Site‐Specific Dual Labeling of Proteins on Cysteine Residues with Chlorotetrazines

Dual‐labeled biomolecules constitute a new generation of bioconjugates with promising applications in therapy and diagnosis. Unfortunately, the development of these new families of biologics is hampered by the technical difficulties associated with their construction. In particular, the site specificity of the conjugation is critical as the number and position of payloads can have a dramatic impact on the pharmacokinetics of the bioconjugate. Herein, we introduce dichlorotetrazine as a trivalent platform for the selective double modification of proteins on cysteine residues. This strategy is applied to the dual labeling of albumin with a macrocyclic chelator for nuclear imaging and a fluorescent probe for fluorescence imaging.     

Hybrid Dextran-gadolinium Nano-suitcases as High-relaxivity MRI Contrast Agents

Dextran-poly(glycidyl methacrylate)(Dex-PGMA) nano-suitcases were synthesized efficiently via a graft copolymerization induced self-assembly(GISA) approach. On this basis, the Dex-PGMA nano-suitcases were modified with hydrazide, and the attachment of multiple chelated Gd(Ⅲ) ions to the interior of the nano-suitcases affords nanoscale MRI contrast agents with high relaxivity values. The highly fenestrated dextran shell of the nano-suitcases assures water exchange which readily occurs between the surrounding environment and the Gd(Ⅲ) ions encapsulated within the hybrid nano-suitcases. The complexation between the hydrophilic hydrazide interior of the nano-suitcases and Gd(Ⅲ) ions results in an impressive Gd payload at 22.6 wt% in the hybrid nano-suitcases. The longitudinal relaxivity(r1) of the hybrid nano-suitcases is reported as 44.4 L/(mmol·s), which is 9-14 folds of that of commercial Gd-DTPA agents. In vivo MRI studies demonstrate that the hybrid nano-suitcases accumulated in the lymph node of the rat due to their nanoscale dimensions and displayed strong signals in vivo. The results indicated that the hybrid nano-suitcases provide a promising platform for the diagnosis of lymph node related diseases.     

Copper-mediated synthesis of N-vinyl ynamides from N-vinyl carbamates

Ynamides are versatile 3-atoms building blocks for organic synthesis as they participate in a variety of ionic, radical and pericyclic processes. Converting ynamides into 5-atom building blocks, such as the yet unreported N-vinyl ynamides, would open new avenues in this fascinating chemistry. We describe herein our efforts towards such goal and demonstrate that the cross-coupling between N-vinyl carbamates and bromo-alkynes using copper(I) thiophene carboxylate, 1,10-phenanthroline and tBuOK in DMSO is a reactive system with an improved profile compared to the classical ynamides syntheses. The advantages and limitations of this copper-mediated reaction are discussed.     

Synthesis and antiproliferative evaluation of glucosylated pyrazole analogs of K252c

Pyrazole analogs of the staurosporine aglycon K252c were recently described as potent inhibitors of the three Pim protein kinase isoforms. To evaluate the impact of the introduction of a sugar moiety on the biological activities of this heterocyclic scaffold, four new glucosylated pyrazole analogs of K252c were synthesized. Their biological evaluation demonstrated that most active compounds 11 and 19 substituted by a β-d-glucosyl moiety at N12 or N13 positions exhibited antiproliferative activities toward HCT116 cells.     

Construction and evaluation of a hermetically sealed accurate ion mobility instrument

Ion mobility spectrometry (IMS) is widely used to detect and identify chemical warfare agents, narcotics, and explosives in the field based on their reduced mobility (K ₀ ) values. Current detection windows for these analytes can only be as narrow as ±2% of the K ₀ values for the analyte being sought. These wide detection windows cause false positive alarms when an interferent with a similar reduced mobility falls within the detection window and triggers an alarm. This results in the loss of time and money as resources are diverted to verify the alarm. A high rate of false positive alarms is caused by a discrepancy in the reported K ₀ values across the literature that is, at best, ± 2% of the average available values. By accurately and precisely measuring the variables affecting an ion’s K ₀ value, an accurate K ₀ value can be produced and the detection windows widths that are established using these reference values can be reduced. Components for accurate analyses have been assembled in the past and here the construction of an accurate ion mobility spectrometry drift tube is described that is accurate to 0.1% of the calculated K ₀ value and can be hermetically sealed without inserting the drift tube into a large vacuum chamber. Having a pressure sealed accurate ion mobility spectrometer will allow for the control of the pressure variable within the K ₀ equation and the safe analysis of hazardous chemicals. Here the construction of an inexpensive and easily reparable sealed drift tube is described.     

Epoxy composites with ceramic core–shell fillers for thermal management in electrical devices

In this work, a novel core–shell material has been manufactured in order to enhance the thermal conductivity of epoxy‐based composites. The polymer derived ceramics technique has been used to produce fillers whose core is composed of a standard material – silica, and whose outer layer consists of a boron nitride or silicon nitride shell. The synthesized filler was characterized by infrared spectroscopy, X‐ray diffraction, and scanning electron microscopy coupled with an energy dispersive spectroscopy analysis. The successful formation of core–shell structure was proven. Composite samples based on an epoxy resin filled with 31 vol% of synthetized core–shell filler have been investigated in order to determine the effective thermal conductivity of the modified system. The resulting core–shell composite samples exhibited improvements in thermal conductivity of almost 30% in relation to standard systems, making them a promising material for heat management applications. Additionally, the temperature dependence of the thermal conductivity was investigated over a broad temperature range indicating that the thermal behavior of the composite with incorporated core–shell filler is stable. This stability is a crucial factor when considering the potential of using this technology in applications such as electronics and power systems. Copyright © 2017 John Wiley & Sons, Ltd.     

Surface and grain boundary segregation in 16MND5 steel

An adequate model of quantification when there are many segregating elements is required for industry and research. Hence, for the first time, surface segregation kinetics on industrial 16MND5 steel was studied by XPS spectroscopy at temperatures ranging from 500 to 600 ^oC. From measurements that highlight the competitive segregation of P, S, Sn, Sb, As, and Cu impurities at the surface, a quantification model was developed and successfully used to deduce the surface concentrations during segregation kinetics as well as derive the corresponding diffusion coefficients. We observed that phosphorus and sulfur are the first elements covering the surface, then they are supplanted by others' impurities. This result may reflect impurities segregation behavior at the grain boundaries that impacts mechanical behavior of the material. Indeed, to further the research, 16MND5 samples were aged in the same range of temperatures. Then, Auger spectroscopy measurements at grain boundaries were conducted on broken samples exhibiting intergranular cracking. Results show that phosphorus is the only segregating element present at grain boundaries after 2 months of aging. Importantly, it appears that phosphorus grain boundary segregation kinetics is significantly lower than at surface. Copyright © 2017 John Wiley & Sons, Ltd.