Unique properties of DNA interstrand cross-links of antitumor oxaliplatin and the effect of chirality of the carrier ligand

The different antitumor and other biological effects of the third-generation antitumor platinum drug oxaliplatin [(1R,2R-diamminocyclohexane)oxalatoplatinum(II)] in comparison with those of conventional cisplatin [cis-diamminedichloridoplatinum(II)] are often explained by the ability of oxaliplatin to form DNA adducts of different conformation and consequently to exhibit different cytotoxic effects. This work describes, for the first time, the structural and biochemical characteristics of the interstrand cross-links of oxaliplatin. We find that: 1) DNA bending, unwinding, thermal destabilization, and delocalization of the conformational alteration induced by the cross-link of oxaliplatin are greater than those observed with the cross-link of cisplatin; 2) the affinity of high-mobility-group proteins (which are known to mediate the antitumor activity of platinum complexes) for the interstrand cross-links of oxaliplatin is markedly lower than for those of cisplatin; and 3) the chirality at the carrier 1,2-diaminocyclohexane ligand can affect some important structural properties of the interstrand cross-links of cisplatin analogues. Thus, the information contained in the present work is also useful for a better understanding of how the stereochemistry of the carrier amine ligands of cisplatin analogues can modulate their anticancer and mutagenic properties. The significance of this study is also reinforced by the fact that, in general, interstrand cross-links formed by various compounds of biological significance result in greater cytotoxicity than is expected for monofunctional adducts or other intrastrand DNA lesions. Therefore, we suggest that the unique properties of the interstrand cross-links of oxaliplatin are at least partly responsible for this drug's unique antitumor effects.     

Synthesis and biological evaluation of cruentaren A analogues

The complex macrolide cruentaren A is a highly selective and potent inhibitor of F-ATPase (F-type adenosine triphosphatase). As it shows some resemblance to benzolactone enamides like apicularen A, it was of interest to perform some structure-activity studies to delineate the key functional groups that are responsible for the activity. Building upon our previously developed route to cruentaren A, which is based on a ring-closing alkyne metathesis reaction (RCAM), several cruentaren analogues were prepared. Replacement of the 3-hydroxy hexanoic part with acids that lack the hydroxy group function resulted in a significant drop in cytotoxicity and F-ATPase inhibition. Furthermore, two enamide analogues 23 and 50 were synthesized. However, these compounds were only cytotoxic in the micromolar range. Under the conditions for cleavage of the C3 aromatic methyl ether, the enamide function was transformed to the corresponding oxazinanone, resulting in analogues 25 and 52.     

Multitargeting Prodrugs that Release Oxaliplatin,Doxorubicin and Gemcitabine are Potent Inhibitors of Tumor Growth and Effective Inducers of Immunogenic Cell Death

A multitargeting prodrug ( 2 ) that releases gemcitabine, oxaliplatin, and doxorubicin in their active form in cancer cells is a potent cytotoxic agent with nM IC_50s; it is highly selective to cancer cells with mean selectivity indices to human (136) and murine (320) cancer cells. It effectively induces release of DAMPs (CALR, ATP & HMGB1) in CT26 cells facilitating more efficient phagocytosis by J774 macrophages than the FDA drugs or their co-administration. The viability of CT26 cells co-cultured with J774 macrophages and treated with 2 was reduced by 32 % compared to the non-treated cells, suggesting a synergistic antiproliferative effect between the chemical and immune reactions. 2 inhibited in vivo tumor growth in two murine models (LLC and CT26) better than the FDA drugs or their co-administration with significantly lower body weight loss. Mice inoculated with CT26 cells treated with 2 showed slightly better tumor free survival than doxorubicin.     

Low temperature rehydration of thermally dehydroxylated Bayer–gibbsite,evolution and transformation of phases

The hexahydrate of europium nitrate hexahydrate Eu(NO₃)₃·6H₂O shows no phase transitions in the range of ?40 to 76 °C when it melts in its own water of crystallization. It was shown that the thermal decomposition is a complex step-wise process, which starts with the simultaneous condensation of 6 mol of the initial monomer Eu(NO₃)₃·6H₂O into a cyclic cluster 6[Eu(NO₃)₃·6H₂O]. This hexamer gradually loses water and nitric acid, and a series of intermediate amorphous oxynitrates is formed. The removal of HNO₃ azeotrope is essentially a continuous process occurring in the liquid phase. At higher temperatures, oxynitrates undergo further degradation, lose water, nitrogen dioxide, and oxygen, and finally, after having lost lattice water, are transformed into europium oxide. All mass losses are satisfactorily accounted for under the proposed scheme of thermal decomposition.     

Fibers and fiber cocktails to improve fire resistance of concrete

Hybrid organic–inorganic resin matrix, i.e., hexa[3,4-dicyano]-phenyl phosphonitrile trimer (HPPT) has been prepared by the reaction of hexachlorophosphonitrile and 4-hydroxyphthalonitrile in the presence of sodium hydride which on heating at 300 °C yielded a high-temperature-stable highly crosslinked hybrid resin (C-HPPT). The elemental analysis (C, H, and N), FTIR, and ¹H and ¹³C-NMR studies were used to characterize the synthesized hybrid resin. The thermal analysis studies viz. TG and DSC were also carried out to determine the thermal stability and glass transition temperature of the cured resin. The isothermal study of the cured resin after 300 h at 300 °C showed only a mass loss of 4.36%.     

The Sorben-Tec system for rapid dosimetric evaluation of <Superscript>137</Superscript>Cs in drinking water

The Sorben-Tec system was developed for rapid evaluation of ¹³⁷Cs in drinking water using a domestic personal dosimeter or beta-radiometer. Linear calibration curves were obtained for dosimetric and beta-radiometric measurement of caesium. In case of 20 L drinking water sample, detection limits of ¹³⁷Cs were found to be 12.3 and 2.0 Bq L^?1 for dosimetric and beta-radiometric measurement respectively. This system is recommended for using by non-professionals who are living at radioactively contaminated areas or near nuclear power plants.     

Crystal Structure and Magnetic Properties of SrNi2–xSb2

The intermetallic phase SrNi_2–xSb₂ was synthesized by arc melting mixtures of the elements and subsequent annealing under argon, and its structure was investigated by means of both powder and single‐crystal X‐ray diffraction methods. It crystallizes with the ThCr₂Si₂ type (tI10, I4/mmm) and has a homogeneity range of x = 0.15(1)–0.28(1), which does not include the exact stoichiometric 1:2:2 composition. The crystal structure of the phase SrNi_2–xSb₂ is built from layers of edge‐sharing Ni_1–xSb₄ tetrahedra, which are separated by Sr atoms along the c direction. Magnetic measurements of SrNi_2–xSb₂ showed no superconductive transition above 1.8 K.     

Laser microsampling and multivariate methods in provenance studies of obsidian artefacts

The provenance of obsidian artefacts and raw materials was studied by the multivariate statistical analysis of forty-five samples using elemental composition data obtained by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). One ICP-MS instrument equipped with a quadrupole mass filter and the other based on a time-of-flight analyser were coupled to the same type of laser ablation device (Nd:YAG 213 nm), thereby affording a comparison of the different mass spectrometers in terms of precision and verification of the consistency of the results. The influence of surface roughness (polished raw material vs artefact) and microinhomogeneity on the LA-ICP-MS signal was studied under the optimised working conditions of the laser ablation device. Principal component analysis, correspondence analysis, independent component analysis, multi-dimensional scaling, Sammon mapping and fuzzy cluster analysis were applied and compared in order to reveal statistically significant compositional differences between particular geological sites and to disclose the provenance of the raw materials used in manufacture of the artefacts. Twenty-seven artefacts and eighteen raw material samples from natural resources in the Czech Republic, Slovakia, Italy, Greece, Syria, Iraq, Turkey, Mexico and Nicaragua were examined with special attention focused on samples from Moravia (Czech Republic) and some Near East sites (Tell Arbid, Tell Asmar). The Carpathian origin of the obsidian artefacts was investigated in the Moravian samples using the Pb, Rb and U contents. The Near East samples were classified according to their Sr, Ba, Zr and REE contents as per-alkaline obsidians (Bingöl A/Nemrut Da?) originating from Southeast Anatolia.