Chemistry - A European Journal最新文献

The growing demand for sustainable and efficient methods for synthesizing fine chemicals has increased interest in innovative approaches for accessing high-quality chiral building blocks, particularly fluoroalcohols, which are relevant for the production of active pharmaceutical ingredients (APIs). This study presents the complete integration of a two-step process in a continuous flow reactor system for the synthesis of (R)-2-fluoro-1-phenylethanol as a reference molecule. To this end, the individual reaction steps and technologies for the decarboxylative fluorination of 3-oxo-3-phenylpropanoic acid in aqueous media, followed by an enantioselective biocatalytic reduction of the prochiral intermediate phenacyl fluoride, were adapted and implemented in a compact laboratory system for performance demonstration. Alcohol dehydrogenase (ADH) from Rhodococcus ruber (RrADH) produced in a plant-derived BY2 cell-free expression system was used as the biocatalyst, which was immobilized via an imine bond on glutaraldehyde-modified silica supraparticles. The immobilized enzymes were used in batch mode for comprehensive kinetic studies of the enantioselective reduction, including evaluations of their operational and storage stability. Excellent enantiomeric excess (> 99.9%) and overall yields of up to 91% were achieved for both synthesis steps. These results are a prerequisite for the targeted and stable use of the enzyme in a continuously operated two-step process, which was achieved by using a serial micro batch reactor (SMBR) setup with a capillary reactor for precise temperature control. This study demonstrates the advantages of combining immobilized biocatalysts with continuous-flow operation for achieving high efficiency and selectivity in the synthesis of chiral fluoroalcohols. The integrated process provides a sustainable and versatile basis for future developments in the green synthesis of fluorinated building blocks relevant to pharmaceutical applications.

A methyl-substituted ladder meta-phenylene macrocycle (MeLMMP) and its corresponding ladder polymer (MeLPMP), a meta-analogue of the well-known ladder-type poly(para-phenylene), LPPP, were synthesized and comprehensively investigated. Both compounds exhibit limited conjugation due to the meta-linked phenylene units, resulting in absorption and emission features shaped by cross-conjugation. Despite having a longer chain, MeLPMP and MeLMMP exhibit nearly identical electronic and photophysical behavior, suggesting that the number of repeat units has minimal influence. MeLPMP exhibits enhanced vibronic resolution compared to MeLMMP due to a broadening of the optical bands of the macrocycle caused by the presence of a mixture of stereoisomers formed during the non-stereoselective ladderization step. A small amount of fluorenone-type keto defects produces a weak emission near 500 nm, more evident in the macrocycle, and introduces radiationless decay pathways that compete with fluorescence. This decay pathway, together with the weak π,π* conjugation in these angular compounds, lowers the fluorescence quantum yield when compared with the linear MeLPPP, while promoting singlet-triplet conversion and phosphorescence. The data indicate the presence of three chromophoric populations: pristine oligo(meta-phenylene) units; units quenched by nearby keto defects; and intramolecular charge-transfer complexes (ICTCs) formed between oligo(meta-phenylene) units and keto defects. These findings clarify the photophysics of meta-phenylene ladder systems, showing that the MeLMMP macrocycle can act as a structural and electronic model for related ladder polymers.

Herein, we are demonstrating an earth-abundant manganese-catalyzed oxidative deamination of linear and branched primary amines to selectively form carboxylic acids and ketones using water as the oxygen atom source. A series of pincer and non-pincer Mn complexes were assessed for these deaminative transformations. A bio-inspired DAFO (4,5-diazafluoren-9-one) ligand-based [(DAFO)Mn(CO)₃Br] complex (Mn-1) was found to be effective for the reaction proceeding under mildly basic aqueous medium, generating NH₃ and H₂ as sole by-products without the requirement of any oxidant. An optimized condition of 5 mol% Mn-1, Na₂CO₃ (1 equiv) at 150°C for 48 h in water/1,4-dioxane mixture furnished 92% of the corresponding benzoic acid from benzylamine. A wide variety of electron-donating and withdrawing para-, meta-, and ortho-substituted benzylamines, including promising hetero and aliphatic linear primary amines, afforded moderate to excellent yield of the desired carboxylate product. We have also examined a few branched primary amines using 5 mol% Mn-1 and catalytic sodium carbonate at 150°C for 48 h, affording good yield of ketones. The reaction was found to be chemo-selective for primary amine moieties over alcohol functionalities. Further, stoichiometric mechanistic investigation and preliminary computational data provide insights into the possible mechanistic steps.

p-Block complexes containing unsupported metal─metal bonds can activate small molecules via mechanisms that complement and contrast with those of d-block metal complexes. Here we report the synthesis of a new family of heterobimetallic Al─Zn complexes [(^ArNacnac)Zn─Al(Cp*)(X)] (Ar = Dep, X = Cl, Br, I; Ar = Dipp, X = Cl, Br; ^ArNacnac = {HC[C(Me)N(Ar)]₂}; Ar = Dep, C₆H₃Et₂-2,6; Dipp, C₆H₃ ⁱPr-2,6; Cp* = C₅Me₅), by insertion of in situ-generated "AlCp*" into the Zn─X bonds of parent dimeric zinc ^ArNacnac halide complexes [Zn(^ArNacnac)(μ-X)]₂. We find that the reactions of the newly formed Al─Zn complexes with N,N'-dicyclohexylcarbodiimide (DCC) proceed by migratory insertion into the Al─Zn bond to give [Zn(^ArNacnac){μ₂-C(NCy)₂-κ¹-C,κ²-N,N'}Al(Cp*)(X)] (Ar = Dep, X = Cl, Br, I; Ar = Dipp, X = Cl, Br) as expected, but for the ^DippNacnac derivatives a second equivalent of DCC inserts into the Al─Cp* moiety to afford [Zn(^DippNacnac){μ₂-C(NCy)₂-κ¹-C,κ²-N,N'}Al(Cl){κ²-(NCy)₂C-η¹-Cp*-κ²-N,N'}] or [Zn(^DippNacnac)(Br){μ₂-C(NCy)₂-κ¹-C,κ²-N,N'}Al{κ²-(NCy)₂C-η¹-Cp*-κ²-N,N'}], with concomitant halide migration giving a Zn─Br bond in the latter complex. These results show that non-innocent reactivity of Al─Cp*, widely assumed to be a spectator ligand in heterobimetallic complexes, can be switched on by subtly tuning ligand steric bulk about Al─Zn bonds.

Hypermodified nucleosides have recently been at the center of scientific attention. They represent a unique group of nucleosides with an alternated structure, such as the addition of functional groups or amino acids. Their distinctive structures and positions in RNAs are crucial for the processes of translation and stability. High demand for oligonucleotides bearing those hypermodified nucleobases led us to the development of a single-step synthesis of acp³U phosphoramidite, as acp³U has been recognized as an important molecule for the structural integrity of tRNA and native immunity. We also present a novel synthesis of cmnm⁵U phosphoramidite and its incorporation into an oligonucleotide from a highly versatile starting material, allowing a transformation into at least two other hypermodified nucleosides.

Carbon dots (CDs) have emerged as a transformative class of luminescent nanomaterials for biomedical applications, offering superior biocompatibility, photostability, and tunability compared to conventional organic dyes and inorganic quantum dots. This review distinguishes itself by establishing a critical "Structure-Property-Application" feedback framework. We comprehensively summarize the rational design of CDs, specifically elucidating how core size, surface chemistry, and heteroatom doping can be precisely engineered to tailor optical emission into the near-infrared II window. Furthermore, the versatile roles of CDs in cancer theranostics are critically discussed, encompassing their utility in subcellular tracking, image-guided surgery, and multifunctional therapeutic platforms such as photothermal therapy (PTT), photodynamic therapy (PDT), and targeted drug delivery. Finally, we address the current challenges regarding scalability, reproducibility, and biosafety, providing a perspective on the future roadmap for the clinical translation of high-performance CD-based agents.

Metal nanoclusters (MNCs)-semiconductor (SC) composite materials have garnered significant attention due to the fascinating and versatile properties exhibited by MNCs. However, there is a scarcity of efforts directed toward incorporating metal nanoparticles (MNPs) into MNCs-SC composites to facilitate charge generation within the system. And the underlying mechanism governing charge transfer in such systems remains elusive. In this work, a straightforward reduction-adsorption strategy was employed to ingeniously introduce AuNCs into the AgNPs@MoS₂ binary nanostructure. This approach effectively improves the electron-donating performance of resulting AuNCs-AgNPs@MoS₂ ternary heterostructures, which were utilized as the substrates for SERS-active p-nitrothiophenol (PNTP)-catalytic reactions. PNTP-catalytic experiments further validated the enhanced catalytic performance arising from the introduction of AuNCs into the ternary heterostructure. Furthermore, the composite mechanism of AuNCs and AgNPs in the nanosystem was elucidated, revealing that AgNPs act as charge bridges and synergistically facilitate charge generation in conjunction with AuNCs. The electron-donating capability was quantified using the concept of charge transfer degree, rendering the impact of AuNCs incorporation on charge yield more intuitive. This study is anticipated to provide a rational approach for the construction of MNCs-MNPs@SC ternary nanostructures and optimizing the synergistic interaction between MNCs and MNPs, thereby enabling their applications across diverse fields.

Early-stage liver fibrosis is potentially reversible, yet its timely diagnosis remains challenging due to the lack of sensitive molecular imaging tools. Hypochlorous acid (HOCl), an inflammation-associated reactive oxygen species has emerged as a key pathogenic mediator and early biomarker of fibrotic progression. Herein, guided by a structure-activity relationship (SAR) strategy, three donor-π-acceptor (D-π-A) fluorescent probes (PMBT, CMBT, and TMBT) were rationally designed and systematically evaluated for HOCl detection. Density functional theory calculations (DFT) and spectroscopic studies reveal donor-dependent electronic distributions and distinct HOCl-responsive behaviors. Among them, PMBT exhibits a rapid turn-on response (<10 s), naked-eye-detectable fluorescence enhancement, and a low detection limit of 11.38 nM, along with favorable mitochondrial localization. Benefiting from its high sensitivity and liver-targeting capability, PMBT enables effective imaging of endogenous HOCl and allows precise visualization of early-stage liver fibrosis in mouse models, highlighting its potential as a powerful diagnostic tool.

Given the synthetic significance of allylic alcohols, developing efficient methods for their preparation remains a central pursuit in organic chemistry. Herein, we report a stereoselective approach to access trifunctionalized Z‑allylic alcohols via a radical‑mediated 1,4‑aryl migration. By employing readily available benzyl propargyl ethers and Togni-II reagent as the CF₃ source, this reaction proceeds through inert C(sp²)-C(sp³) bond cleavage, enabling the modular assembly of valuable trifluoromethylated Z‑allylic alcohols under mild, photoredox‑neutral conditions. The protocol exhibits a broad substrate scope, excellent functional‑group tolerance, and high regio- and stereo-selectivity.

The exploitation of molecular self-assembly, which leads to the formation of aggregates, represents one of the most crucial approaches in the fabrication of advanced functional materials. A fundamental aspect in this area is the development of novel strategies to construct supramolecular architectures with new (unusual) properties, in particular, strongly fluorescent H-aggregates. Using 2-(2-carboalkoxy-3,4,5-trichloro-6-hydroxyphenyl)benzoxazoles (HBOs) as building blocks, H-aggregates were successfully obtained in both aqueous binary mixtures and the crystalline state. These aggregates exhibit intense fluorescence despite the prohibition imposed by Kasha's rule. This violation seems to result from the deactivation mechanism of the excited excitonic state in HBO H-aggregates, which involves, along with internal conversion, a photochemical channel induced by excited-state intramolecular proton transfer (ESIPT) rather than a radiative one. The consequence of ESIPT is monomeric fluorescence from the keto forms of HBOs. The fluorescence quantum yields of HBOs in the crystalline state are significantly higher than those in solution, ranging from 0.81 to 0.91. This enhancement is due to intramolecular hydrogen bonds as well as the dense molecular packing of HBOs, which suppresses conformational transformations.