Search Results (91)

Inspired by naturally occurring bis-isochromans such as penicisteckins, we envisaged the first synthesis of biaryl-type bis-1-arylisochromans containing a stereogenic ortho-trisubstituted biaryl axis. We achieved the stereoselective synthesis of 5,5′-linked heterodimeric bis-isochromans containing both central and axial chirality elements by performing diastereoselective Suzuki–Miyaura biaryl coupling reactions on two optically active 1-arylpropan-2-ol derivatives, followed by two oxa-Pictet–Spengler cyclizations with aryl aldehydes or methoxymethyl chloride. We studied the diastereoselectivity of the cyclization step, separated the stereoisomeric products with chiral preparative HPLC and determined the absolute configuration through a combination of vibrational circular dichroism (VCD), NMR and single-crystal X-ray diffraction analysis. We demonstrated that different aryl groups could be introduced into the two isochroman subunits, since the dimethoxyaryl subunit reacted faster, enabling the two oxa-Pictet–Spengler cyclizations to be performed separately with different aryl aldehydes. We also explored the acid-catalyzed isomerization and oxidation to axially chiral ortho-quinones in order to produce stereoisomeric and oxidized analogs, respectively. We identified the antibacterial activity of our target bis-isochromans against Bacillus subtilis and Enterococcus faecalis with minimum inhibitory concentrations down to 4.0 and 0.5 μg/mL, respectively, which depend on the stereochemistry and substitution pattern of the bis-isochroman skeleton. Full article

Utilizing isomeric monomers to construct covalent organic frameworks (COFs) could easily and precisely regulate their structure in order to raise the photocatalytic performance towards two-step single-electron oxygen reduction reaction (ORR) to hydrogen peroxide (H₂O₂). Herein, isomeric anthraquinone (AQ)-based COFs (designated as 1,4-DQTP and 2,6-DQTP) were successfully fabricated through a simple yet effective one-step solvothermal synthesis approach, only utilizing isomeric monomers with alterations in the catalysts. Specifically, the black 1,4-DQTP displayed a high photocatalytic H₂O₂ production rate of 865.4 µmol g⁻¹ h⁻¹, with 2.44-fold enhancement compared to 2,6-DQTP (354.7 µmol g⁻¹ h⁻¹). Through a series of experiments such as electron paramagnetic resonance (EPR) spectroscopy and the free radical quenching experiments, as well as density functional theory (DFT) calculations, the photocatalytic mechanism revealed that compared with 2,6-DQTP, 1,4-DQTP possessed a stronger and broader visible light absorption capacity, and thus generated more photogenerated e⁻-h⁺ pairs. Ultimately, more photogenerated electrons were enriched on the AQ motif via a more apparent electron push–pull effect, which provided a stable transfer channel for e⁻ and thus facilitated the generation of superoxide anion radical intermediates (•O₂⁻). On the other hand, the negative charge region of AQ’s carbonyl group evidently overlapped with that of TP, indicating that 1,4-DQTP had a higher chemical affinity for the uptake of protons, and thus afforded a more favorable hydrogen donation for H⁺. As a consequence, the rational design of COFs utilizing isomeric monomers could synergistically raise the proton-coupled electron transfer (PCET) kinetics for two-step single-electron ORR to H₂O₂ under visible light illumination. This work provides some insights for the design and fabrication of COFs through rational isomer engineering to modulate their photocatalytic activities. Full article

Rhodopsin, a G-protein-coupled receptor (GPCR) comprising the protein opsin covalently linked to the chromophore 11-cis retinal, is pivotal in visual phototransduction. Mutations in the gene encoding rhodopsin (RHO) can cause opsin misfolding or reduce its stability, resulting in retinal degenerative disorders such as retinitis pigmentosa (RP). Current therapeutic strategies employing retinoid-based chaperones partially rescue the folding and trafficking of mutant rhodopsin, but are limited by inherent toxicity and instability due to photoinduced isomerization. In the present work, a pharmacophore-based virtual screening protocol combined with molecular docking and molecular dynamics simulations was employed, leading to the identification of a novel non-retinoid opsin ligand that can potentially act as a pharmacological chaperone. Biological validation confirmed that the compound VS1 binds opsin effectively, representing a valuable starting point for structure-based optimization studies aimed at identifying new opsin stabilizers. Full article

Unguisins, a class of structurally complex cyclic peptides featuring a γ-aminobutyric acid residue embedded in the skeleton, exhibit diverse biological activities. Here, a new unguisin K, along with three known congeners, was isolated from the marine-derived fungus Aspergillus candidus MEFC1001. The biosynthetic pathway was elucidated through gene disruption coupled with in vitro enzymatic characterization. The ugs biosynthetic gene cluster (BGC) containing ugsA and ugsB, in conjunction with an extra-clustered gene ugsC, collaborates to synthesize these unguisins. The alanine racemase (AR) UgsC catalyzes the isomerization of Ala and provides d-Ala as the starter unit for the non-ribosomal peptide synthetase (NRPS). The unique localization of ugsC outside the ugs BGC is different from previously reported unguisin-producing systems where AR genes reside within BGCs. The methyltransferase UgsB mediates a key pre-modification step by methylating phenylpyruvic acid to yield β-methylphenylpyruvate, which is subsequently incorporated as β-methylphenylalanine during NRPS assembly. This represents the first experimental evidence of the β-carbon methylation of Phe residue occurring at the precursor level rather than through post-assembly modification. The NRPS UgsA recruits a variety of amino acids for assembly and cyclization to form mature unguisins. Additionally, genome mining utilizing UgsA as a query identified homologous NRPSs in diverse fungal species, highlighting the potential for unguisin production in fungi. This study enriches the biosynthetic diversity of cyclic peptides and provides guidance for exploring unguisin-like natural products derived from fungi. Full article

Isomeric B-substituted anthracenyl and pyrenyl derivatives of ortho-carborane containing polycyclic aromatic substituents both in the position of the carborane cage most distant from the carbon atoms (position 9) and in the neighboring position (position 3) were synthesized by Pd-catalyzed cross-coupling of the corresponding iodo derivatives of ortho-carborane with polycyclic aryl zinc bromides. The derivative containing two pyrenyl substituents at the positions most distant from the carbon atoms of the ortho-carborane cage, 9,12-di(pyren-1′-yl)-ortho-carborane, was obtained in a similar way starting from 9,12-diiodo-ortho-carborane. The solid-state structures of the pyrene-containing derivatives 3-pyren-1′-yl-ortho-carborane, 9-pyren-1′-yl-ortho-carborane, and 9,12-di(pyren-1′-yl)-ortho-carborane were determined by single-crystal X-ray diffraction. Full article

The Asian larch bark beetle, I. subelongatus Motschulsky, is a severe pest of various Larix species in its natural range. This study reports the degree of similarity among cuticular hydrocarbon (CHC) profiles of six populations of I. subelongatus in northeastern China. Thirty individual or isomeric mixtures of hydrocarbons were identified by solid-phase microextraction (SPME) coupled with gas chromatography–mass spectrometry (GC–MS). The hydrocarbon components consist of straight-chain alkanes, alkenes, and methyl-branched hydrocarbons with carbon chain lengths ranging from 24 to 31. Among these, four CHCs (n-C₂₅, 9-C_27:1, n-C₂₇, and 3-meC₂₇) can serve as chemotaxonomic markers to identify I. subelongatus. No qualitative differences were detected between males and females in any of the six populations, but significant quantitative differences were observed in some CHCs. Phylogenetic analysis based on CHC profiles showed only minor differences compared to analysis based on partial mtDNA COI sequences regarding bark beetle species affinity. These results establish a rapid chemotaxonomic method and provide a basis for further investigations into the functions of CHCs in I. subelongatus. Full article

Prolyl cis/trans isomerization is a rate-limiting step in protein folding, often coupling directly to the acquisition of native structure. Here, we investigated the interplay between folding and prolyl isomerization in the N2 domain of the gene-3-protein from filamentous phage fd, which adopts a native-state cis/trans equilibrium at Pro161. Using mutational and Φ-value analysis, we identified a discrete folding nucleus encompassing the β-strands surrounding Pro161. These native-like interactions form early in the folding pathway and provide the energy to shift the cis/trans equilibrium toward the cis form. Variations distant from the Pro161-loop have minimal impact on the cis/trans ratio, underscoring the spatial specificity and localized control of the isomerization process. Using NMR spectroscopy, we determined the structures for both native N2 forms. The cis- and trans-Pro161 conformations are overall identical and exhibit only slight differences around the Pro161-loop. The cis-conformation adopts a more compact structure with improved backbone hydrogen bonding, explaining the approximately 10 kJ·mol⁻¹ stability increase of the cis state. Our findings highlight that prolyl isomerization in the N2 domain is governed by a localized folding nucleus rather than global stability changes. This localized energetic coupling ensures that proline isomerization is not simply a passive, slow step but an integral component of the folding landscape, optimizing both the formation of native structure and the establishment of the cis-conformation. Full article

This work aims to determine the mechanism of the photomechanical response of poly(Methyl methacrylate) polymer doped with the photo-isomerizable dye Disperse Red 1 using the non-isomerizable dye Disperse Orange 11 as a control to isolate photoisomerization. Samples are free-standing thin films with thickness that is small compared with the optical skin depth to assure uniform illumination and photomechanical response throughout their volume, which differentiates these studies from most others. Polarization-dependent measurements of the photomechanical stress response are used to deconvolute the contributions of angular hole burning, molecular reorientation and photothermal heating. While photo-isomerization of dopant molecules is commonly observed in dye-doped polymers, the shape changes of a molecule might not couple strongly to the host polymer through steric mechanical interactions, thus not contributing substantially to a macroscopic shape change. To gain insights into the effectiveness of such mechanical coupling, we directly probe the dopant molecules using dichroism measurements simultaneously while measuring the photomechanical response and find mechanical coupling to be small enough to make photothermal heating—mediated by the transfer of optical energy as heat to the polymer—the dominant mechanism. We also predict the fraction of light energy converted to mechanical energy using a model whose parameters are thermodynamic material properties that are measured with independent experiments. We find that in the thin-film geometry, these dye-doped glassy polymers are as efficient as any other material but their large Young’s modulus relative to other organic materials, such as liquid crystal elastomers, makes them suitable in applications that require mechanically strong materials. The mechanical properties and the photomechanical response of thin films are observed to be significantly different than in fibers, suggesting that the geometry of the material and surface effects might play an important role. Full article

In the present study, we analyzed the bioactive curcuminoids content in eight capsules (DS-1-DS-7 and DS-9), one tablet (DS-8), three ground turmeric samples (DS-10-DS-12), and three ground turmeric rhizomes (TR-1, TR-2, and TR-3). Initial screening with infrared and ultraviolet–visible spectroscopy coupled with a principal component analysis (PCA) revealed distinct differences between the samples analyzed. Hence, targeted and untargeted analyses were performed using ultra-high-performance liquid chromatography and gas chromatography coupled with mass spectrometry detections. The results show that the total curcuminoids content ranged from 1.3 to 69.8 mg/100 mg and the volatile component ranged from 0.7 to 9.1 mg/100 mg. The percentage ratio of the three prominent curcuminoids, bisdesmethoxycurcumin (BMC), desmethoxycurcumin (DMC), and curcumin (CUR), also varied remarkably compared to the expected ratio (BMC:DMC:CUR ratio of 1:2:6) described in the literature. The three prominent volatile compounds identified in most samples were ar-turmerone, turmerone, and curlone. The results demonstrated significant differences in the volatile compound levels among the DS and dried rhizome samples. The non-targeted analysis resulted in the identification of over 40 compounds, including bioactives such as piperine, phenolic acids, and amino acids. A disintegration study was performed on limited DS according to the United States Pharmacopeia protocol. The results reveal that all the selected DS samples passed the disintegration test. An analysis of curcuminoids from DS samples in neutral and acidic solutions demonstrated that all curcuminoids (BMC, DMC, and CUR) existed in the keto and enol forms and their concentrations changed with pH. This study will be of significant interest to manufacturers, consumers, and pharmacologists to accurately understand the bioactivities of three curcuminoids in different isomeric forms. Full article

Biliverdin reductase B (BLVRB) is a redox regulator that catalyzes nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductions of multiple substrates, including flavins and biliverdin-β. BLVRB has emerging roles in redox regulation and post-translational modifications, highlighting its importance in various physiological contexts. In this study, we explore the structural and functional differences between human BLVRB and its hyrax homologue, focusing on evolutionary adaptations at the active site and allosteric regions. Using NMR spectroscopy, we compared coenzyme binding, catalytic turnover, and dynamic behavior between the two homologues. Despite lacking the arginine “clamp” present in human BLVRB, hyrax BLVRB still undergoes conformational changes in response to the oxidative state of the coenzyme. Mutations at the allosteric site (position 164) show that threonine at this position enhances coenzyme discrimination and allosteric coupling in human BLVRB, while hyrax BLVRB does not display the same allosteric effects. Relaxation experiments revealed distinct dynamic behaviors in hyrax BLVRB, with increased flexibility in its holo form due to the absence of the clamp. Our findings suggest that the evolutionary loss of the active site clamp and modifications at position 164 in hyrax BLVRB alter the enzyme’s conformational dynamics and coenzyme interactions. Identified similarities and differences underscore how key regions modulate catalytic efficiency and suggest that coenzyme isomerization may represent the rate-limiting step in both homologues. Full article

In this paper, we define and investigate a system of coupled regular diffusion equations in which each concentration acts as a driving term in the next diffusion equation. Such systems can be understood as a kind of cascade process which appear in different fields of physics like diffusion and reaction processes or turbulence. As a solution, we apply the time-dependent self-similar Ansatz method, the obtained solutions can be expressed as the product of a Gaussian and a Kummer’s function. This model physically means that the first diffusion works as a catalyst in the second diffusion system. The coupling of these diffusion systems is only one way. In the second part of the study we investigate mutually coupled diffusion equations which also have the self-similar trial function. The derived solutions show some similarities to the former one. To make our investigation more complete, different kinds of couplings were examined like the linear, the power-law, and the Lorentzian. Finally, a special coupling was investigated which is capable of describing isomerization with temporal decay. Full article

Long-range HNCO NMR spectra for proteins show crosspeaks due to ¹J_NC′, ²J_NC′, ³J_NCγ, and ^h3J_NC′ couplings. The ^h3J_NC′ couplings are transmitted through hydrogen bonds and their sizes are correlated to hydrogen bond lengths. We collected long-range HNCO data at a series of temperatures for four protein structures. P22i and CUS-3i are six-stranded beta-barrel I-domains from phages P22 and CUS-3 that share less than 40% sequence identity. The cis and trans states of the C-terminal domain from pore-forming toxin hemolysin ΙΙ (HlyIIC) arise from the isomerization of a single G404-P405 peptide bond. For P22i and CUS-3i, hydrogen bonds detected by NMR agree with those observed in the corresponding domains from cryoEM structures of the two phages. Hydrogen bond lengths derived from the ^h3J_NC′ couplings, however, are poorly conserved between the distantly related CUS-3i and P22i domains and show differences even between the closely related cis and trans state structures of HlyIIC. This is consistent with hydrogen bond lengths being determined by local differences in structure rather than the overall folding topology. With increasing temperature, hydrogen bonds typically show an apparent increase in length that has been attributed to protein thermal expansion. Some hydrogen bonds are invariant with temperature, however, while others show apparent decreases in length, suggesting they become stabilized with increasing temperature. Considering the data for the three proteins in this study and previously published data for ubiquitin and GB3, lowered protein folding stability and cooperativity corresponds with a larger range of temperature responses for hydrogen bonds. This suggests a partial uncoupling of hydrogen bond energetics from global unfolding cooperativity as protein stability decreases. Full article

1,2-Dihydroisoquinolines are important compounds due to their biological and medicinal activities, and numerous approaches to their synthesis have been reported. Recently, we reported a facile synthesis of trisubstituted allenamides via N-acetylation followed by DBU-promoted isomerization, where various substituted allenamides were conveniently synthesized from readily available propargylamines with high efficiency. In light of this research background, we focused on the utility of this methodology for the synthesis of substituted 1,2-dihydroisoquinolines. In this study, a palladium-catalyzed cascade cyclization–coupling of trisubstituted allenamides containing a bromoaryl moiety with arylboronic acids is described. When N-acetyl diphenyl-substituted trisubstituted allenamide and phenylboronic acid were treated with 10 mol% of Pd(OAc)₂, 20 mol% of P(o-tolyl)₃, and 5 equivalents of NaOH in dioxane/H₂O (4/1) at 80 °C, the reaction proceeded to afford a substituted 1,2-dihydroisoquinoline. The reaction proceeded via intramolecular cyclization, followed by transmetallation with the arylboronic acid of the resulting allylpalladium intermediate. A variety of highly substituted 1,2-dihydroisoquinolines were concisely obtained using this methodology because the allenamides, as reaction substrates, were prepared from readily available propargylamines in one step. Full article

The geometrical r_e parameters of trans-azobenzene (E-AB) free molecule were refined by gas electron diffraction (GED) method using available experimental data obtained previously by S. Konaka and coworkers. Structural analysis was carried out by various techniques. First of all, these included the widely used molecular orbital constrained gas electron diffraction method and regularization method. The results of the refinements using different models were also compared—a semirigid model, three variants of one-dimensional dynamic models, and a two-dimensional pseudoconformer model. Several descriptions have been used due to the fact that E-AB has a shallow potential energy surface along the rotation coordinates of phenyl groups. Despite this, it turned out that the semirigid model is suitable for use for E-AB and allows good agreement with experimental data to be achieved. According to the results of GED structural analysis, coupled with the results of DLPNO-CCSD(T0) calculations, E-AB has a planar structure. Based only on GED data, it is impossible to unambiguously determine the rotational angle of the phenyl group due to the facts that (i) with rotation over a wide range of angles, the bonded distances in the molecule change insignificantly and (ii) potential function in a structural analysis within a dynamic model is not determined with the necessary accuracy. This work also examines the sensitivity of the GED method to structural changes caused by trans-cis isomerization. The paper also analyzes the applicability of different variants of density functional theory (DFT) calculations in GED structural analysis using E-AB as an example. There are not enough similar methodological works in the literature. This experimental and methodological information is especially important and relevant for planning and implementing GED experiments and corresponding processing of the results for azobenzene derivatives, in which the conformer and isomeric diversity are even more complicated due to the presence of different substituents. Full article

The relationship between the structure characteristics and performances of coal-based hydrogenation isomeric (CTL) base oil and metallocene-catalyzed coal-based poly-alpha-olefin (mPAO) base oil is clarified in this paper. CTL and mPAO were compared with typical petroleum-based and natural gas-based commercial API III and IV base oils. Pressurized differential scanning calorimetry (PDSC), the rotary bomb oxidation test (RBOT), and a four-ball friction tester were used to evaluate the oxidation stability and lubrication performance of base oils under different working conditions. The sensitivity of different base oils to typical antioxidants and extreme-pressure antiwear agents was compared. In particular, the composition and structure of CTL base oil are clearly different from GTL and mineral base oil. The coal-based CTL and mPAO base oils exhibit commendable viscosity–temperature properties, coupled with low-temperature fluidity, fire safety, and minimal evaporation loss. The lubricating properties, oxidation stability, and sensitivity to extreme-pressure antiwear agents of CTL are close to those of similar base oils. However, the sensitivity of CTL to typical antioxidants is relatively poor. In addition, compared with commercial PAO base oil, mPAO has a lower isomerization degree and fewer isomerization types. The oxidation stability and sensitivity to typical antioxidants of mPAO base oil are comparable with those of commercial PAO base oil, while its lubrication performance and sensitivity to typical extreme-pressure antiwear agents are significantly better than those of commercial PAO base oil. Full article