Assessment of the in vitro toxicity of calixarenes and a metal-seamed calixarene: a chemical pathway for clinical application

Calixarenes are known to form host–guest complexes and supramolecular nanoassemblies with well-defined architectures. However, the use of these materials in conjunction with drug moieties is still under explored. One reason is the insufficient biocompatibility studies. Our present study represents a systematic in vitro investigation of the cytotoxicity associated with C-methylresorcin[4]arene, C-methylpyrogallol[4]arene, p-phosphonated calix[8]arene and a metal-seamed calixarene–copper(II) complex, using human HEK293 and rat C6G cell lines and two different cell viability assays (MTT and CellTiter-Glo) to avoid species-biased results. All compounds showed low to moderate toxicity. The trend in the CC₅₀ values indicated that the suppression of the coordination ability and the presence of phosphonate groups decrease the overall cytotoxicity of the compounds. The results of this study not only establish calixarenes and their immediate families as potential drug carriers and drug modifiers, but also reveal a pathway for fine-tuning their toxicological behaviour by appropriate chemical modification.     

Parallel Versus Antiparallel β-Sheet Structure in Cyclic Peptide Hybrids Containing γ- or δ-Cyclic Amino Acids

Cyclic peptides with disc-shaped structures have emerged as potent building blocks for the preparation of new biomaterials in fields ranging from biological to material science. In this work, we analyze in depth the self-assembling properties of a new type of cyclic peptides based on the alternation of α-residues and cyclic δ-amino acids (α,δ-CPs). To examine the preferred stacking properties adopted by cyclic peptides bearing this type of amino acids, we carried out a synergistic in vitro/in silico approximation by using simple dimeric models and then extended to nanotubes. Although these new cyclic peptides (α,δ-CPs) can interact either in a parallel or antiparallel fashion, our results confirm that although the parallel β-sheet is more stable, it can be switched to the antiparallel stacking by choosing residues that can establish favorable cross-strand interactions. Moreover, the subsequent comparison by using the same methodology but applied to α,γ-CPs models, up to the moment assumed as antiparallel-like d,l -α-CPs, led to unforeseen conclusions that put into question preliminary conjectures about these systems. Surprisingly, they tend to adopt a parallel β-sheet directed by the skeleton interactions. These results imply a change of paradigm with respect to cyclic peptide designs that should be considered for dimers and nanotubes.     

Cycloaddition Reactions of an Active Cyclic Phosphane/Borane Pair with Alkenes,Alkynes, and Carbon Dioxide

The active six-membered cyclo-FLP 6 undergoes a rapid P/B addition reaction to carbon dioxide. At elevated temperature, the resulting heterobicyclo[2.2.2]octane derived product 7 undergoes ring opening and equilibrates with the cyclotetramer (7)₄ . In the large macrocyclic structure, four monomeric six-membered cyclo-FLP units are connected by four CO₂ molecules to form the supramolecular ring system. The P/B cyclo-FLP 6 undergoes a variety of additional cycloaddition reactions.     

上覆荷载作用下胀缩性土干湿循环过程中胀缩变形规律研究

进行了限制侧向膨胀、允许侧向收缩时压实膨胀土、压实红黏土在不同上覆荷载作用下干湿循环试验,定量分析了在干湿循环过程中膨胀土、红黏土的胀缩变形规律.研究结果表明:在相同的干湿循环次数下,膨胀土、红黏土试样的胀缩变形幅度随上覆荷载的增加而逐渐减小,上覆荷载的作用能够不同程度地抑制膨胀性土的胀缩变形.     

固壁近旁Stokes流中粘性液滴的运动和变形

发展了一种模拟固壁近旁轴对称Stokes流中粘性液滴的运动和变形及直接计算固壁上应力的边界积分方法．用此方法对不同的液滴-固壁初始相对间距、粘度比、表面张力和浮力联合参数以及环境流动参数情况进行了数值实验．数值结果显示,由于环境流动和浮力的作用,随着时间的推进,液滴在轴向压缩,在径向拉伸．当环境流动的作用弱于浮力作用时,随着时间的推移,液滴上升并向上弯,固壁上由液滴运动所引起的应力不断减小．当环境流动的作用强于浮力作用时,随着时间的推移,液滴变得越来越扁．在这种情形,当大初始间距时,壁面上的应力随液滴的演变而增大;当小初始间距时,由环境流动、浮力及壁面对流动的较强作用的联合影响,此应力随液滴的演变而减小．由于液滴运动所引起的壁面应力的有效作用仅限于对称轴附近的一个小范围内,且此范围随液滴与固壁的初始间距增大而增大．应力的大小随初始间距增大而大为减小．表面张力对液滴变形有阻止作用．液滴粘性会减小液滴的变形和位置迁移．     

Okamoto model for necrosis and its expansions,CD38-cyclic ADP-ribose signal system for intracellular Ca2+ mobilization and Reg (Regenerating gene protein)-Reg receptor system for cell regeneration

In pancreatic islet cell culture models and animal models, we studied the molecular mechanisms involved in the development of insulin-dependent diabetes. The diabetogenic agents, alloxan and streptozotocin, caused DNA strand breaks, which in turn activated poly(ADP-ribose) polymerase/synthetase (PARP) to deplete NAD⁺, thereby inhibiting islet β-cell functions such as proinsulin synthesis and ultimately leading to β-cell necrosis. Radical scavengers protected against the formation of DNA strand breaks and inhibition of proinsulin synthesis. Inhibitors of PARP prevented the NAD⁺ depletion, inhibition of proinsulin synthesis and β-cell death. These findings led to the proposed unifying concept for β-cell damage and its prevention (the Okamoto model). The model met one proof with PARP knockout animals and was further extended by the discovery of cyclic ADP-ribose as the second messenger for Ca²⁺ mobilization in glucose-induced insulin secretion and by the identification of Reg (Regenerating gene) for β-cell regeneration. Physiological and pathological events found in pancreatic β-cells have been observed in other cells and tissues.     

Antioxidant behaviour of 2′‐hydroxy‐chalcones: a study of their electrochemical properties

The electrochemical behaviour of 13 chalcone analogues was systematically studied by means of cyclic voltammetry and chronoamperometry at a glassy carbon (GC), gold and platinum working electrodes using two different supporting electrolyte/solvent combinations. It was found that chalcone analogues can be easily oxidized at both GC and gold working electrodes, but not at a platinum electrode. Principal component analysis was further employed to reveal similarities/dissimilarities between oxidation potentials, chronoamperometric signals and ability of the compounds to scavenge the reactive oxygen species H₂O₂. The study reveals the inverse proportional relationship between the scavenging ability of H₂O₂, expressed as IC₅₀, and chronoamperometric signal at 800 mV using gold as working electrode. Copyright © 2012 John Wiley & Sons, Ltd.     

Homogeneous Cu–Fe supersaturated solid solutions prepared by severe plastic deformation

A Cu–Fe nanocomposite containing 50 nm thick iron filaments dispersed in a copper matrix was processed by torsion under high pressure at various strain rates and temperatures. The resulting nanostructures were characterized by transmission electron microscopy, atom probe tomography (APT) and Mössbauer spectrometry. It is shown that α-Fe filaments are dissolved during severe plastic deformation leading to the formation of a homogeneous supersaturated solid solution of about 12 at% Fe in fcc Cu. The dissolution rate is proportional to the total plastic strain but is not very sensitive to strain rate. Similar results were found for samples processed at liquid nitrogen temperature. APT data revealed asymmetric composition gradients resulting from deformation-induced intermixing. On the basis of these experimental data, the formation of the supersaturated solid solutions is discussed.     

Cyclic codes of length 2 m

In this paper explicit expressions ofm + 1 idempotents in the ring are given. Cyclic codes of length 2 ^m over the finite fieldF _q, of odd characteristic, are defined in terms of their generator polynomials. The exact minimum distance and the dimension of the codes are obtained.