The area of small molecule Mdm2/X-p53 interaction inhibitor development is progressing fast. Several Phase I clinical studies and preclinical programs are now in progress, however, the clinical proof concept has yet to be demonstrated. Multiple available compounds inhibit Mdm2-p53 interaction with nanomolar affinities, but MdmX is still missing such potent binders. Since research points to a complementary mode of Mdm2 and MdmX action, the future compound classes will possibly want to include dual actions versus Mdm2 and MdmX.

Here, we examine the photophysical properties of five ruthenium(II) complexes comprising two 4,7-diphenyl-1,10-phenanthroline (dip) ligands and functionalized bipyridine (R1bpy-R2, where R1 = H or CH3, R2 = H, CH3, COO−,4-[3-(2-nitro-1H-imidazol-1-yl)propyl] or 1,3-dicyclohexyl-1-carbonyl-urea) towards development of luminescence probes for cellular imaging. These complexes have been shown to interact with albumin and the formed adducts exhibited up to eightfold increase in the luminescence quantum yield as well as the average lifetime of emission. It was demonstrated that they cannot bind to DNA through the intercalation mode and its luminescence in the presence of DNA is quenching. Cell viability experiments indicated that all complexes possess significant dose-dependent cytotoxicity (with IC50 5–19 μM) on 4T1 breast cancer cell line and their anti-proliferative activity correlates very well with their lipophilicity. Cellular uptake was studied by measuring the ruthenium content in cells using ICP-MS technique. As expected, the better uptake is directly related to higher lipophilicity of doubly charged ruthenium complexes while uptake of monocationic one is much lower in spite of the highest lipophilicity. Additionally staining properties were assessed using flow cytometry and fluorescence microscopy. These experiments showed that complex with 1,3-dicyclohexyl-1-carbonyl-urea substituent exhibits the best staining properties in spite of the lowest luminescence quantum yield in buffered solution (pH 7.4). Our results point out that both the imaging and cytotoxic properties of the studied ruthenium complexes are strongly influence by the level of internalization and protein interaction.Electronic supplementary materialThe online version of this article (doi:10.1007/s00775-014-1187-5) contains supplementary material, which is available to authorized users.

DFT/B3LYP calculations of the ground-state conformation of eight cyclic and acyclic acetals are presented and compared with experimental data. Results of single-point GIAO/DFT calculations at five different levels of theory show that isotropic shieldings need to be empirically scaled to achieve agreement with experimental chemical shifts. Statistical evaluation of data indicates that the most accurate prediction of 13C chemical shifts is achieved at the MPW1PW91/6-311G** level of theory. An empirical equation describing the relationship between delta values and shielding constants is postulated. This equation has been applied to the non-chair ground-state conformation of the six-membered acetonide and to the conformationally flexible benzodioxonine derivative. The agreement observed between the experimental and predicted chemical shifts shows that calculations at the MPW1PW91/6-311G** level of theory are adequate for addressing questions of conformation.

Hydrogen peroxide was encapsulated into a silica xerogel matrix by the sol-gel technique. The composite was tested as an oxidizing agent both under conventional and microwave conditions in a few model reactions: Noyori’s method of octanal and 2-octanol oxidation and cycloctene epoxidation in a 1,1,1-trifluoroethanol/Na2WO4 system. The results were compared with yields obtained for reactions with 30% H2O2 and urea-hydrogen peroxide (UHP) as oxidizing agents. It was found that the composite has activity similar to 30% H2O2 and has a several advantages over UHP such as the fact that silica and H2O are the only products of the composite decomposition or no contamination by urea or its derivatives occurs; the xerogel is easier to heated by microwave irradiation than UHP and could be used as both an oxidizing agent and as solid support for microwave assisted solvent-free oxidations.

The title compounds were synthesized, and their structure and conformational behavior in solution (NMR and DFT), in the gas phase (DFT), and, for some of them, in the solid state (X-ray) were investigated. The variable-temperature NMR spectra were employed to determine the conformational equilibria and the activation energy of the conformational changes of the eight-membered ring. The coalescence effects are assigned to racemization of the chiral ground-state conformation with a ring inversion barrier in the range of 38-100 kJ mol(-1) depending on the relative setting of the two strong conformational constraints: benzoannulation and the amide function. The second conformational process, interconversion between two different conformers, in the molecules of benzo[c]azocin-3-one, benzo[d]azocin-2-one, and benzo[d]azocin-4-one was observed. The natures of the conformers observed in solution were elucidated by analysis of experimental and calculated NMR data. The present results are discussed in conjunction with previous experimental and theoretical data on (Z,Z)-cyclooctadienes and their benzo analogues.