65 research outputs found
Genetically programmed chiral organoborane synthesis
Recent advances in enzyme engineering and design have expanded natureâs catalytic repertoire to functions that are new to biology. However, only a subset of these engineered enzymes can function in living systems. Finding enzymatic pathways that form chemical bonds that are not found in biology is particularly difficult in the cellular environment, as this depends on the discovery not only of new enzyme activities, but also of reagents that are both sufficiently reactive for the desired transformation and stable in vivo. Here we report the discovery, evolution and generalization of a fully genetically encoded platform for producing chiral organoboranes in bacteria. Escherichia coli cells harbouring wild-type cytochrome c from Rhodothermus marinus8 (Rma cyt c) were found to form carbonâboron bonds in the presence of boraneâLewis base complexes, through carbene insertion into boronâhydrogen bonds. Directed evolution of Rma cyt c in the bacterial catalyst provided access to 16 novel chiral organoboranes. The catalyst is suitable for gram-scale biosynthesis, providing up to 15,300 turnovers, a turnover frequency of 6,100âh^(â1), a 99:1 enantiomeric ratio and 100% chemoselectivity. The enantiopreference of the biocatalyst could also be tuned to provide either enantiomer of the organoborane products. Evolved in the context of whole-cell catalysts, the proteins were more active in the whole-cell system than in purified forms. This study establishes a DNA-encoded and readily engineered bacterial platform for borylation; engineering can be accomplished at a pace that rivals the development of chemical synthetic methods, with the ability to achieve turnovers that are two orders of magnitude (over 400-fold) greater than those of known chiral catalysts for the same class of transformation. This tunable method for manipulating boron in cells could expand the scope of boron chemistry in living systems
Panchromatic Photopolymerizable Cationic Films Using Indoline and Squaraine Dye Based Photoinitiating Systems
Julolidine or Fluorenone Based PushâPull Dyes for Polymerization upon Soft Polychromatic Visible Light or Green Light
International audienceTwo pushâpull dyes (a julolidine derivative DCJTB and a fluorenone-co-amino phenyl derivative h-B3FL), incorporated in multicomponent photoinitiating systems have been investigated for the cationic polymerization of epoxides or the radical polymerization of acrylates under visible light irradiations (household halogen lamp or green laser diode at 532 nm). The DCJTB/iodonium salt (and optionally Nvinylcarbazole) based systems are pretty efficient for the cationic polymerization of epoxides. Both dyes, when combining with an amine and 2,4,6-tris(trichloromethyl)- 1,3,5-triazine, exhibit a good efficiency in the radical polymerization of acrylates. The photochemical mechanisms are studied by steady state photolysis, fluorescence, cyclic voltammetry, laser flash photolysis, and electron spin resonance spin trapping technique
Therapeutic Landscape of Metastatic Non-Small-Cell Lung Cancer in Canada in 2020
Lung cancer is the most commonly diagnosed cancer in Canada and remains associated with high mortality. Nevertheless, recent advances in the fields of immuno-oncology and precision medicine have led to significant improvements in clinical outcome in metastatic non-small-cell lung cancer (nsclc). Those improvements were facilitated by a greater understanding of the biologic classification of nsclc, which catalyzed discoveries of novel therapies. Here, we present a comprehensive review of the recent avalanche of practice-changing trials in metastatic nsclc, and we offer an approach to the management of this disease from a Canadian perspective. We begin with an overview of the pathologic and molecular characterization of metastatic nsclc. Next, we review the indications for currently approved immune checkpoint inhibitors, and we provide an approach to the management of disease with a driver mutation. Finally, we address future avenues in both diagnostics and therapeutics for patients with advanced and metastatic nsclc
Julolidine or Fluorenone Based PushâPull Dyes for Polymerization upon Soft Polychromatic Visible Light or Green Light.
Structural Effects in the Indanedione Skeleton for the Design of Low Intensity 300â500 nm Light Sensitive Initiators
International audienceNewly synthesized indanedione derivatives combined with an iodonium salt, N-vinylcarbazole, amine, phenacyl bromide, or 2,4,6-tris- (trichloromethyl)-1,3,5-triazine have been used as photoinitiating systems upon very low visible light intensities: blue lights (e.g., household blue LED bulb at 462 nm) or even a halogen lamp exposure. One of them (ID2) is particularly efficient for cationic, radical and thiolâene photopolymerizations as well as for the synthesis of interpenetrated polymer networks (IPNs). It can be useful to overcome the oxygen inhibition. ID2 based photoinitiating systems can also be selected for the reduction of Ag+ and the in situ formation of Ag(0) nanoparticles in the synthesized polymers. The (photo)chemical mechanisms are studied by electron spin resonance spin trapping, fluorescence, cyclic voltammetry, laser flash photolysis, and steady state photolysis techniques
Structural Effects in the Indanedione Skeleton for the Design of Low Intensity 300â500 nm Light Sensitive Initiators.
Variations on the Benzophenone Skeleton: Novel High Performance Blue Light Sensitive Photoinitiating Systems
Design of Novel Photoinitiators for Radical and Cationic Photopolymerizations under Near UV and Visible LEDs (385, 395, and 405 nm).
Characteristics and treatment effect of senior patients with metastatic colorectal cancer (mCRC): A retrospective analysis.
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