ABSTRACT Developing circularly polarized luminescence (CPL) materials with large luminescent dissymmetry factors ( g lum ) through hierarchical self‐assembly remains a significant challenge. Herein, we report an ultrasound‐triggered hierarchical assembly strategy that enables the construction of heterojunction helices exhibiting inverted supramolecular chirality and substantially amplified CPL. A tetraphenylethylene‐alanine derivative forms chiral nanohelices upon heating‐cooling in DMSO. The addition of MeCN promotes the growth of nanohelices along with residual monomers into microhelices. Notably, ultrasound following MeCN addition induces reorganization at the termini of the nanohelices, leading to heterojunction helices composed of core and dendritic helical subunits with opposite handedness. These heterojunction helices display inverted and amplified CPL, with a g lum value of 0.2 and a fluorescence quantum yield of 50%. Experimental and density functional theory calculations suggest that the ultrasound mechanical force changes the types of hydrogen bonds within extended monomers, thereby redirecting the self‐assembly pathway from the ends of nanohelices and newly generated folded monomers. Enhanced interchromophoric interactions and well‐ordered dendritic helices contribute to the inversion and amplification of CPL. This study not only presents the first example of heterojunction helices derived from the same chiral molecule but also provides new insights into an ultrasound‐triggered pathway for amplifying CPL via hierarchical assembly.

Colorectal cancer is among the most leading cancers in China, characterized by activating mutations in PIK3CA or aberrant AKT signaling in approximately 30

The natural products ciquitin A and ciquitin B exhibit two distinct sets of NMR signals in solution, a phenomenon previously attributed to an equilibrium between its ring-open and ring-closed hemiacetal isomers. Through a comprehensive re-evaluation of NMR data, complemented by variable-temperature NMR experiments, potential energy surface (PES) scanning, and magnetic shielding constant calculations, we have redefined ciquitin A as a natural pseudo-resonance structure. Prior to successful crystallization for X-ray analysis, structural identification remained challenging when facing two sets of NMR spectra. However, conversion of any pseudo-resonance structure (like ciquitin A, a hemiacetal type) to its corresponding acetal derivatives (in this case (9S)-naproxyl-ciquitin A) resulted in a single set, thereby enabling clear identification of the structure. This work represents one of the most unequivocal examples of such a structure discovered in nature.

Two amines, (4-chlorophenyl)methanamine and 2-(4-chlorophenyl)ethan-1-amine were used for syntheses of two substituted isoindolin-1-ones (4 and 5), in which the framework isoindolin-1-one exhibited some bioactivities. In this report, two sets of NMR signals were recorded for the both 4 and 5, which are different from the traditional framework. Variable-temperature (VT) 1H NMR exhibited that the two sets of NMR signals did not coalesce into one set in high temperatures. Potential energy surface (PES) scan was performed at the omega B97XD/ 6-31+G(d) level. The effects of the sample's concentrations and four deuterated solvents on the NMR spectra were investigated. Finally, the compound 5 was transferred to the corresponding methyl ether 6, which just had one set of NMR spectra. All results exhibit that formation of H-bond between two structures (4 or 5) plays the key role to produce the two sets of NMR data.

Four substituted isoindolin‐1‐one derivatives were synthesized from the corresponding fluorine‐containing aromatic amines. In CDCl₃ solution, all compounds exhibited two sets of NMR signals with ratios from 1:0.7 to 1:0.8. In contrast, only one major set of NMR signals was observed in CD₃OD, the minor signals showing ratio ∼1:0.07–0.20. Variable‐temperature (VT) ¹H NMR experiments revealed that the two sets of signals did not coalesce into a single set from 298–348 K. By converting one pseudo‐resonance structure into its corresponding methyl ether, it displayed only one set of NMR spectrum instead of two in CDCl 3 . One absorption near 1674–1697 cm −1 was recorded for amide carbonyl for all compounds' IR spectra in CDCl 3 solution. No any aldehyde signals was observed in IR or 1 H NMR spectra. All results showed that the pure compound did not process the ring‐opening and ring‐closing via aldehyde to afford two hemiacetals with about 1:0.7 to 0.8 in CDCl 3 solution.

Recent developments in chirality chemistry have revealed remarkable instances of atropisomers featuring multiple chiral elements. Despite significant progress in the synthesis and application of atropisomers, developing a synthetic protocol for the simultaneous introduction of axial and point chirality is still a fascinating challenge. In this context, we present a convenient and versatile method for synthesizing novel atropisomers with axial and point chirality. This approach, based on a new reaction mechanism with nickel-controlled Si–C bond activation, facilitates the controllable migratory insertion of aldehydes into the Ni–C bond. We utilize multidimensional strategies of desymmetrization, kinetic resolution and dynamic kinetic resolution to complete enantioselective nickel-catalyzed ring expansion of benzosilacyclobutenes with aldehydes. The design of multidimensional kinetic resolution, desymmetrization, and dynamic resolution, features a straightforward catalytic system, mild reaction conditions, and broad functional group tolerances. Various axially chiral biaryl oxasilacycles bearing carbon- or silicon-stereogenic centers are obtained with excellent diastereo- and enantio-selectivities (up to >20:1 dr and >99.9

A racemic compound, (S*)-3-[(1R*,3R*)-3-hydroxy-1,3-dihydroisobenzofuran-1-yl]-2-(naphthalen-1-yl)-isoindolin-1-one (3), was synthesized and found to exhibit four distinct sets of 1H and 13C NMR signals in CDCl3 solution. The four sets of 1H NMR signals displayed relative integration ratios of approximately 1:1:0.8:0.8. Subsequent PCC oxidation of 3 yielded racemic (S*)-2-(naphthalen-1-yl)-3-[(R*)-3-oxo-1,3-dihydroisobenzofuran-1-yl]-isoindolin-1-one (5), which showed simplified NMR behavior with only two sets of 1H and 13C NMR signals (1:1 ratio) in CDCl3. Interestingly, compound 5 exhibited two sets of 1H NMR signals in DMSO-d 6 that gradually coalesced into a single set upon variable-temperature NMR analysis (298-353 K). To further investigate the structural dynamics, racemate 3 was converted to its corresponding acetate derivative (8) in CHCl3. Notably, the acetate 8 displayed only two sets of NMR signals (near 1:0.9 ratio) in CDCl3, contrasting with the original four sets (1:1:0.8:0.8) observed for compound 3. This critical observation eliminated the possibility that hemiacetal isomeric structures were responsible for the NMR multiplicity in CDCl3. These findings suggest that the two sets of 1H NMR signals with 0.8:0.8 integration ratios originated from two atropisomers with near 1:1 ratios.

Although chiral nanostructures have been extensively studied, the fabrication of topological entities such as toroidal assemblies and their higher-order fused or catenated structures remains a formidable challenge. Here, we demonstrate a hierarchical assembly paradigm using a C3-symmetric benzene-1,3,5-tricarboxamide that enables the topological evolution of varied nanoarchitectures, such as discrete nanotoroids, fused super-nanotoroids containing up to 21 toroidal units, and nano-[2]catenanes. Our experimental and calculation results demonstrated that C3 molecules tended to form helical nanofibers with unexpected curvature due to both molecular chirality and bulky side chains. Further longitudinal extension and lateral lamellar packing of primary one-dimensional stacks led to the formation of dominant nanotoroids and stochastic nano-[2]catenanes with chiroptical signals and circularly polarized luminescence through an adaptive templating method. This work presents a cyclization-driven precise assembly of topologically discrete, fused, and catenated nanotoroids, unveiling the synergistic merging of chiral hierarchy and topological architectures in supramolecular self-assembly systems.

Sulfur-containing natural products are distinguished by their unique chemical structures and notable biological activities, rendering them highly valuable in drug discovery and development. Recent advancements in chemical epigenetic modifications, sulfur source regulation, and fungal co-cultivation have significantly facilitated the discovery of novel sulfur-containing compounds. In this study, the modulating culture method, incorporating DMSO and sea salt into the culture medium, was utilized to induce the marine-derived fungus Penicillium sp. to produce novel disulfide-linked resorcylic acid lactone dimers, dipenirestone A and B (1 and 2), along with their monomeric precursors (3-13). The absolute configurations of the new compounds 1-6 were elucidated through calculated NMR and ECD methods, as well as X-ray crystallography. Notably, the dimeric compounds (1 and 2) exhibited significantly enhanced anti-proliferative activity against HGC-27 cells compared to the monomers 3-13. It was revealed that compounds 1 and 2 exerted an antiproliferative effect through the modulation of the PI3K/AKT/mTOR signaling pathway. This was manifested as cell cycle arrest in the G1 phase, reduction in mitochondrial membrane potential, and induction of apoptosis.

A novel kind of framework containing axial 5-OH L-bitryptophane was synthesized under the mild reaction conditions. This synthetic strategy provides an efficient method to construct axial catalysts based on the new framework, which can be easily and economically separated from each other using silica gel column chromatography because the coupling products were atropisomers. For its promising application of the framework, eight catalysts were prepared and the relationship of the different catalytic centers on the enantioselectivity was tested using known and widely used model reactions and good enantiomeric ratios were recorded. Quantum methods were applied for the absolute configurations assignment of the new framework, the transition states (TSs) calculations for reaction mechanism study. The theoretical results agree well with the experiments. One best catalyst 8B with a 13-membered ring was found in the model reaction.

The pre-transmetalation intermediates are critically important in Suzuki-Miyaura cross-coupling (SMC) reactions and have become a hot spot of the current research. However, the pre-transmetalation intermediates under base-free conditions have not been clear. Herein, a comprehensive theoretical study is performed on the base-free Pd-catalyzed desulfonative SMC reaction. The fragile coordination feature and the acceleration role of the RuPhos chelate ligand are revealed. The hydrogen-bond complex between the Pd-F complex and aryl boronic acid is identified as an important pre-transmetalation intermediate, which increases the energy span to 32.5 kcal/mol. The controlling factor for the formation of the hydrogen-bond complexes is attributed to the electronegativities of halogen atoms in the metal halide complexes. What is more, other reported SMC reaction systems involving metal halide complexes and aryl boronic acids are reconsidered and suggest that the hydrogen-bond complexes widely exist as stable pre-transmetalation intermediates with influencing the catalytic activities. The earth-abundant Ni-catalyzed desulfonative SMC reaction is further designed and predicted to have a higher activity than the original Pd-catalyzed SMC reaction.

In chiral pseudo-resonance alcohols, two conformers A and B possess different sizes since their corresponding bond lengths and angles are different. Both conformers A and B co-exist together in general via an intermolecular H -bonds. (S)-3-((1R,3R)-3-hydroxy-1,3-dihydroisobenzofuran-1-yl)-2-isopropylisoindolin-1-one (lactone) and natural alcohol talaromytin were investigated to study the stability of H -bonds using variable-temperature 1H NMR spectra. The experimental results show that the H -bonds between two conformers A and B of the lactone could remain in DMSO-d6 at 353 K while the H -bonds in talaromytin were broken near 343 K in DMSO-d6. The alternative bond length changes were partially recorded using quantum theory at the B3LYP/6-311+G(d) level for two conformers A and B of the lactone.

Apple ring rot, caused by the pathogenic fungus Botryosphaeria dothidea, has inflicted substantial economic losses and caused significant food safety concerns. In this study, a pimarane-type diterpenoid, diaporthein B (DTB), isolated from a marine-derived fungus, exhibited significant antifungal activity against B. dothidea, with an EC50 value of 8.8 mu g/mL. Transcriptome, metabolome, and physiological assays revealed that DTB may target mitochondria and disrupt the tricarboxylic acid (TCA) cycle and oxidative phosphorylation processes. This interference led to increased accumulation of reactive oxygen species and subsequent lipid peroxidation, ultimately inhibiting fungal growth. Furthermore, DTB exhibited an inhibitory potency against apple ring rot at a concentration of 31.2 mu g/mL, achieving rates ranging from 67.7 to 81.6% across four distinct apple cultivars. These results indicated that DTB could serve as a novel fungicide for controlling apple ring rot in apple cultivation, transportation, and storage.

Alzheimer′s disease (AD) is a neurodegenerative disease with extremely complex pathogenesis, characterized by cognitive dysfunction and memory loss, involving in a variety of physiological and pathophysiological processes. Early diagnosis is a key factor for the prevention and treatment of AD. Positron emission tomography (PET) technology can accurately detect subtle physiological changes in neurons and brain tissues at the molecular level, providing evidence for early diagnosis of AD. Starting from the classification of biomarkers, the relevant targets of protein degeneration and neuronal damage in the brain were introduced, and the research status of various PET tracers was reviewed according to several important parameters such as affinity, half-life, binding region, pharmacokinetics, analysis method and correlation of results, etc. Additionally, the current problems faced by the development of PET tracers were pointed out, and it was believed that future research should be carried out from the following aspects: The development of PET tracers related to neuroinflammation; Further evaluation and optimization of existing tracers; Normalization and standardization of methods for the analysis of tracer results.

Curcumin, originally isolated as natural product from the rhizome of Curcuma longa L., is widely known for its anticancer properties. However, the clinical application of curcumin is still limited due to its poor absorption and rapid metabolism. In this study, structural modification of curcumin by introducing active small organic acids into its pyrazole ring intermediate, was employed to yield five curcumin derivatives 5a-5e. All the target compounds were characterised by 1H NMR,13C NMR and ESI-MS. Biological evaluation through the CCK-8 method indicated that nearly all these derivatives displayed higher proliferation inhibitory effect on A549 cells than that of curcumin. Among them, 5d bearing biotin moiety exhibited even stronger cytotoxicity action (2.25 μmol/L) than the positive control drug Doxorubicin (3.99 μmol/L) and therefore became the most promising lead compound for further investigation. Our findings provided a potential approach for the structural optimisation of curcumin derivatization in cancer treatment.

The realization of persistent luminescence and in particular circularly polarized luminescence (CPL) of organic radicals remains a challenge due to their sensitivity to oxygen at ambient conditions and elusive excited state chirality control. Here, it is reported that UV-irradiation on a supramolecular gel from a chiral triarylamine derivative, TPA-Ala, led to the formation of luminescent radicals with bright CPL. TPA-Ala can form an organogel in chloroform with blue emission and supramolecular chirality as demonstrated by both CD and CPL signals. Upon UV 365 nm irradiation, an emission color change from blue to cyan is observed due to the formation of photo-induced radicals. Interestingly, it is found that the supramolecular gel radicals showed stable luminescence with a lifetime approximate to 10 days in dark environments and inverted CPL, which represents a scarce example with persistent CPL from doublet-state due to oxygen isolation ability of the gel network. Furthermore, doping a guest dye, Rhodamine B (RhB), into the supramolecular gel (RhB/TPA-Ala = 30% in molar ratio) successfully obtained a transient white-light CPL through the superposition of photo-induced radical and guest dye emissions. This work provides a useful methodology for the fabrication of radical-based CPL materials via a supramolecular assembly approach.

Obesity has become a worldwide health problem. Seeking natural products with anti-obesity activity from lots of fungi has drawn the attention of pharmacologists. In our study, dipenipenoids A and B (1 and 2), the first dimeric indole-diterpenoids with a rare C-20–C-22′ linkage, and their monomers (3 and 4), were isolated from a marine-derived Penicillium sp. CF-06 fungus from Suaeda salsa. The absolute configurations of 1–3 were assigned by the calculated TDDFT ECD method. The structure of 4 was verified by a single-crystal X-ray diffraction method for the first time. Interestingly, 1 and 2 displayed significant effects on the differentiation of 3T3-L1 adipocytes by down-regulating the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha (C/EBPα) proteins, while monomers 3 and 4 exhibited no activity. Molecular docking results explained the mechanism that the interaction between dimer 1 and PPARγ was stronger than that between monomer 3 and PPARγ. Our research could provide new insight for the discovery of anti-obesity drugs.

The non-racemic enantiomers may exist with very small %ee values, which formed by some asymmetric factors (such as symmetry breaking) during their synthesis in the prebiotic pool in the absence of other chiral sources. We now conclude a mathematic formula by concerning the organic reaction principles. We found that the tiny %ee (%ee1) values of non-racemic enantiomers can be enhanced to a reasonable large %ee values (%ee2) after the non-racemic enantiomers react with bis-functional group reagents (such as oxalaldehyde). Theoretically, if the %ee1 is extremely small, the enhancement/amplification multiples (%ee2/%ee1) should increase greatly. The is necessary to enrich the %ee values in prebiotic pool for the chiral compounds (such as L-amino acids) with very small %ee values. Finally, about 1% of L-tryptophan methyl ester （L-TME） was used to react with CHOCHO, and the %ee2 of the L-TME remained in solution increased to 3.4%. The largest amplification multiple is 1.9 (from 6.1% of %ee1 to enrich to 11.7% (%ee2)); The largest increasement of the %ee (Δ%ee=%ee2-%ee1) is 12.3% (from 44.2% to 56.5%).

A general method is presented that permits enantiomers, originally present in a low enantiomeric excess (%ee1), to accumulate in a high %ee (%ee2) without a chiral source present. An equation was derived that demonstrates the final %ee2 of any unreacted chiral starting material will become higher when that starting material has reacted to generate an additional chiral center, hence forming two sets of diastereomeric enantiomeric products. Importantly, chiral amplification factor (multiples), %ee2/%ee1, depends on the yield of this reaction (p), which exhibits a nonlinear increase in amplification as p approaches 100%. This process is inevitable. It represents a possible route by which small initial %ee1 values of prebiotic molecules could have been raised to high %ee2 contents during the pre-evolution of life period on Earth, without the need for an added chiral source to be present. This predicted behavior was then experimentally verified in Pictet-Spengler reactions of L-tryptophane methyl ester (L-TME) samples present in low enantiomeric excess (%ee1) with biacetyl or oxaldehyde (model reactions) run to various yields. Each reaction generates stereoisomer products, and chiral amplification of the L-TME’s initial %ee1 values to higher %ee2 values occurs in the unreacted (recovered) L-TME. Repeated cycles of these reactions create very high L-TME %ee values. Self-cyclodimerization of low %ee1 L-amino acids with their D-enantiomers to generate L,L-, D,D- and L,D-cyclic products were computationally studied, leading to the same conclusion. Small %ee1 values are enhanced to larger %ee2 in the unreacted starting materials.