Journal of the American Chemical Society最新文献

Organic ferroelectrics show great applications in the fields of biomedicine, including disease treatment, biosensors, and tissue engineering. Organosilicon pharmaceutical intermediates generally include chiral centers and have satisfying biosafety, biocompatibility, or even biodegradability, which provide versatile platforms for the design of ferroelectricity. However, their academic values in ferroelectricity have long been long overlooked. Here, we demonstrated the ferroelectric properties of 4-acetoxy-azacyclic butanone (4-AA), a key synthetic organosilicon-based intermediate of carbapenem drugs. This compound undergoes a 222F2-type ferroelectric-ferroelastic phase transition at 326 K. As an organic piezoelectric material, 4-AA can produce reactive oxygen species when subjected to ultrasonic vibrations. Combined with its desirable biocompatibility, this material may contribute to antimicrobial and wound healing, tumor treatment, etc. This work will provide inspiration for the discovery of multifunctional biomedical ferroelectric materials as well as their related application prospects.

Polyketide synthases (PKSs) are renowned for the structural diversity of the polyketide natural products they produce, but sulfur-containing functionalities are rarely installed by PKSs. We previously characterized thiocysteine lyase (SH) domains involved in the biosynthesis of the leinamycin (LNM) family of natural products, exemplified by LnmJ-SH and guangnanmycin (GnmT-SH). Here we report a detailed investigation into the PLP-dependent reaction catalyzed by the SH domains, guided by a 1.8 Å resolution crystal structure of GnmT-SH. A series of elaborate substrate mimics were synthesized to answer specific questions garnered from the crystal structure and from the biosynthetic logic of the LNM family of natural products. Through a combination of bioinformatics, molecular modeling, in vitro assays, and mutagenesis, we have developed a detailed model of acyl carrier protein (ACP)-tethered substrate-SH, and interdomain interactions, that contribute to the observed substrate specificity. Comparison of the GnmT-SH structure with archetypical PLP-dependent enzyme structures revealed how Nature, via evolution, has modified a common protein structural motif to accommodate an ACP-tethered substrate, which is significantly larger than any of those previously characterized. Overall, this study demonstrates how PLP-dependent chemistry can be incorporated into the context of PKS assembly lines and sets the stage for engineering PKSs to produce sulfur-containing polyketides.

The precise asymmetric photochemical transformation of organic compounds containing multiple reactive sites presents significant progress in synthetic chemistry. Herein, we report an unprecedented visible-light-induced cascade transformation of tropolone cyclic triene derivatives by using chiral photoactive metal-organic cages (cPMOCs) as enzyme-mimicking multipocket photocatalysts. The cage-confined photocatalysis promotes three successive elementary steps, i.e., enantioselective [2 + 2] photocycloaddition with chalcone, regio-, and diastereoselective α-ketol rearrangement, and a stereoselective 1,3-acyl shift, resulting in bicyclo[3.2.2]nonane skeleton with multichiral-centers unattainable by other methods. This study demonstrates how complex synthetic challenges of peri-, chemo-, and stereoselectivities could be subtly manipulated by cage-confined supramolecular catalysis for exploration of new reactivities.

The interaction between a solid and water at their interface, especially proton transfer, impacts molecular-scale catalysis, macroscopic environmental science, and geoscience. Although being highly desired, directly probing proton transfer between a solid and water is a great challenge, given the subnanometer to nanometer scale of the interface. The fundamental challenge lies in the lack of a measurement tool to sensitively observe local proton concentration without introducing an exogenous electrode or nanoparticle with a minimum size of tens of nanometers. Here, we demonstrate an azo-enhanced Raman scattering strategy to design a 2 nm long small-molecule pH probe with a chelating group anchoring to the solid surface. Empowered by the intramolecular Raman enhancing sensitivity, the probe directly observes proton transfer between water and nanoscale zero-valent iron (nZVI), a famous environmental material for pollution control. This molecular-scale interfacial probing methodology offers a powerful tool to pave the way for advanced environmental and geochemical discernment and management.

Here, we report the synthesis of a family of chiral Zn^II₄L₄ tetrahedral cages by subcomponent self-assembly. These cages contain a flexible trialdehyde subcomponent that allows them to adopt stereochemically distinct configurations. The incorporation of enantiopure 1-phenylethylamine produced Δ₄ and Λ₄ enantiopure cages, in contrast to the racemates that resulted from the incorporation of achiral 4-methoxyaniline. The stereochemistry of these Zn^II₄L₄ tetrahedra was characterized by X-ray crystallography and chiroptical spectroscopy. Upon binding the enantiopure natural product podocarpic acid, the Zn^II stereocenters of the enantiopure Δ₄-Zn^II₄L₄ cage retained their Δ handedness. In contrast, the metal stereocenters of the enantiomeric Λ₄-Zn^II₄L₄ cage underwent inversion to a Δ configuration upon encapsulation of the same guest. Insights gained about the stereochemical communication between host and guest enabled the design of a process for acid/base-responsive guest uptake and release, which could be followed by chiroptical spectroscopy.

Colloidal nanocrystals (NCs) are active materials in different applications, wherein their shape dictates their properties, such as optical or catalytic properties, and, thus, their performance. Hence, learning to tune the NC shape is an important goal in chemistry, with implications in other fields of research. A knowledge gap exists in the chemistry of non-noble metals, wherein design rules for shape control of NCs are still poorly defined compared to those of other classes of materials. Herein, we demonstrate that tuning the precursor reactivity is crucial to obtaining a continuous shape modulation from single-crystalline to twinned and stacking fault-lined Cu NCs. This tunability is unprecedented for non-noble metal NCs. We achieve this result by using diphenylphosphine in place of the most commonly used trioctylphosphine. Using in situ X-ray absorption spectroscopy, we show that the temperature modifies the reaction kinetics of an in situ-forming copper(I)bromide-diphenylphosphine complex during the synthesis of Cu NCs. We propose the presence of a P-H functionality in the phosphine to explain the higher reactivity of this precursor complex formed with diphenylphosphine compared to that formed with trioctylphosphine. This work inspires future studies on the role of phosphine ligands during the synthesis of Cu NCs to rationally target new morphologies, such as high-index faceted Cu NCs, and can be conceptually translated to other transition-metal NCs.

Cysteine reactive groups are a mainstay in the design of covalent drugs and probe molecules, yet only a handful of electrophiles are routinely used to target this amino acid. Here, we report the development of scalable thiol reactivity (STRP), a method which enables the facile interrogation of large chemical libraries for intrinsic reactivity with cysteine. High throughput screening using STRP identified the azetidinyl oxadiazole as a moiety that selectively reacts with cysteine through a ring opening-based mechanism, capable of covalently engaging cysteine residues broadly across the human proteome. We show the utility of this reactive group with the discovery of an azetidinyl oxadiazole containing a small molecule that augments the catalytic activity of the deubiquitinase UCHL1 in vitro and in cells by covalently modifying a cysteine distal to its enzymatic active site. This study adds a novel cysteine targeting group to the electrophilic lexicon and provides robust methodology to rapidly surveil libraries for reactivity with cysteine.

On-purpose atomic scale design of catalytic sites, specifically active and selective at low temperature for a target reaction, is a key challenge. Here, we report teamed Pd₁ and Mo₁ single-atom sites that exhibit high activity and selectivity for anisole hydrodeoxygenation to benzene at low temperatures, 100-150 °C, where a Pd metal nanoparticle catalyst or a MoO₃ nanoparticle catalyst is individually inactive. The catalysts built from Pd₁ or Mo₁ single-atom sites alone are much less effective, although the catalyst with Pd₁ sites shows some activity but low selectivity. Similarly, less dispersed nanoparticle catalysts are much less effective. Computational studies show that the Pd₁ and Mo₁ single-atom sites activate H₂ and anisole, respectively, and their combination triggers the hydrodeoxygenation of anisole in this low-temperature range. The Co₃O₄ support is inactive for anisole hydrodeoxygenation by itself but participates in the chemistry by transferring H atoms from Pd₁ to the Mo₁ site. This finding opens an avenue for designing catalysts active for a target reaction channel such as conversion of biomass derivatives at a low temperature where neither metal nor oxide nanoparticles are.

Because an individual single-walled carbon nanotube (SWNT) can absorb multiple photons, the exciton density within a single tube depends upon excitation conditions. In SWNT-based energy conversion systems, interactions between excitons and charges make it possible for multiple types of charge transfer reactions. We exploit a SWNT-molecular donor-acceptor hybrid system (R-PBN(b)-Ph₆-PDI-[(6,5) SWNT]) that fixes spatial organization and stoichiometry of perylene diimide (PDI) electron acceptors on the nanotube surface, to elucidate how excitation fluence affects ultrafast charge separation (CS) and the nature of charge recombination (CR) dynamics triggered upon SWNT near-infrared excitation. Pump-probe data characterizing these photoinduced CS and thermal CR reactions were acquired over excitation fluences that produce ∼5-125 excitons per 700 nm long nanotube. These experiments show that optical excitation gives rise to CS states in which PDI radical anions (PDI^-•) and SWNT hole polarons (SWNT^•+) have geminate and nongeminate spatial relationships. Under low excitation fluences, the observed dynamics reflect CR reactions of these geminate and nongeminate CS states. As excitation fluence increases, persistent excitons, which have not undergone CS, undergo reaction with ([SWNT(^•+)ⁿ]-(PDI^-•)_n) CS states to produce lower-energy CS states that are characterized by hole (SWNT^•+) and electron (SWNT^•-) polarons. When nongeminate SWNT^•+ and SWNT^•- charge carriers are generated, CR dynamics depend on the time scale required for these oppositely charged solvated SWNT polarons to encounter each other. Because SWNT excitons have substantial excited-state reduction (¹E^-/*) and excited-state oxidation (¹E^*/+) potentials, they can drive additional charge transfer reactions involving initially prepared CS states under experimental conditions where excess excitons are present.