The interaction of lower rim calix(4)arene derivatives containing ester (1) and ketone (2) functional groups and bivalent (alkaline-earth, transition- and heavy-metal) cations has been investigated in various solvents (methanol, N,N-dimethylformamide, acetonitrile, and benzonitrile). Thus, 1H NMR studies in CD3OD, C3D7NO, and CD3CN show that the interaction of these ligands with bivalent cations (Mg2+, Ca2+, Sr2+, Ba2+, Hg2+, Pb2+, Cd2+) is only observed in CD3CN. These findings are corroborated by conductance measurements in these solvents including benzonitrile, where changes upon the addition of the appropriate ligand (1 or 2) to the metal-ion salt only occur in acetonitrile. Thus, in this solvent, plots of molar conductance against the ligand/metal cation ratio reveal the formation of 1:1 complexes between these ligands and bivalent cations. Four metal-ion complex salts resulting from the interaction of 1 and 2 with cadmium and lead, respectively, were isolated and characterized by X-ray crystallography. All four structures show an acetonitrile molecule sitting in the hydrophobic cavity of the ligand. The mode of interaction of the neutral guest in the cadmium(II) complexes differs from each other and from that found in the lead(II) complexes and provides evidence of the versatile behavior of acetonitrile in binding processes involving calix(4)arene derivatives. The thermodynamics of complexation of these ligands and bivalent cations in acetonitrile is reported. Thus, the selective behavior of 1 and 2 for bivalent cations is for the first time demonstrated. The role of acetonitrile in the complexation process in solution is discussed on the basis of 1H NMR and X-ray crystallographic studies. It is suggested that the complexation of 1 and 2 with bivalent cations is likely to involve the ligand-solvent adducts rather than the free ligand. Plots of complexation Gibbs energies against the corresponding data for cation hydration show a selectivity peak which is explained in terms of the predominant role played by cation desolvation and ligand binding energy in complex formation involving metal cations and macrocycles in solution. A similar peak is found in terms of enthalpy suggesting that for most cations (except Mg2+) the selectivity is enthalpically controlled. The ligand effect on the complexation process is quantitatively assessed. Final conclusions are given highlighting the role of the solvent in complexation processes involving calix(4)arene derivatives and metal cations.

Samples of vegetable oils were oxidized at isothermal conditions in the cell of a Pressure Differential Scanning Calorimeter (PDSC) and in the Methrom Rancimat apparatus. The PDSC and Rancimat experiments were carried out at a temperature in the range of 90-160 7C. From resulting PDSC exotherms their times to reach the peak maximum (t PDSC ) were determined and used for the assessment of the oxidative stability of the samples. Similarly the measured Rancimat induction times (t Rancimat ) were used. As PDSC and Rancimat results were obtained at different temperatures the equations for temperature extrapolations of the t PDSC and t Rancimat values have been proposed. Using the Arrhenius type correlation between induction times and temperature and activated complex theory the reaction rate constants, activation energies, activation enthalpies and activation entropies for oils oxidation have been calculated.

, and the others in South Asia. Cymbopogon exuosus and Cymbopogon citratus represent the two major species vastly cultivated for their essential oils in different regions of the world. C. citratus is known by numerous international common names, such as West Indian lemon grass or lemon grass (English), citronelle or verveine des indes (French), hierba limon or zacate de limón (Spanish), xiang mao (Chinese), capimcidrao or capim-santo (Portuguese), and locally there are identi ed more than 28 indigenous names from different countries of the world. The genus Cymbopogon has been reviewed comprehensively in several articles [Avoseh et al., 2015; Haque et al., 2018]. C. citratus is an aromatic, evergreen, clump-forming, perennial grass producing numerous stiff stems arising from a short rhizomatous rootstock, and growing around 1.5 m tall. It rarely produces owers. The leaves are blue-green in colour, at, erect, linear in shape and give off a characteristic lemon avour when they are crushed. C. citratus is considered to have its origin in Malaysia, nowadays it is widely cultivated in the Central and South America and parts of Africa, Southeast Asia, and the Indian Ocean Islands, both on a commercial scale and in gardens especially in the South

Four samples of olive oil were oxidized under polythermal (dynamic) conditions in the cell of a normalpressure differential scanning calorimeter (DSC) and in the Metrohm Rancimat apparatus. The DSC experiments were carried out in an oxygen flow atmosphere using different linearly programmed heating rates in the range of 4-20 7C/min. Through DSC exotherms, the extrapolated onset temperatures were determined and used for the assessment of the thermal-oxidative stabilities of the samples. Using the Ozawa-Flynn-Wall method and the Arrhenius equation, the activation energies (E a ), pre-exponential factors (Z) and reaction rate constants (k) for oil oxidation under DSC conditions were calculated. The Rancimat measurements of oxidation induction times were carried out under isothermal conditions in an air atmosphere at temperatures from 100 to 140 7C with intervals of 10 7C. Using the Arrhenius-type correlation between the inverse of the induction times and the absolute temperature of the measurements, E a , Z, and k for oil oxidation under Rancimat conditions were calculated. The primary kinetic parameters derived from both methods were qualitatively consistent and they help to evaluate the oxidative stabilities of oils at increased temperatures.

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Prohormone convertase (PC)1/3 is a eukaryotic serine protease in the subtilase family that participates in the proteolytic maturation of prohormone and neuropeptide precursors such as proinsulin and proopiomelanocortin. Despite the important role of this enzyme in peptide synthesis, how PC1/3 activity is regulated is still poorly understood. Using ion exchange chromatography and two-dimensional gel electrophoresis we found that natural PC1/3 present in AtT-20 cells and bovine chromaffin granules, as well as recombinant PC1/3 secreted from overexpressing Chinese hamster ovary cells, exists as multiple ionic forms. Gel filtration and cross-linking studies revealed that protein oligomerization and aggregation contribute greatly to variability in surface charge. The most acidic forms of PC1/3 contained both inactive aggregates as well as oligomerized 87-kDa PC1/3 that exhibited stable activity which was partially latent and could be revealed by dilution. No such latency was observed for the more basic, 66/74-kDa forms of PC1/3. Fractions containing these species were stabilized by preincubation with micromolar concentrations of either fluorogenic substrate or peptides containing pairs of basic residues. In addition, the most active form of 87-kDa PC1/3, a probable homodimer, was activated by preincubation with these same peptides. Cleavage by PC1/3 is often the initiating step in the biosynthetic pathway for peptide hormones, implying that this is a natural step for regulation. Our data suggest that enzyme oligomerization and peptide stabilization represent important contributing factors for the control of PC1/3 activity within secretory granules.

The proprotein convertases are believed to be responsible for the proteolytic maturation of a large number of peptide hormone precursors. Although potent furin inhibitors have been identified, thus far, no small-molecule prohormone convertase 1/3 or prohormone convertase 2 (PC2) inhibitors have been described. After screening 38 small-molecule positional scanning libraries against recombinant mouse PC2, two promising chemical scaffolds were identified: bicyclic guanidines, and pyrrolidine bis-piperazines. A set of individual compounds was designed from each library and tested against PC2. Pyrrolidine bis-piperazines were irreversible, time-dependent inhibitors of PC2, exhibiting noncompetitive inhibition kinetics; the most potent inhibitor exhibited a K i value for PC2 of 0.54 M. In contrast, the most potent bicyclic guanidine inhibitor exhibited a K i value of 3.3 M. Cross-reactivity with other convertases was limited: pyrrolidine bis-piperazines exhibited K i values greater than 25 M for PC1/3 or furin, whereas the K i values of bicyclic guanidines for these other convertases were more than 15 M. We conclude that pyrrolidine bis-piperazines and bicyclic guanidines represent promising initial leads for the optimization of therapeutically active PC2 inhibitors. PC2-specific inhibitors may be useful in the pharmacological blockade of PC2-dependent cleavage events, such as glucagon production in the pancreas and ectopic peptide production in small-cell carcinoma, and to study PC2-dependent proteolytic events, such as opioid peptide production.

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