Hydroxy Moiety Research Articles

Design, synthesis and molecular docking studies of imidazole and benzimidazole linked ethionamide derivatives as inhibitors of InhA and antituberculosis agents

To explore effective antituberculosis agents, a new class of imidazoles and benzimidazoles linked ethionamide analogs were designed and synthesized. The elemental analysis, 1H NMR, 13C NMR and mass spectral data were used to characterize all of the novel analogs. In vitro activity against Mycobacterium tuberculosis (Mtb) H37Rv was assessed for all of the target compounds. The hydroxy and nitrile moieties on the imidazole ring, as well as the hydroxy and methoxy groups on the benzimidazole ring connected to the ethionamide side chain, were shown to be advantageous. In our cell viability experiment against the Vero cell line, all of the compounds were non-cytotoxic even at 100 μM. To confirm the powerful analogs target identification, we investigated their in vitro inhibitory action on an M. tuberculosis InhA over-expressing (Mtb InhA-OE) strain, which yielded MICs nearly twice those of the Mtb H37Rv strain. Furthermore, the results of molecular docking confirmed the experimental findings. Additionally, the molecules were evaluated in silico for ADMET and drug similarity features. The experimental observation enables the newly generated ethionamide derivatives to be attractive candidates for the creation of newer and better anti-TB agents.

Concentration-Dependent Association of Flavylium Chloride with Differential Hydroxy Moieties in Ethanol

Flavylium ions (6a–6e) were synthesized using Aldol condensation to compare the spectroscopic properties caused by the different numbers and locations of hydroxy groups on the flavylium cations (AH+). Without the addition of acid, increasing the concentration of flavylium ions to 10 mM in ethanol led to the following observation. The flavylium ions with the least number of OH groups (6a and 6b) showed a change in peak at higher concentrations, whereas 6c and 6d did not show the same degree of change in their 1H-NMR signals. This suggests an equilibrium that shifts the isomers B, CE, and Cz more towards the flavylium ion with more OH groups even at low concentrations. One possibility for the cause of this shift is that the flavylium ions become more stable through aggregation. In addition to the NMR results, the UV measurements confirmed that isomers with fewer OH groups showed a more dramatic shift towards the flavylium ion at higher concentrations. Using modeling data at DFT//B3LYP/6311**G(d) level, the self-association was investigated to show that the hydrogen bonding of OH groups is the main player but cannot stabilize entirely without the presence of the chloride ion in the complex.

RAFT Polymerization of a Renewable Ricinoleic Acid‐Derived Monomer and Subsequent Post‐Polymerization Modification via the Biginelli‐3‐Component Reaction

AbstractThe search for renewable monomers for radical polymerization techniques is of current interest due to the awareness of sustainability requirements in the chemical sciences. Herein, the synthesis and reversible addition‐fragmentation chain‐transfer (RAFT) polymerization of a renewable methacrylate monomer based on ricinoleic acid as sustainable starting material is presented. In addition, the hydroxy moiety of the ricinoleic acid is converted to an acetoacetate in order to allow for a post‐polymerization modification (PPM) using the Biginelli‐three‐component reaction (B‐3CR), rendering the presented monomer a renewable and highly flexible reactant for the synthesis of polymer materials. Consequently, RAFT polymerization yields macromolecules with a molecular weight of up to 15 000 g mol−1 and expectedly narrow molecular weight distributions with Ðs around 1.13. The feasibility of chain extension and block copolymer synthesis is demonstrated. Eventually, the PPM of the acetoacetate moiety of the polymer repeating units using the B‐3CR is proven to be efficient with conversions of up to 95% of the acetoacetates, while the modification allows for a pronounced increase of the glass transition temperature to approximately room temperature compared to the unmodified polymers (Tg = −50 °C).

Chiral deaza-coelenterazine analogs for probing a substrate-binding site in the Ca2+-binding photoprotein aequorin.

The Ca2+-binding photoprotein aequorin is a complex of apoAequorin (apoprotein) and (S)-2-peroxycoelenterazine. Aequorin can be regenerated by the incubation of apoAequorin with coelenterazine and molecular oxygen (O2). In this study, to investigate the molecular recognition of apoAequorin for coelenterazine using chemical probes, the chiral deaza-analogs of (S)- and (R)-deaza-CTZ (daCTZ) for coelenterazine and of (S)-2- and (R)-2-hydroxymethyl-deaza-CTZ (HM-daCTZ) for 2-peroxycoelenterazine were efficiently prepared by the improvement method. The chiral deaza-analogs of (S)-daCTZ and (S)-HM-daCTZ selectively inhibited the regeneration step to aequorin by binding the catalytic site of coelenterazine in the apoAequorin molecule. The crystal structures of the apoAequorin complexes with (S)-daCTZ and (S)-HM-daCTZ were determined, suggesting that the hydroxy moiety at the C6-hydroxyphenyl group and the carbonyl moiety of the imidazopyrazinone ring in coelenterazine are essential to bind the apoAequorin molecule through hydrogen bonding. Therefore, the chiral deaza-analogs of coelenterazine can be used as a probe to study the interaction between coelenterazine and the related proteins including photoprotein, luciferase, and coelenterazine-binding protein.

In silico studies of selected multi-drug targeting against 3CLpro and nsp12 RNA-dependent RNA-polymerase proteins of SARS-CoV-2 and SARS-CoV.

An outbreak of a cluster of viral pneumonia cases, subsequently identified as coronavirus disease 2019 (COVID-19), due to a novel SARS-CoV-2 necessitates an urgent need for a vaccine to prevent infection or an approved medication for a cure. In our in silico molecular docking study, a total of 173 compounds, including FDA-approved antiviral drugs, with good ADME descriptors, and some other nucleotide analogues were screened. The results show that these compounds demonstrate strong binding affinity for the residues at the active sites of RNA-dependent RNA-polymerase (RdRp) modelled structures and Chymotrypsin-like cysteine protease (3CLpro) of the HCoV proteins. Free energies (ΔG’s) of binding for SARS-CoV-2 and SARS-CoV RdRp range from – 5.4 to – 8.8 kcal/mol and – 4.9 to – 8.7 kcal/mol, respectively. Also, SARS-CoV-2 and SARS-CoV 3CLpro gave ΔG values ranging from − 5.1 to − 8.4 kcal/mol and − 5.5 to − 8.6 kcal/mol, respectively. Interesting results are obtained for ivermectin, an antiparasitic agent with broad spectrum activity, which gave the highest binding energy value (− 8.8 kcal/mol) against the 3CLpro of SARS-CoV-2 and RdRps of both SARS-CoV and SARS-CoV-2. The reason for such high binding energy values is probably due to the presence of hydroxy, methoxy and sugar moieties in its structure. The stability of the protein–ligand complexes of polymerase inhibitors considered in this investigation, such as Sofosbuvir, Remdesivir, Tenofovir, Ribavirin, Galidesivir, 5c3, 5h1 and 7a1, show strong to moderate hydrogen bonding and hydrophobic interactions (π–π stacked, π–π T-shaped, π-sigma and π-alkyl). The stability provided from such interactions translate into greater antiviral activity or inhibitory effect of the ligands. Assessment of the average free energies of binding of the FDA approved drugs are highly comparable for conformers of a particular inhibitor, indicating similar modes of binding within the pockets.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13721-021-00299-2.

Elucidation of Gut Microbiota-Associated Lipids Using LC-MS/MS and 16S rRNA Sequence Analyses.

SummaryHost-microbiota interactions create a unique metabolic milieu that modulates intestinal environments. Integration of 16S ribosomal RNA (rRNA) sequences and mass spectrometry (MS)-based lipidomics has a great potential to reveal the relationship between bacterial composition and the complex metabolic network in the gut. In this study, we conducted untargeted lipidomics followed by a feature-based molecular MS/MS spectral networking to characterize gut bacteria-dependent lipid subclasses in mice. An estimated 24.8% of lipid molecules in feces were microbiota-dependent, as judged by > 10-fold decrease in antibiotic-treated mice. Among these, there was a series of unique and microbiota-related lipid structures, including acyl alpha-hydroxyl fatty acid (AAHFA) that was newly identified in this study. Based on the integrated analysis of 985 lipid profiles and 16S rRNA sequence data providing 2,494 operational taxonomic units, we could successfully predict the bacterial species responsible for the biosynthesis of these unique lipids, including AAHFA.

Methyltransferase Contingencies in the Pathway of Everninomicin D Antibiotics and Analogues.

Everninomicins are orthoester oligosaccharide antibiotics with potent activity against multidrug-resistant bacterial pathogens. Everninomicins act by disrupting ribosomal assembly in a distinct region in comparison to clinically prescribed drugs. We employed microporous intergeneric conjugation with Escherichia coli to manipulate Micromonospora for targeted gene-replacement studies of multiple putative methyltransferases across the octasaccharide scaffold of everninomicin effecting the A1 , C, F, and H rings. Analyses of gene-replacement and genetic complementation mutants established the mutability of the everninomicin scaffold through the generation of 12 previously unreported analogues and, together with previous results, permitted assignment of the ten methyltransferases required for everninomicin biosynthesis. The in vitro activity of A1 - and H-ring-modifying methyltransferases demonstrated the ability to catalyze late-stage modification of the scaffold on an A1 -ring phenol and H-ring C-4' hydroxy moiety. Together these results establish the potential of the everninomicin scaffold for modification through mutagenesis and in vitro modification of advanced biosynthetic intermediates.

Synthesis, Characterization, Antitubercular Activity and Docking Studies of 2-(benzo [d]oxazol-2-ylthio)-1-(3-(4-fluoro-3- methylphenyl)-5-(substituted aryl)-4,5-dihydro-1H-pyrazol-1-yl) ethanone

A new series of 2-(benzo[d]oxazol-2-ylthio)-1-(3-(4-fluoro-3-methylphenyl)-5- (substituted aryl)-4,5-dihydro-1H-pyrazol-1-yl)ethanone (6a-6j) were designed and synthesized from the intermediate chalcones (1a-1j). The synthesized compounds were characterized by FT-IR, 1H-NMR, Mass spectroscopy and bases of elemental analysis. The agar dilution method (In vitro M. tuberculosis method) was employed for anti-tubercular screening. From the study, it was revealed that compounds 6b and 6h showed increased potency. In phenyl ring attached to 4,5-dihydropyrazole ring presence of electron donating substituent like dimethylamino, hydroxy and methoxy moiety mightbe responsible for the powerful anti-mycobacterial activity displayed by derivatives 6b and 6h. Further docking studies were performed to predict the interactions of the target compounds 6a-6j within the Mycobacterium tuberculosis enoyl reductase enzyme by their scores and mode of binding to amino acids. In addition, drug-likeness score and molecular properties responsible for a good pharmacokinetic profile were calculated by Osiris property explorer and Molinspiration online toolkit, respectively. From the results, it was revealed that the synthesized compounds with electron releasing groups showed the most potent activity compared to that of standard drug. Key words: Anti-tubercular activity, Benzo[d]oxazole-2-thiol, Chalcones, Docking studies, Pyrazolines.

Toosendanin relatives, trypanocidal principles from Meliae Cortex.

Africa Trypanosomiasis remains a serious health problem, but the approved drugs for this disease are so few that novel trypanocidal compounds are demanded. In search for trypanocidal principles from medicinal plants, we found MeOH extracts of Meliae Cortex with potent activity through the screening from about 300 kinds of methanolic extract. By bioassay-guided fractionation from this extract through the liquid-liquid partition and subsequent chromatographic technique using silica gel and ODS, finally we disclosed toosendanin (1) and its relatives as active principles. These active congeners showed not only potent trypanocidal activity but also little cytotoxicity to display the excellent selective index. Taking the isolated amount as well as trypanocidal activity into consideration, 1 was disclosed to be the responsible active principle in Meliae Cortex. Additionally, the derivatives of 1 were chemically prepared from 1 and bioactivity of them were also evaluated. Through the comparison with their trypanocidal activity among the isolated relatives and the synthesized derivatives of 1, the epoxide moiety was revealed to be essential for their potent trypanocidal activity. Furthermore, 3-O-acetyl group and 7-hydroxyl group were presumed to be important functional groups and introduction of methylpropionyl group into hemiacetal hydroxy moiety was clarified to enhance their typanocidal activity.

6-Amino[1,2,5]oxadiazolo[3,4-b]pyrazin-5-ol Derivatives as Efficacious Mitochondrial Uncouplers in STAM Mouse Model of Nonalcoholic Steatohepatitis.

Small molecule mitochondrial uncouplers have recently garnered great interest for their potential in treating nonalcoholic steatohepatitis (NASH). In this study, we report the structure-activity relationship profiling of a 6-amino[1,2,5]oxadiazolo[3,4-b]pyrazin-5-ol core, which utilizes the hydroxy moiety as the proton transporter across the mitochondrial inner membrane. We demonstrate that a wide array of substituents is tolerated with this novel scaffold that increased cellular metabolic rates in vitro using changes in oxygen consumption rate as a readout. In particular, compound SHS4121705 (12i) displayed an EC50 of 4.3 μM in L6 myoblast cells and excellent oral bioavailability and liver exposure in mice. In the STAM mouse model of NASH, administration of 12i at 25 mg kg-1 day-1 lowered liver triglyceride levels and improved liver markers such as alanine aminotransferase, NAFLD activity score, and fibrosis. Importantly, no changes in body temperature or food intake were observed. As potential treatment of NASH, mitochondrial uncouplers show promise for future development.

Characterization of a caffeoyl-CoA O-methyltransferase-like enzyme involved in biosynthesis of polymethoxylated flavones in Citrus reticulata.

Polymethoxylated flavones (PMFs), which accumulate exclusively in fruit peel of citrus, play important physiological and pharmacological roles but the genetic basis for the methylation of flavonoids has not been fully elucidated in citrus. Here we characterize a caffeoyl-CoA O-methyltransferase-like enzyme, designated CrOMT1. The expression pattern of CrOMT1 was highly correlated with the concentration of the three major PMFs in two different citrus fruit tissues during fruit maturation. Exposure of fruit to UV-B radiation sharply increased the level of CrOMT1 transcripts and also led to the accumulation of three PMFs. The potential role of CrOMT1 was studied by testing the catalytic activity of recombinant CrOMT1 with numerous possible substrates in vitro. The enzyme could most efficiently methylate flavones with neighboring hydroxy moieties, with high catalytic efficiencies found with 6-OH- and 8-OH-containing compounds, preferences that correspond precisely with the essential methylation sites involved in the synthesis of the three naturally occurring PMFs in Citrus reticulata. This indicates that CrOMT1 is capable of in vitro methylation reactions required to synthesize PMFs in vivo. Furthermore, transient overexpression of CrOMT1 increased levels of the three major PMFs in fruit, indicating that CrOMT1 is likely to play an essential role in the biosynthesis of PMFs in citrus.

Concise Synthesis and Evaluation of ortho-Naphthoquinones Containing a Phenolic Hydroxy Moiety

Concise Synthesis and Evaluation of ortho-Naphthoquinones Containing a Phenolic Hydroxy Moiety

Impact of hydroxy moieties at the benzo[7]annulene ring system of GluN2B ligands: Design, synthesis and biological evaluation

In this study, the impact of one or two hydroxy moieties at the benzo[7]annulene scaffold on the GluN2B affinity and cytoprotective activity was analyzed. The key intermediate for the synthesis of OH-substituted benzo[7]annulenamines 11–13 and 17 was the epoxyketone 8. Reductive epoxide opening of 8 resulted with high regioselectivity in the 5-hydroxyketone 9 (Pd(OAc)2, HCO2H, phosphane ligand) or the 6-hydroxyketone 10 (H2, Pd/C), whereas hydrolysis in aqueous dioxane led to the dihydroxyketone 14. Reductive amination of these ketones with primary amines and NaBH(OAc)3 afforded the benzo[7]annulenamines 11–13 and 17. In receptor binding studies 5-OH derivatives 11 and 12 showed higher GluN2B affinity than 6-OH derivatives 13, which in turn were more active than 5,6-di-OH derivative 17a. The same order was found for the cytoprotective activity of the ligands. The tertiary amine 12a with one OH moiety in 5-position represents the most promising GluN2B negative allosteric modulator with a binding affinity of Ki = 49 nM and a cytoprotective activity of IC50 = 580 nM. In the binding pocket 12a shows a crucial H-bond between the benzylic OH moiety and the backbone carbonyl O-atom of Ser132 (GluN1b). It was concluded that a 5-OH moiety is essential for the inhibition of the NMDA receptor associated ion channel, whereas a OH moiety in 6-position is detrimental for binding and inhibition. An OH or CH2OH moiety at 2-position results in binding at the ifenprodil binding site, but very weak ion channel inhibition.

Oxidative phase I metabolism of the UV absorber 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV 328) in an in vitro model with human liver microsomes

2-(2H-Benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV 328, CAS: 25973-55-1) is an ultraviolet light (UV) absorber which is used as an additive for plastics and other polymeric substances to prevent the host material from light induced degradation reactions. However, no information about human exposure, metabolism and kinetics is available for this substance so far. Therefore, in vitro experiments with human liver microsomes were performed to derive oxidative phase I metabolites of UV 328 in an explorative approach using liquid-chromatography coupled with tandem mass spectrometry. Initially, a suspect screening mode was applied to the incubated samples. Six metabolites with hydroxy or oxo groups as well as a metabolite carrying both hydroxy and carbonyl moieties at the alkyl side chains were postulated and custom synthesized as reference standards. Afterwards, the results were verified in a target screening approach. Thereby, five of the six investigated analyte structures were confirmed. Quantitative estimations of the generated transformation products revealed 2-(2H-benzotriazol-2-yl)-6-(3-hydroxy-2-methylbutan-2-yl)-4-(tert-pentyl)phenol (UV 328-6/3-OH), 2-(2H-benzotriazol-2-yl)-4-(3-hydroxy-2-methylbutan-2-yl)-6-(tert-pentyl)phenol (UV 328-4/3-OH) and 2-(2H-benzotriazol-2-yl)-4-(2-methylbutan-3-on-2-yl)-6-(3-hydroxy-2-methylbutan-2-yl)phenol (UV 328-4/3-CO-6/3-OH) as most promising parameters. In summary, oxidation of both alkyl side chains at the phenol moiety was proven, but no metabolic transformations at the benzotriazole moiety were observed.

Cobalamin-Dependent Apparent Intramolecular Methyl Transfer for Biocatalytic Constitutional Isomerization of Catechol Monomethyl Ethers.

Isomerization is a fundamental reaction in chemistry. However, isomerization of phenyl methyl ethers has not been described yet. Using a cobalamin-dependent methyl transferase, a reversible shuttle concept was investigated for isomerization of catechol monomethyl ethers. The methyl ether of substituted catechol derivatives was successfully transferred onto the adjacent hydroxy moiety. For instance, the cobalamin-dependent biocatalyst transformed isovanillin to its regioisomer vanillin with significant regioisomeric excess (68% vanillin). To the best of our knowledge, isomerization by methyl transfer employing a methyl transferase has not been reported before.

New Insights Into the Polar Lipid Composition of Extremely Halo(alkali)philic Euryarchaea From Hypersaline Lakes.

We analyzed the polar membrane lipids of 13 strains of halo(alkali)philic euryarchaea from hypersaline lakes. Nine belong to the class Halobacteria, representing two functional groups: aerobic polysaccharide utilizers and sulfur-respiring anaerobes. The other four strains represent halo(alkali)philic methanogens from the class Methanomicrobia and a recently discovered class Methanonatronarchaeia. A wide range of polar lipids were detected across the 13 strains including dialkyl glycerol diethers (archaeols), membrane-spanning glycerol tetraethers and diether-based cardiolipins. The archaeols contained a range of core lipid structures, including combinations of C20 and C25 isoprenoidal alkyl chains, unsaturations, and hydroxy moieties. Several diether lipids were novel, including: (a) a phosphatidylglycerolhexose (PG-Gly) headgroup, (b) a N,N,N-trimethyl aminopentanetetrol (APT)-like lipid with a methoxy group in place of a hydroxy group on the pentanetetrol, (c) a series of polar lipids with a headgroup with elemental composition of either C12H25NO13S or C12H25NO16S2, and (d) novel cardiolipins containing a putative phosphatidylglycerolphosphate glycerophosphate (PGPGP) polar moiety. We found that the lipid distribution of the 13 strains could be generally separated into two groups, the methanogens (group) and the Halobacteria (class) based on the presence of specific core lipids. Within the methanogens, adaption to a high or more moderate salt concentration resulted in different ratios of glycerol dialkyl glycerol tetraethers (GDGTs) to archaeol. The methanogen Methanosalsum natronophilum AME2T had the most complex diether lipid composition of any of the 13 strains, including hydroxy archaeol and macrocyclic archaeol which we surmise is an order-specific membrane adaption. The zwitterionic headgroups APT and APT-Me were detected only in the Methanomicrobiales member Methanocalculus alkaliphilus AMF2T which also contained the highest level of unsaturated lipids. Only alkaliphilic members of the Natrialbales order contained PGPGP cardiolipins and the PG-Gly headgroup. The four analyzed neutrophilic members of the Halobacteria were characterized by the presence of sulfur-containing headgroups and glycolipids. The presence of cardiolipins with one or more i-C25 alkyl chains, generally termed extended archaeol (EXT-AR), in one of the Methanonatronarchaeia strains was unexpected as only one other order of methanogenic archaea has been reported to produce EXT-AR. We examined this further by looking into the genomic potential of various archaea to produce EXT-AR.

Selective Separation of Scheelite from Calcite by Self-Assembly of H2SiO3 Polymer Using Al3+ in Pb-BHA Flotation

The flotation separation of scheelite from calcite is problematic, where sodium silicate modified by polyvalent metal ions has shown some advantages for selective depression. In this study, an Al-Na2SiO3 polymer was used as the depressant for the flotation separation of scheelite from calcite using a lead complex of benzohydroxamic acid (Pb-BHA) as the collector. Furthermore, a number of measurements were conducted to investigate the structure of the Al-Na2SiO3 polymer and its adsorption behavior with Pb-BHA complexes on the mineral surface. Flotation experiments indicated that the Al-Na2SiO3 polymer shows good selectivity for the flotation separation of scheelite from calcite at pH 8, where the optimum ratio of sodium silicate to aluminum sulfate was 2:1. Fourier-Transform Infrared (FTIR) and solution chemical analyses revealed that aluminum hydroxide complexes and the hydroxy moiety of silicic acid are able to self-assemble via condensation affording an Al-Na2SiO3 polymer, i.e., a composite aluminosilicate polymer. The zeta potential measurements and adsorption capacity measurements indicated that, upon adsorption of the Al-Na2SiO3 polymer and Pb-BHA complexes on the mineral surface, the Al-Na2SiO3 polymer had less influence on the adsorption of Pb-BHA complexes on the scheelite surface, while the opposite was true for calcite. Therefore, more Pb-BHA complexes and fewer Al-Na2SiO3 polymers were deposited on the scheelite surface, while fewer Pb-BHA complexes and more Al-Na2SiO3 polymers were adsorbed on the calcite surface. The selective separation of scheelite from calcite was attributed to the cooperative selectivity of the Pb-BHA complexes and Al-Na2SiO3 polymer.

Crystal structures and Hirshfeld surface analyses of the di- and tri-hydrates of (5α,17E)-17-hydrazonoandrostan-3-ol: Significant differences in the hydrogen bonding patterns and supramolecular arrangements

The crystal structures, Hirshfeld surface analyses and electrostatic potential surfaces of the di- and tri-hydrates of (5α,17E)-17-hydrazonoandrostan-3-ol, 3, namely [3·(H2O)2] and [3·(H2O)3], are reported. The trihydrate, isolated from a solution of 3 in moist methanol, recrystallizes in the orthorhombic space group, P212121, while that of the dihydrate, isolated from a 1:1 aqueous methanol solution, recrystallizes in the monoclinic space group, P21. The asymmetric unit of the trihydrate involves one steroid and three water molecules, while that of the dihydrate has two similar but independent steroid molecules and four hydrate molecules. Very similar conformations are found for the steroid molecules in both hydrates. As expected, the different mole ratios of water: steroid have major influences on the structures. In both cases, complex crystal structures are constructed from various classical hydrogen bonds, involving the hydrate molecules and the hydroxy and hydrazonyl moieties of the steroid. In the trihydrate, there are no direct connections between the steroid molecules, instead the water molecules link the steroid molecules, with only weak van der Waals forces between the steroid molecules. There are some direct links between the steroid molecules in the dihydrate, involving OH(steroid hydroxyl)⋯O(steroid oxo) hydrogen bonds, in a head to head fashion, and OH⋯N(hydrazonyl) hydrogen bonds, in a head to tail fashion. However, the major occurrence throughout the structure is of steroid molecules linked by water molecules.

Biomimetic antifouling PDMS surface developed via well-defined polymer brushes for cardiovascular applications

Despite the distinct advantages of poly(dimethylsiloxane) (PDMS) for biomedical applications, because of its hydrophobic nature, suffers from non-specific protein adsorption and platelet adhesion and activation when used as a blood-contacting material. To confer hydrophilicity and biomolecules repelling characteristics, well-defined and high-density poly(2-hydroxyethyl methacrylate) (PHEMA) brushes are synthesized via surface-initiated atom transfer radical polymerization (SI-ATRP) on the PDMS substrate. First, PDMS surface is activated using an ultraviolet/ozone (UVO) wet treatment in water media to introduce hydroxy moieties without scarifying the surface property resulting a crack-free SiO2 surface. Then, 3-(2-bromoisobutyramido)propyl(trimethoxy)silane (BrTMOS), the active ATRP initiator, is immobilized on the UVO-treated PDMS surface to prepare a thin layer of hydrophilic PHEMA brush on PDMS substrate exhibiting excellent protein and platelet resistance. PHEMA brushes supply a biomimetic feature by combining antifouling properties due to hydrophilic characteristic with bioactive properties resulted from the presence of a high density hydroxy groups, which are subsequently used for biomolecules conjugation. The results indicate that grafting of PHEMA chains on the PDMS surface enhances the surface wettability which leads to a decrease in non-specific protein adsorption and platelet adhesion compared to the bare PDMS substrate. The adhered platelets on the PHEMA-tethered PDMS substrate maintain their normal round morphology. Furthermore, the conjugated gelatin macromolecules onto the tethered PHEMA chains promote the adherence and growth of human umbilical vein endothelial cells via ligand-receptor interactions.

A new crystal form and anti-microbial activity of (E)-1-[3-(2-hy-droxy-benzyl-idene-amino)-phen-yl]ethanone.

The title Schiff base compound, C15H13NO2, crystallizes in a new crystal form in the space group P212121, which is different from the monoclinic P21/n space group reported previously [De et al. (2009 ▸). Indian J. Chem. Sect. B, 48, 595-598]. An intra-molecular O-H⋯N hydrogen bond occurs between the hy-droxy and azomethine moieties. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds into supra-molecular chains propagating along the b-axis direction with a C(8) graph-set motif. The contribution of these two contacts in Hirshfeld surface area are around 19 and 21%, respectively. The title compound was screened for its anti-bacterial activity against two gram-negative (Escherichia coli and Salmonella typhimurium) and one gram-positive (Staphyloccus aureus) bacteria. The results of this study reveal that this Schiff base shows good activity against only one bacterium, i.e. Salmonella typhimurium.