Concentric liquid reactors for chemical synthesis and separation.

Recent years have witnessed increased interest in systems that are capable of supporting multistep chemical processes without the need for manual handling of intermediates. These systems have been based either on collections of batch reactors1 or on flow-chemistry designs2-4, both of which require considerable engineering effort to set up and control. Here we develop an out-of-equilibrium system in which different reaction zones self-organize into a geometry that can dictate the progress of an entire process sequence. Multiple (routinely around 10, and in some cases more than 20) immiscible or pairwise-immiscible liquids of different densities are placed into a rotating container, in which they experience a centrifugal force that dominates over surface tension. As a result, the liquids organize into concentric layers, with thicknesses as low as 150 micrometres and theoretically reaching tens of micrometres. The layers are robust, yet can be internally mixed by accelerating or decelerating the rotation, and each layer can be individually addressed, enabling the addition, sampling or even withdrawal of entire layers during rotation. These features are combined in proof-of-concept experiments that demonstrate, for example, multistep syntheses of small molecules of medicinal interest, simultaneous acid-base extractions, and selective separations from complex mixtures mediated by chemical shuttles. We propose that 'wall-less' concentric liquid reactors could become a useful addition to the toolbox of process chemistry at small to medium scales and, in a broader context, illustrate the advantages of transplanting material and/or chemical systems from traditional, static settings into a rotating frame of reference.

Active learning guides discovery of a champion four-metal perovskite oxide for oxygen evolution electrocatalysis.

Multi-metal oxides in general and perovskite oxides in particular have attracted considerable attention as oxygen evolution electrocatalysts. Although numerous theoretical studies have been undertaken, the most promising perovskite-based catalysts continue to emerge from human-driven experimental campaigns rather than data-driven machine learning protocols, which are often limited by the scarcity of experimental data on which to train the models. This work promises to break this impasse by demonstrating that active learning on even small datasets-but supplemented by informative structural-characterization data and coupled with closed-loop experimentation-can yield materials of outstanding performance. The model we develop not only reproduces several non-obvious and actively studied experimental trends but also identifies a composition of a perovskite oxide electrocatalyst exhibiting an intrinsic overpotential at 10 mA cm-2oxide of 391 mV, which is among the lowest known of four-metal perovskite oxides.

Stirring-Controlled Synthesis of Ultrastable, Fluorescent Silver Nanoclusters.

This paper describes how macroscopic stirring of a reaction mixture can be used to produce nanostructures exhibiting properties not readily achievable via other protocols. In particular, it is shown that by simply adjusting the stirring rate, a standard glutathione-based method-to date, used to produce only marginally stable fluorescent silver nanoclusters, Ag NCs-can be boosted to yield nanoclusters retaining fluorescence for unprecedented periods of over 2 years. This enhancement derives not simply from increased homogenization of the reaction mixture but mainly from an appropriately timed delivery of oxygen from above the reaction mixture. In effect, oxygen serves as a reagent that dictates size, structure, stability, and functional properties of the growing nanoobjects.

The Influence of Distant Substrates on the Outcome of Contact Electrification.

The magnitudes of the charges developed on contact-electrified polymers depend on not only the properties of these materials but also the nature of distant substrates on which the polymers are supported. In particular, image charges induced in conductive substrates can decrease charges on the polymers by arc discharge through the surrounding gas. This mode of charge dissipation occurs on timescales of milliseconds and can be prevented by insulating the sharp edges of the conductive supports.

Mixed-Charge Nanocarriers Allow for Selective Targeting of Mitochondria by Otherwise Nonselective Dyes.

Targeted delivery of molecular cargos to specific organelles is of paramount importance for developing precise and effective therapeutics and imaging probes. This work describes a disulfide-based delivery method in which mixed-charged nanoparticles traveling through the endolysosomal tract deliver noncovalently bound dye molecules selectively into mitochondria. This system comprises three elements: (1) The nanoparticles deliver their payloads by a kiss-and-go mechanism - that is, they drop off their dye cargos proximate to mitochondria but do not localize therein; (2) the dye molecules are by themselves nonspecific to any cellular structures but become so with the help of mixed-charge nanocarriers; and (3) the dye is engineered in such a way as to remain in mitochondria for a long time, up to days, allowing for observing dynamic remodeling of mitochondrial networks and long-term tracking of mitochondria even in dividing cells. The selectivity of delivery and long-lasting staining derive from the ability to engineer charge-imbalanced, mixed [+/-] on-particle monolayers and from the structural features of the cargo. Regarding the former, the balance of [+] and [-] ligands can be adjusted to limit cytotoxicity and control the number of dye molecules adsorbed onto the particles' surfaces. Regarding the latter, comparative studies with multiple dye derivatives we synthesized rationalize the importance of polar groups, long alkyl chains, and disulfide moieties in the assembly of fluorescent nanoconstructs and long-lasting staining of mitochondria. Overall, this strategy could be useful for delivering hydrophilic and/or anionic small-molecule drugs difficult to target to mitochondria by classical approaches.

Additive Contact Polarization of Nonferroelectric Polymers for Patterning of Multilevel Memory Elements.

When a thin polymer film supported by a conductive substrate is contacted by and then separated from a micropatterned polymeric stamp, the so-called contact electrification creates electrical charges over the stamped regions. Simultaneously, image charges are induced in the conductive substrate. Together, the surface and image charges establish large fields within the film, in effect polarizing it. Upon consecutive stampings, the magnitudes of polarization add up, enabling imprinting of multilevel polarization patterns. Because the electric field is high only within the film but low across the Gaussian surface surrounding the film/substrate system, the discharge of surface charges is slow and the polarization patterns are relatively long-lived. These findings are significant since multilevel polarization states have, to date, been achieved only in ferroelectrics or some specialized polymers-the current method extends them to common polymers such as poly(methyl methacrylate), poly(vinyl pyrrolidone), or poly(vinyl acetate).

Targeted crystallization of mixed-charge nanoparticles in lysosomes induces selective death of cancer cells.

Lysosomes have become an important target for anticancer therapeutics because lysosomal cell death bypasses the classical caspase-dependent apoptosis pathway, enabling the targeting of apoptosis- and drug-resistant cancers. However, only a few small molecules-mostly repurposed drugs-have been tested so far, and these typically exhibit low cancer selectivity, making them suitable only for combination therapies. Here, we show that mixed-charge nanoparticles covered with certain ratios of positively and negatively charged ligands can selectively target lysosomes in cancerous cells while exhibiting only marginal cytotoxicity towards normal cells. This selectivity results from distinct pH-dependent aggregation events, starting from the formation of small, endocytosis-prone clusters at cell surfaces and ending with the formation of large and well-ordered nanoparticle assemblies and crystals inside cancer lysosomes. These assemblies cannot be cleared by exocytosis and cause lysosome swelling, which gradually disrupts the integrity of lysosomal membranes, ultimately impairing lysosomal functions and triggering cell death.