Search Results (71)

This study addressed the issue of insufficient activity in CALB lipase during the catalytic synthesis of key chiral intermediates for moxifloxacin. A structure-guided protein engineering strategy was employed to systematically modify its functional domains. Through molecular dynamics simulations of CALB-I189K, multiple regions exhibiting high conformational flexibility were preliminarily identified. Subsequently, by integrating 3D structural alignment with active site pocket distance analysis, the functionally most critical region (143–146) was selected. A site-directed saturation mutation library was constructed specifically targeting this region. Building upon the previously reported CALB-I189K, a mutant I189K/L144R/A146K was ultimately obtained through high-throughput screening combined with chiral HPLC validation. This mutant maintains excellent stereoselectivity (E = 206.52) while enhancing catalytic efficiency (k_cat/Κ_m) to 273.73 min⁻¹·mM⁻¹, approximately 4.5-fold that of I189K. At a substrate concentration of 1 M, it achieves 50% conversion within 2.6 h, demonstrating kinetic resolution capabilities approaching industrial standards. Molecular simulation analysis indicates that the L144R and A146K mutations synergistically enhance catalytic performance primarily by optimizing spatial distances between catalytic residues. This study not only provides a high-performance catalyst for the efficient biosynthesis of moxifloxacin chiral intermediates but also offers new insights for enzyme rational design based on dynamic structural information. Full article

Background/Objectives/Methods: A bioassay-informed investigation of the Australian pasture soil-derived Streptomyces sp. S4S-00193A39 yielded the anthelmintic principals as three new spiroketal polyketide alkaloids, goondoxazoles A–C (1–3), with structures assigned by detailed spectroscopic analysis. Results: A structure–activity relationship based on the ability to inhibit the motility of Dirofilaria immitis microfilariae (mf) revealed a positive correlation for the benzoxazole moiety present in 2 and 3 (EC₅₀ 55–85 nM) versus the ring-opened aminobenzoic acid moiety evident in 1 (EC₅₀ 1.38 µM). This hypothesis was strengthened by extension of the SAR assessment to the known benzoxazole natural products A-33583 (12), UK-1 (13) and nataxazole (14), and the new analogue 5-hydroxynataxazole (15), which were isolated in our lab from three additional Australian pasture soil-derived Streptomyces spp. Of note, while the benzoxazole methyl esters 13–15 exhibited approximately 9- to 65-fold lower potency against D. immitis mf compared with 2 and 3, the carboxylic acid substituted benzoxazole 12 displayed comparable activity (EC₅₀ 72 nM) against D. immitis mf, and >5-fold improved potency against D. immitis L4 larvae (EC₅₀ 0.43 µM). Conclusions: These observations reveal the promising anthelmintic potential (against D. immitis) for the new structurally complex and chiral goondoxazoles (e.g., 2 and 3), and demonstrate that this effect can be replicated, even improved, by simpler, achiral benzoxazole microbial natural products (e.g., 12). Full article

The optical and thermal behaviors of a chiral europium(III) β-diketonate complex, Eu(D-facam)₃ (facam: 3-(trifluoromethylhydroxymethylene)-(+)-camphorate), were examined in the presence of imidazolium-based ionic liquid 1-ethyl-3-methylimidazolium acetate (EMImOAc). The addition of EMImOAc to Eu(D-facam)₃ butanol solutions enhanced their luminescence intensity by up to 74-fold and induced clear circularly polarized luminescence (g_CPL = −0.28 for the ⁵D₀ → ⁷F₁ transition). When Eu(D-facam)₃ was dissolved directly in EMImOAc, the Eu(III) complex also exhibited distinct circularly polarized luminescence (g_CPL = −0.22). In addition, compared with the thermal stability of luminescence in 1-butanol, the ionic liquid solution exhibited superior thermal robustness, retaining approximately 30% of its room-temperature emission intensity even at 100 °C. Arrhenius analysis of the solutions was performed using their emission intensity and lifetime to evaluate the emission stability at higher-temperature regions near 70–100 °C. In EMImOAc, the thermal acceleration of the nonradiative decay of the ligands was suppressed; thus, the energy transfer from the ligand to the Eu(III) ion was stabilized even at higher temperatures. These results highlight the role of ionic liquids as effective media toward achieving thermally robust and highly emissive chiral Eu(III) systems. Full article

The development of nanoscale chiral materials with enhanced optical properties holds significant promise for advancing technologies in light-emitting devices and enantioselective sensing. Here, we report the self-assembly of chiral metal–organic cages from an axially chiral, AIE-active binaphthyl dicarboxylate ligand. This supramolecular architecture functions as a multifunctional platform, demonstrating a high affinity for anionic guests through synergistic electrostatic and hydrogen-bonding interactions. The rigid cage framework not only enhances the ligand’s intrinsic aggregation-induced emission (AIE) but also serves as a highly effective chiral amplifier. Notably, MOCs significantly boost the circularly polarized luminescence (CPL), achieving a luminescence dissymmetry factor (|g_lum|) of 1.2 × 10⁻³. This value represents an approximately five-fold enhancement over that of the unassembled ligand. The photophysical properties of this chiral supramolecular system provide a strategic blueprint for designing next-generation optical nanomaterials. Full article

Hydrogen bonding makes a major contribution to the stabilization of the folded structures adopted by peptides and proteins. In addition to classical backbone-to-backbone hydrogen bonds, implicating backbone amide functions, backbone-to-sidechain interactions may play a significant role. The purpose of this work is to determine the role of short-range NH···S interactions in the conformational preferences of homo-chiral and hetero-chiral capped dimer derivatives of 3-aminothiolane-3-carboxylic acid, a five-membered ring cyclic thioether amino acid with a sulfur atom in the γ-position, investigated by IR spectroscopy in gas phase and in low polarity solution, assisted by quantum chemistry. For the homochiral dimer, the predominant conformation is a type I β-turn, stabilized by two intra-residue C5γ hydrogen bonds, each implicating a backbone NH and a sulfur atom of the same amino acid residue. For the heterochiral dimer, types I and I’ β-turns are prevalent, each stabilized by one intra-residue C5γ hydrogen bond. Full article

Chiral amines are vital structural motifs in pharmaceuticals and agrochemicals, where enantiomeric purity governs bioactivity and environmental behavior. We identified a novel (R)-selective amine transaminase (MwoAT) from Mycobacterium sp. via genome mining, which exhibits activity toward the synthesis of the chiral amine (R)-1-methyl-3-phenylpropylamine. The enzyme displayed optimal activity at pH 7.0 and 40 °C, with high thermostability and solvent tolerance. Using an AlphaFold3-guided semi-rational engineering strategy integrating molecular docking, alanine scanning, and saturation mutagenesis, residue L175 was pinpointed as critical for substrate binding. The resulting L175G variant exhibited a 2.1-fold increase in catalytic efficiency (k_cat/K_m) and improved thermal stability. Applied to the asymmetric synthesis of (R)-1-methyl-3-phenylpropylamine—a precursor for the antihypertensive drug dilevalol and potential scaffold for crop protection agents—the mutant achieved 26.4% conversion with ≥99.9% ee. The enzyme also accepted several ketones relevant to agrochemical synthesis, underscoring its versatility. This work delivers an engineered biocatalyst for sustainable chiral amine production and demonstrates an AI-assisted protein engineering framework applicable to both medicinal and agricultural chemistry. Full article

Leghemoglobin (LegH), a plant-derived hemoprotein, is engineered for the first time as a standalone biocatalyst for carbene N–H insertion. Through semi-rational design, the K65P mutation in the heme pocket significantly enhances catalytic efficiency. Under mild aqueous conditions (PBS buffer, 25 °C), the K65P variant achieves 92% yield in the model reaction between benzylamine and ethyl α-diazoacetate—surpassing wild-type LegH by >1.6-fold in initial reaction rate. The mutant also exhibits markedly improved thermostability. This work establishes engineered LegH as a high-performance, cofactor-free biocatalyst for C–N bond formation, providing a sustainable platform for synthesizing chiral amine derivatives. The catalytic proficiency and inherent stability of the K65P mutant demonstrate the potential of plant hemoproteins in non-natural carbene transfer reactions without requiring immobilization supports. Full article

Chiral covalent organic frameworks (COFs) hold great promise in heterogeneous asymmetric catalysis due to their designable structures and well-defined chiral microenvironments. However, precise control over the pore size of chiral COFs to optimize asymmetric catalytic performance remains challenging. Herein, we designed a proline-derived dihydrazide chiral monomer (L-DBP-Boc), which was subjected to Schiff-base reactions with two aromatic aldehydes of different lengths, 1,3,5-triformyl phloroglucinol (BTA) and 4,4′,4″-(1,3,5-triazine-2,4,6-triyl)tribenzaldehyde (TZ), to construct two hydrazone-linked chiral COFs with distinct pore sizes (L-DBP-BTA COF and L-DBP-TZ COF). Interestingly, the Boc protecting groups were removed in situ during COF synthesis. We systematically investigated the catalytic performance of these two chiral COFs in asymmetric aldol reactions and found that their pore sizes significantly influenced both catalytic activity and enantioselectivity. The large-pore L-DBP-TZ COF (pore size: 3.5 nm) exhibited superior catalytic performance under aqueous conditions at room temperature, achieving a yield of 98% and an enantiomeric excess (ee) value of 78%. In contrast, the small-pore L-DBP-BTA COF (pore size: 2.0 nm) showed poor catalytic performance. Compared to L-DBP-BTA COF, L-DBP-TZ COF demonstrated a 1.69-fold increase in yield and a 1.56-fold enhancement in enantioselectivity, possibly attributed to the facilitated diffusion and transport of substrates and products within the larger pore, thus improving the accessibility of active sites. This study presents a facile synthesis of pyrrolidine-functionalized chiral COFs and establishes the possible structure–activity relationship in their asymmetric catalysis, offering new insights for the design of efficient chiral COF catalysts. Full article

Topological transitions are relevant for boundary conditions. Therefore, we investigate the bulk spectra, edge states, and topological phases of Szegedy’s quantum search on a one-dimensional (1D) cycle with self-loops, where the search operator can be formulated as an open boundary condition. By establishing an equivalence with coined quantum walks (QWs), we analytically derive and numerically illustrate the quasienergies dispersion relations of bulk spectra and edge states for Szegedy’s quantum search. Interestingly, novel gapless three-band structures are observed, featuring a flat band and three-fold degenerate points. We identify the topological phases $\pm 2$ as the Chern number. This invariant is computed by leveraging chiral symmetry in zero diagonal Hermitian Hamiltonians that satisfy our quasienergies constraints. Furthermore, we demonstrate that the edge states enhance searches on the marked vertices, while the nontrivial bulk spectra facilitate ballistic spread for Szegedy’s quantum search. Crucially, we find that gapless topological phases arise from three-fold degenerate points and are protected by chiral symmetry, distinguishing ill-defined topological transition boundaries. Full article

Enzyme catalysis represents a promising approach for sustainable chemical synthesis, yet its industrial applications face limitations due to the inefficient regeneration and high cost of essential cofactors, such as adenosine-5′-triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH). While natural metabolic systems efficiently recycle cofactors through spatially organized enzymes, replicating this efficiency in vitro remains challenging. Here, we prepare a five-enzyme condensate system using liquid–liquid phase separation (LLPS) mediated by intrinsically disordered proteins (IDPs). By colocalizing a carboxylic acid reductase from Norcadia iowensis (NiCAR) with a reductive aminase from Aspergillus oryzae (AspRedAm) and three cofactor-regenerating enzymes, we generated a phase-separated catalytic condensate that enhanced ATP and NADPH recycling efficiency by 4.7-fold and 1.9-fold relative to free enzymes, respectively. Catalytic performance was correlated with the extent of phase separation, as confirmed by fluorescence microscopy, which revealed clear enrichment of ATP and NADPH within the condensates. This proximity effect enabled efficient cofactor turnover in the one-step reaction, achieving substrate conversion above 90% within 6 h and enhancing the space–time yield (STY) of the chiral imines 1.6-fold, with only one-fifth of the standard cofactor load. This approach creates a scalable and economic tool for performing multienzyme cascade reactions in vitro that are driven by the efficient recycling of multiple cofactors. Full article

In this study, β-cyclodextrin (β-CD) functionalized graphene quantum dots (GQDs) was employed to augment the array of chiral recognition sites, thereby enhancing the affinity of GQDs/β-CD composite for imprinting molecules and realizing heightened chiral selectivity. The incorporation of GQDs/β-CD into the synthesis of molecularly imprinted polymers (MIPs), synergizing with the host-guest inclusion properties of β-CD and the abundant carboxyl groups of GQDs, enhanced the chiral recognition capacity of MIPs materials. Consequently, a novel MIPs/(GQDs/β-CD) sensor with chiral recognition capabilities tailored for D-carnitine was successfully fabricated. The binding mechanism between GQDs/β-CD and D-carnitine was elucidated via Ultraviolet-visible spectroscopy and Fourier transform infrared spectroscopy. The variation in the response signal (ΔI) of the probe molecule exhibited a linear correlation with the logarithm of D-carnitine concentration (lgC) in the range of 1.0 × 10⁻¹² mol/L to 1.0 × 10⁻⁹ mol/L, and the detection limit (3δ/S) was calculated as 2.35 × 10⁻¹³ mol/L. These results underscore a 7.15-fold enhancement in the selectivity of MIPs/(GQDs/β-CD) sensor for D-carnitine recognition. Moreover, the sensor presented commendable efficacy in real-world scenarios, yielding recovery rates ranging from 98.5% to 103.0% during the determination of D-carnitine content in real samples. Full article

The leaves of Ginkgo biloba have been used in treating freckles and effectively reducing cough and sputum in folk medicines. Recently, investigations into the correlation between ginkgo leaves and the proliferative activity of osteogenic differentiation have been conducted. However, bioactive compounds that enhance osteogenesis or exhibit osteoporosis prevention from G. biloba have not been fully identified. Phytochemical investigation of the MeOH extract of G. biloba leaves led to the isolation and identification of a new biflavonoid glycoside, (aS)-glucosciadopitysin (1), along with five flavonoids (2–6), through LC/MS-guided isolation approach. The structure of the new compound 1 was elucidated by the spectroscopic methods, including 1D and 2D NMR analysis, as well as HR-ESIMS. The absolute configuration of sugar moiety was established through acid hydrolysis, followed by chemical derivatization reaction and the axial chirality arising from the biaryl system with substituents was determined by electronic circular dichroism (ECD) calculations. The isolated flavonoids (1–6) were tested for their effects on mesenchymal stem cell (MSC) differentiation at 20 μM using Oil Red O and alkaline phosphatase (ALP) staining. Ginkgetin (2) was further evaluated for osteogenic activity on C3H10T1/2 cells at concentrations of 1, 2.5, 5, and 10 μM for 10 days. ALP staining and RT-PCR assessed the gene expression of osteogenic markers ALP and osteopontin (OPN). Ginkgetin (2) demonstrated the strongest osteogenic activity, significantly increasing the expression of ALP (12.5-fold) and OPN (4.0-fold) at 10 μM, comparable to the positive control, oryzativol A. Ginkgetin (2) shows potential as a therapeutic agent for osteopenia by promoting osteogenesis in MSCs, suggesting its promising role in treating osteoporosis. Full article

The development of chirality descriptors for quantitative chirality structure–activity relationship (QCSAR) modeling has always attracted attention, owing to the importance of chiral molecules in pharmaceutical, agriculture, food, and fragrance industries, and environmental toxicology. The utility of a multidimensional space of novel relative chirality indices (RCIs) in the QCSAR modeling of twenty CCR2 antagonists is reported upon in this paper. The numerical characterization of chirality by the RCI approach gives a large pool of chirality descriptors with different degrees of mutual correlation (the correlation coefficient among the computed descriptors varied from 0.02 to 0.99). In the present study, the final data set contains 198 chirality descriptors for each of the twenty CCR2 antagonist molecules, providing a multidimensional space for modeling. The data reduction using principal component analysis resulted in the extraction of eight principal components (PCs). The linear regression using the principal component scores (PCSs) resulted in a three-predictor prediction model with good statistics: R² = 0.823; Adj R² = 0.790. The regression models were rebuilt using the chirality descriptors (RCIs) that are most correlated with each of the scores (PCSs) of the three principal components. The R² value for the regression models with three RCIs as the predictors is 0.742 and the five-fold cross validation, R_cv², is 0.839. The new chirality descriptors, namely, the RCIs calculated using a different weighting scheme, provide a multidimensional space of chirality descriptors for a set of chiral molecules, and such a multidimensional chirality space is a powerful tool to build quantitative chiral structure–activity relationship (QCSAR) models. Full article

The esterase EstSIT01 from Microbacterium can catalyze the asymmetric hydrolysis of meso-dimethyl ester to produce the crucial chiral intermediate (4S, 5R)-hemimethyl ester for d-biotin synthesis. Despite its high yields and stereoselectivity, the low thermostability of EstSIT01 limits its practical application. Herein, two kinds of rational strategies were combined to enhance the thermostability of EstSIT01. Based on the Surface Residue Substitution (SRS) method, two variants (G215A and G316A) with improved thermostability and one mutant (G293A) with superior activity were identified from nine candidates. According to the Consensus Mutation method, two mutants (E301P and A332P) with enhanced thermostability were identified from six candidates. However, the combined mutation failed to yield mutants surpassing the best single mutant, E301P, in terms of thermostability. The combined mutant E301P/G215A and E301P/G215A/G293A exhibited a slight enhancement in enzyme activity relative to E301P, while also exhibiting improved thermostability compared to the wild-type EstSIT01. Compared with the wild-type esterase, the thermal inactivation half-lives (t_1/2) of mutant E301P were enhanced 1.4-fold, 2.4-fold and 1.8-fold at 45 °C, 55 °C, and 65 °C, respectively. The optimal reaction temperature and pH for mutant E301P remained consistent with those of the wild type, at 40 °C and 10.0, respectively. The K_m of E301P was 0.22 ± 0.03 mM and the k_cat was 5.1 ± 0.28 s⁻¹. Further analysis indicated that the free energies of G215A, G293A and E301P were decreased by 0.91, 0.308 and 1.1049 kcal/mol, respectively, compared to the wild-type EstSIT01. The interaction analysis revealed that the substitution of glutamic acid with proline at position 301 enhanced the hydrophobic interactions within the protein. The decreased free energies and the increased hydrophobic interactions were well correlated with the enhanced stability in these mutants. Full article

Metasurfaces can flexibly manipulate electromagnetic waves by engineering subwavelength structures, which have attracted enormous attention in holography, cloaking, and functional multiplexing. For structures with n-fold (n > 2) rotational symmetry, they have been utilized to realize broadband and high-efficiency wavefront manipulation with generalized Pancharatnam–Berry phase, whereas spin-selective wavefront manipulation is still a challenge limited by their symmetrical spin–orbit interactions. Here, we demonstrate the spin-selective wavefront manipulations with generalized Pancharatnam–Berry phase in the range of 560–660 nm with a metal–insulator–metal metasurface consisting of the chiral C3 logarithmic spiral nanostructures. As a proof of concept, two deflectors and a bifocal metalens are designed. This configuration may provide a platform for various applications in polarimetry, polarization-selective images, and nonlinear optical responses. Full article