Analytical Chemistry
DOI: 10.1021/acs.analchem.3c03486
[ASAP] Visualization of Lysosomal Dynamics during Autophagy by Fluorescent Probe
Analytical Chemistry
DOI: 10.1021/acs.analchem.3c03329
Dense NiCo2O4 Nanoneedles Grown on Carbon Foam Showing Excellent Electrochemical and Microwave Absorption Properties
Electromagnetic pollution could harm sensitive electronic equipment due to the rising use of electronic devices and communication infrastructure. The supercapacitor's electrochemical performance should be enhanced, and electromagnetic damage should be prevented. This study proposes NiCo2O4/CF composites for supercapacitors and microwave absorption. They are made by combining hydrothermal and annealing processes. Dense NiCo2O4 nanoneedles were uniformly grown on the outer layer of carbon foam (CF) as a growth skeleton, preventing the agglomeration of NiCo2O4. The composite had a specific capacitance of 537.5 F/g at 1 A/g. When the current density was set to 1 A/g, the supercapacitor that used NiCo2O4/CF as the cathode had a specific capacitance of 70.7 F/g, and when the current density was increased to 10 A/g, the original specific capacitance of 87.2% could still be maintained after 5000 charge-discharge cycles. At a power density of 3695.5 W/kg, an energy density of 22.1 Wh/kg could be maintained. Furthermore, we performed a microwave absorption test and determined its reflection loss curve for various sample thicknesses. Recombination enhanced the composite material's microwave absorption capability by greatly reducing the dielectric loss and the magnetic loss.
[ASAP] An Integrated Sweat Sensor for Synchronous Detection of Multiple Atherosclerosis Biomarkers
Analytical Chemistry
DOI: 10.1021/acs.analchem.3c03310
[ASAP] Dynamic Mapping of Electrochemiluminescence Reactivity in Space: Application to Bead-Based Assays
Analytical Chemistry
DOI: 10.1021/acs.analchem.3c02960
[ASAP] Selective Deionization of Thin-Layer Samples Using Tandem Carbon Nanotubes–Polymeric Membranes
Analytical Chemistry
DOI: 10.1021/acs.analchem.3c02965
Improving the Enantioselectivity of CHMOBrevi1 for Asymmetric Synthesis of Podophyllotoxin Precursor
Semi-rational design of the cyclohexanone monooxygenase CHMO Brevi1 generated the L145A mutant with improved enantioselectivity (96.8 % ee) for the synthesis of (R)-β-piperonyl-γ-butyrolactone, a precursor of anti-cancer drug podophyllotoxin, compared with the wild type (75 % ee). Coupled with the cofactor regeneration system, 9.3 mM substrate was converted completely in a 100-mL scale reaction.
Abstract
(R)-β-piperonyl-γ-butyrolactones are key building blocks for the synthesis of podophyllotoxin, which have demonstrated remarkable potential in cancer treatment. Baeyer-Villiger monooxygenases (BVMOs)-mediated asymmetric oxidation is a green approach to produce chiral lactones. While several BVMOs were able to oxidize the corresponding cyclobutanone, most BVMOs gave the (S) enantiomer while Cyclohexanone monooxygenase (CHMO) from Brevibacterium sp. HCU1 gave (R) enantiomer, but with a low enantioselectivity (75 % ee). In this study, we use a strategy called “focused rational iterative site-specific mutagenesis” (FRISM) at residues ranging from 6 Å from substrate. The mutations by using a restricted set of rationally chosen amino acids allow the formation of a small mutant library. By generating and screening less than 60 variants, we achieved a high ee of 96.8 %. Coupled with the cofactor regeneration system, 9.3 mM substrate was converted completely in a 100-mL scale reaction. Therefore, our work reveals a promising synthetic method for (R)-β-piperonyl-γ-butyrolactone with the highest enantioselectivity, and provides a new opportunity for the chem-enzymatic synthesis of podophyllotoxin.
Higher‐Order Electrocyclizations in Biological and Synthetic Processes
Beyond n=1: This focused review describes 10 π–18 π electrocyclizations reported in the literature. The use of these processes for the synthesis of complex cyclic scaffolds is also briefly described. DFT mechanistic analysis of the reported pericyclic reactions are discussed. It was found that, for some of these reactions, the Woodward-Hoffmann rules for thermal electrocyclizations are not followed.
Abstract
In general, electrocyclizations follow the Woodward-Hoffmann's rules of conservation of orbital symmetry. These rules have been extensively verified in low-order processes, both in thermal and photochemical reactions, up to eight π-electrons. However, when the number of π-electrons in the system increases, some deviations of that general rules can be found. This focused review highlights the main features of reported higher-order electrocyclizations involving 10, 12, 14, 16 and 18 π-electrons. Some of these examples constitute useful intermediates in the synthesis of biologically active compounds. When computational studies were not included in the reported examples, DFT calculations have been performed to be included in this review. Analysis of the respective pericyclic topologies shows the importance of computational tools for understanding the selectivity observed experimentally.
A Degron Blocking Strategy Towards Improved CRL4CRBN Recruiting PROTAC Selectivity
The generation of CRL4CRBN recruiting PROteolysis TArgeting Chimeras (PROTACs) is currently still a largely empirical process and the design principles are still to be deciphered. Herein, a design strategy to generate CRL4CRBN PROTACs selective for a target of interest by dialling-out the molecular glue function of thalidomide derivatives is reported.
Abstract
Small molecules inducing protein degradation are important pharmacological tools to interrogate complex biology and are rapidly translating into clinical agents. However, to fully realise the potential of these molecules, selectivity remains a limiting challenge. Herein, we addressed the issue of selectivity in the design of CRL4CRBN recruiting PROteolysis TArgeting Chimeras (PROTACs). Thalidomide derivatives used to generate CRL4CRBN recruiting PROTACs have well described intrinsic monovalent degradation profiles by inducing the recruitment of neo-substrates, such as GSPT1, Ikaros and Aiolos. We leveraged structural insights from known CRL4CRBN neo-substrates to attenuate and indeed remove this monovalent degradation function in well-known CRL4CRBN molecular glues degraders, namely CC-885 and Pomalidomide. We then applied these design principles on a previously published BRD9 PROTAC (dBRD9-A) and generated an analogue with improved selectivity profile. Finally, we implemented a computational modelling pipeline to show that our degron blocking design does not impact PROTAC-induced ternary complex formation. We believe that the tools and principles presented in this work will be valuable to support the development of targeted protein degradation.
Bispidine as a Versatile Scaffold: From Topological Hosts to Transmembrane Transporters
We delineate a highly versatile strategy for the synthesis of topologically intriguing molecule and self-assembling macrocycles. The self-assembly of the macrocycle to nanotube displays unconventional interactions such as dihydrogen bonding. The nanotubular assembly acts as a channel for transmembrane ion transport as evident from patch clamp experiments.
Abstract
The development of designer topological structures is a synthetically challenging endeavor. We present herein bispidine as a platform for the design of molecules with various topologies and functions. The bispidine-based acyclic molecule, which shows intriguing S-shape topology, is discussed. Single-crystal X-ray diffraction studies revealed that this molecule exists in the solid state as two conformational enantiomers. In addition, bispidine-based designer macrocycles were synthesized and investigated for ionophoric properties. Patch clamp experiments revealed that these macrocycles transport both anions and cations non-specifically with at least tenfold higher chloride conductance over the cations under the given experimental conditions. Ultramicroscopy and single-crystal X-ray crystallographic studies indicated that the self-assembling macrocycle forms a tubular assembly. Our design highlights the use of unconventional dihydrogen interactions in nanotube fabrication.