ACS Central Science最新文献

Neutral water microdroplets formed by condensation were introduced into a mass spectrometer with a standard stainless-steel capillary atmospheric interface. Placing volatile samples near the mass spectrometer inlet led to spectra comparable to those of electrospray ionization of the same compounds. Neutral microdroplets introduced into a charge detection instrument through a nearly identical atmospheric sampling interface resulted in charged microdroplets with diameters between 165 nm (∼3,000 charge detection threshold) and 2.8 μm (200,000+ charges). The vast majority of 100,000+ aqueous microdroplets analyzed were positively charged. Aerodynamic acceleration led to average velocities of ∼270 m/s and ∼210 m/s for the smallest and largest microdroplets, respectively, with corresponding energies ranging from a few MeV to 300+ MeV for the largest microdroplets. Current measured on the capillary and other results indicate that interactions between the neutral microdroplets and the capillary can strip off hundreds of thousands of electrons to form positively charged droplets. Negatively charged microdroplets indicate a minor process in which neutral microdroplets are broken up into smaller microdroplets of both polarities. The MeV+ energy involved in these interactions is sufficient to drive many chemical reactions and may lead to unusual and unexpected chemistry when analysis is done using mass spectrometers with atmospheric sampling interfaces.

Acceleration of neutral water droplets in atmospheric sampling mass spectrometers produces droplets with MeV kinetic energies and thousands of charges by contact electrification.

Thermally triggered depolymerization has traditionally been viewed through the lens of sustainability and recycling, not as a constructive tool for materials design. Herein, we show that selective, thermally triggered depolymerization to gaseous monomer serves as a solvent-free strategy for generating porosity in nanostructured polymer materials, offering a means to bypass the mass transport limitations inherent in conventional solution-based etching. As a demonstration platform, we employed polymerization-induced microphase separation (PIMS) to generate disordered bicontinuous block copolymer structures with embedded depolymerizable domains. By incorporating a methacrylate block susceptible to thermal depolymerization within a cross-linked, depolymerization-resistant styrenic matrix, we developed a process we term depolymerization etching of polymerization-induced microphase separations (DEPIMS). This approach enables highly selective and efficient domain removal via reversion to monomer to produce mesoporous materials with high surface areas (>200 m²/g). Subsequent surface functionalization yielded mesoporous adsorbents with tunable uptake kinetics and among the highest dye adsorption capacities reported for PIMS-derived materials, demonstrating the adaptability of the DEPIMS platform for chemical separations. DEPIMS can also be extended to a gram-scale, one-pot approach to yield mesoporous materials with recoverable monomer in under 12 h. These findings reposition thermal depolymerization from a sustainability tool to a broadly enabling strategy for scalable, on-demand fabrication of functional nanostructured materials.

Selective, rapid, and efficient thermal depolymerization of cross-linked block copolymers can generate high-surface area porous materials with attractive absorbent properties.

Near-infrared (NIR, 700–1700 nm)- and telecom (∼1260–1625 nm)-emissive molecules are good candidates for biological imaging and quantum sensing applications, respectively; however, bright low energy emission is rare due to exponentially increasing nonradiative decay rates in these regions, a phenomenon known as the energy gap law. Recent literature has emphasized the importance of minimizing skeletal modes to prevent increased nonradiative decay rates, but most organic lumiphores in these regions utilize large, conjugated scaffolds containing many C═C modes. Here we report a compact, telecom-emissive scaffold, tetrathiafulvalene-2,3,6,7-tetraselenate, or TTFts, that displays remarkable air, water, and acid stability, exhibits record quantum yields and brightness values, and retains quantum coherence under ambient conditions. These properties are enabled through methodical selenium substitution, which bathochromically shifts emission while shifting skeletal vibrations to lower energies. This new scaffold validates heavy heteroatom substitution strategies and establishes a new class of bright telecom emitters and robust qubits.

The coordination chemistry of TTFts is explored for the first time. This selenium-rich linker enables near-1400 nm organic-based emission with record brightness, effectively breaking the energy gap law.

Nucleotides with a carbon substitution for heteroatoms are common in biological and therapeutic RNAs. Important examples include the C-nucleosides pseudouridine and N1-methylpseudouridine; these modifications were reported to slow the degradation of large RNAs, but the mechanism is unknown. We measured kinetics of spontaneous and enzymatic cleavage at a single bond of synthetically modified RNAs and found that carbon substitution markedly reduces strand cleavage rates in RNA by both mechanisms. Studies of nucleophilic acylation reactions of RNAs and small alcohols of varied pK_a suggest that reduced inductive effects resulting from carbon substitution for electronegative atoms results in both higher pK_a and lower nucleophilicity. The results provide insight into native transcriptome modifications as well as RNA therapies.

This study reveals mechanisms by which modifications found in native and therapeutic RNAs enhance RNA stability. Carbon substitution for nitrogen or oxygen results in reduced 2′-OH nucleophilicity.

A viral neuraminidase-specific sensor has been developed to directly detect influenza via the tongue.

Design of modular, transferable protein assemblies has broad applicability and in structural biology could help with the ever-troublesome crystallization bottleneck, including finding robustly behaved protein crystals for rapidly characterizing ligands or drug candidates or generating multiple polymorphs to illuminate diverse conformations. Nanobodies as crystallization chaperones are well-established but still unreliable, as we show here. Instead, we show an exemplar of how robust crystallization behavior can be engineered by exploring many combinations (>200) of nanobody surface mutations over several iterations. Critically, what needed testing was crystallization and diffraction quality, since target–nanobody binding affinity is decoupled from crystallizability enhancement. Our study yielded multiple polymorphs, all mediated by the same interface, with dramatically improved resolution and diffraction reliability for some mutants; we thus name them ‘Gluebodies’ (Gbs). We further demonstrate that these Gb mutations do transfer to some other targets, both for achieving robust crystallization in alternative packing forms and for establishing the ability to crystallize a key early stage readout. Since the Gb interface is evidently a favored interaction, it may be broadly applicable for modular assembly; more specifically, this work suggests that Gbs should be routinely attempted for crystallization whenever nanobodies are available.

Engineered nanobody scaffolds, ‘Gluebodies’, enhance crystal reliability and diversity via transferable mutations that promote robust target-independent interfaces.

Abdelrahman and co-workers developed a device to measure transient charge transfer during hydrogen dissociation on a Pt surface.

Once a testing ground for Soviet weapons, the country is using a unique facility to find materials that withstand plasma 10 times as hot as the sun’s core.

Targeted protein degradation (TPD) is an emergent therapeutic strategy with the potential to circumvent challenges associated with targets unamenable to conventional pharmacological inhibition. Among TPD approaches, proteolysis-targeting chimeras (PROTACs) have shown marked advancement, with numerous candidates in clinical development. Despite their potential, most PROTACs utilize advanced small-molecule inhibitors, inherently limiting the scope of this approach. More generally, the fraction of the proteome tractable to small-molecule-induced degradation strategies is unknown. Here we describe a chemical proteomic strategy for the agnostic discovery of degradable proteins in cells using a new class of bifunctional degrader molecules called “AgnoTACs”. Proteome-wide screening of 72 AgnoTACs in human cells uncovered downregulation events spanning >50 functionally and structurally diverse proteins, most of which lack chemical probes. While many events progressed through canonical degradation pathways, we also observed instances of alternative mechanisms, indicating that AgnoTACs can impact protein stability via multiple modes of action. Our findings highlight the potential of function-biased chemical libraries coupled with proteomic profiling to discover degrader starting points as well as furnish a blueprint for expanding our understanding of the chemically degradable proteome.

A general chemical proteomic strategy using target-agnostic degraders (AgnoTACs) for the proteome-wide identification of degradable proteins lacking established small-molecule ligands is described.

Vitamin D receptor (VDR) activation has demonstrated beneficial effects on psoriasis. However, its crucial role in calcium metabolism limits clinical applications due to the risk of health-threatening dysregulation in serum calcium. In the present study, we have designed, synthesized, and biologically tested highly potent light-controllable VDR agonists containing a photoswitchable azobenzene moiety in the drug scaffold. The optimized molecule PhotoVDRM is inactive in the dark and can be selectively activated with light using specific wavelengths, including nonphototoxic visible blue light and UVB that is currently used in skin treatments. We used a modified hydrogen/deuterium exchange method to identify the binding site and study VDR dynamics upon ligand binding. Importantly, testing PhotoVDRM in a psoriasis mouse model demonstrates that it can spatiotemporally activate VDR in localized diseased areas. Strikingly, this targeted activation results in a robust therapeutic effect without systemic hypercalcemia, thereby addressing at the preclinical level a major historic impediment to VDR agonist treatments in clinical trials. This photopharmacology-based strategy enables the discovery of innovative targeted medicines using light-controlled agonists to spatiotemporally activate the VDR at pathological sites.

Locally activated VDR agonist PhotoVDRM shows strong psoriasis relief in mice without systemic calcium issues. Hydrogen/deuterium exchange experiments reveal binding and receptor activation dynamics.