Chem最新文献

Synthetic anion transporters that mediate electroneutral (H⁺/Cl⁻) transport have demonstrated anti-cancer activity due to their ability to disrupt subcellular homeostatic environments. Elucidation of the cell death mechanism revealed the transporters’ ability to neutralize lysosomal pH gradients and inhibit autophagy. However, their effects on other subcellular compartments are unknown. Herein, we disclose the first subcellular targeted anionophores that accumulate in various membrane-bound organelles to bias their natural propensity to depolarize lysosomes. Confocal microscopy revealed that the naphthalimide-based transporters effectively localized within their intended organelles. Analogs containing endoplasmic reticulum (ER) and lysosomal targeting motifs showed an enhanced H⁺/Cl⁻ transport ability and greater cytotoxicity compared with non-targeted analogs. Moreover, lysosomal accumulation improved cancer cell selectivity, while ER and mitochondrial localization enhanced apoptosis in cancer cells. Our work provides an alternative approach to the design of therapeutically focused synthetic anion transporters and an insight into possible subcellular compartment-specific effects on homeostasis.

Coulomb repulsion in multiply charged ions (MCIs) is mitigated by long-range electrostatic interaction with the distant charge separation and delocalized systems. Meanwhile, MCIs featuring the charged centers located at two directly connected atoms (E^+/−–E^+/−) bear a strong repulsive force, which leads to electron detachment or molecular fragmentation, namely, Coulomb explosion. Here, we describe the synthesis of a trianionic triangular triboron species (B₃R₆³⁻) through the reductive dealumination from a Cp∗AlB₃R₆ anion (Cp∗, 1,2,3,4,5-pentamethylcyclopentadienyl). X-ray crystallographic and spectroscopic analyses with the aid of quantum chemical calculations reveal that despite the triply negatively charged skeleton, the B₃ core is tightly held by electron-precise B–B bonds, overcoming Coulomb repulsion. In contrast to the extant electron-deficient triborate rings, this molecule exhibits reducing ability and nucleophilicity; thus, it undergoes not only electron transfer but also cyclization and salt metathesis reactions, demonstrating its trait as elusive (R₂B⁻) and ([R₂B]₂²⁻) surrogates.

The natural product (NP) class of syrbactins are potent proteasome inhibitors produced by hybrids of non-ribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs). Here, we describe the stepwise reassembly of an entire NRPS/PKS hybrid to produce a new syrbactin derivative by utilizing the recently described “eXchange Unit between Thiolation domains” (XUTs) approach. Remarkably, XUT-based engineering allowed the direct assembly of PKS and NRPS modules to introduce an α,β-unsaturated Michael system in a macrolactam moiety, which represents the inhibitory warhead of syrbactins. The novel derivative was produced in E. coli, isolated, and examined for its ability to inhibit yeast (yCP), human constitutive (cCP), and immunoproteasome (iCP). The engineered NP maintained the inhibitory activities of the syrbactin class but, due to rational modifications, inhibited iCP most strongly. Moreover, analysis of the crystal structure of yCP in complex with the derivative revealed further design strategies for even more specific iCP inhibition.

Despite enormous advances in the edge extension chemistry of nanographenes, examples of peri-annulations and the knowledge of their effect on molecular properties remain scarce. Here, we show the synthesis of a curved C₆₀S₅ nanographene comprising quintuple [5]thiahelicenes arranged in a C₅-symmetric fashion on the zigzag edge (L-region) of a bowl-shaped corannulene core. The synthesis is achieved with the help of Stille coupling, alkynyl thiolation, sulfide/aryne cyclization, and direct arylation reactions. The prepared bowl-helix chiral structure absorbs and emits in the visible and near-IR regions. It assembles into persistent molecular bilayer graphene stacks in solution, solid state, and gas phase. The concave cavities of the supramolecular dimers can recognize the convex surfaces of fullerene C₆₀ through shape complementarity and π-π stacking interactions in the solid state. A properties comparison with ortho-annulated analogs and archetypical nanographenes indicates the superiority of peri-annulations in the design of molecular graphenes.

The nitrogen cycle is one of the most important biochemical cycles. However, the development of human society has led to a substantial release of nitrogen oxide species, both as ions (NO_x⁻) and gases (NO_x), into the environment, causing a considerable burden on the natural denitrification processes. Electrocatalytic reduction of NO_x⁻ and NO_x emerges as a promising approach to transform these waste products into valuable ammonia, thereby contributing to the restoration of the nitrogen cycle. This review provides a concise overview of recent advances in electrocatalytic NO_x⁻ and NO_x reduction to ammonia, including detailed reaction mechanisms, catalyst development strategies based on both theoretical and experimental results, and the design and selection of electrolytic cells. Furthermore, it highlights key challenges associated with scaling up the reaction from laboratory-scale to practical industrial-scale application and explores potential opportunities to upgrade this reaction.

The use of photochromic materials in volumetric three-dimensional (3D) displays can allow rich visual experiences by representing 3D content that occupies a real volume of physical space. We discovered that doping visible-light-activated azo-BF₂ switches into polydimethylsiloxane (PDMS) polymers can result in volumetric beam-addressable canvases. The straightforward manipulation of the canvas with red and blue light illumination using digital light processing and/or heat (i.e., thermal back isomerization) generates tunable, reversible, and high-contrast and -resolution images. These properties were used in designing a rewritable, solid-state, and handheld volumetric 3D photochromic display that can be recursively used for showcasing static volumetric 3D images and dynamic 2D animations.

The exploration of symmetry-breaking charge separation (SB-CS) is imperative when designing functional light-harvesting materials. Past explorations, however, have been confined to covalent systems, more often than not requiring complicated/demanding syntheses and facing inconvenient regulation of charge transfer processes. Here, we present a concept that regulates the efficiency of SB-CS through molecular recognition utilizing a pyridinium-based cyclophane as a host. This host undergoes photo-driven excited-state SB-CS. By employing different guests with distinct frontier molecular orbital energy levels, we have achieved comprehensive control of electron transfer pathways in the cyclophane, modulating between accelerated (>10-fold) intramolecular SB-CS involving superexchange and direct intermolecular electron transfer between the host and guest. The improvement in SB-CS efficiency results in catalytic activity for the photo-oxidation of a sulfur-mustard simulant. This research offers an opportunity for tuning SB-CS by utilizing molecular recognition, which holds the potential for achieving precise regulation without complicated organic syntheses.