A study of the interactions between carboplatin and blood plasma proteins using size exclusion chromatography coupled to inductively coupled plasma mass spectrometry

To study the carboplatin–protein interaction, a sensitive method using size exclusion chromatography coupled to inductively coupled plasma mass spectrometry (SEC–ICP–MS) was developed. The complexes formed between plasma proteins and carboplatin were monitored and identified with this method. Composite blood plasma samples from patients who were undergoing chemotherapy were analyzed, and carboplatin was found to bind plasma proteins. In addition, blank plasma samples were spiked with carboplatin and were analyzed as a time course study, and the results confirmed that carboplatin formed complexes with plasma proteins, primarily albumin and γ-globulin. To further substantiate the study, these two proteins were incubated with carboplatin. The binding between carboplatin and these proteins was then characterized qualitatively and quantitatively. In addition to a one-to-one binding of Pt to protein, protein aggregation was observed. The kinetics of the binding process of carboplatin to albumin and γ-globulin was also studied. The initial reaction rate constant of carboplatin binding to albumin was determined to be 0.74 M⁻¹ min⁻¹, while that for γ-globulin was 1.01 M⁻¹ min⁻¹, which are both lower than the rate constant of the cisplatin–albumin reaction previously reported.     

The giant magnetoresistance of Co/Cu superlattices grown by MBE

We report the first observation of a giant magnetoresistance (MR) in Co/Cu superlattices grown by MBE. The maximum value of the MR is - 26% and this is found in a specimen for which the copper layers are about 7 Å thick and which includes a thin 10 Å layer of gold in the buffer region between the substrate and the superlattice. From RHEED and X-ray diffraction it is shown that the metallic layers in the specimens grown in this way are extremely flat and that the orientation of the copper is (111).     

A comparative study of acquisition schemes for diffusion tensor imaging using MRI

This study has investigated the effects of the selection of the diffusion-weighted (DW) gradient directions on the precision of a diffusion tensor imaging (DTI) experiment. The theoretical analysis provided a quantitative framework in which the noise performance of DTI schemes could be assessed objectively and for the development of novel DTI schemes, which employ multiple DW gradient directions. This generic framework was first applied to the examination of two commonly used DTI schemes, which employed 6 DW gradient directions and hitherto were used indiscriminately under the sole condition of noncollinearity. It was then used to design and assess a novel 12-DW-gradient-direction DTI protocol, which employed the same total number of DW acquisitions as the two conventional schemes (12). This theoretical investigation was then corroborated using rigorous simulation and DTI experiments on both an isotropic phantom and a healthy human brain. Both the theoretical and the experimental analysis demonstrated that the two conventional schemes showed a significantly different noise performance and that use of the new multiple-DW-gradient-direction scheme clearly improved the precision of the DTI measurements.     

Reactive ligand influence on initiation in phenylene catalyst‐transfer polymerization

Synthesizing conjugated polymers via catalyst‐transfer polymerization (CTP) has led to unprecedented control over polymer sequence and molecular weight. Yet many challenges remain, including broadening the monomer scope and narrowing the molecular weight dispersities. Broad polymer dispersities can arise from nonliving pathways as well as slow initiation. Previously, slow initiation was observed in Ni‐mediated CTP of phenylene monomers. Although precatalysts with faster initiation rates have been reported, the rates still do not exceed propagation. Herein a second‐ and third‐generation of reactive ligands are described, along with a simple method for measuring initiation rates. A precatalyst with an initiation rate that exceeds propagation is now reported, however, the resulting polymer samples still exhibit broad dispersities, suggesting that slow initiation is not the most significant contributing factor in Ni‐mediated phenylene polymerizations. In addition, initiation rates measured under authentic polymerization conditions revealed that both exogenous triphenylphosphine and an ortho‐trifluoroethoxy substituent on the reactive ligand have a strong influence. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1530–1535     

Specific Design of Titanium(IV) Phenolato Chelates Yields Stable and Accessible,Effective and Selective Anticancer Agents

Octahedral titanium(IV) complexes of phenolato hexadentate ligands were developed and showed very high stability for days in water solutions. In vitro cytotoxicity studies showed that, whereas tetrakis(phenolato) systems are generally of low activity presumably due to inaccessibility, smaller bis(phenolato)bis(alkoxo) complexes feature high anticancer activity and accessibility even without formulations, also toward a cisplatin‐resistant cell line. An all‐aliphatic control complex was unstable and inactive. A leading phenolato complex also revealed: 1) high durability in fully aqueous solutions; accordingly, negligible loss of activity after preincubation for three days in medium or in serum; 2) maximal cellular accumulation and induction of apoptosis following 24–48 h of administration; 3) reduced impact on noncancerous fibroblast cells; 4) in vivo efficacy toward lymphoma cells in murine model; 5) high activity in NCI‐60 panel, with average GI₅₀ of 4.6±2 μm . This newly developed family of Ti^IV complexes is thus of great potential for anticancer therapy.     

Detoxification of Chemical Warfare Agents Using a Zr6‐Based Metal–Organic Framework/Polymer Mixture

Owing to their high surface area, periodic distribution of metal sites, and water stability, zirconium‐based metal–organic frameworks (Zr₆‐MOFs) have shown promising activity for the hydrolysis of nerve agents GD and VX, as well as the simulant, dimethyl 4‐nitrophenylphosphate (DMNP), in buffered solutions. A hurdle to using MOFs for this application is the current need for a buffer solution. Here the destruction of the simulant DMNP, as well as the chemical warfare agents (GD and VX) through hydrolysis using a MOF catalyst mixed with a non‐volatile, water‐insoluble, heterogeneous buffer is reported. The hydrolysis of the simulant and nerve agents in the presence of the heterogeneous buffer was fast and effective.     

Chemical action: what is it,and why does it really matter?

Nanotechnology, as with many technologies before it, places a strain on existing legislation and poses a challenge to all administrative agencies tasked with regulating technology-based products. It is easy to see how statutory schemes become outdated, as our ability to understand and affect the world progresses. In this article, we address the regulatory problems that nanotechnology posses for the Food and Drug Administration’s (FDA) classification structure for “drugs” and “devices.” The last major modification to these terms was in 1976, with the enactment of the Medical Device Amendments. There are serious practical differences for a classification as a drug or device in terms of time to market and research. Drugs are classified, primarily, as acting by “chemical action.” We lay out some legal, philosophic, and scientific tools that serve to provide a useful, as well as legally and scientifically faithful, distinction between drugs and devices for the purpose of regulatory classification. These issues we raise are worth the consideration of anyone who is interested in the regulation of nano-products or other novel technologies.