IR Tools: a MATLAB package of iterative regularization methods and large-scale test problems

Numerical Algorithms - This paper describes a new MATLAB software package of iterative regularization methods and test problems for large-scale linear inverse problems. The software package, called...     

Solar Thermal Energy Storage in a Photochromic Macrocycle

The conversion and efficient storage of solar energy is recognized to hold significant potential with regard to future energy solutions. Molecular solar thermal batteries based on photochromic systems exemplify one possible technology able to harness and apply this potential. Herein is described the synthesis of a macrocycle based on a dimer of the dihydroazulene/vinylheptafulvene (DHA/VHF) photo/thermal couple. By taking advantage of conformational strain, this DHA–DHA macrocycle presents an improved ability to absorb and store incident light energy in chemical bonds (VHF–VHF). A stepwise energy release over two sequential ring‐closing reactions (VHF→DHA) combines the advantages of an initially fast discharge, hypothetically addressing immediate energy consumption needs, followed by a slow process for consistent, long‐term use. This exemplifies another step forward in the molecular engineering and design of functional organic materials towards solar thermal energy storage and release.     

Facile synthesis of dopa‐functional polycarbonates via thiol‐Ene‐coupling chemistry towards self‐healing gels

Since extraction of the naturally occurring mussel‐foot proteins is expensive and time‐consuming, routes towards synthetic analogues are continuously being explored. Often, these methods involve several protection and deprotection steps, making the synthesis of synthetic analogues time‐consuming and expensive as well. Herein, we show that UV‐initiated thiol‐ene coupling between a thiol‐functional dopamine derivative and an allyl‐functional aliphatic polycarbonate can be used as a fast and facile route to dopa‐functional materials. Different thiol‐to‐allyl ratios and irradiation protocols were used and it was found that nearly 50% of the allyl groups could be functionalized with dopa within short reaction times, without the need of protecting the catechol. It is also demonstrated herein that the dopa‐functional polymers can be used to form self‐healing gels through complexation with Fe³⁺ ions at increased pH. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2370–2378     

Validation of a robust and rapid liquid chromatography tandem mass spectrometric method for the quantitative analysis of navitoclax

The Bcl-2 family small molecule inhibitor navitoclax is being clinically evaluated to treat multiple cancers including lymphoid malignancies and small cell lung cancer. A sensitive and reliable method was developed to quantitate navitoclax in human plasma using liquid chromatography with tandem mass spectrometry with which to perform detailed pharmacokinetic studies. Sample preparation involved protein precipitation using acetonitrile. Separation of navitoclax and the internal standard, navitoclax-d8, was achieved with a Waters Acquity UPLC BEH C₁₈ column using isocratic flow over a 3 min total analytical run time. A SCIEX 4500 triple quadrupole mass spectrometer operated in positive electrospray ionization mode was used for the detection of navitoclax. The assay range was 5–5,000 ng/ml and proved to be accurate (89.5–104.9%) and precise (CV ≤ 11%). Long-term frozen plasma stability for navitoclax at −70°C was at least 43 months. The method was applied for the measurement of total plasma concentration of navitoclax in a patient receiving a 250 mg daily oral dose.     

Gapmer Antisense Oligonucleotides Containing 2′,3′-Dideoxy-2′-fluoro-3′-C-hydroxymethyl-β-d-lyxofuranosyl Nucleotides Display Site-Specific RNase H Cleavage and Induce Gene Silencing

Off-target effects remain a significant challenge in the therapeutic use of gapmer antisense oligonucleotides (AONs). Over the years various modifications have been synthesized and incorporated into AONs, however, precise control of RNase H-induced cleavage and target sequence selectivity has yet to be realized. Herein, the synthesis of the uracil and cytosine derivatives of a novel class of 2′-deoxy-2′-fluoro-3′-C-hydroxymethyl-β-d -lyxo-configured nucleotides has been accomplished and the target molecules have been incorporated into AONs. Experiments on exonuclease degradation showed improved nucleolytic stability relative to the unmodified control. Upon the introduction of one or two of the novel 2′-fluoro-3′-C-hydroxymethyl nucleotides as modifications in the gap region of a gapmer AON was associated with efficient RNase H-mediated cleavage of the RNA strand of the corresponding AON:RNA duplex. Notably, a tailored single cleavage event could be engineered depending on the positioning of a single modification. The effect of single mismatched base pairs was scanned along the full gap region demonstrating that the modification enables a remarkable specificity of RNase H cleavage. A cell-based model system was used to demonstrate the potential of gapmer AONs containing the novel modification to mediate gene silencing.     

Absolute Asymmetric Synthesis of a Tetrahedral Silver Complex

Even though the isolation of tetrahedral stereoisomers usually presents a synthetic challenge, a highly enantioenriched tetrahedral silver complex could be easily accessed by either crystallization or Viedma ripening. The overall preparation may be regarded as an example of absolute asymmetric synthesis. Experimental results indicate that both crystallization and Viedma ripening follow a similar cluster‐controlled mechanism.