Innovative On-DNA Synthesis of Sulfides and Sulfoximines: Enriching the DEL Synthesis Toolbox.

DNA-encoded library (DEL) technologies enable the fast exploration of gigantic chemical space to identify ligands for the target protein of interest and have become a powerful hit finding tool for drug discovery projects. However, amenable DEL chemistry is restricted to a handful of reactions, limiting the creativity of drug hunters. Here, we describe a new on-DNA synthetic pathway to access sulfides and sulfoximines. These moieties, usually contemplated as challenging to achieve through alkylation and oxidation, can now be leveraged in routine DEL selection campaigns.

Simple and Practical DNA Quantification Method for DNA-Encoded Library Synthesis.

Over the past three decades, DNA-encoded library (DEL) technologies have become one of the most relevant strategies for hit-finding. Recent advances in synthetic methodologies for DNA-encoded libraries rendered the increased chemical space available, but it is unknown how every variety of chemistry affects DNA's integrity. Available assays to quantify DNA damage are restricted to electrophoresis, ligation efficiency, and mostly qPCR quantification and sequencing, which may contain predisposition and inconsistency. We developed an external standard method through LC-MS analysis to accurately quantify DNA damage throughout the chemical transformations. An assessment was conducted on on-DNA chemical reactions that are frequently employed in DEL synthesis, and these results were compared to traditional qPCR measurements. Our study provides a simple, practicable, and accurate measurement for DNA degradation during DEL synthesis. Our finding reveals substantial disagreement among the usual DNA-damaging assessment methods, which have been largely neglected so far.

Constructive On-DNA Abramov Reaction and Pudovik Reaction for DEL Synthesis.

Organophosphonic compounds are distinctive among natural products in terms of stability and mimicry. Numerous synthetic organophosphonic compounds, including pamidronic acid, fosmidromycin, and zoledronic acid, are approved drugs. DNA encoded library technology (DELT) is a well-established platform for identifying small molecule recognition to target protein of interest (POI). Therefore, it is imperative to create an efficient procedure for the on-DNA synthesis of α-hydroxy phosphonates for DEL builds.

N-Type Polyoxadiazole Conductive Polymer Binders Derived High-Performance Silicon Anodes Enabled by Crosslinking Metal Cations.

The dilemma of employing high-capacity battery materials and maintaining the electrodes' electrical and mechanical integrity requires a unique binder system design. Polyoxadiazole (POD) is an n-type conductive polymer with excellent electronic and ionic conductive properties, which has acted as a silicon binder to achieve high specific capacity and rate performance. However, due to its linear structure, it cannot effectively alleviate the enormous volume change of silicon during the process of lithiation/delithiation, resulting in poor cycle stability. This paper systematically studied metal ion (i.e., Li+, Na+, Mg2+, Ca2+, and Sr2+)-crosslinked PODs as silicon anode binders. The results show that the ionic radius and valence state remarkably influence the polymer's mechanical properties and the electrolyte's infiltration. Electrochemical methods have thoroughly explored the effects of different ion crosslinks on the ionic and electronic conductivity of POD in the intrinsic and n-doped states. Attributed to the excellent mechanical strength and good elasticity, Ca-POD can better maintain the overall integrity of the electrode structure and conductive network, significantly improving the cycling stability of the silicon anode. The cell with such binders still retains a capacity of 1770.1 mA h g-1 after 100 cycles at 0.2 C, which is ∼285% that of the cell with the PAALi binder (620.6 mA h g-1). This novel strategy using metal-ion crosslinking polymer binders and the unique experimental design provides a new pathway of high-performance binders for next-generation rechargeable batteries.

DNA Compatible Oxidization and Amidation of Terminal Alkynes.

Through a modified Kinugasa reaction, a novel method of amidation on terminal oligo alkyne conjugates by copper-promoted oxidation with nitrones has been developed. Unprotected bifunctional carboxylic acid-amine reagents can be transformed directly to the respective amide products under these edited Kinugasa reaction conditions. 3-Cycle DNA-encoded libraries (DELs) can be built in three steps of chemical conversion.

The Separation of Chlorobenzene Compounds from Environmental Water Using a Magnetic Molecularly Imprinted Chitosan Membrane.

In this work, a magnetic molecularly imprinted chitosan membrane (MMICM) was synthesized for the extraction of chlorobenzene compounds in environmental water using the membrane separation method. The optimal extraction amount for chlorobenzene (9.64 mg·L-1) was found to be a 1:2 solid to liquid ratio, with a 20 min extraction time and 35 °C extraction temperature. This method proved to be successfully applied for the separation and trace quantification of chlorobenzene compounds in environmental water, with the limit of detection (LOD) (0.0016-0.057 ng·L-1), limit of quantification (LOQ) (0.0026-0.098 ng·L-1), and the recoveries ranging (89.02-106.97%).

N-Alkyl Linkers for DNA-Encoded Chemical Libraries.

A series of novel N-alkyl linkers that connect small-molecule library members with their encoding DNA oligonucleotides has been developed. In comparison with the standard amide linker (usually constructed with oligo-AOP-NH2 ), the N-alkyl linker is not only more chemically stable, but also provides better structural diversity at the linkage point. Chemical variety in the vicinity of the polyglycol terminus, in particular, could affect binding interactions with the target protein. It could have been neglected in previous DNA-encoded chemical library (DEL) synthesis and screening studies due to the limited linkage alternatives. With these linkers, one can produce versatile key intermediates as Cycle 1 products directly amenable to Cycle 2 chemistry without the use of protecting groups. As a result, a DEL synthesis process that uses the fewest chemical conversions, such as 3-step, 3-cycle DELs, can achieve higher synthetic efficiency while creating less DNA tag degradation, resulting in higher quality DELs.

In-situ Formation of Amorphous Co-Al-P Layer on CoAl Layered Double Hydroxide Nanoarray as Neutral Electrocatalysts for Hydrogen Evolution Reaction.

Exploration of high-efficiency and inexpensive electrode catalysts is of vital importance for the hydrogen evolution reaction (HER). In this research, an amorphous Co-Al-P layer was constructed on the surface of CoAl layered double hydroxide (CoAl-LDH) via an in-situ wet phosphidation strategy. The core-shell CoAl-LDH@Co-Al-P on Ti mesh (CoAl-LDH@Co-Al-P/TM) as an active HER electrocatalyst demands an overpotential of 150 mV to achieve a current density of 10 mA cm-2 at neutral pH. Moreover, CoAl-LDH@Co-Al-P/TM also exhibits good electrochemical stability and a superior Faradic efficiency of nearly 100%.

FeCoNi Sulfides Derived From In situ Sulfurization of Precursor Oxides as Oxygen Evolution Reaction Catalyst.

It is highly promising to design and develop efficient and economical electrocatalysts for oxygen evolution reaction (OER) in alkaline solution. In this work, we prepare FeCoNi sulfide composites (including FeS, Co3S4, and Ni3S4) derived from in situ sulfurization of precursor oxides on carbon cloth (CC), which are used to become an OER catalyst. Such catalyst shows excellent OER performance, low overpotential, small Tafel slope, and high electrochemical stability, and it is a promising electrocatalyst for OER in alkaline media.

Ultrasensitive SERS detection of highly homologous miRNAs by generating 3D organic-nanoclusters and a functionalized chip with locked nucleic acid probes.

Herein, a new finding is reported that 3D organic-nanoclusters (3DONs) with superior SERS properties as an original reporter could accurately and sensitively distinguish microRNAs (miRNAs) with highly similar sequences, even with a single-nucleotide difference, as a result of a functionalized chip with locked nucleic acid probes (LNAP-chip) and rolling circle replication (RCA). Furthermore, the innovative SERS-method could be used to broadly discriminate cancer cells from normal cells and evaluate changes in the expression levels of intracellular miRNAs.

Starch-graft-polyacrylonitrile nanofibers by electrospinning.

Graft copolymer starch-graft-polyacrylonitrile (St-g-PAN) was synthesized by homo-grafting acrylonitrile (AN) from water soluble starch as Ce(IV) was used as an initiator. St-g-PAN nanofibers were prepared via electrospinning St-g-PAN solution in dimethyl sulfoxide (DMSO). The effects of the spinning parameters such as flow rate, spinning voltage, and collector distance on the St-g-PAN nanofiber diameter were investigated. Fourier transform infrared spectra (FT-IR), solid-state nuclear magnetic resonance (13C NMR) and scanning electron microscope (SEM) were used to characterize the structure and surface morphology of the nanofibers. The results showed that the nanofiber diameter depended strongly on the processing parameters. Moreover, the nanofiber had good water resistance, biocompatibility, and tensile intensity. As the cyano groups on St-g-PAN nanofibers were transformed to amidoxime groups, the obtained St-g-PAO nanofiber displayed an excellent adsorption ability, with the adsorption of Cr 533.4 mg·g-1 at pH = 2.0 as K2Cr2O7 solution 500 mg·L-1 in water was used as the adsorption target. Therefore, these St-g-PAN nanofibers may find potential applications in a wide variety of fields such as tissue engineering, pharmaceutics, energy, and environmental science and engineering.

A 3D porous Ni-CeO2 nanosheet array as a highly efficient electrocatalyst toward alkaline hydrogen evolution.

In this Communication, we report a 3D porous Ni-CeO2 nanosheet array supported on a Ti mesh (Ni-CeO2/TM) as an excellent electrocatalyst toward the alkaline hydrogen evolution reaction. To afford a current density of 10 mA cm-2, Ni-CeO2/TM requires an overpotential as low as 67 mV, 77 mV lower than that of Ni/TM. Furthermore, the electrocatalyst shows good electrochemical durability with nearly 100% faradaic efficiency.

Efficient alkaline hydrogen evolution electrocatalysis enabled by an amorphous Co-Mo-B film.

An amorphous Co-Mo-B film on a Ti mesh (Co-Mo-B/Ti) is fabricated via one-step electrodeposition exhibiting a dramatically enhanced hydrogen evolution reaction (HER) performance in alkaline media. To attain a current density of 20 mA cm-2, such Co-Mo-B/Ti demands only an overpotential of 110 mV, 190 mV lower than that of the counterpart Co-B/Ti, with strong electrochemical durability to maintain its catalytic activity for at least 32 h.

MRI/Fluorescence bimodal amplification system for cellular GSH detection and tumor cell imaging based on manganese dioxide nanosheet.

Here, we report a novel magnetic resonance imaging (MRI)/fluorescence bimodal amplification platform for the detection of glutathione (GSH) on the basis of redoxable manganese dioxide (MnO2) nanosheets, which can be readily applied as a DNA nanocarrier, fluorescence quencher, and intracellular GSH-activated MRI contrast agent. The binding of aptamers that absorbed on the MnO2 nanosheets to their target can facilitating the endocytosis of target-nanoprobes. Once endocytosed, the MnO2 nanosheets can react with cellular GSH, resulting in the disintegration of nanosheets to generate plenty of Mn2+ ions for MRI and releases the primers which were adsorbed on the MnO2 nanosheets. Then the rolling circle amplification (RCA) reaction was initiated to amplify the fluorescence signal. In addition, after treatment with GSH, the MnO2 nanosheets were reduced and then most of the fluorescence was recovered. Therefore, this MnO2 nanoprobe exhibits excellent selectivity, suggesting a potential detection platform for analyzing the glutathione level in cells.

Quantitative control of CaCO3 growth on quartz crystal microbalance sensors as a signal amplification method.

The surface crystallization of CaCO3 on gold was monitored by a quartz crystal microbalance (QCM). Quantitative control of the grown crystals was realized by adjusting the ratio of two functional groups, -N(CH3)3 and -COOH, on SAMs. Crystals with uniform size, morphology and polymorphism were obtained. The amount of crystals formed was found to increase with an increase in the -COOH group. The proposed quantitative control of crystallization can be an effective mass amplification strategy for QCM to enhance its assay sensitivity.

Integration of intracellular telomerase monitoring by electrochemiluminescence technology and targeted cancer therapy by reactive oxygen species.

Cancer therapies based on reactive oxygen species (ROS) have emerged as promising clinical treatments. Electrochemiluminescence (ECL) technology has also attracted considerable attention in the field of clinical diagnosis. However, studies about the integration of ECL diagnosis and ROS cancer therapy are very rare. Here we introduce a novel strategy that employs ECL technology and ROS to fill the above vacancy. Briefly, an ITO electrode was electrodeposited with polyluminol-Pt NPs composite films and modified with aptamer DNA to capture HL-60 cancer cells with high specificity. After that, mesoporous silica nanoparticles (MSNs) filled with phorbol 12-myristate 13-acetate (PMA) were closed by the telomerase primer DNA (T-primer DNA) and aptamer. After aptamer on MSN@PMA recognized and combined with the HL-60 cancer cells with high specificity, T-primer DNA on MSN@PMA could be moved away from the MSN@PMA surface after extension by telomerase in the HL-60 cancer cells and PMA was released to induce the production of ROS by the HL-60 cancer cells. After that, the polyluminol-Pt NPs composite films could react with hydrogen peroxide (a major ROS) and generate an ECL signal. Thus the intracellular telomerase activity of the HL-60 cancer cells could be detected in situ. Besides, ROS could induce apoptosis in the HL-60 cancer cells with high efficacy by causing oxidative damage to the lipids, protein, and DNA. Above all, the designed platform could not only detect intracellular telomerase activity instead of that of extracted telomerase, but could also kill targeted tumors by ECL technology and ROS.