Theoretical Insights into the Effect of Different Numbers of Thiophene Groups on Hydrogen Bond Interaction and Excited-State Intramolecular Proton-Transfer Process for Flavonoid Derivatives.

In this study, we systematically explored the impact of varying the number of thiophene groups on the hydrogen bond interaction and excited-state intramolecular proton-transfer (ESIPT) processes in flavonoid derivatives (STF, DTF, and TTF) using the density functional theory and time-dependent density functional theory methods. Initially, a thorough analysis of the optimized geometric structures revealed that the intramolecular hydrogen bond in the S1 state is enhanced and gradually weakened as the number of thiophene groups increases. To gain a deeper understanding of the hydrogen bond interaction, topological analysis, interaction region indicator scatter plots, and isosurface plots were employed. These images provide further insights that align with the structural analysis. Additionally, we observed a red-shift in the electronic spectra (absorption and fluorescence spectra), which is primarily attributed to the narrowing of the energy gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital, as elucidated by the frontier molecular orbitals. Furthermore, a combined analysis between the hole-electron distribution and the transition density matrix heat map shows that electron excitation involves the unidirectional charge-transfer mechanism. In the end, by conducting relaxed potential energy curve scans, we found that an increase in the number of thiophene groups elevates the energy barrier for ESIPT, making it more challenging for the reaction. In summary, our study underscores the vital effect of thiophene-substituted numbers in modulating the ESIPT process, which is able to provide valuable insights for the design and synthesis of desired organic fluorescent probes in the future.

Design, Synthesis, and Structure-Activity relationships of Evodiamine-Based topoisomerase (Top)/Histone deacetylase (HDAC) dual inhibitors.

On the basis of synergistic effect between topoisomerase (Top) and histone deacetylase (HDAC) inhibitors, a series of novel evodiamine-based Top/HDAC dual inhibitors were designed and synthesized. Systematic structure-activity relationship (SAR) studies led to the discovery of compounds 29b and 45b, which simultaneously inhibited Top and HDAC and exhibited potent antitumor activities against the HCT116 cell line. Compounds 29b and 45b efficiently induced apoptosis with G2 cell cycle arrest and significantly inhibited cellular HDACs in HCT116 cells with good in vitro metabolic stabilities. Collectively, this work provides valuable SAR information and lead compounds for evodiamine-based Top/HDAC dual inhibitors.

Density-matrix formalism for modal coupling and dispersion in mode-division multiplexing communications systems.

Borrowing methodology from quantum mechanics, we propose and develop a density-matrix formalism for modal coupling and dispersion in mode-division multiplexing communications systems. The central concept in our formalism is the density matrix, from which all observable information of an optical field can be handily accessed. In the formalism, we derive fundamental evolution equations and concatenation rules for the key elements that characterize essential modal properties, and construct a statistical model ready for the numerical analysis of stochastic light propagation in randomly perturbed fibers. Unlike the Stokes-vector formalism that requires J2 - 1 auxiliary Gell-Mann matrices, the density-matrix formalism can be directly formulated for arbitrary modal-space dimension J. Based on the density-matrix formalism, the statistical modal properties of a 4-mode fiber under random perturbation are numerically investigated, which raises an interesting possibility of optimizing the modal dispersion by manipulation of the random perturbation.

Efficient synthesis of an antiviral drug intermediate using an enhanced short-chain dehydrogenase in an aqueous-organic solvent system.

(2R,3S)-N-tert-Butoxycarbonyl-3-amino-1-chloro-2-hydroxy-4-phenylbutane (1b) is key for the synthesis of the antiviral drug atazanavir. It can be obtained via the stereoselective bioreduction of (3S)-3-(N-Boc-amino)-1-chloro-4-phenyl-butanone (1a) with short-chain dehydrogenase/reductase (SDR). However, the stereoselective bioreduction of this hydrophobic and bulky substrate still remained a challenge because of the steric hindrance effect and low mass transfer rate. In this study, SDR isolated from Novosphingobium aromaticivorans (NaSDR) having low activity to 1a, which was engineered to enhance catalytic efficiency through active pocket iterative saturation mutagenesis (ISM). The obtained mutant (muSDR) (G141V/I195L) had 3.57 times higher kcat than the wild type (WT) towards 1a. Molecular docking analysis revealed considerable differences in the distance between the substrate and catalytic residues in WT and mutant SDR. Moreover, muSDR reduced 15 ketones with excellent enantioselectivity, indicating broad substrate acceptance. After optimization of expression and reaction conditions, the conversion was completed in a scale-up reaction (500 mL) using 50% toluene with 500 mM substrate without additional NADH. These results show that muSDR may be a valuable biocatalyst for future industrial applications.

Tailor-made ion-imprinted polymer based on functionalized graphene oxide for the preconcentration and determination of trace copper in food samples.

A tailor-made Cu(II) ion-imprinted polymer based on large-surface-area graphene oxide sheets has been synthesized for the preconcentration and determination of trace copper from food samples by solid-phase extraction. Attributed to the ultrahigh surface area and hydrophilicity of graphene oxide, the Cu(II) ion-imprinted polymer prepared by the surface ion-imprinting technique exhibited a high binding capacity and a fast adsorption rate under the optimized experimental conditions. In the static adsorption experiments, the maximum adsorption capacity of Cu(II) ion-imprinted polymer is 109.38 mg/g at 25°C, which is much higher than that of the nonimprinted polymer (32.12 mg/g). Meanwhile, the adsorption is very rapid and equilibrium is reached after approximately 30 min. The adsorption mechanism is found to follow Langmuir adsorption model and the pseudo-second-order adsorption process. The Cu(II) ion-imprinted polymer was used for extracting and detecting Cu(II) in food samples combined with graphite flame atomic adsorption spectrometry with high recoveries in the range of 97.6-103.3%. The relative standard deviation and limit of detection of the method were evaluated as 1.2% and 0.37 µg/L, respectively. The results showed that the novel absorbent can be utilized as an effective material for the selective enrichment and determination of Cu(II) from food samples.

Preparation of a Two-Dimensional Ion-Imprinted Polymer Based on a Graphene Oxide/SiO2 Composite for the Selective Adsorption of Nickel Ions.

In the present work, a novel two-dimensional (2D) nickel ion-imprinted polymer (RAFT-IIP) has been successfully synthesized based on the graphene oxide/SiO2 composite by reversible addition-fragmentation chain-transfer (RAFT) polymerization. The imprinted materials obtained are characterized by Fourier transmission infrared spectrometry (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The results show that the thermal stability of the graphene oxide/SiO2 composite is obviously higher than that of graphene oxide. RAFT-IIP possesses an excellent 2D homogeneous imprinted polymer layer, which is a well-preserved unique structure of graphene oxide/SiO2. Owing to the intrinsic advantages of RAFT polymerization and 2D imprinted material, RAFT-IIP demonstrate a superior specific adsorption capacity (81.73 mg/g) and faster adsorption kinetics (30 min) for Ni(II) in comparison to the ion-imprinted polymer prepared by traditional radical polymerization and based on the common carbon material. Furthermore, the adsorption isotherm and selectivity toward Ni(II) onto RAFT-IIP and nonimprinted polymer (NIP) are investigated, indicating that RAFT-IIP has splendid recognizing ability and a nearly 3 times larger adsorption capacity than that of NIP (30.94 mg/g). Moreover, a three-level Box-Behnken experimental design with three factors combining the response surface method is utilized to optimize the desorption process. The optimal conditions for the desorption of Ni(II) from RAFT-IIP are as follows: an HCl-type eluent, an eluent concentration of 2.0 mol/L, and an eluent volume of 10 mL.

Influence of atomic electronegativity on ESIPT behaviour for the BTDI and its derivatives: Theoretical exploration.

In this work, we theoretically explored the influence of atomic electronegativity on excited-state intramolecular proton transfer (ESIPT) behavior among novel fluorescent probes BTDI and its derivatives (BODI and BSeDI). A thorough examination of the optimized structural parameters and infrared vibrational spectra reveals an enhancement in intramolecular hydrogen bonding within BTDI and its derivatives upon light excitation. This finding is further reinforced by topological analysis and interaction region indicator scatter plots, which underscores the sensitivity of atomic electronegativity to variations in hydrogen bonding strength. With regards to absorption and fluorescence spectra, the decrease in atomic electronegativity leads to a pronounced redshift, primarily attributed to the narrowing of the energy gap. Additionally, an analysis of potential energy curves and the exploration of intrinsic reaction coordinate paths based on transition state structures afford a deeper understanding of the mechanism underlying ESIPT and being modulated through the manipulation of atomic electronegativity. We anticipate that this work on atomic electronegativity regulating ESIPT behavior will serve as a catalyst for novel fluorescent probes in the future, offering fresh perspectives and insights.

Speciation, adsorption and determination of chromium(III) and chromium(VI) on a mesoporous surface imprinted polymer adsorbent by combining inductively coupled plasma atomic emission spectrometry and UV spectrophotometry.

In the present study, a Cr(III)-imprinted polymer (Cr(III)-IIP) was prepared by an easy one-step sol-gel reaction with a surface imprinting technique on the support of silica mesoporous material. A new SPE method for the speciation, separation, preconcentration, and determination of Cr(III) and Cr(VI) by inductively coupled plasma atomic emission spectrometry and UV on the mesoporous-imprinted polymer adsorbent was developed. The structure of the imprinted polymer was characterized by Fourier transform infrared spectroscopy, X-ray powder diffraction, transmission electron microscopy, and nitrogen adsorption-desorption isotherms. The adsorption kinetics, thermodynamics behavior, and recognition ability toward Cr(III) on Cr(III)-IIP and nonimprinted polymer were compared. The results showed that Cr(III)-IIP had higher selectivity and nearly a two times larger Langmuir adsorption capacity (38.50 mg/g) than that of NIP. The proposed method has been successfully applied in the determination and speciation of chromium in natural water samples with satisfactory results.

Ginsenoside Rg1 Inhibits STAT3 Expression by miR-15b-5p to Attenuate Lung Injury in Mice with Type 2 Diabetes Mellitus-Associated Pulmonary Tuberculosis.

Type 2 diabetes mellitus (T2DM) has been regarded as a critical risk factor for pulmonary tuberculosis (PTB). Ginsenoside Rg1 has been identified as a potential therapeutic agent for T2DM by suppressing the inflammatory response. However, the effect of Rg1 on T2DM-associated PTB has not been reported. In this study, we aimed to explore the function of Rg1 in the regulation of T2DM-associated PTB. We established a T2DM-associated PTB mouse model and found that the fibrosis of lung tissues was inhibited by Rg1 in T2DM-associated PTB mice. The lung injury of T2DM-associated PTB mice was repressed by Rg1. Moreover, the levels of IL-6, TNF-α, and IL-1ß in the lung tissues and serum were decreased by Rg1 in T2DM-associated PTB mice. The treatment with Rg1 inhibited the levels of free fatty acid and enhanced the expression of miR-15b-5p in lung tissues of T2DM-associated PTB mice. MiR-15b-5p targeted and inhibited the STAT3 expression. The expression of STAT3 was downregulated by Rg1, while the inhibition of miR-15b-5p reversed the downregulation. The expression of miR-15b-5p was reduced, but the expression of STAT3 was upregulated in the lung tissues of T2DM-associated PTB mice. We validated that miR-15b-5p attenuated inflammation and lung injury in the T2DM-associated PTB mouse model. The overexpression of STAT3 or the suppression of miR-15b-5p restored lung fibrosis and injury inhibited by Rg1 in T2DM-associated PTB mice. Meanwhile, the Rg1-repressed levels of IL-6, TNF-α, and IL-1ß were enhanced by the overexpression of STAT3 or the suppression of miR-15b-5p. In addition, the levels of free fatty acid repressed by Rg1 were reversed by STAT3 overexpression and miR-15b-5p inhibition. Thus, we conclude that ginsenoside Rg1 inhibits the STAT3 expression by miR-15b-5p to attenuate lung injury in mice with type 2 diabetes mellitus-associated pulmonary tuberculosis.

Length-controllable catalyzing-synthesis and length-corresponding properties of FeCo/Pt nanorods.

Newly designed magnetic-alloy/noble-metal FeCo/Pt nanorods have been first reported and fabricated through a length-controllable catalyzing-synthesis process in which the growth of FeCo nanorods was induced on Pt nanotips. The length of FeCo/Pt nanorods depends on the number of platinum nanotips. The proposed synthesis mechanism was corroborated by scanning electron microscopy, transition electron microscopy, X-ray diffraction, energy dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. With the decrease of Fe content in Fe(x)Co(96-x)/Pt(4) nanoalloys from 77 to 15, the morphology changes from nanorods with different lengths to nanoparticles. The analysis of the magnetic hysteresis loops indicated that the magnetic saturation and coercivity were strongly dependent on the length of the nanorods in which maximum saturation magnetization and minimum coercivity were obtained for Fe(77)Co(19)/Pt(4) nanorods with the length of ∼2.5 µm. In particular, FeCo/Pt exhibited length-dependent reactivity towards 1,1,2,2-tetrachloroethane, and Fe(77)Co(19)/Pt(4) nanorods with the length of ∼2.5 µm yielded the greatest dechlorination rate. Moreover, Pt can enhance the dechlorination of 1,1,2,2-tetrachloroethane.

Discovery, Structure-Activity Relationship, and Mechanistic Studies of 1-((3R,4S)-3-((Dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)piperidin-1-yl)-2-(2,4,5-trifluorophenyl)ethan-1-one as a Novel Potent Analgesic.

Management of moderate to severe pain relies heavily on opioid analgesics such as morphine, oxycodone, and fentanyl in clinics. However, their prolonged use was associated with undesirable side effects. Many new strategies to reduce side effects have been proposed, but not without disadvantages. Using a hot plate model as a phenotypic screening method, our studies identified (3R,4S)-9d with a new scaffold as a potent analgesic with ED50 values of 0.54 mg/kg and 0.021 mg/kg in hot plate and antiwrithing models, respectively. Mechanistic studies showed that it elicited its analgesic effect via the active metabolite (3R,4S)-10a. The mechanism of (3R,4S)-10a-induced activation of the µ opioid receptor (MOR) was proposed by means of molecular dynamics (MD) simulation.

A simple liquid chromatography tandem mass spectrometric method for fast detection of hydrogen sulfide based on thiolysis of 7-nitro-2, 1, 3-benzoxadiazole ether.

The long identified toxic gas, hydrogen sulfide (H2S), which has also been confirmed as the third gaseous signaling molecule following NO and CO, plays important roles in various physiological and pathological process. The current most established quantification method for H2S is HPLC method coupled with fluorescence detection after derivatization with a costly fluorescent reagent, Monobromobimane (MBB). However, The MBB method is characterized by strict reaction condition, long reaction time, tedious operation, and inconsistent reported results. In this study, based on the thiolysis reaction of 7-nitro-2, 1, 3-benzoxadiazole (NBD) ether, the commonly used chromatographic modifier 4-chloro-7-nitro-2,1,3- benzoxadiazole (NBDCl) and four probes (NBDOMe, NBDOEt, NBDOTFE and NBDOCMR) synthesized from NBDCl were tested as alternatives for fast quantification of H2S by LC-MS/MS. The reaction product between NBD ethers/NBDCl and H2S showed special pink color visible to the naked eye and was easy to synthesize and separate in lab; it also showed good retention on common chromatographic columns and high instrument response; therefore it is a good determinand. After establishment of LC-MS/MS methods for all the related compounds, the reaction conditions were optimized for all the probes with H2S. Then the stability, selectivity, reaction rate, sensitivity and quantitative linear relationship between the reaction product and H2S concentration were studied for each probe. Finally, NBDOEt was selected for LC-MS/MS detection of H2S. In comparision with the MBB method, the established NBDOEt method showed matched sensitivity and linearity, better selectivity, and higher repeatability; and had the advantages of easy operation, simple reaction condition, and cheap raw materials. The method was successfully validated and applied to determination of Na2S content in Na2S∙9H2O bulk drug and injection. In conclusion, NBDOEt is a promising option for quantification of H2S in abiotic matrix.

New azaphilones, phomopsones A-C with biological activities from an endophytic fungus Phomopsis sp. CGMCC No.5416.

Three undescribed azaphilones, phomopsones A-C (1-3) and two known azaphilones (4-5) were isolated from the culture of endophytic fungus Phomopsis sp. CGMCC No.5416 from the stems of Achyranthes bidentata. Their structures were determined by spectroscopic analysis (HRESIMS, 1D and 2D NMR), and the absolute configurations were determined by CD spectroscopy. Compounds 2 and 3 showed significant inhibitory activities against HIV-1 with against HIV-1 with IC50 values of 7.6 and 0.5 µmol/L, respectively. Compounds 2 and 3 also displayed moderate cytotoxicity with CC50 values of 3.2-303 µmol/L against A549, MDA-MB-231 and PANC-1 cell lines. Moreover, compound 3 can induce the early apoptosis of PANC-1 cancer cells with the apoptosis rate of 28.54%.

Improving the biotransformation of phytosterols to 9α-hydroxy-4-androstene-3,17-dione by deleting embC associated with the assembly of cell envelope in Mycobacterium neoaurum.

The conversion of low value-added phytosterols into 9α-hydroxy-4-androstene-3,17-dione (9-OHAD) by mycobacteria is an important step in the steroid pharmaceutical industry. However, the highly dense cell envelope with extremely low permeability largely affects the overall transformation efficiency. Here, we preliminarily located the key gene embC required for the synthesis of lipoarabinomannan from lipomannan in Mycobacterium neoaurum. The genetic manipulation of embC indicated that it might be the only functional enzyme catalyzing the above synthesis process. The deficiency of lipoarabinomannan led to a significantly increased cell permeability, which in turn caused the enhanced uptake capacity of cells. The sterol substrate conversion efficiency of mycobacterial cells was increased by about 52.4 % after 72-h conversion. Ultimately, the absence of embC increased the productivity from 0.0927 g/L/h to 0.1031 g/L/h, as confirmed by a resting cell system. This study verified the feasibility of improving the efficiency of the microbial conversion system through the cell envelope engineering strategy.

Preclinical Absorption, Distribution, Metabolism, and Excretion of Sodium Danshensu, One of the Main Water-Soluble Ingredients in Salvia miltiorrhiza, in Rats.

In this study, the absorption, distribution, metabolism and excretion (ADME) of sodium danshensu (Sodium DL-ß-(3, 4-dihydroxyphenyl)lactate), one of the main water-soluble active constituents in Salvia miltiorrhiza, were evaluated in rats. Pharmacokinetic study was evaluated in doses of 15, 30, and 60 mg/kg after intravenous administration of sodium danshensu. Bioavailability study was evaluated by comparing between 30 mg/kg (I.V.) and 180 mg/kg (P.O.) of sodium danshensu. Tissue distribution, metabolism, and excretion were evaluated at 30 mg/kg (I.V.) of sodium danshensu. Following intravenous administration, sodium danshensu exhibited linear pharmacokinetics in the dose range of 15-60 mg/kg. Sodium danshensu appeared to be poorly absorbed after oral administration, with an absolute bioavailability of 13.72%. The primary distribution tissue was kidney, but it was also distributed to lung, stomach, muscle, uterus, heart, etc. Within 96 h after intravenous administration, 46.99% was excreted via urine and 1.16% was excreted via feces as the parent drug. Biliary excretion of sodium danshensu was about 0.83% for 24 h. Metabolites in urine were identified as methylation, sulfation, both methylation and sulfation, and acetylation of danshensu. Sodium danshensu can be developed as an injection because of its poor oral bioavailability. In conclusion, sodium danshensu is widely distributed, mainly phase II metabolized and excreted primarily in urine as an unchanged drug in rats.

[Studies on properties of aggregates and Langmuir-Blodgett films for centrosymmetric naphthalocyanine molecules].

Deposition of Langmuir-Blodgett films and the aggregative properties of three centrosymmetric naphthalocyanine derivatives were investigated by using linear absorption spectra. Good LB films could be formed for all the three compounds. In dilute solution,the monomers are the main formation for the tetra-tert-butyl-cyan naphthalocyanine. Due to atomic zinc action, the tetra-tert-butyl naphthalocyanine zinc molecules could not only form H-aggregates, but also form J-aggregates. The tetra-tert-butyl naphthalocyanine zinc molecules mainly are aggregates in dilute solution. In the Langmuir-Blodgett films, both tetra-tert-butyl-cyan naphthalocyanine and tetra-tert-butyl-cyan naphthalocyanine zinc formed H-aggregates. The monomers are the main formation for the bi-( tetra-tertbutyl-naphthalocyaninato)-orbium in dilute solution and Langmuir-Blodgett films.

Influence of heat treatments upon the mechanical properties and in vitro bioactivity of ZrO2-toughened MgO-CaO-SiO2-P2O5-CaF2 glass-ceramics.

Zirconia-toughened MgO-CaO-SiO2-P2O5-CaF2 glass-ceramics are prepared using sintering techniques, and a series of heat treatment procedures are designed to obtain a glass-ceramic with improved properties. The crystallization behavior, phase composition, and morphology of the glass-ceramics are characterized. The bending strength, elastic modulus, fracture toughness, and microhardness of the glass-ceramics are investigated, and the effect mechanism of heat treatments upon the mechanical properties is discussed. The bioactivity of glass-ceramics is then evaluated using the in vitro simulated body fluid (SBF) soaking test, and the mechanism whereby apatite forms on the glass-ceramic surfaces in the SBF solution is discussed. The results indicate that the main crystal phase of the G-24 sample undergoing two heat treatment procedures is Ca5(PO4)3F (fluorapatite), and those of the G-2444 sample undergoing four heat treatment procedures are Ca5(PO4)3F and ß-CaSiO3 (ß-wollastonite). The heat treatment procedures are found to greatly influence the mechanical properties of the glass-ceramic, and an apatite layer is induced on the glass-ceramic surface after soaking in the SBF solution.

An ion-imprinted functionalized SBA-15 adsorbent synthesized by surface imprinting technique via reversible addition-fragmentation chain transfer polymerization for selective removal of Ce(III) from aqueous solution.

A novel Ce(III) ion-imprinted polymer (Ce(III)-IIP) has been prepared by surface imprinting technique with reversible addition-fragmentation chain transfer (RAFT) polymerization based on support matrix of SBA-15. The prepared adsorbent is characterized by FT-IR, XRD, SEM, TEM, nitrogen adsorption-desorption, GPC, and TGA. The results suggest that the surface imprinted polymer synthesized by RAFT is a thin layer. For adsorption experiments, Ce(III)-IIP is investigated to remove Ce(III) by column study at different flow rates, initial metal ion concentrations, and adsorption temperature. The dynamic kinetics analyses reveal that the overall adsorption process is successfully fitted with the pseudo-first-order kinetic model and the equilibrium time was 60 min. Meanwhile, the experimental data is in good agreement with Thomas model. Ce(III)-IIP has the excellent selectivity and regenerate property. Meanwhile, the proposed method has been successfully applied in the removal of Ce(III) in natural water samples with satisfactory results. All the results suggest that Ce(III)-IIP could be used as an excellent adsorbent for efficient removal of Ce(III) from aqueous solution.