Open-chain Structure Research Articles

Bixin Combined with Metformin Ameliorates Insulin Resistance and Antioxidant Defenses in Obese Mice.

Bixin (C25H30O4; 394.51 g/mol) is the main apocarotenoid found in annatto seeds. It has a 25-carbon open chain structure with a methyl ester group and carboxylic acid. Bixin increases the expression of antioxidant enzymes, which may be interesting for counteracting oxidative stress. This study investigated whether bixin-rich annatto extract combined with metformin was able to improve the disturbances observed in high-fat diet (HFD)-induced obesity in mice, with an emphasis on markers of oxidative damage and antioxidant defenses. HFD-fed mice were treated for 8 weeks with metformin (50 mg/kg) plus bixin-rich annatto extract (5.5 and 11 mg/kg). This study assessed glucose tolerance, insulin sensitivity, lipid profile and paraoxonase 1 (PON-1) activity in plasma, fluorescent AGEs (advanced glycation end products), TBARSs (thiobarbituric acid-reactive substances), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in the liver and kidneys. Treatment with bixin plus metformin decreased body weight gain, improved insulin sensitivity, and decreased AGEs and TBARSs in the plasma, liver, and kidneys. Bixin plus metformin increased the activities of PON-1, SOD, CAT, and GSH-Px. Bixin combined with metformin improved the endogenous antioxidant defenses in the obese mice, showing that this combined therapy may have the potential to contrast the metabolic complications resulting from oxidative stress.

Dynamic Scheduling Optimization of Automatic Guide Vehicle for Terminal Delivery under Uncertain Conditions

As an important part of urban terminal delivery, automated guided vehicles (AGVs) have been widely used in the field of takeout delivery. Due to the real-time generation of takeout orders, the delivery system is required to be extremely dynamic, so the AGV needs to be dynamically scheduled. At the same time, the uncertainty in the delivery process (such as the meal preparation time) further increases the complexity and difficulty of AGV scheduling. Considering the influence of these two factors, the method of embedding a stochastic programming model into a rolling mechanism is adopted to optimize the AGV delivery routing. Specifically, to handle real-time orders under dynamic demand, an optimization mechanism based on a rolling scheduling framework is proposed, which allows the AGV’s route to be continuously updated. Unlike most VRP models, an open chain structure is used to describe the dynamic delivery path of AGVs. In order to deal with the impact of uncertain meal preparation time on route planning, a stochastic programming model is formulated with the purpose of minimizing the expected order timeout rate and the total customer waiting time. In addition, an effective path merging strategy and after-effects strategy are also considered in the model. In order to solve the proposed mathematical programming model, a multi-objective optimization algorithm based on a NSGA-III framework is developed. Finally, a series of experimental results demonstrate the effectiveness and superiority of the proposed model and algorithm.

Azobenzene-Imidazolium ionic liquid crystals: Phase properties and photoisomerization in solution state

This is the first report of phase properties and photoisomerization behaviour of a series of amphiphilic azobenzene-imidazolium derivatives. The cationic imidazolium moiety was functionalised with varying alkyl chain length (C10-C18) and connected to an azobenzene via a flexible ether spacer. Their phase transitional properties and photoisomerization in solution were modulated by the alkyl chains in the imidazolium moiety. C14 was the shortest chain length to induce the formation of a liquid crystal phase, wherein compounds having C14-C18 exhibited stable smectic A phase. All compounds photo switched from trans-to-cis isomers in solution when illuminated with UV radiation. DFT calculations revealed that the trans isomers could adopt two geometries, however, folded geometry (global minima) was thermodynamically more stable than the open chain structure. The long conjugate (C16) had a higher trans-cis isomerization barrier due to the multilayer folding geometry that reduced its structural flexibility as compared to the C10 homologue. The photo conversion efficiency (CE) was alkyl chain length dependent. The C10 salt had a larger CE than C16 homologue due to the transition gap between S1 excited state and ground surface is smaller in the former (0.211 eV) than that in the latter (0.278 eV), thus resulting in efficient photoisomerization in the former.

Synthesis, Biological Evaluation, and Docking Studies of Open-Chain Carbohydrate Amides as Acetylcholinesterase Inhibitors.

Alzheimer's disease is a multifactorial syndrome, which is not yet fully understood, causing memory loss, dementia, and, ultimately, death. Acetylcholinesterase inhibitors are the mainstay drugs that are used in disease-symptomatic treatment. In this work, we report a new synthetic route yielding sugar amides as low to moderate acetylcholinesterase inhibitors. Commercially available diacetone glucose was converted into perbenzyl D-glucono-1,4- lactone, which reacted with aromatic or aliphatic amines to afford the corresponding new amides in a high isolated yield. Docking studies of the most promising hydroxybutylamide and benzylamide were performed to assign binding interactions with acetylcholinesterase and determine the key features for bioactivity. The inhibitors are accommodated in enzyme gorge, blocking the access to Ser203 mainly due to π-π stacking interactions of sugar benzyl groups with the aromatic gorge residues, Tyr337 and Tyr341 for both inhibitors and Trp439 only for the hydroxybutylamide. Bonding is also significant through sugar interaction with the residues Tyr124 and Ser125-OH in both inhibitors. Flexibility of these open-chain structures seems to be quite relevant for the observed binding to acetylcholinesterase.

Effects of chain conformation on uranium adsorption performance of amidoxime adsorbents

The amidoxime group has received widespread attention owing to its high affinity for uranium. Since this property was discovered, various amidoxime-based adsorbents have been developed for uranium adsorption. However, the effect of chain conformation on the uranium adsorption performance (in terms of adsorption capacity, stability, selectivity, etc.) of amidoxime adsorbents has rarely been studied. Herein, three amidoxime-based adsorbents with different chain conformations (linear, multi-armed, and rigid) were constructed via tert-butyl hydroperoxide-initiated surface graft polymerization by incorporating different monomer structures. Adsorption experiments revealed that the linear structure of P-E-PAO exhibited the highest adsorption capacity owing to the highest monomer-grafting ratio; the multi-arm structure of P-E-PMGO was affected by pH and ionic strength because of the most cyclic imide dioxime structure; and the rigid structure of P-E-PEBO showed the highest selectivity owing to the most open-chain amidoxime structure. These findings are expected to have strong implications in the optimization of adsorption material designs.

Effect of temperature on Electron-Phonon coupling of carotenoids by Two-Dimensional correlation resonance Raman spectroscopy

Carotenoids, the most prevalent light-absorbing pigments in nature, perform many functions in photosynthetic systems. The Raman and absorption spectra of carotenoids (including lycopene and β-carotene) were measured in the temperature range between 303 K and 83 K. As the temperature decreased, the Huang-Rhys factor and the electron–phonon coupling constant also decreased. Nevertheless, the Raman scattering cross-section increased. The results suggested that lycopene was more sensitive to changes in temperature due to the longer conjugated length and the different open-chain structure as compared to β-carotene. Two-dimensional correlation resonance Raman spectroscopy (2DCRRS) showed a correlation between electron–phonon coupling and changes in temperature. Moreover, the complex mode evolution of lycopene rendered the molecule more sensitive to temperature. Density functional theory (DFT) simulation was used to optimize the geometrical structure, and bond length alternation (BLA) calculation was performed. The result can be applied to investigate the temperature dependence of electron-coupling in π-conjugated molecules.

Insights into the Phase Diagram of Pluronic L64 Using Coarse-Grained Molecular Dynamics Simulations.

We investigate the concentration-dependent phase diagram of pluronic L64 in aqueous media at 300 and 320 K using coarse-grained (CG) molecular dynamics (MD) simulations. The CG model is derived by adapting the Martini model for nonbonded interactions along with the Boltzmann inversion (BI) of bonded interactions from all-atom (AA) simulations. Our derived CG model successfully captures the experimentally observed micellar-, hexagonal-, lamellar-, and polymer-rich solution phase. The end-to-end distance reveals the conformational change from an open-chain structure in the micellar phase to a folded-chain structure in the lamellar phase, increasing the orientational order. An increase in temperature leads to expulsion of water molecules from the L64 moiety, suggesting an increase in L64 hydrophobicity. Thermodynamic analysis using the two-phase thermodynamics (2PT) method suggests the entropy of the system decreases with increasing L64 concentration and the decrease in free energy (F) with temperature is mainly driven by the entropic factor (-TS). Further, the increase in aggregation number at lower concentrations and self-assembly at very high concentrations is energetically driven, whereas the change from the micellar phase to the lamellar phase with increasing L64 concentration is entropically driven. Our model provides molecular insights into L64 phases which can be further explored to design functionality-based suprastructures for drug delivery and tissue engineering applications.

Influence of Open Chain and Cyclic Structure of Peptidomimetics on Antibacterial Activity in E. coli Strains.

An efficient method for the synthesis of functionalized peptidomimetics via multicomponent Ugi reaction has been developed. The application of trifluoroethanol (TFE) as a reaction medium provided desired products with good yields. Further, using the developed cyclisation reaction, the obtained peptidomimetics were transformed into the cyclic analogues (diketopiperazines, DKPs). The goal of the performed studies was to revised and compare whether the structure of the obtained structurally flexible acyclic peptidomimetics and their rigid cycling analogue DKPs affect antimicrobial activity. We studied the potential of synthesized peptidomimetics, both cyclic and acyclic, as antimicrobial drugs on model E. coli bacteria strains (k12, R2–R4). The biological assays reveal that DKPs hold more potential as antimicrobial drugs compared to open chain Ugi peptidomimetics. We believe that it can be due to the rigid cyclic structure of DKPs which promotes the membrane penetration in the cell of studied pathogens. The obtained data clearly indicate the high antibiotic potential of synthesized diketopiperazine derivatives over tested antibiotics.

Polysilicon Microchips Functionalized with Bipyridinium-Based Cyclophanes for a Highly Efficient Cytotoxicity in Cancerous Cells.

The use of micrometric-sized vehicles could greatly improve selectivity of cytotoxic compounds as their lack of self-diffusion could maximize their retention in tissues. We have used polysilicon microparticles (SiμP) to conjugate bipyridinium-based compounds, able to induce cytotoxicity under regular intracellular conditions. Homogeneous functionalization in suspension was achieved, where the open-chain structure exhibits a more dense packing than cyclic analogues. The microparticles internalized induce high cytotoxicity per particle in cancerous HeLa cells, and the less densely packed functionalization using cyclophanes promotes higher cytotoxicity per bipy than with open-chain analogues. The self-renewing ability of the particles and their proximity to cell membranes may account for increased lipid peroxidation, achieving toxicity at much lower concentrations than that in solution and in less time, inducing highly efficient cytotoxicity in cancerous cells.

Synthesis of Four-Membered BN3 Heterocycles by the Borylation of Triazenes.

Borylated triazenes were synthesized by the dehydrocoupling of triazenes with 9-borabicyclo(3.3.1)nonane, by the condensation of triazenes with BEt3, or by the reaction of sodium triazenides with dialkyl- or diarylboron halides. The structures of the products were found to depend on the size of the substituents. Sterically demanding mesityl groups at boron or nitrogen gave rise to open-chain structures, whereas smaller substituents led to the formation of novel BN3 heterocycles.

Design of synthetic polymer nanoparticles that inhibit glucose absorption from the intestine

Synthetic polymers prepared using several functional monomers have attracted attention as cost-effective protein affinity reagents and alternative to antibodies. We previously reported the synthesis of poly NIPAm-based nanoparticles (NPs) using several functional monomers that can capture target molecules. In this study, we designed NPs for capturing glucose and inhibiting intestinal absorption in living mice. For capturing glucose, we focused on the Maillard reaction between primary amines and aldehyde residues. We hypothesized that the primary amine-containing NPs can capture the open-chain structure of glucose via the Maillard reaction and inhibit intestinal absorption. NPs were prepared by the precipitation polymerization of NIPAm, N-tert-butylacrylamide (TBAm), trifluoroacetate-protected N-(3-aminopropyl)methacrylamide (T-APM), and N,N′-methylenebisacrylamide. Then, T-APM in NPs was deprotected by NH3 (aq). The amount of glucose captured by NPs depended on the percentage of TBAm and APM in vitro. After 24 h, only 2% of orally administered NPs remained in the body after administration, suggesting that many NPs were excreted without being absorbed. The prepared NPs significantly inhibited an increase in blood glucose concentration after the oral administration of glucose and NPs, indicating that NPs capture glucose and inhibit intestinal absorption. These results show the potential of using synthetic polymer nanoparticles for inhibiting postprandial hyperglycemia.

The melibiose-derived glycation product mimics a unique epitope present in human and animal tissues

Non-enzymatic modification of proteins by carbohydrates, known as glycation, leads to generation of advanced glycation end-products (AGEs). In our study we used in vitro generated AGEs to model glycation in vivo. We discovered in vivo analogs of unusual melibiose-adducts designated MAGEs (mel-derived AGEs) synthesized in vitro under anhydrous conditions with bovine serum albumin and myoglobin. Using nuclear magnetic resonance spectroscopy we have identified MAGEs as a set of isomers, with open-chain and cyclic structures, of the fructosamine moiety. We generated a mouse anti-MAGE monoclonal antibody and show for the first time that the native and previously undescribed analogous glycation product exists in living organisms and is naturally present in tissues of both invertebrates and vertebrates, including humans. We also report MAGE cross-reactive auto-antibodies in patients with diabetes. We anticipate our approach for modeling glycation in vivo will be a foundational methodology in cell biology. Further studies relevant to the discovery of MAGE may contribute to clarifying disease mechanisms and to the development of novel therapeutic options for diabetic complications, neuropathology, and cancer.

A novel neck brace to characterize neck mobility impairments following neck dissection in head and neck cancer patients.

This article introduces a dynamic neck brace to measure the full range of motion (RoM) of the head-neck. This easy-to-wear brace was used, along with surface electromyography (EMG), to study changes in movement characteristics after neck dissection (ND) in a clinical setting. The brace was inspired by the head-neck anatomy and was designed based on the head-neck movement of 10 healthy individuals. A 6 degrees-of-freedom open-chain structure was adopted to allow full RoM of the head-neck with respect to the shoulders. The physical model was realized by 3D printed materials and inexpensive sensors. Five subjects, who underwent unilateral selective ND, were assessed preoperative and postoperative using this prototype during the head-neck motions. Concurrent EMG measurements of their sternocleidomastoid, splenius capitis, and trapezius muscles were made. Reduced RoM during lateral bending on both sides of the neck was observed after surgery, with a mean angle change of 8.03° on the dissected side (95% confidence intervals [CI], 3.11-12.94) and 9.29° on the nondissected side (95% CI, 4.88-13.69), where CI denotes the confidence interval. Axial rotation showed a reduction in the RoM by 5.37° (95% CI, 2.34-8.39) on the nondissection side. Neck extension showed a slight increase in the RoM by 3.15° (95% CI, 0.81-5.49) postoperatively. This brace may serve as a simple but useful tool in the clinic to document head-neck RoM changes in patients undergoing ND. Such a characterization may help clinicians evaluate the surgical procedure and guide the recovery of patients.

Design and chemical synthesis of root gravitropism inhibitors: Bridged analogues of ku-76 have more potent activity

Previously, we found (2Z,4E)-5-phenylpenta-2,4-dienoic acid (ku-76) to be a selective inhibitor of root gravitropic bending of lettuce radicles at 5 μM, with no concomitant growth inhibition, and revealed the structure–activity relationship in this inhibitory activity. The conformation of ku-76 is flexible owing to the open-chain structure of pentan-2,4-dienoic acid with freely rotating single bonds, and the (2Z)-alkene moiety may be isomerized by external factors. To develop more potent inhibitors and obtain insight into the target biomolecules, various analogues of ku-76, fixed through conformation and/or configuration, were synthesized and evaluated. Stereochemical fixation was effective in improving the potency of gravitropic bending inhibition. Finally, we found highly potent conformational and/or configurational analogues (ku-257, ku-294 and ku-308), that did not inhibit root growth. The inhibition of root curvature by these analogues was comparable to that of naptalam.

Monosaccharides are the Basic Structural Units of Glycans

Free monosaccharides can exist in open-chain or ring structures. Ring types of the monosaccharides are the standard in oligosaccharides, which are straight or stretched chains of monosaccharides appended to each other by means of glycosidic linkages the expression polysaccharide is regularly utilized for enormous glycans made out of rehashing oligosaccharide themes. Glycobiology is the investigation of the structure, capacity and science of starches, additionally called glycans. Glycans are available in each living being. Glycobiology is a quickly developing field in science, with importance to biomedicine, biotechnology and essential exploration. In eukaryotic cells, most of proteins are post-translationally altered. One of the most widely recognized alterations, basic for cell reasonability, is the connection of glycans, or glycosylation. There are two sorts of glycosylation: N-connected (the glycan is joined to an asparagine) and O- connected (the glycan is appended to a serine or threonine).

Thiols in Natural Organic Matter: Molecular Forms, Acidity, and Reactivity with Mercury(II) from First-Principles Calculations and High Energy-Resolution X-ray Absorption Near-Edge Structure Spectroscopy

Thiol functional groups in natural organic matter form strong complexes with Hg(II) and other soft metal cations and therefore are an important component of sulfur and metal cycling in the environment. However, characterizing thiol reactivity is difficult because natural organic molecules are complex both in composition and molecular structure. Here, reactivity was assessed by calculating the Gibbs free energies of thiolation and thiol deprotonation reactions for model structures considered to form during abiotic sulfurization of natural organic matter. Gaussian calculations were performed at the CCSD(T) level of theory. Thiol addition is predicted to be faster by as much as 8 orders of magnitude on unsaturated cyclic structures rich in ketone and ether linkages than on open-chain carbonyl structures. The pKa values of thiols added to carboxyl-rich alicyclic molecules are predicted to be above 10, whereas pKa values of thiols bonded to lignin-derived polyhydroxyphenols are predicted to be between 2 and 6....

THE CHEMISTRY AND BIOLOGY OF LYCOPENE : ANTIOXIDANT FOR HUMAN HEALTH

More than 600 carotenoids are known to be naturally occurring. These predominantly colourful molecules, found in plants, fungi and bacteria undergoing photosynthesis, are widespread in vegetables and fruits. Carotenoids are divided into two main groups. Of them, the highly unsaturated hydrocarbons consisting of lycopene, α-, β-, and γ-carotene build the first group, whereas xanthophylls, such as β-cryptoxanthin, lutein and zeaxanthin are considered as the second big carotenoid group. Lycopene, a representative of the hydrocarbon carotenoids with the molecular formula of C40H56, has an acyclic open-chain structure consisting of 13 double-bonds. Two of them are non-conjugated, whereas eleven are conjugated double bonds, thereby building a chromatophore. This distinctive conjugated polyene structure accounts for the ruby colour and the antioxidant properties of lycopene. It has a distinct lipophilic character, which makes it nearly insoluble in ethanol, methanol and water. Due to its acyclic structure and the absence of a β-ionone ring, there is no pro-vitamin A activity to be found in lycopene, which is the reason for its differing biochemistry, as compared to α- and β-carotene. Due to its polyene-structure, providing an electron-rich system, lycopene is an eligible target for electrophilic reagents. Thus, it shows an extreme reactivity towards oxygen and free radicals. Lycopene is known to be the most potent oxygen quenching reagent among carotenoids, and furthermore, it provides the ability to intervene in reactions initiated by free radicals, like OH−· or peroxy radicals. Its excellent anti-oxidant properties are most likely the basis for its preventive role towards cancer and other chronic diseases. However, the lycopene concentration in fresh fruits and vegetables shows a great variability, depending on seasonal environmental conditions, geographic location, climatic situation, species and maturity which may be taken as indices for the best sowing season, place, species/varieties to be planted and date/time of harvest. The vegetables and fruits thus obtained would be rich in lycopene content, which in turn would have a major beneficial impact on human health.

Many unknowns below or close to the experimentally known cumulene carbene – A case study of C9H2 isomers

Twenty-five low-lying isomers of C9H2 lying within 2 eV (∼46.12 kcal mol−1) have been theoretically investigated using high-level quantum chemical calculations. Among them, the linear triplet isomer (1), the cyclopropenylidene derivatives (2 and 3) and the cumulene carbene isomer (11) have already been detected in the laboratory. The present theoretical study proposes fourteen cyclic structures and four open-chain structures that have not been investigated before. On the basis of relative energies obtained from coupled-cluster calculations, the current theoretical study reveals that six isomers (4 and 6–10), which energetically lie below 11, and fourteen isomers (12–25), which energetically lie above 11, are remaining elusive in the laboratory to date. Considering the astronomical importance of cyclopropenylidene and cumulene carbenes, the current quantum chemical data may be of relevance to molecular spectroscopists in identifying new C9H2 isomers in the laboratory. Consequently, such studies may benefit radioastronomers in confirming or neglecting C9H2 isomers in the interstellar medium.

Studies of Arabinose- and Mannose-Related Anionic Species and Comparison to Ribose and Fructose.

Gas phase, isolated monosaccharides arabinose- and mannose-related anionic species generated through the matrix-assisted laser desorption ionization (MALDI) method are investigated via negative ion photoelectron spectroscopy (PES) and density functional theory (DFT) calculations. The vertical detachment energies (VDEs) of the observed anionic species are experimentally determined: the corresponding structures are assigned based on good agreement between experimental and theoretical VDEs. Arabinose- parent anion is found to exist as open chain structures in the gas phase, while mannose- parent anionic species are not observed. Both monosaccharides undergo dissociation through loss of H and loss of H2O. (saccharide-H)- anions evidence coexisting positional and conformational isomers. (saccharide-H2O)- species have only two positional isomers, each with conformational differences. The present results for arabinose and mannose are further compared to those previously reported for ribose and fructose. This comparison is based on the anions observed and identified through the same PES/DFT techniques for the four saccharides (arabinose, mannose, ribose, and fructose). The issue of natural selection of ribose as the sugar backbone constituent of RNA is thereby explored from the point of view of anionic electronic structure and stability of the four species. Saccharide phosphates are also discussed in the present work with regard to addressing the unique natural selection of ribose for the backbone support of RNA and DNA.

Synthesis of Mono- and Disaccharide 4-[(ω-Sulfanylalkyl)oxy]benzoylhydrazones as Potential Glycoligands for Noble Metal Nanoparticles

A procedure has been developed for the synthesis of previously unknown aldose 4-[(ω-sulfanylalkyl) oxy]benzoylhydrazones (where alkyl is hexyl or decyl and aldoses are D-glucose, D-galactose, D-maltose, and D-lactose) that a repromising glycoligands for noble metal nanoparticles. According to the 1H and 13C NMR data, 4-[(ω-sulfanylalkyl)oxy]benzoylhydrazones derived from D-glucose, D-maltose, and D-lactose in crystal and in DMSO-d6 solution have exclusively the cyclic pyranose structure (α- and β-anomers). D-Galactose 4-[(ω-sulfanylalkyl)oxy]benzoylhydrazones in DMSO-d6 solution exist as tautomeric mixtures of cyclic pyranose and open-chain acylhydrazone structures.