Publications by authors named "Yongmin Zhang"

183 Publications

Effects of different personalized sound therapies in tinnitus patients with hearing loss of various extents.

Int J Clin Pract 2021 Sep 19:e14893. Epub 2021 Sep 19.

E.N.T. Department, Chongqing University Three Gorges Hospital, Chongqing, China.

Background: Limited by difficulties in choosing the appropriate sound, sound therapies could only effectively restrain the development of tinnitus in some patients. Thus, individualized sound therapies are of urgent needs.

Objective: The purpose of this study was to determine the therapeutic effect of different individualized sound therapies in tinnitus patients complicated with hearing loss of various extents.

Research Design: Participants were assigned to two different personalized sound therapies as counterbalanced by age and gender in this observational study.

Study Sample: Ninety-two tinnitus patients with hearing loss admitted to our hospital from Jan. 2018 to Jan. 2020 were enrolled and evenly grouped as the observation group and the control group in accordance with the random number table.

Data Collection And Analyses: Tinnitus characteristics of both groups were determined before treatment. Patients from the observation group received pure tone sound therapy composed of 7 octaves (0.125, 0.25, 0.5, 1, 2, 4, and 8 kHz) based on frequencies determined from their tinnitus characteristics. The control group received pure tone sound therapy composed of 9 one-third octaves based on their tinnitus characteristics.

Results: The observation group had better therapeutic effects than that in the control group (91.30% vs 73.91%, P<0.05). After 1 week, and 1 to 3-month(s) treatment, patients in the observation group all presented with decreased tinnitus handicap, decreased tinnitus volume and improved sleep quality compared to the control group (P<0.05).

Conclusion: The present study found that both personalized sound therapies were effective in tinnitus treatment while 7-octave pure tone adjusted from tinnitus frequencies were more promising in decreasing tinnitus handicap and tinnitus volume.
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http://dx.doi.org/10.1111/ijcp.14893DOI Listing
September 2021

Chemoenzymatic synthesis and biological evaluation of ganglioside GM3 and lyso-GM3 as potential agents for cancer therapy.

Carbohydr Res 2021 Sep 3;509:108431. Epub 2021 Sep 3.

Key Laboratory of Industrial Microbiology, Ministry of Education, College of Biotechnology, Tianjin University of Science and Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Tianjin 300457, PR China. Electronic address:

A highly efficient chemoenzymatic method for synthesizing ganglioside GM3 and lyso-GM3 was reported here. Enzymatic extension of the chemically synthesized lactosyl sphingosine using efficient one-pot multienzyme (OPME) reaction allowed glycosylation to be carried out in aqueous solutions realizing the greening of reactions. Ganglioside GM3 was synthesized through 10 steps with a total yield of 22%. Lyso-GM3 was very useful for kinds of derivatization. The anti-proliferation activity studies demonstrated that these compounds 14-16 with sphingosine exhibited more potency than the corresponding lyso-GM3 with ceramide. All ganglioside GM3 and lyso-GM3 can effectively inhibit the migration of melanoma B16-F10 cells. These chemoenzymaticlly synthesized GM3 and lyso-GM3 exhibited antitumor activities, which can provide valuable sights to search new antitumor agents for cancer therapy.
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http://dx.doi.org/10.1016/j.carres.2021.108431DOI Listing
September 2021

Platinum complexes inhibit HER-2 enriched and triple-negative breast cancer cells metabolism to suppress growth, stemness and migration by targeting PKM/LDHA and CCND1/BCL2/ATG3 signaling pathways.

Eur J Med Chem 2021 Jul 7;224:113689. Epub 2021 Jul 7.

Inner Mongolia University Research Center for Glycochemistry of Characteristic Medicinal Resources, School of Chemistry and Chemical Engineering, Inner Mongolia University, Hohhot, 010021, PR China. Electronic address:

Triple-negative-breast cancer (TNBC) and HER-2 enriched positive aggressive types of breast cancer and are highly metastatic in nature. Anticancer agents those target TNBC and HER-2 enriched positive breast cancers are considered important in the field of breast cancer research. In search of the effective anticancer agents, we synthesized Pt(II) complexes to target these cancers. Platinum complexes (C1-C8) were prepared in single step by the reaction of commercially available KPtCl with the readily prepared ligands (L1-L8). All these compounds were characterized successfully by different spectroscopic and spectrophotometric analyses. Structures of C1, C3 and C8 were characterized by single crystal X-ray analysis that confirmed the exact chelation mode of the SNO-triply coordinated ligand. All these complexes inhibited the in vitro growth of MCF-7 (luminal-like), MDA-MB-231 (TNBC) and SKBR3 (HER-2 enriched) breast cancer cells. C1, C3 and C7 induced cell death and suppressed the clonogenic potential of these cancer cells. Importantly, C1, C3 and C7 showed potentials to suppress cancer stem cells/mammosphere formation and cell migration ability of MDA-MB-231 and SKBR3 breast cancer cells. These complexes also induced cellular senescence in MDA-MB-231 and SKBR3 cells, thus suggesting a cell retardation mechanism. Similarly, these complexes induced DNA damage by activating p-H2AX expression and promoted autophagy via ATG3/LC3B axis activation in MDA-MB-231 and SKBR3 cells. Furthermore, these complexes decreased the expression of oncogenic proteins such as BCL2 and cylin-D1 those are involved in cancer cell survival and cell cycle progression. To further gain insight, we found that C1 and C7 targeted glycolytic pathways by regulating PKM and LDHA expression, which are involved in glycolysis. Moreover, C1 and C7 suppressed the formation of ATP production that is required for cancer cell growth. Taken together, the easy synthesis and biological assays results point towards the importance of these complexes in MDA-MB-231 (TNBC) and SKBR3 (HER-2 enriched) breast cancer cells by targeting multiple signaling pathways those are considered important during breast cancer progression. This study produces bases for further deeper in vitro or in vivo study that could lead to the effective breast cancer agents which we are working on.
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http://dx.doi.org/10.1016/j.ejmech.2021.113689DOI Listing
July 2021

Corrigendum to "Inhibition of influenza virus infection by multivalent pentacyclic triterpene-functionalized per-O-methylated cyclodextrin conjugates" [Eur. J. Med. Chem. 134(2017) 133-139].

Eur J Med Chem 2021 Nov 18;223:113647. Epub 2021 Jun 18.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China. Electronic address:

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http://dx.doi.org/10.1016/j.ejmech.2021.113647DOI Listing
November 2021

Iminosugar C-Glycosides Work as Pharmacological Chaperones of NAGLU, a Glycosidase Involved in MPS IIIB Rare Disease*.

Chemistry 2021 Aug 2;27(44):11291-11297. Epub 2021 Jul 2.

Glycochemistry Group of "OrgaSynth" Team, IC2MP, UMR-CNRS 7285, Université de Poitiers, 4 rue Michel Brunet, 86073, Poitiers Cedex 9, France.

Mucopolysaccharidosis type IIIB is a devastating neurological disease caused by a lack of the lysosomal enzyme, α-N-acetylglucosaminidase (NAGLU), leading to a toxic accumulation of heparan sulfate. Herein we explored a pharmacological chaperone approach to enhance the residual activity of NAGLU in patient fibroblasts. Capitalizing on the three-dimensional structures of two modest homoiminosugar-based NAGLU inhibitors in complex with bacterial homolog of NAGLU, CpGH89, we have synthesized a library of 17 iminosugar C-glycosides mimicking N-acetyl-D-glucosamine and bearing various pseudo-anomeric substituents of both α- and β-configuration. Elaboration of the aglycon moiety results in low micromolar selective inhibitors of human recombinant NAGLU, but surprisingly it is the non-functionalized and wrongly configured β-homoiminosugar that was proved to act as the most promising pharmacological chaperone, promoting a 2.4 fold activity enhancement of mutant NAGLU at its optimal concentration.
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http://dx.doi.org/10.1002/chem.202101408DOI Listing
August 2021

Synthesis of novel diosgenyl saponin analogs and evaluation effects of rhamnose moeity on their cytotoxic activity.

Carbohydr Res 2021 Aug 31;506:108359. Epub 2021 May 31.

Department of Pharmacy, Qilu Hospital of Shandong University, Jinan, 250012, Shandong Province, PR China. Electronic address:

Diosgenyl saponins, as a type of natural products derived from plants, are the main active component of traditional chinese medicine. Inspiringly, a large number of natural diosgensyl saponins have been shown to exert excellent toxicity to hepatocellular cancer (HCC) cells. In order to better understand the relationship between the structures and their biological effects, a group of diosgenyl saponins (1-4 as natural products and 5 and 6 as their analogs) were efficiently synthesized. The cytotoxic activity of these compounds was evaluated on human hepatocellular carcinoma (HepG2) cells. Structure-activity relationship studies showed that the pentasaccharide or hexasaccharide saponin analogs were relatively less active than their corresponding disaccharide analogue or dioscin. The extension of 4-branched rhamnose moiety on these saponin does not exhibit significant effect on their cytotoxic activity, which disclosed that a certain number and the linkage mode of rhamnose moieties could influence the cytotoxicity of steroid saponins on HepG2 cells.
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http://dx.doi.org/10.1016/j.carres.2021.108359DOI Listing
August 2021

New organoselenides (NSAIDs-Se derivatives) as potential anticancer agents: Synthesis, biological evaluation and in silico calculations.

Eur J Med Chem 2021 Jun 20;218:113384. Epub 2021 Mar 20.

Institute for Interdisciplinary Research, Jianghan University, Wuhan Economic and Technological Development Zone, Wuhan, 430056, China; Institut Parisien de Chimie Moléculaire, CNRS UMR 8232, Sorbonne Université, 4 Place Jussieu, 75005, Paris, France. Electronic address:

Herein we reported the synthesis of twenty new organoselenium compounds (2a-2j and 3a-3j) based on the hybridization of nonsteroidal antiinflammatory drugs (NSAIDs) skeleton and organoselenium motif (-SeCN and -SeCF), the anticancer activity was evaluated against four types of cancer cell lines, Caco-2 (human colon adenocarcinoma cells), BGC-823 (human gastric cancer cells), MCF-7 (human breast adenocarcinoma cells), PC-3 (human prostatic cancer cells). Interestingly, the introduction of the -SeCN or -SeCF moiety in corresponding parent NSAIDs results in the significant effect on cancer cell lines. Moreover, the most active compound 3a showed IC values lower than 5 μM against the four cancer cell lines, particularly to BGC-823 and MCF-7 with IC values of 2.5 and 2.7 μM, respectively. Furthermore, three compounds 3a, 3g and 3i were selected to investigate their ability to induce apoptosis in BGC-823 cells via modulating the expression of anti-apoptotic Bcl-2 protein, pro-inflammatory cytokines (IL-2) and proapoptotic caspase-8 protein. The redox properties of the NSAIDs-Se derivatives prepared herein were conducted by 2, 2-didiphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like assays. Finally, molecular docking study revealed that an interaction with the active site of thioredoxin reductase 1 (TrxR1) and predicted the anticancer activity of the synthesized candidates. Overall, these results could serve a promising launch point for further design of NSAIDs-Se derivatives as potential anticancer agents.
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http://dx.doi.org/10.1016/j.ejmech.2021.113384DOI Listing
June 2021

Mapping C-H⋅⋅⋅M Interactions in Confined Spaces: (α-ICyD )Au, Ag, Cu Complexes Reveal "Contra-electrostatic H Bonds" Masquerading as Anagostic Interactions*.

Chemistry 2021 Jun 6;27(31):8127-8142. Epub 2021 May 6.

Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, UMR 8232, 4 place Jussieu, 75005, Paris, France.

What happens when a C-H bond is forced to interact with unpaired pairs of electrons at a positively charged metal? Such interactions can be considered as "contra-electrostatic" H-bonds, which combine the familiar orbital interaction pattern characteristic for the covalent contribution to the conventional H-bonding with an unusual contra-electrostatic component. While electrostatics is strongly stabilizing component in the conventional C-H⋅⋅⋅X bonds where X is an electronegative main group element, it is destabilizing in the C-H⋅⋅⋅M contacts when M is Au(I), Ag(I), or Cu(I) of NHC-M-Cl systems. Such remarkable C-H⋅⋅⋅M interaction became experimentally accessible within (α-ICyD )MCl, NHC-Metal complexes embedded into cyclodextrins. Computational analysis of the model systems suggests that the overall interaction energies are relatively insensitive to moderate variations in the directionality of interaction between a C-H bond and the metal center, indicating stereoelectronic promiscuity of fully filled set of d-orbitals. A combination of experimental and computational data demonstrates that metal encapsulation inside the cyclodextrin cavity forces the C-H bond to point toward the metal, and reveals a still attractive "contra-electrostatic" H-bonding interaction.
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http://dx.doi.org/10.1002/chem.202100263DOI Listing
June 2021

Poly ethylene glycol (PEG)-Related controllable and sustainable antidiabetic drug delivery systems.

Eur J Med Chem 2021 May 11;217:113372. Epub 2021 Mar 11.

China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, 300457, Tianjin, China. Electronic address:

Diabetes mellitus is one of the most challenging threats to global public health. To improve the therapy efficacy of antidiabetic drugs, numerous drug delivery systems have been developed. Polyethylene glycol (PEG) is a polymeric family sharing the same skeleton but with different molecular weights which is considered as a promising material for drug delivery. In the delivery of antidiabetic drugs, PEG captures much attention in the designing and preparation of sustainable and controllable release systems due to its unique features including hydrophilicity, biocompatibility and biodegradability. Due to the unique architecture, PEG molecules are also able to shelter delivery systems to decrease their immunogenicity and avoid undesirable enzymolysis. PEG has been applied in plenty of delivery systems such as micelles, vesicles, nanoparticles and hydrogels. In this review, we summarized several commonly used PEG-contained antidiabetic drug delivery systems and emphasized the advantages of stimuli-responsive function in these sustainable and controllable formations.
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http://dx.doi.org/10.1016/j.ejmech.2021.113372DOI Listing
May 2021

Viscoelastic Fluid Formed by Ultralong-Chain Erucic Acid-Base Ionic Liquid Surfactant Responds to Acid/Alkaline, CO, and Light.

J Agric Food Chem 2021 Mar 8;69(10):3094-3102. Epub 2021 Mar 8.

Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical & Materials Engineering, Jiangnan University, No.1800 Lihu Avenue, Wuxi 214122, P. R. China.

As a leftover of grease processing, the efficient utilization of erucic acid is still a challenge. An alternative strategy is to develop erucic acid-derived surfactants. However, erucic acid-based ionic liquid surfactants were barely involved. Here, a novel ionic liquid surfactant, benzyltrimethylammonium erucate (ErBTA), was developed by a simple neutralization reaction, and its aggregations in the diluted and concentrated solution were systematically studied by surface tension, conductivity, rheology, and cryo-TEM techniques. The results showed that ErBTA has a very low metaling point (-7.03 °C) and possesses excellent water solubility (Krafft temperature <4 °C). ErBTA alone starts to form micelles at a very low concentration (0.028 mmol/L) and then to form worm-based viscoelastic fluid at 4.07 mmol/L without any additives, exhibiting excellent self-assembly ability and thickening ability. This viscoelastic fluid formed by ErBTA can simultaneously respond to three stimuli: common acid/alkaline, CO gas, and light, accompanied by an interesting gel-sol conversion, reflecting microstructure transition from wormlike micelles to spherical micelles. Although in essence CO and light also act as pH regulators in the current system, they provide more sophisticated approaches to tune pH. Such a viscoelastic fluid with the characteristics of easy availability, renewability of raw materials, the simplicity of fabrication, good water-solubility, and excellent thickening ability may be an attractive candidate for clean fracturing in oil/gas recovery and fluid drag reduction.
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http://dx.doi.org/10.1021/acs.jafc.0c07466DOI Listing
March 2021

Programmed Synthesis of Hepta-Differentiated β-Cyclodextrin: 1 out of 117655 Arrangements.

Angew Chem Int Ed Engl 2021 05 16;60(21):12090-12096. Epub 2021 Apr 16.

Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire (IPCM), UMR 8232, 4, place Jussieu, 75005, Paris, France.

Cyclodextrin poly-functionalization has fueled progress in their use in multiple applications such as enzyme mimicry, but also in the polymer sciences, luminescence, as sensors or for biomedical applications. However, regioselective access to a given pattern of functions on β-cyclodextrin is still very limited. We uncover a new orienting group, the thioacetate, that expands the toolbox available for cyclodextrin poly-hetero-functionalization using diisobutylaluminum hydride (DIBAL-H) promoted debenzylation. The usefulness of this group is illustrated in the first synthesis of a precisely hepta-hetero-functionalized β-cyclodextrin. By way of comparison, a random hepta-functionalization would give 117655 different molecules. This synthesis is not simply the vain quest for the Holy Grail of CD hetero-functionalization, but it illustrates the versatility of the DIBAL-H oriented hetero-functionalization strategy, opening the way to a multitude of useful functionalization patterns for new practical applications.
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http://dx.doi.org/10.1002/anie.202102182DOI Listing
May 2021

Oxidation-Induced Breakage of the Imine Bond and Aggregate Transition in a Se-Containing Dynamic Covalent Surfactant.

Langmuir 2021 Mar 21;37(8):2833-2842. Epub 2021 Feb 21.

The Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical & Materials Engineering, Jiangnan University, Wuxi 214122, P. R. China.

Controlling the dynamic imine bonds upon a novel trigger except for pH and temperature is still a significant challenge. Here, a Se-containing imine-based dynamic covalent surfactant (HOBAB-BSeEA) was developed for the first time by mixing two precursors in situ: an asymmetric double-chain cationic surfactant bearing a formyl group at the terminal of one hydrophobic tail and a Se-containing amine (2-(benzylselanyl)ethan-1-amine) in order to confirm the effect of redox on the imine bonds. The imine bond in HOBAB-BSeEA can be regulated not only upon changing the pH as well as other common imine-based surfactants but also by oxidation. The conversion efficiency of imine bonds is closely related with the degree of oxidation and pH. Complete oxidation can decrease the conversion efficiency from ∼87 to 48%, which is comparable to the result of changing the pH from 10.0 to 7.0. With the formation and breaking of imine bonds, the surfactant can be reversibly switched between symmetric and asymmetric structures, accompanied by a morphological transition from vesicles to spherical micelles. Although oxidation cannot demolish all imine bonds, it can completely convert vesicles to spherical micelles, which is mainly ascribed to an increase in the polarity of the micellar microenvironment stemming from the oxidation of Se. However, this transition can only be achieved by reducing the pH to 5.0 instead of 7.0. Nile red loaded in HOBAB-BSeEA vesicles can be quickly, controllably, and step-by-step released upon oxidation stimulus but not pH. Understanding the mechanism of oxidation-induced breakage of imine bonds and disruption of vesicles would be useful in designing redox-responsive imine-based carriers that can unload cargoes according to the level of the local reactive oxygen species.
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http://dx.doi.org/10.1021/acs.langmuir.0c03609DOI Listing
March 2021

CO and Temperature Control over Nanoaggregates in Surfactant-Free Microemulsion.

Langmuir 2021 Feb 29;37(5):1983-1990. Epub 2021 Jan 29.

The Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical & Materials Engineering, Jiangnan University, Wuxi 214122, P. R. China.

Smart microemulsions (MEs) recently have attracted significant interests. However, MEs, especially surfactant-free MEs (SFMEs) that respond to more than one stimulus, are rarely reported to date. Here, we reported the first example of dual-responsive SFME in which a CO-sensitive hydroxyethylamine was used as an amphisolvent. This SFME was investigated utilizing ternary phase diagram, dynamic light scattering, and UV-visible spectrum techniques. It was found that three hydroxyethylamines could stabilize the octanol-water mixture to form transparent and isotropic SFMEs including nanoaggregates-rich pre-ouzo zone, regardless of the number of the hydroxyl group. Among them, 2-(dimethyl amino) ethanol (DMEA)-based SFME possesses the largest single-phase region and most sensitive to CO and the changes in temperature. With bubbling of CO/N or decreasing/increasing temperature, both the single-phase region and pre-ouzo zone reversibly shrink and expand, as well as with breathing. However, CO/N-induced change is more significant than that induced by temperature. The former is mainly ascribed to the reversible protonation and deprotonation of DMEA, while the latter is generally interpreted as the effects of temperature on hydrogen bond interaction. Note that CO leads to a thorough demusification from Winsor IV ME to oil-rich and water-rich two phases without nanoaggregates, while cooling only causes to a particular phase separation, producing two new MEs phases, not typical Winsor I or II MEs. Such a unique dual-responsive SFME can not only be applied in the remediation of contaminated soil, drug delivery, and nanoparticles preparation but also opens a new door to switchable emulsion.
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http://dx.doi.org/10.1021/acs.langmuir.0c03527DOI Listing
February 2021

Cyclodextrins based delivery systems for macro biomolecules.

Eur J Med Chem 2021 Feb 16;212:113105. Epub 2020 Dec 16.

China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, College of Biotechnology, Tianjin University of Science & Technology, 300457, Tianjin, China. Electronic address:

Macro biomolecules are of vital importance in regulating the biofunctions in organisms, in which proteins (including peptides when mentioned below) and nucleic acids (NAs) are the most important. Therefore, these proteins and NAs can be applied as "drugs" to regulate the biofunctions from abnormal to normal. Either for proteins and NAs, the most challenging thing is to avoid the biodegradation or physicochemical degradation before they reach the targeted location, and then functions as complete functional structures. Hence, appropriate delivery systems are very important which can protect them from these degradations. Cyclodextrins (CDs) based delivery systems achieved mega successes due to their outstanding pharmaceutical properties and there have been several reviews on CDs based small molecule drug delivery systems recently. But for biomolecules, which are getting more and more important for modern therapies, however, there are very few reviews to systematically summarize and analyze the CDs-based macro biomolecules delivery systems, especially for proteins. In this review, there were some of the notable examples were summarized for the macro biomolecules (proteins and NAs) delivery based on CDs. For proteins, this review included insulin, lysozyme, bovine serum albumin (BSA), green fluorescent protein (GFP) and IgG's, etc. deliveries in slow release, stimulating responsive release or targeting release manners. For NAs, this review summarized cationic CD-polymers and CD-cluster monomers as NAs carriers, notably, including the multicomponents targeting CD-based carriers and the virus-like RNA assembly method siRNA carriers.
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http://dx.doi.org/10.1016/j.ejmech.2020.113105DOI Listing
February 2021

Developing a Library of Mannose-Based Mono- and Disaccharides: A General Chemoenzymatic Approach to Monohydroxylated Building Blocks.

Molecules 2020 Dec 7;25(23). Epub 2020 Dec 7.

Department of Drug Sciences, University of Pavia, viale Taramelli 12, I-27100 Pavia, Italy.

Regioselective deprotection of acetylated mannose-based mono- and disaccharides differently functionalized in anomeric position was achieved by enzymatic hydrolysis. lipase (CRL) and acetyl xylan esterase (AXE) were immobilized on octyl-Sepharose and glyoxyl-agarose, respectively. The regioselectivity of the biocatalysts was affected by the sugar structure and functionalization in anomeric position. Generally, CRL was able to catalyze regioselective deprotection of acetylated monosaccharides in C6 position. When acetylated disaccharides were used as substrates, AXE exhibited a marked preference for the C2, or C6 position when C2 was involved in the glycosidic bond. By selecting the best enzyme for each substrate in terms of activity and regioselectivity, we prepared a small library of differently monohydroxylated building blocks that could be used as intermediates for the synthesis of mannosylated glycoconjugate vaccines targeting mannose receptors of antigen presenting cells.
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http://dx.doi.org/10.3390/molecules25235764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730743PMC
December 2020

Exosomes from different cells: Characteristics, modifications, and therapeutic applications.

Eur J Med Chem 2020 Dec 11;207:112784. Epub 2020 Sep 11.

College of Biotechnology, China International Science and Technology, Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Tianjin International Cooperation Research Centre of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science & Technology/Tianjin Enterprise Key Laboratory for Application Research of Hyaluronic Acid, Tianjin, 300457, China. Electronic address:

Exosomes are cystic vesicles secreted by living cells with a phospholipid bilayer membrane. Importantly, these vesicles could serve to carry lipids, proteins, genetic materials, and transmit biological information in vivo. The cell-specific proteins and genetic materials in exosomes are capable of reflecting their cell origin and physiological status. Based on the different tissues and cells (macrophage, dendritic cells, tumor cells, mesenchymal stem cells, various body fluids, and so on), exosomes exhibit different characteristics and functions. Furthermore, owing to their high delivery efficiency, biocompatibility, and multifunctional properties, exosomes are expected to become a new means of drug delivery, disease diagnosis, immunotherapy, and precise treatment. At the same time, in order to supplement or enhance the therapeutic applicability of exosomes, chemical or biological modifications can be used to broaden, change or improve their therapeutic capabilities. This review focuses on three aspects: the characteristics and original functions of exosomes secreted by different cells, the modification and transformation of exosomes, and the application of exosomes in different diseases.
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http://dx.doi.org/10.1016/j.ejmech.2020.112784DOI Listing
December 2020

Synthesis and biological evaluation of organoselenium (NSAIDs-SeCN and SeCF) derivatives as potential anticancer agents.

Eur J Med Chem 2020 Dec 20;208:112864. Epub 2020 Sep 20.

Institute for Interdisciplinary Research, Jianghan University, Wuhan Economic and Technological Development Zone, Wuhan, 430056, China; Institut Parisien de Chimie Moléculaire, UMR 8232, CNRS, Sorbonne Université, 4 Place Jussieu, 75005, Paris, France. Electronic address:

A series of organoselenium compounds based on the hybridization of nonsteroidal antiinflammatory drugs (NSAIDs) scaffolds and Se functionalities (-SeCN and -SeCF) were synthesized and characterized, and evaluated against four types of cancer cell lines, SW480 (human colon adenocarcinoma cells), HeLa (human cervical cancer cells), A549 (human lung carcinoma cells), MCF-7 (human breast adenocarcinoma cells). Interestingly, most of the investigated compounds showed active in reducing the viability of different cancer cell lines. The most active compound 3h showed IC values lower than 20 μM against the four cancer cell lines, particularly to SW480 and MCF-7 with IC 50 values of 4.9 and 3.4 μM, respectively. Furthermore, NSAIDs-SeCN derivatives (2h and 2i) and NSAIDs-SeCF derivatives (3h and 3i) were selected to investigate their ability to induce apoptosis in MCF-7 cells via modulation the expression of anti-apoptotic Bcl-2 protein, pro-inflammatory cytokines (IL-2) and proapoptotic caspase-3 protein. Moreover, the redox properties of the synthesized organoselenium candidates were conducted by 2, 2-didiphenyl-1-picrylhydrazyl (DPPH), bleomycin dependent DNA damage and glutathione peroxidase (GPx)-like assays. Taken together, these NSAIDs-Se candidates could provide promising new lead derivatives for further potential anticancer drug development.
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http://dx.doi.org/10.1016/j.ejmech.2020.112864DOI Listing
December 2020

Functional Role of Glycosphingolipids in Cancer.

Curr Med Chem 2021 ;28(20):3913-3924

Sorbonne Universite, CNRS, Institut Parisien de Chimie Moleculaire (UMR 8232), 4 Place Jussieu, 75005 Paris, France.

Glycosphingolipids (GSLs) are ubiquitous components on animal cell membranes, and exposed on the outer surface. Various studies have demonstrated that they play key roles in cell proliferation, adhesion, motility and differentiation. Usually, the specific types of GSLs are expressed more highly in tumors than in normal tissues, which are known as tumorassociated antigens. It has been revealed that most tumor cells show altered GSLs patterns on their surface, abnormal GSLs signaling and biosynthesis, which together play a major role in tumor development. Tumor-associated GSL antigens have been used in the development of antitumor vaccines. There is no doubt that GSLs play a crucial role in tumor progression and would be a promising target for cancer treatment.
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http://dx.doi.org/10.2174/0929867327666200831132200DOI Listing
July 2021

A high-efficiency phenanthrene-degrading Diaphorobacter sp. isolated from PAH-contaminated river sediment.

Sci Total Environ 2020 Dec 24;746:140455. Epub 2020 Jun 24.

College of Energy and Environment, Anhui University of Technology, Maanshan 243002, China.

Polycyclic aromatic hydrocarbons (PAHs) are typical persistent organic pollutants that accumulate in the environment, mainly from anthropogenic activities. Microbial degradation is the main pathway of PAHs degradation in the natural environment. Therefore, the widen of the available bank of microbial resources and exploration of the molecular degradation mechanisms of PAHs are crucial to the proper management of PAHs-polluted sites. In this work, a bacterial strain, YM-6, which has a high ability to utilize phenanthrene (PHE) as its sole source of carbon and energy, was isolated from sediment contaminated with PAHs. The strain YM-6 was found to degrade 96.3% of 100 mg/L of PHE in liquid cultures within 52 h. The strain was identified as Diaphorobacter sp. by 16S rDNA sequencing. The optimum growth conditions of the YM-6 strain were studied, and the results indicated that the optimum growth temperature of the strain was 30 °C, and the optimum growth pH was 7. The stain is well-suited for high-temperature stress (40 °C), and it could withstand 400 mg/L of PHE. The strain's PHE metabolism was assayed using GC-MS analyses. The results revealed that the YM-6 strain metabolized PHE via the phthalic acid pathway because the intermediates, such as phthalic acid, diethyl ester and phthalaldehydic acid, methyl ester, were detected. The use of this strain may be an attractive alternative for the bioremediation of polycyclic aromatic hydrocarbons in an aquatic environment.
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http://dx.doi.org/10.1016/j.scitotenv.2020.140455DOI Listing
December 2020

A water-soluble and incubate-free fluorescent environment-sensitive probe for ultrafast visualization of protein thiols within living cells.

Anal Chim Acta 2020 Aug 18;1126:72-81. Epub 2020 Jun 18.

Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, College of Chemistry & Materials Science, Northwest University, Xi'an, Shaanxi, 710127, PR China.

The amount of protein thiols play a crucial role in maintaining the cellular redox homeostasis and have significant implications to indicate a series of diseases. Therefore, it is necessary to develop an ideal probe for protein thiol detection in a simple and readily implementable method. Consequently, a water-soluble and incubate-free fluorescent environment-sensitive probe DMTs-OCC was synthesized using 7-diethylamincoumarin as the fluorophore and 4-(5-Methanesulfonyl- [1,2,3,4]tetrazol-1-yl)-phenol (MSTP) as a thiol receptor reagent. The blue-shift emission spectra of probe DMTs-OCC was observed by ultrafast binding to protein sulfhydryl groups from the excited intramolecular charge transfer (ICT) to the twisted intramolecular charge transfer (TICT) conversion process in aqueous solution. The experimental results showed that probe DMTs-OCC exhibited an excellent selectivity to protein thiols and biocompatibility in aqueous solution, as well as terrific cell membrane permeability which enabled the successful visualization of BSA protein thiol in living cells. Moreover, no excess probe was cleaned and no incubation time was needed in cell experiments. Therefore, it could provide a new method to the construction of fluorescent probes for protein thiols labelling and visualization.
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http://dx.doi.org/10.1016/j.aca.2020.06.026DOI Listing
August 2020

Chemoenzymatic synthesis of arabinomannan (AM) glycoconjugates as potential vaccines for tuberculosis.

Eur J Med Chem 2020 Oct 15;204:112578. Epub 2020 Jul 15.

Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, UMR 8232, 4 Place Jussieu, 75005, Paris, France; Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, College of Chemistry & Chemical Engineering, Hainan Normal University, Haikou 571158, China. Electronic address:

Mycobacteria infection resulting in tuberculosis (TB) is one of the top ten leading causes of death worldwide in 2018, and lipoarabinomannan (LAM) has been confirmed to be the most important antigenic polysaccharide on the TB cell surface. In this study, a convenient synthetic method has been developed for synthesizing three branched oligosaccharides derived from LAM, in which a core building block was prepared by enzymatic hydrolysis in flow chemistry with excellent yield. After several steps of glycosylations, the obtained oligosaccharides were conjugated with recombinant human serum albumin (rHSA) and the ex-vivo ELISA tests were performed using serum obtained from several TB-infected patients, in order to evaluate the affinity of the glycoconjugate products for the human LAM-antibodies. The evaluation results are positive, especially compound 21 that exhibited excellent activity which could be considered as a lead compound for the future development of a new glycoconjugated vaccine against TB.
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http://dx.doi.org/10.1016/j.ejmech.2020.112578DOI Listing
October 2020

Temperature-Switchable Surfactant-Free Microemulsion.

Langmuir 2020 Jul 25;36(26):7356-7364. Epub 2020 Jun 25.

Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical & Materials Engineering, Jiangnan University, Wuxi 214122, P. R. China.

Stimuli-responsive microemulsions have recently attracted significant interest due to their unique properties. Here, we developed a novel surfactant-free microemulsion (SFME) in a nontoxic ternary mixture, in which dimethyl sulfoxide (DMSO) was used as an amphisolvent, n-butanol was used as a nonpolar phase, and water was used as a polar phase. The DLS results confirmed the presence of the preouzo zone, and the polarity experiment revealed that the single-phase region can be further divided into oil-in-water, bicontinuous, and water-in-oil subregions. The size of droplets increased upon increasing the water or n-butanol content but decreased with increasing DMSO content. With increasing temperature, the area of the single-phase region increased, accompanied by a decrease in the size of the droplets, and the critical point moved to the corner of n-butanol. No matter in what subregion the formulation was found, decreasing temperature to below the phase-transition temperature (PTT) will induce a transition from monophasic MEs to complete phase separation and vice versa. This is mainly attributed to the effect of temperature on the hydrogen-bond interaction. Ag nanoparticles (Ag NPs) can be prepared above the PTT and facilely separated below PTT. The Ag NPs obtained from the current SFME showed higher catalytic activity than that obtained from a common surfactant-based ME.
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http://dx.doi.org/10.1021/acs.langmuir.0c00828DOI Listing
July 2020

F7 and topotecan co-loaded thermosensitive liposome as a nano-drug delivery system for tumor hyperthermia.

Drug Deliv 2020 Dec;27(1):836-847

College of Biotechnology, China International Science and Technology, Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Tianjin International Cooperation Research Centre of Food Nutrition/Safety and Medicinal Chemistry, Tianjin University of Science & Technology/Tianjin Enterprise Key Laboratory for Application Research of Hyaluronic Acid, Tianjin, China.

In order to enhance the targeting efficiency and reduce anti-tumor drug's side effects, topotecan (TPT) and F7 were co-loaded in thermosensitive liposomes (F7-TPT-TSL), which show enhanced permeability and retention in tumors, as well as local controlled release by heating . TPT is a water-soluble inhibitor of topoisomerase I that is converted to an inactive carboxylate structure under physiological conditions (pH 7.4). F7 is a novel drug significantly resistant to cyclin-dependent kinase but its use was restricted by its high toxicity. F7-TPT-TSL had excellent particle distribution (about 103 nm), high entrapment efficiency (>95%), obvious thermosensitive property, and good stability. Confocal microscopy demonstrated specific higher accumulation of TSL in tumor cells. MTT proved F7-TPT-TSL/H had strongest cell lethality compared with other formulations. Then therapeutic efficacy revealed synergism of TPT and F7 co-loaded in TSL, together with hyperthermia. Therefore, the F7-TPT-TSL may serve as a promising system for temperature triggered cancer treatment.
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http://dx.doi.org/10.1080/10717544.2020.1772409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216433PMC
December 2020

Permethylated NHC-Capped α- and β-Cyclodextrins (ICyD ) Regioselective and Enantioselective Gold-Catalysis in Pure Water.

Chemistry 2020 Dec 7;26(68):15901-15909. Epub 2020 Oct 7.

Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire (IPCM), UMR 8232, 4, place Jussieu, 75005, Paris, France.

A series of water-soluble encapsulated copper(I), silver(I) or gold(I) complexes based on NHC-capped permethylated cyclodextrins (ICyD ) were developed and used as catalysts in pure water for hydration, lactonization, hydroarylation and cycloisomerization reactions. ICyD ligands gave cavity-based high regioselectivity in hydroarylations, and high enantioselectivities in gold-catalyzed cycloisomerizations reactions giving up to 98 % ee in water. These ICyD are therefore useful ligands for selective catalysis in pure water.
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http://dx.doi.org/10.1002/chem.202001990DOI Listing
December 2020

An Epoxide Intermediate in Glycosidase Catalysis.

ACS Cent Sci 2020 May 16;6(5):760-770. Epub 2020 Apr 16.

School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.

Retaining glycoside hydrolases cleave their substrates through stereochemical retention at the anomeric position. Typically, this involves two-step mechanisms using either an enzymatic nucleophile via a covalent glycosyl enzyme intermediate or neighboring-group participation by a substrate-borne 2-acetamido neighboring group via an oxazoline intermediate; no enzymatic mechanism with participation of the sugar 2-hydroxyl has been reported. Here, we detail structural, computational, and kinetic evidence for neighboring-group participation by a mannose 2-hydroxyl in glycoside hydrolase family 99 -α-1,2-mannanases. We present a series of crystallographic snapshots of key species along the reaction coordinate: a Michaelis complex with a tetrasaccharide substrate; complexes with intermediate mimics, a sugar-shaped cyclitol β-1,2-aziridine and β-1,2-epoxide; and a product complex. The 1,2-epoxide intermediate mimic displayed hydrolytic and transfer reactivity analogous to that expected for the 1,2-anhydro sugar intermediate supporting its catalytic equivalence. Quantum mechanics/molecular mechanics modeling of the reaction coordinate predicted a reaction pathway through a 1,2-anhydro sugar via a transition state in an unusual flattened, envelope ( ) conformation. Kinetic isotope effects ( / ) for anomeric-H and anomeric-C support an oxocarbenium ion-like transition state, and that for C2-O (1.052 ± 0.006) directly implicates nucleophilic participation by the C2-hydroxyl. Collectively, these data substantiate this unprecedented and long-imagined enzymatic mechanism.
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http://dx.doi.org/10.1021/acscentsci.0c00111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256955PMC
May 2020

Synthesis of 2'-paclitaxel 2-deoxy-2-fluoro-glucopyranosyl carbonate for specific targeted delivery to cancer cells.

Carbohydr Res 2020 Jul 25;493:108034. Epub 2020 May 25.

Department of Pharmacy, Qilu Hospital of Shandong University, Jinan, 250012, Shandong Province, PR China.

A novel 2-fluorodeoxyglucose conjugated derivative of paclitaxel was efficiently synthesized using a linker between 2'-OH of paclitaxel and C1-hydroxyl group of 2-fluorodeoxyglucose. In preparation of the prodrug, allyl carbonates were selected as the protective group and the efficient one-step removal of allyloxycarbonyl groups at the end of the synthesis using palladium chemistry gave the target molecule in good yield. The prodrug not only improved the pharmaceutical properties of paclitaxel, such as solubility and stability, but also demonstrated enhanced cytotoxicity and selectivity for cancer cells and less toxicity toward normal HUVEC cells.
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http://dx.doi.org/10.1016/j.carres.2020.108034DOI Listing
July 2020

Synthesis of a Hexavalent Betulinic Acid Derivative as a Hemagglutinin-Targeted Influenza Virus Entry Inhibitor.

Mol Pharm 2020 07 1;17(7):2546-2554. Epub 2020 Jun 1.

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

Naturally occurring pentacyclic triterpenes, such as betulinic acid (BA) and its derivatives, exhibit various pharmaceutical activities and have been the subject of great interest, in particular for their antiviral properties. Here, we found a new anti-influenza virus conjugate, hexakis 6-deoxy-6-[4--(3β-hydroxy-lup-20(29)-en-28-oate)aminomethyl-1-1,2,3-triazol-1-yl]-2,3-di--acetyl-α-cyclodextrin (CYY1-11, ), in a mini library of pentacyclic triterpene-cyclodextrin conjugates by performing a cell-based screening assay and then exploring the underlying mechanisms. Our results showed that conjugate possessed a high-level activity against the influenza virus A/WSN/33 with an IC value of 5.20 μM (SI > 38.4). The study of the mechanism of action indicated that conjugate inhibited viral replication by directly targeting the influenza hemagglutinin protein ( = 1.50 μM), thus efficiently preventing the attachment of the virion to its receptors on host cells and subsequent infection. This study suggests that multivalent BA derivatives have possible use as a new class of influenza virus entry inhibitors.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c00244DOI Listing
July 2020

Synthesis and Potential Anticancer Activity of Some Novel Selenocyanates and Diselenides.

Chem Biodivers 2020 May 15;17(5):e1900603. Epub 2020 May 15.

Institute for Interdisciplinary Research, Jianghan University, Wuhan Economic and Technological Development Zone, Wuhan, 430056, P. R. China.

In the present study, twenty-four selenocyanate and diselenide compounds were synthesized and characterized, and their anticancer activities against the human cancer cell lines Caco2, BGC-823, MCF-7 and PC-3 were determined. Interestingly, most of the new compounds were active in reducing the viability of different cancer cell lines. Two compounds exhibited higher promising activities than other derivatives. The most active compound showed the least IC values against the four cancer cell lines, particularly to PC-3 with IC values below 5 μm. Two compounds were selected to monitor the expression levels of Bcl-2, IL-2 and caspase-3 molecular biomarkers. Interestingly, the two compounds downregulated the Bcl-2 expression levels and upregulated the expression of IL-2 and caspase-3 in PC-3 cells compared to untreated cells. Moreover, most of the synthesized organoselenides exhibited good Gpx-like activities comparable to ebselen. These results appear that introduction of selenocyanate (-SeCN) or diselenides (-Se-Se-) moiety to some carboxy derivatives could serve as a promising launch point for the further design of this type of organic selenium anticancer agent.
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http://dx.doi.org/10.1002/cbdv.201900603DOI Listing
May 2020

Multistimuli-Responsive Pickering Emulsion Stabilized by Se-Containing Surfactant-Modified Chitosan.

J Agric Food Chem 2020 Apr 24;68(13):3986-3994. Epub 2020 Mar 24.

Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical & Materials Engineering, Jiangnan University, Wuxi 214122, People's Republic of China.

Particle-stabilized emulsions that can respond to external stimuli have attracted significant concerns due to their intelligent-controlled stability, whereas particle-stabilized Pickering emulsions responding to multistimuli but based on biomass have been rarely reported. Here, a multistimuli-responsive Pickering emulsion was developed using the modified chitosan as stabilizer. Due to electrostatic attraction, Se-containing anionic surfactant, sodium 11-(butylselenyl)undecylsulfate (CSeCS), can bind with CS at an acidic pH and form CS-CSeCS complexes which can further self-associate to form micrometer-sized particles with the character of partially hydrophobicity. Therefore, at pH < p, an oil-in-water Pickering emulsion can be formed using CS-CSeCS particles as stabilizers and can spontaneously respond to redox, ion, and pH. First, with the addition of oxidation, the hydrophilicity of CSeCS was enhanced, and thus, hydrophobic association of CS-CSeCS decreased, leading to the disruption of CS-CSeCS particles. Hence, the emulsion destabilized. The demulsification process is closely related with the dosage of oxidant and the oxidation time. Second, introduction of a competitive ion (e.g., CTAB) could break the binding between CSeCS and CS, leading to the disruption of particle emulsifier. Thereby, demulsification occurred. Third, with sequentially increasing/decreasing pH, the emulsion can be switched from stable to unstable and then to stable again accordingly. Such a unique pH-responsive behavior has never been discovered in other pH-responsive Pickering emulsions. All of the stimuli-responsive behaviors were reversible. Upon alternately adding oxidant/reductant, CTAB/CSeCS, or base/acid, the current emulsion can be reversibly switched off (destabilization) and on (stabilization). Such a Pickering emulsion may be a good candidate as a vehicle of functional ingredient.
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http://dx.doi.org/10.1021/acs.jafc.0c00010DOI Listing
April 2020

Reversible-Tuning Krafft Temperature of Selenium-Containing Ionic Surfactants by Redox Chemistry.

Langmuir 2020 Apr 24;36(13):3514-3521. Epub 2020 Mar 24.

Zanyu Technology Group Company Ltd., Hangzhou 310009, P. R. China.

An easy, effective, and reversible strategy for tuning the Krafft temperature () of selenium-containing ionic surfactants, with head groups ranging in nature from anionic to amphoteric, has been achieved for the first time via the redox chemistry of selenium. After oxidation with HO, the selenide group was converted to a more hydrophilic selenoxide group. This made the oxidized forms of the surfactants more water-soluble, which results in a marked reduction in the . In contrast, the hydrophilic selenoxide was restored to its reduced form of selenide via reduction reaction, which allowed the value to return to its initial value. By alternating the oxidization and reduction treatments, the of the selenium-containing surfactants in this work could be reversibly switched over 5-10 cycles without causing obvious adverse distortions.
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http://dx.doi.org/10.1021/acs.langmuir.9b03747DOI Listing
April 2020
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