Am(m)ines Make the Difference: Organoruthenium Am(m)ine Complexes and Their Chemistry in Anticancer Drug Development

With the aim of systematically studying fundamental structure–activity relationships as a basis for the development of Ru^II arene complexes (arene=p‐cymene or biphenyl) bearing mono‐, bi‐, or tridentate am(m)ine ligands as anticancer agents, a series of ammine, ethylenediamine, and diethylenetriamine complexes were prepared by different synthetic routes. Especially the synthesis of mono‐, di‐, and triammine complexes was found to be highly dependent on the reaction conditions, such as stoichiometry, temperature, and time. Hydrolysis and protein‐binding studies were performed to determine the reactivity of the compounds, and only those containing chlorido ligands undergo aquation or form protein adducts. These properties correlate well with in vitro tumor‐inhibiting potency of the compounds. The complexes were found to be active in anticancer assays when meeting the following criteria: stability in aqueous solution and low rates of hydrolysis and binding to proteins. Therefore, the complexes least reactive to proteins were found to be the most cytotoxic in cancer cells. In general, complexes with biphenyl as arene ligand inhibited the growth of tumor cells more effectively than the cymene analogues, consistent with the increase in lipophilicity. This study highlights the importance of finding a proper balance between reactivity and stability in the development of organometallic anticancer agents.     

The phenomenon of simplified scattering from rough surfaces to reflection in fractional space

In this paper, the scattering of incident plane waves from rough surfaces has been modeled in a fractional space. It is shown how wave scattering from a rough surface could correspond to a simple reflection problem in a fractional space. In an integer dimensional space, fluctuations of the surface result in wave scattering, while in the fractional space, these fluctuations are compensated by the geometry of space. In the fractional space, reflection is equivalent to scattering from the integer dimensional space. Comparing scattered wave functions from different self-affine rough surfaces in the framework of the Kirchhoff theory with the results from the fractional space, we see good agreement between them.     

Folding Assessment of Incorporation of Noncanonical Amino Acids Facilitates Expansion of Functional-Group Diversity for Enzyme Engineering

Protein design is limited by the diversity of functional groups provided by the canonical protein „building blocks“. Incorporating noncanonical amino acids (ncAAs) into enzymes enables a dramatic expansion of their catalytic features. For this, quick identification of fully translated and correctly folded variants is decisive. Herein, we report the engineering of the enantioselectivity of an esterase utilizing several ncAAs. Key for the identification of active and soluble protein variants was the use of the split-GFP method, which is crucial as it allows simple determination of the expression levels of enzyme variants with ncAA incorporations by fluorescence. Several identified variants led to improved enantioselectivity or even inverted enantiopreference in the kinetic resolution of ethyl 3-phenylbutyrate.     

High-performance transformation of protein structure representation from internal to Cartesian coordinates

We present a highly parallel algorithm to convert internal coordinates of a polymeric molecule into Cartesian coordinates. Traditionally, converting the structures of polymers (e.g., proteins) from internal to Cartesian coordinates has been performed serially, due to an inherent linear dependency along the polymer chain. We show this dependency can be removed using a tree-based concatenation of coordinate transforms between segments, and then parallelized efficiently on graphics processing units (GPUs). The conversion algorithm is applicable to protein engineering and fitting protein structures to experimental data, and we observe an order of magnitude speedup using parallel processing on a GPU compared to serial execution on a CPU.     

Electrocatalytic oxidation of hydrazine at poly(4,5-dihydroxy-1,3-benzenedisulfonic acid) multiwall carbon nanotubes modified-glassy carbon electrode: Improvement of the catalytic activity

A stable electroactive thin film of poly(4,5-dihydroxy-1,3-benzenedisulfonic acid) was electrochemically deposited at the surface of multiwall carbon nanotubes-glassy carbon electrode. The electrocatalytic oxidation of hydrazine has been studied at the surface of the modified electrode using cyclic voltammetry, chronoamperometry and linear sweep voltammetry as diagnostic techniques. The modified electrode exhibits good electrocatalytic activity for the oxidation of hydrazine with a good sensitivity. Linear calibration range was in the wide concentration range of 10–3540 μM hydrazine with a detection limit of 1.8 μM and a sensitivity of 85.3 nA/μM. A Tafel plot, derived from voltammograms, indicated a one-electron transfer process to be the rate-limiting step and the overall number of electrons involved in the catalytic oxidation of hydrazine was found to be four. The influences of potentially interfering substances were studied. The diffusion coefficient of hydrazine was also evaluated. Finally, the proposed modified electrode was used for the determination of hydrazine in spiked water samples.     

Robust stability of impulsive synchronization in hyperchaotic systems

In this paper the impulsive synchronization of general continuous chaotic and hyperchaotic systems is investigated. The robust stability of the synchronization method is examined in the presence of uncertainties both on linear and nonlinear parts of the system dynamics and the channel noise. Conditions on the impulse distances are derived for different cases. Numerical simulations are presented to show the effectiveness of the method.     

Combining a Click–Multicomponent Reaction: One-Pot Synthesis of 1,2,3-Triazol-4-ylmethyl 3-Amino-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carboxylate Derivatives

(1,2,3-Triazol-4-yl)methyl-3-amino-5,10-dihydro-5,10-dioxo-1H-pyrazolo[1,2-b]phthalazine-2-carboxylate derivatives were synthesized by a four-component, one-pot condensation reaction of benzaldehyde derivatives, an active methylene compound (prop-2-ynyl-2-cyanoacetate), azides, and phthalhydrazide in the presence of Cu(OAc)₂/sodium ascorbate as catalysts and 1-methyl-1H-imidazolium trifluoroacetate ([Hmim]TFA) as an ionic liquid medium in good to excellent yields.     

Rapid Detection of Antibody in Biological Fluids on a Bioarray Chip

A bioarray chip was developed for the rapid and sensitive detection of the antibody (Ab) in nanoliter volumes of biological fluids. The chip was used to detect the anti-hemagglutinin (anti-HA) Ab from mouse ascites fluids. On the bioarray chip, lanes of antigens (i.e., a 13-amino acid peptide, HA, that is bound by anti-HA Ab) were printed in one dimension on the chip surface. The antigens probed the protein samples (i.e., mouse anti-HA) obtained from biological fluids flowing in channels arranged in the perpendicular dimension. To determine if the detection sensitivity was increased by using different fluorescent labeling methods, two types of labeling reagents were compared, namely AlexaFluor 647-labeled goat anti-mouse Ab (AxIgG), and biotin-labeled anti-mouse Ab (BioIgG) followed by cyanine 5-tagged streptavidin (SA-Cy5). In addition, the assay procedure was shortened by omitting the reduction and blocking steps, while maintaining the sensitivity. In conclusion, a bioarray chip was adopted to detect as low as 10?pM mouse monoclonal antibody (anti-HA) in 500 nL of biological fluids (i.e., corresponding to 5 attomoles of antibody). Our results demonstrate that on-chip detection using this bioarray format is more sensitive and less time-consuming than traditional analyses.     

Catalytic decomposition of Bismarck brown by nanostructured CuS in mild conditions

Two samples of nanostructured CuS were synthesized by two different methods, and were used for degradation of Bismarck Brown, as an azo dye. The first sample consists an assembly of nanosheets, and the second one has prolat-like spheroid structure. It is shown that CuS nanosheets have higher catalytic activity than the second sample for degradation of Bismarck Brown in the presence of H₂O₂. The catalytic activity of the CuS nanosheets was investigated by different variables such as reaction time, solution temperature, volume of H₂O₂, catalyst mass, dye concentration and presence of NaCl. CuS nanosheets have high degradation efficiency under mild conditions and in the dark medium. It was found that the rate of dye degradation by H₂O₂ is fast in the presence of CuS nanosheets, and most of the reactant molecules are degraded within 10?minute. As the main products of dye degradation by the CuS nanosheet, and in presence of H₂O₂ are CO₂ and CO, it is a good catalyst for water purification. Another advantage of this catalyst is its reusability and recyclability, which maintains its stability after several cycles. Finally, the catalytic performance of CuS nanosheets was investigated for degradation of dye mixture (Bismarck Brown and Methyl violet).