to 2.21 with glacial acetic acid) (50:50, v/v) at a flow rate of 1.5 mL min^?1, 25 °C column temperature and detection at 260 nm. Total analysis time was shortened to about 8 min. Finally, the method was successfully validated and subsequently applied to the analysis of commercially available carbamazepine tablets.