Signal amplification and detection via a supramolecular allosteric catalyst

The design of a supramolecular allosteric catalyst system for catalytic signal amplification and detection is presented. The catalyst was switched "on" by the introduction of an analyte that also behaves as an allosteric activator. Concentrations of Cl- ions as low as 800 nM were catalytically amplified and detected. The signal was transduced via a pH-sensitive fluorescent probe and observed visually using a laboratory, handheld UV lamp and by spectrophotometry. Furthermore, the allosteric effect was quantified using gas chromatography for a range of Cl- concentrations. This three-part detection scheme involving analyte binding, allosteric catalyst activation, and signal transduction represents a new approach to small-molecule detection.     

Acid Exfoliation of Imine‐linked Covalent Organic Frameworks Enables Solution Processing into Crystalline Thin Films

Covalent organic frameworks (COFs) are highly modular porous crystalline polymers that are of interest for applications such as charge‐storage devices, nanofiltration membranes, and optoelectronic devices. COFs are typically synthesized as microcrystalline powders, which limits their performance in these applications, and their limited solubility precludes large‐scale processing into more useful morphologies and devices. We report a general, scalable method to exfoliate two‐dimensional imine‐linked COF powders by temporarily protonating their linkages. The resulting suspensions were cast into continuous crystalline COF films up to 10 cm in diameter, with thicknesses ranging from 50 nm to 20 μm depending on the suspension composition, concentration, and casting protocol. Furthermore, we demonstrate that the film fabrication process proceeds through a partial depolymerization/repolymerization mechanism, providing mechanically robust films that can be easily separated from their substrates.     

A new ternary Cu (II) complex with 4,7-dimethyl-1,10-phenanthroline and NOO-type tridentate Schiff base ligand: Synthesis,crystal structure,biomacromolecular interactions,and radical scavenging activities

NOO-type tridentate Schiff base, N-salicylidene-2-aminobenzoic acid, (H₂L), and its ternary Cu (II) complex containing H₂L Schiff base and 4,7-dimethyl-1,10-phenanthroline (4,7-dmphen), [Cu(4,7-dmphen)(H₂L)]₂7H₂O, have been synthesized and characterized by CHN analysis, ESI-MS, FTIR, and single-crystal X-ray diffraction techniques. The interaction of alone H₂L Schiff base ligand and ternary Cu (II) complex with biomacramolecules {calf thymus DNA (CT-DNA) and bovine serum albumin (BSA)} has been investigated by electronic absorption and fluorescence spectroscopy. The experimental results indicate that H₂L Schiff base ligand and ternary Cu (II) complex bind to CT-DNA by means of a moderate intercalation mode. Furthermore, the fluorescence quenching mechanism between H₂L Schiff base ligand and ternary Cu (II) complex with BSA possesses a static quenching process. Radical scavenging activity of H₂L Schiff base ligand and ternary Cu (II) complex was measured in terms of EC₅₀, using the DPPH and H₂O₂ methods. Biomacromolecule interactions and scavenging activity studies revealed that ternary Cu (II) complex yielded better results than H₂L Schiff base ligand alone.     

Peptide Brush Polymers for Efficient Delivery of a Gene Editing Protein to Stem Cells

The scarcity of effective means to deliver functional proteins to living cells is a central problem in biotechnology and medicine. Herein, we report the efficient delivery of an active DNA‐modifying enzyme to human stem cells through high‐density cell penetrating peptide brush polymers. Cre recombinase is mixed with a fluorophore‐tagged polymer carrier and then applied directly to induced pluripotent stem cells or HEK293T cells. This results in efficient delivery of Cre protein as measured by activation of a genomically integrated Cre‐mediated recombination reporter. We observed that brush polymer formulations utilizing cell penetrating peptides promoted Cre delivery but oligopeptides alone or oligopeptides displayed on nanoparticles did not. Overall, we report the efficient delivery of a genome‐modifying enzyme to stem cells that may be generalizable to other, difficult‐to‐transduce cell types.     

Cyclic (Alkyl)(Amino)Carbene (CAAC) Gold(I) Complexes as Chemotherapeutic Agents

Cyclic (Alkyl)(Amino)Carbenes (CAACs) have become forceful ligands for gold due to their ability to form very strong ligand-metal bonds. Inspired by the success of Auranofin and other gold complexes as antitumor agents, we have studied the cytotoxicity of bis- and mono-CAAC-gold complexes on different cancer cell lines: HeLa (cervical cancer), A549 (lung cancer), HT1080 (fibrosarcoma) and Caov-3 (ovarian cancer). Further investigations aimed at elucidating their mechanism of action are described. This includes quantification of affinities for TrxR, evaluation of their bioavailability and determination of associated cell death process. Moreover, Transmission Electron Microscopy (TEM) was used to study morphological changes upon exposure. Noticeably, a significant reduction in non-specific binding to serum proteins was observed with CAAC complexes when compared to Auranofin. These results confirm the potential of CAAC-gold complexes in biological environments, which may result in more specific drug-target interactions and decreased side effects.