Search Results (173)

A new bicyclic polyketide, amesilide (1), along with the previously reported metabolites, chamisides A (2), B (3), and E (4), chaetoconvosins B (5) and C (6), and chaetochromins A (7) and B (8), were isolated from the marine fungus Amesia nigricolor MUT6601. The structures of the compounds were determined by extensive spectrometric (HRMS) and spectroscopic (1D and 2D NMR) analyses, as well as specific rotation. Absolute configurations of the stereogenic centers of amesilide (1) were determined by a comparison of its experimental circular dichroism (CD) spectrum with its time-dependent density functional theory (TD-DFT) electronic circular dichroism (ECD) spectra. Among them, chaetochromins A (7) and B (8) showed strong antibacterial activity against Staphylococcus aureus S25 (MBC values of 12.50 µM and MIC values of 6.25 µM) and a moderate cytotoxicity against monocytes (THP-1) and peripheral blood cells (PBMC) (IC₅₀ values of 33.65–40.01 µM). Full article

The EGCG/PPN composite, prepared by combining pea protein nanofibrils (PPNs) with epigallocatechin gallate (EGCG), could be used as a multifunctional nanocarrier. Compared to pea protein isolate (PPI), EGCG/PPN composites exhibited remarkably higher turbidity and zeta potential, along with similar UV spectra. Intrinsic fluorescence spectroscopy, ThT fluorescence spectroscopy, and surface hydrophobicity analysis suggested that the interactions between EGCG and PPN were primarily driven by hydrophobic forces. UV spectra indicated that the microenvironment of amino acid residues in the tertiary structure of the protein changes upon complexation, and circular dichroism (CD) revealed that the incorporation of EGCG increases the β-sheet content in the protein’s secondary structure. Analyses of DPPH and ABTS radical scavenging activity, as well as reducing power, demonstrated that the synergistic effect between EGCG and PPN did not hinder the inherent antioxidant properties of EGCG but rather enhanced them significantly. Transmission electron microscopy (TEM) images showed that the addition of EGCG reconstructed the fibril morphology, thereby affecting the properties of PPNs. Overall, the composite fabricated through the interaction between PPN and EGCG shows great potential as a nanocarrier in the processing of functional foods. Full article

Background/Objective: Avapritinib is an orally bioavailable tyrosine kinase inhibitor and was approved by the FDA in 2020 for gastrointestinal stromal tumor treatments. Although avapritinib is known to be chiral, its stereochemistry was initially established randomly. This study aims to develop a definitive method for determining avapritinib’s absolute configuration and propose a universal methodology for stereochemical characterization of flexible chiral drugs. Methods: The absolute configuration of avapritinib was determined through an integrated approach combining chiral resolution, chiroptical spectroscopy and synthetic validation. Enantiomeric separation was achieved via chiral liquid chromatography, followed by comprehensive chiroptical characterization including electronic circular dichroism (ECD), specific optical rotation and optical rotatory dispersion. Conformational analysis and density functional theory (DFT) calculations correlated experimental spectra with theoretical predictions, facilitating definitive configurational assignment. The stereochemical determination were further verified through ECD derivatization and chemical synthesis. Finally, the enantiomers’ kinase inhibition profiles against c-KIT D816V were quantitatively assessed. Results: Two enantiomers of avapritinib were resolved via chiral HPLC and a Chiralpak IG column. Through combined experimental ECD spectra and time-dependent DFT calculations employing the core extraction method, the levo-isomer was unambiguously determined as S configuration. This stereochemical assignment was confirmed by p-cyanobenzaldehyde derivatization and de novo synthesis. Biological evaluation revealed (S)-(−)-avapritinib exhibited superior c-KIT D816V inhibitory activity compared to its (R)-(+)-counterpart, a finding corroborated by molecular docking studies elucidating their differential target interactions. Conclusions: This study advances avapritinib stereochemical understanding and establishes a definitive protocol for its absolute configuration assignment, serving as a paradigm for flexible chiral drug characterization. Full article

Chemical investigation on the whole herb of Peperomia heyneana Miq. resulted in the isolation of six lignans, including two previously undescribed compounds, named peperomianan A and B (1–2), and four known compounds, 1,2-cyclobutanedicarboxylic acid (3), (+)-medioresinol (4), (+)-pinoresinol (5), and (+)-yangambin (6). Their structures were established by extensive spectroscopic analyses. The absolute configuration of compound 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Subsequently, the effects of all isolates on BPH-1 cells were evaluated in vitro by MTT assay. Full article

A spherical amide with C₃ symmetry was synthesized by a one-step cyclization reaction using triphenylphosphine and hexachloroethane as coupling reagents. This method enabled synthesis of N-benzyl and N-allyl derivatives, which could not be obtained by the previously reported method. The optical resolution of each compound was measured, and their electronic circular dichroism spectra revealed that they were mirror images. The high structural symmetry resulted in a higher Δε (molar absorption difference against right or left circular polarization: ε_L − ε_R value compared to that of another structural isomer synthesized previously. The absolute structure of the enantiopure crystal of the N-benzyl derivative was determined using the Flack parameter obtained by X-ray crystallographic analysis. Full article

Vibrational circular dichroism (VCD) enhancement by low-lying electronic states (LLESs) is a fascinating phenomenon, but accounting for it theoretically remains a challenge despite significant research efforts over the past 20 years. In this article, we synthesized two transition metal complexes using the tetradentate Schiff base ligands (R,R)- and (S,S)-N,N′-Bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine with Co(II) and Mn(III), referred to as Co(II)-salen-chxn and Mn(III)-Cl-salen-chxn, respectively. Their stereochemical properties were explored through a combined experimental chiroptical spectroscopic and theoretical approach, with a focus on Co(II)-salen-chxn. Extensive conformational searches in CDCl₃ for both high- and low-spin states were carried out and the associated infrared (IR), VCD, ultraviolet-visible (UV-Vis) absorption, and electronic circular dichroism (ECD) spectra were simulated. A good agreement between experimental and simulated data was achieved for IR, VCD, UV-Vis, and ECD, except in the case of VCD of Co(II)-salen-chxn which exhibits significant intensity enhancement and monosignate VCD bands, attributed to the LLESs. Interestingly, detailed comparisons with Mn(III)-Cl-salen-chxn and previously reported Ni(II)-salen-chxn and Cu(II)-salen-chxn complexes suggest that the enhancement factor is predicted by the current density functional theory simulations. However, the monosignate signatures observed in the experimental Co(II) VCD spectrum were not captured theoretically. Based on the experiment and theoretical VCD and ECD comparison, it is tentatively suggested that Co(II)-salen-chxn exists in both low- and high-spin states, with the former being dominant, while Mn(III)-Cl-salen-chxn in the high-spin state. The study indicates that VCD enhancement by LLESs is at least partially captured by the existing theoretical simulation, while the symmetry consideration in vibronic coupling provides further insight into the mechanisms behind the VCD sign-flip. Full article

The fruits of Phyllanthus acidus, rich in various secondary metabolites and possessing significant antioxidant activity, have been consumed widely by many Southeast Asian people, including the Thai, Vietnamese, Burmese, Laotians, and Cambodians. An extensive investigation of the secondary metabolites of the fruits resulted in our obtaining 17 compounds, including four new compounds (1–4). The absolute configurations of 1, 3, and 4 were determined by comparing their experimental electronic circular dichroism (ECD) spectra with both reference data and computed ECD profiles. At a concentration of 40μM, terpenoids (1 and 5–9) showed no cytotoxic activity against five strains of human tumor cells and one of normal cells. Notably, the known lignan 13 and phenylpropanoid 15 showed obvious ABTS⁺ radical scavenging activities with IC₅₀ values of 203.7 and 232.9 μM, which have a comparable impact to the positive control, Trolox (IC₅₀ = 176.5 ± 2.0 μM). The results indicated that P. acidus fruits could be a promising sources of antioxidant food supplement. Full article

This study investigates the synthesis and characterization of alkyne-based multilayered three-dimensional (3D) polymers, which exhibit a subtle aggregation-induced emission (AIE) phenomenon. The polymers demonstrate significant potential as fluorescent probes for the selective detection of chromium (VI) ions (Cr⁶⁺), showcasing their utility in environmental sensing applications. Additionally, the circular dichroism (CD) spectra reveal a pronounced cotton effect, indicative of chiral properties, while scanning electron microscopy (SEM) and dynamic light scatting (DLS) analysis reveal a distinctive rock-like surface morphology and Cr⁶⁺ sensitive anti-aggregation. These findings highlight the multifunctional capabilities of alkyne-based multilayered 3D polymers, suggesting their applicability in both fluorescence-based sensing and materials science. The insights gained from this research contribute to the development of advanced materials with tailored optical properties for environmental monitoring and other practical applications. Full article

Hydantoins, a class of five-membered heterocyclic compounds, exhibit diverse biological activities. The aim of this study was to synthesize and characterize a series of novel 3,5-disubstituted hydantoins and to investigate their antiproliferative activity against human cancer cell lines. The new hydantoin derivatives 5a–i were prepared as racemic mixtures of syn- and anti-isomers via a base-assisted intramolecular amidolysis of C-3 functionalized β-lactams. The enantiomers of syn-5a and anti-hydantoins 5b were separated by preparative high-performance liquid chromatography (HPLC) using n-hexane/2-propanol (90/10, v/v) as the mobile phase. The absolute configuration of the four allyl hydantoin enantiomers 5a was assigned based on a comparison of the experimental electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectra with those calculated using density functional theory (DFT). The antiproliferative activity evaluated in vitro against three different human cancer cell lines: HepG2 (liver hepatocellular carcinoma), A2780 (ovarian carcinoma), and MCF7 (breast adenocarcinoma), and on the non-tumor cell line HFF1 (normal human foreskin fibroblasts) using the MTT cell proliferation assay. In silico drug-like properties and ADMET profiles were estimated using the ADMET Predictor ver. 9.5 and the online server admetSAR. Eighteen new 3,5-disubstituted hydantoins were synthesized and characterized. The compound anti-5c showed potent cytotoxic activity against the human tumor cell line MCF7 (IC₅₀ = 4.5 µmol/L) and the non-tumor cell line HFF1 (IC₅₀ = 12.0 µmol/L). In silico analyzes revealed that the compounds exhibited moderate water solubility and membrane permeability and are likely substrates for CYP3A4 and P-glycoprotein and have a high probability of antiarthritic activity. Full article

Four new alkaloids, vibripyrrolidine A (1), vibripiperazine A (2), and vibridiazinane A, B (3, 4), comprising one pyrrolidine, one piperazine, and two diazinane alkaloids, along with two known analogs (5, 6), were isolated from the marine bacterium Vibrio ruber ZXR-93 cultured in ISP2 medium. Their chemical structures were elucidated by analysis of their 1D and 2D NMR, mass spectra, and electronic circular dichroism (ECD) calculations. Compounds 1 and 3–6 showed vigorous antibacterial activity against Staphylococcus aureus, with MIC values ranging from 0.96 to 7.81 μg/mL. Moreover, compound 1 exhibited robust anti-inflammatory activity in vitro using the LPS-induced RAW264.7 macrophage model. All compounds also showed moderate antineoplastic activity against cervical cancer cells (HeLa) and gastric cancer cells (SGC-7901). Full article

Five new diterpenes including four diterpenes with 1,2,3,4,4a,5,6,8a-octalin skeleton talaroacids A–D (1–4) and an isopimarane diterpenoid talaromarane A (5) were isolated from the mangrove endophytic fungus Talaromyces sp. JNQQJ-4. Their structures and absolute configurations were determined by analysis of high-resolution electrospray ionization mass spectroscopy (HRESIMS), 1D/2D Nuclear Magnetic Resonance (NMR) spectra, single-crystal X-ray diffraction, quantum chemical calculation, and electronic circular dichroism (ECD). Talaromarane A (5) contains a rare 2-oxabicyclo [3.2.1] octan moiety in isopimarane diterpenoids. In bioassays, compounds 1, 2, 4, and 5 displayed significant anti-inflammatory activities with the IC₅₀ value from 4.59 to 21.60 μM. Full article

A simplified molecular-dynamics-based electronic circular dichroism (ECD) approach was tested on three condensed derivatives with limited conformational flexibility and an isochroman-2H-chromene hybrid, the ECD spectra of which could not be precisely reproduced by the conventional ECD calculation protocol. Application of explicit solvent molecules at the molecular mechanics (MD) level in the dynamics simulations and subsequent TDDFT-ECD calculation for the unoptimized MD structures was able to improve the agreements between experimental and computed spectra. Since enhancements were achieved even for molecules with limited conformational flexibility, deformations caused by the solvent molecules and multitudes of conformers produced with unoptimized geometries seem to be key factors for better agreement. The MD approach could confirm that aggregation of the phenanthrene natural product luzulin A had a significant contribution to a specific wavelength range of the experimental ECD. The MD approach has proved that dimer formation occurred in solution and this was responsible for the anomalous ECD spectrum. The scope and limitations of the method have also been discussed. Full article

Self-assembled peptide-based nanobiomaterials exhibit promising prospects for drug delivery applications owing to their commendable biocompatibility and biodegradability, facile tissue uptake and utilization, and minimal or negligible unexpected toxicity. TFF3 is an active peptide autonomously secreted by gastric mucosal cells, possessing multiple biological functions. It acts on the surface of the gastric mucosa, facilitating the repair process of gastric mucosal damage. However, when used as a drug, TFF3 faces significant challenges, including short retention time in the gastric mucosal cavity and deactivation due to degradation by stomach acid. In response to this challenge, we developed a self−assembled short peptide hydrogel, Rqdl10, designed as a delivery vehicle for TFF3. Our investigation encompasses an assessment of its properties, biocompatibility, controlled release of TFF3, and the mechanism underlying the promotion of gastric mucosal injury repair. Congo red/aniline blue staining revealed that Rqdl10 promptly self-assembled in PBS, forming hydrogels. Circular dichroism spectra indicated the presence of a stable β-sheet secondary structure in the Rqdl10 hydrogel. Cryo-scanning electron microscopy and atomic force microscopy observations demonstrated that the Rqdl10 formed vesicle-like structures in the PBS, which were interconnected to construct a three-dimensional nanostructure. Moreover, the Rqdl10 hydrogel exhibited outstanding biocompatibility and could sustainably and slowly release TFF3. The utilization of the Rqdl10 hydrogel as a carrier for TFF3 substantially augmented its proliferative and migratory capabilities, while concurrently bolstering its anti-inflammatory and anti-apoptotic attributes following gastric mucosal injury. Our findings underscore the immense potential of the self-assembled peptide hydrogel Rqdl10 for biomedical applications, promising significant contributions to healthcare science. Full article

This study explores the quantum size effects on the optical properties of pillar[n]arene (n = 5, 6, 7, 8) utilizing density functional theory (DFT) and wave function analysis. The mechanisms of electron transitions in one-photon absorption (OPA) and two-photon absorption (TPA) spectra are investigated, alongside the calculation of electron circular dichroism (ECD) for these systems. Transition Density Matrix (TDM) and electron–hole pair density maps are employed to study the electron excitation characteristics, unveiling a notable size dependency. Analysis of the transition electric dipole moment (TEDM) and the transition magnetic dipole moment (TMDM) reveals the electromagnetic interaction mechanism within pillar[n]arene. Raman spectra computations further elucidate vibrational modes, while interactions with external environments are studied using electrostatic potential (ESP) analysis, and electron delocalization is assessed under an external magnetic field, providing insights into the magnetically induced current phenomena within these supramolecular structures. The thermal stability of pillar[n]arene was investigated by ab initio molecular dynamics (AIMD). Full article

Effects of different ionic strengths (0.2, 0.4, and 0.6 mol/L) and different hydrodynamic cavitation (HC) treatment times (0, 1, 2, 3, and 4 min) on the conformation and gel properties of tilapia myofibrillar proteins (TMP) were investigated. The results showed that the solubility of TMP was significantly enhanced (p < 0.05) with the increase in NaCl concentration, and the gel characteristics were significantly improved. After HC treatment of TMP, the average particle size was significantly reduced (p < 0.05) and solubility was significantly enhanced (p < 0.05) with the increase in treatment time, the internal hydrophobic groups and reactive sulfhydryl groups were exposed. The intrinsic fluorescence spectra showed the unfolding of the spatial tertiary structure of proteins, and the circular dichroism spectroscopy showed the significant reduction in the content of α-helix in the secondary structure of the proteins (p < 0.05). In addition, the WHC and gel strength of the TMP heat-induced gels were enhanced, which improved the microstructure of the gels, and scanning electron microscopy showed that the gel network of the TMP gels became denser and more homogeneous. Dynamic rheology results showed that HC treatment resulted in a significant increase in the final G’ and G” values of TMP. In conclusion, HC treatment was able to improve the physicochemical structure and gel properties of TMP at different ionic strengths. This study presents a novel processing technique for the quality maintenance aspect of salt-reduced surimi gel products. Full article