Relationship between Antioxidant Activity and Ligand Basicity in the Dipicolinate Series of Oxovanadium(IV) and Dioxovanadium(V) Complexes.

Oxidative stress plays an important role in the pathogenesis of many serious diseases, including cancer, atherosclerosis, coronary artery disease, Parkinson's disease, Alzheimer's disease, stroke and myocardial infarction. In the body's natural biochemical processes, harmful free radicals are formed, which can be removed with the help of appropriate enzymes, a balanced diet or the supply of synthetic antioxidant substances such as flavonoids, vitamins or anthocyanins to the body. Due to the growing demand for antioxidant substances, new complex compounds of transition metal ions with potential antioxidant activity are constantly being sought. In this study, four oxovanadium(IV) and dioxovanadium(V) dipicolinate (dipic) complexes with 1,10-phenanthroline (phen), 2,2'-bipyridyl (bipy) and the protonated form of 2-phenylpyridine (2-phephyH): (1) [VO(dipic)(H2O)2]·2 H2O, (2) [VO(dipic)(phen)]·3 H2O, (3) [VO(dipic)(bipy)]·H2O and (4) [VOO(dipic)](2-phepyH)·H2O were synthesized including one new complex, so far unknown and not described in the literature, i.e., [VOO(dipic)](2-phepyH)·H2O. The oxovanadium(IV) dipicolinate complexes with 1,10-phenanthroline and 2,2'-bipyridyl have been characterized by several physicochemical methods: NMR, MALDI-TOF-MS, IR, but new complex [VOO(dipic)](2-phepyH)·H2O has been examined by XRD to confirm its structure. The antioxidant activities of four complexes have been examined by the nitrotetrazolium blue (NBT) method towards superoxide anion. All complexes exhibit high reactivity with superoxide anion and [VOO(dipic)](2-phepyH)·H2O has higher antioxidant activity than L-ascorbic acid. Our studies confirmed that high basicity of the auxiliary ligand increases the reactivity of the complex with the superoxide radical.

Cat-CrNP as new material with catalytic properties for 2-chloro-2-propen-1-ol and ethylene oligomerizations.

The contemporary search for new catalysts for olefin oligomerization and polymerization is based on the study of coordinating compounds and/or organometallic compounds as post-metallocene catalysts. However known catalysts are suffered by many flaws, among others unsatisfactory activity, requirement of high pressure or instability at high temperatures. In this paper, we present a new catalyst i.e. the crystalline complex compound possesing high catalytic activity in the oligomerization of olefins, such as 2-chloro-2-propen-1-ol and ethylene under very mild conditions (room temperature, 0.12 bar for ethylene oligomerization, atmospheric pressure for 2-chloro-2-propen-1-ol oligomerization). New material-Cat-CrNP ([nitrilotriacetato-1,10-phenanthroline]chromium(III) tetrahydrate) has been obtained as crystalline form of the nitrilotriacetate complex compound of chromium(III) with 1,10-phenanthroline and characterized in terms of its crystal structure by the XRD method and by multi-analytical investigations towards its physicochemical propeties The yield of catalytic oligomerization over Cat-CrNP reached to 213.92 g · mmol-1 · h-1· bar-1 and 3232 g · mmol-1 · h-1 · bar-1 for the 2-chloro-2-propen-1-ol and ethylene, respectively. Furthemore, the synthesis of Cat-CrNP is cheap, easy to perform and solvents used during preparation are environmentally friendly.

Oxidovanadium(IV) Complex Disrupts Mitochondrial Membrane Potential and Induces Apoptosis in Pancreatic Cancer Cells.

BACKGROUND: At the present time, there is a growing interest in metal-based anticancer agents. Metal complexes exhibit many valuable clinical properties, however, due to toxicity, only a few clinically useful complexes have been discovered. It has been demonstrated that synthetic vanadium complexes exhibit many biological activities, including anti-cancer properties, however, cellular and molecular mechanisms still are not fully understood. OBJECTIVE: This investigation examined the potential effects of three newly synthesized oxidovanadium(IV) complexes with 2-amino-3-hydroxypyridine against pancreatic cancer cells. METHODS: We measured cytotoxicity by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, antiproliferative activity by bromodeoxyuridine assay and necrosis as well as late apoptosis by lactate dehydrogenase assay. Reactive oxygen species generation, apoptosis and mitochondrial membrane potential were determined by a flow cytometry technique. Cell morphology was evaluated by using a transmission electron microscope. RESULTS: The results showed that oxidovanadium(IV) complexes were cytotoxic on pancreatic cancer cells (PANC-1 and MIA PaCa2) over the concentration range of 12.5-200µM, following 48h incubation. Additionally, the cellular mechanism of cytotoxic activity of [2-NH2-3-OH(py)H]4[V2O2(pmida)2]·6H2O (V3) complex was dependent on ROS generation, induction apoptosis with simultaneous disruption of mitochondrial membrane potential. CONCLUSION: We have proven that oxidovanadium (IV) complexes show therapeutic potential in pancreatic cancer therapy. The results of our research will help to understand the cellular mechanisms of the cytotoxic activity of the vanadium complexes and will allow a more effective design structure of new vanadium-based compounds in the future.

5-(N-Trifluoromethylcarboxy)aminouracil as a Potential DNA Radiosensitizer and Its Radiochemical Conversion into N-Uracil-5-yloxamic Acid.

Hypoxia-a hallmark of solid tumors-dramatically impairs radiotherapy, one of the most common anticancer modalities. The adverse effect of the low-oxygen state can be eliminated by the concomitant use of a hypoxic cell radiosensitizer. In the present paper, we show that 5-(N-trifluoromethylcarboxy) aminouracil (CF3CONHU) can be considered as an effective radiosensitizer of DNA damage, working under hypoxia. The title compound was synthesized in the reaction of 5-aminouracil and trifluoroacetic anhydride in trifluoroacetic acid. Then, an aqueous and deoxygenated solution of the HPLC purified compound containing tert-butanol as a hydroxyl radical scavenger was irradiated with X-rays. Radiodegradation in a 26.67 ± 0.31% yield resulted in only one major product-N-uracil-5-yloxamic acid. The mechanism that is possibly responsible for the formation of the observed radioproduct has been elucidated with the use of DFT calculations. The cytotoxic test against the PC3 prostate cancer cell line and HDFa human dermal fibroblasts confirmed the low cytotoxicity of CF3CONHU. Finally, a clonogenic assay and flow cytometric analysis of histone H2A.X phosphorylation proved the radiosensitization in vitro.

Uracil-5-yl O-Sulfamate: An Illusive Radiosensitizer. Pitfalls in Modeling the Radiosensitizing Derivatives of Nucleobases.

Efficient radiotherapy requires the concomitant use of ionizing radiation (IR) and a radiosensitizer. In the present work uracil-5-yl O-sulfamate (SU) is tested against its radiosensitizing potential. The compound possesses appropriate dissociative electron attachment (DEA) characteristics calculated at the M06-2X/6-31++G(d,p) level. Crossed electron-molecular beam experiments in the gas phase demonstrate that SU undergoes efficient DEA processes, and the single C-O or S-O bond dissociations account for the majority of fragments induced by electron attachment. Most DEAs proceed already for electrons with kinetic energies of ∼0 eV, which is supported by the exothermic thresholds calculated at the M06-2X/aug-cc-pVTZ level. However, in water solution under reductive conditions and physiological pH, SU does not undergo radiolysis, which demonstrates the crucial influence of aqueous environment on the radiosensitizing properties of modified nucleosides.

Synthesis, structure, and biological activity of novel heterocyclic sulfonyl-carboximidamides.

ABSTRACT: A series of novel heterocyclic sulfonyl-carboximidamides were synthesized in satisfactory yields via condensation of heterocyclic methyl carbimidates with 2-chlorobenzenesulfonamide and 4-chloropyridine-3-sulfonamide. New structures were confirmed by IR and NMR spectra as well as elemental analyses. X-ray crystallography of two derivatives was performed. The single-crystal structures confirmed the presence of a primary amine group in the amidine moiety. All the compounds were screened for their tuberculostatic, antibacterial, and anticancer activities. Preliminary results indicated that target compounds exhibited weak tuberculostatic and antibacterial activities. Seven compounds inhibited the growth of some cancer cell lines, whereas one of the 2-quinoline derivatives displayed favorable activity against all tested cancer cells with GI50 values of 0.92-13 µM.

Methyl 6-deoxy-6-iodo-alpha-D-glucopyranoside: crystal structure and high-resolution NMR spectroscopy.

Single-crystal X-ray diffraction and high-resolution (1)H and (13)C NMR spectral data for methyl 6-deoxy-6-iodo-alpha-D-glucopyranoside are reported. The (4)C(1) conformation was found to be the preferred form for this compound, both in the crystal lattice and in solution. The rotational preferences of all the groups bound to the pyranose ring are presented. The stabilization of the crystal structure by a network of O-H...O intra- and intermolecular interactions as well as the short contacts of the iodine atoms is discussed.