Glutaric Anhydride Research Articles

Synthesis of N-succinyl- and N-glutaryl-chitosan derivatives and their antioxidant, antiplatelet, and anticoagulant activity

The effects of temperature, reactant ratio, pH, and reaction time were studied on the polymers formed by the reactions of succinic and glutaric anhydrides with chitosan under both homogeneous and heterogeneous conditions. As a result, protocols were developed for the synthesis of succinyl- and glutaryl-chitosan derivatives (SC and GC, respectively) with a specific degree of substitution. The polymers were characterized by NMR spectroscopy, including two-dimensional NMR techniques, that confirms N-substitution of chitosan under reaction conditions used. SC and GC both show pronounced and similar antioxidant activity, which slightly increases with an increase in the degree of substitution. Both SC and GC showed antiplatelet and anticoagulant activity. The platelet aggregation is suppressed more strongly in the experiments with GC than with SC, although the latter exhibits a more pronounced anticoagulant activity.

Characteristic NH3 and CO losses from sodiated peptides C-terminated by glutamine residues.

Under certain conditions some amino acid (AA) residues undergo special reactions in the gas phase, generating characteristic neutral losses and product ions. Taking these special fragments into account and understanding the effect of AA residues on peptide cleavages will consummate database search algorithms and manual data interpretation in peptide sequencing by mass spectrometry (MS). In this study, the details of the characteristic NH3 and CO losses of glutamine (Gln) residues located at the C-terminus of peptides are presented. A number of selected peptides were fragmented under collision-induced dissociation (CID) in electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOF-MS). Density functional theory (DFT) quantum mechanical calculations at the B3LYP/6-31+G(d,p) level were carried out to optimize the geometry of peptide ions and provide energy barriers of ions in each step during fragmentations. Two characteristic peaks appear near the precursor ions of sodiated Gln C-terminated peptides, suggesting the loss of neutral NH3 and CO via a two-step process. The proposed mechanism of their formation is as follows: after losing NH3 , a non-classical bn * ion is formed with a glutaric anhydride structure that further dissociates to lose CO. The sodiated peptides show more intensive peaks corresponding to the loss of neutral molecules than the protonated ones. This type of neutral loss can also occur at the Gln residue that is rearranged to the C-terminus of sodiated peptides. The experiments and calculations suggest that the two-step characteristic NH3 and CO loss of sodiated peptides is energetically favored, and can be applied to identify C-terminated Gln residues. This study provides a mechanistic insight into the role of sodium ion during peptide fragmentation. Copyright © 2017 John Wiley & Sons, Ltd.

Investigation of Glutaric Anhydride as an Electrolyte Additive for Graphite/LiNi0.5Mn0.3Co0.2O2 Full Cells

The effects of glutaric anhydride (GA) as an electrolyte additive for graphite/LiNi0.5Mn0.3Co0.2O2 full cells operating between 3.0–4.4 V were investigated. Linear scan voltammetry (LSV) revealed that GA preferentially oxidized prior to the carbonate-based electrolyte while Li/graphite half cells revealed that GA can suppress electrolyte decomposition on the graphite electrode giving rise to the bifunctional nature of this additive. The addition of both 0.5 and 1.0 wt% of GA into the carbonate-based electrolyte resulted in superior cycling performance compared to the baseline electrolyte as demonstrated by the slight increase in initial capacities and significant increases in capacity retention over 117 cycles at C/3. Electrochemical impedance spectroscopy (EIS) showed that while the overall impedance of the GA containing cells was higher than the cells with the baseline electrolyte the change in impedance between post-formation and post-cycling was smallest for the cells containing GA. Additionally, X-ray photoelectron spectroscopy (XPS) analysis confirmed that GA decomposed on the cathode surface leading to an increase in oxygen-containing species, a decrease in LiF species and a simultaneous increase in LixPOyFz species.

New Dicarboxylic Acid Anhydride for Ambient‐Temperature Castagnoli‐Cushman Reactions

AbstractA novel 3‐phenyl‐4‐thiaglutaric anhydride was employed as a highly reactive partner for the Castagnoli‐Cushman reaction. This, in combination with the use of DMF as a reaction medium, resulted in a drastic lowering of the reaction temperature to ambient (compared to the 110–150 °C range typical for similar processes involving glutaric anhydride) and an extended reaction scope (with respect to substitution pattern in the imine component). Diastereomeric products were separated, in the form of respective methyl esters, and their comparative NMR characterization led to preliminary generalizations regarding the syn‐ and anti‐series.

Design of a doxorubicin-peptidomimetic conjugate that targets HER2-positive cancer cells

Doxorubicin (DOX) belongs to the anthracycline class of drugs that are used in the treatment of various cancers. It has limited cystostatic effects in therapeutic doses, but higher doses can cause cardiotoxicity. In the current approach, we conjugated a peptidomimetic (Arg-aminonaphthylpropionic acid-Phe, compound 5) known to bind to HER2 protein to DOX via a glutaric anhydride linker. Antiproliferative assays suggest that the DOX-peptidomimetic conjugate has activity in the lower micromolar range. The conjugate exhibited higher toxicity in HER2-overexpressed cells than in MCF-7 and MCF-10A cells that do not overexpress HER2 protein. Cellular uptake studies using confocal microscope experiments showed that the conjugate binds to HER2-overexpressed cells and DOX is taken up into the cells in 4 h compared to conjugate in MCF-7 cells. Binding studies using surface plasmon resonance indicated that the conjugate binds to the HER2 extracellular domain with high affinity compared to compound 5 or DOX alone. The conjugate was stable in the presence of cells with a half-life of nearly 4 h and 1 h in human serum. DOX is released from the conjugate and internalized into the cells in 4 h, causing cellular toxicity. These results suggest that this conjugate can be used to target DOX to HER2-overexpressing cells and can improve the therapeutic index of DOX for HER2-positive cancer.

Systematic Derivatization of Curcumin and its Effect on Antioxidant Capacity and Action Mechanism. Cyclic Voltammetry and DFT as Tools of Analysis

Eight curcumin derivatives were synthesized by esterification of its phenol groups with first and second generation polyester dendrons (dendronization) or glutaric anhydride (glutarization), in a systematic scheme where mono and disubstitutions were carried out. The dendronization of curcumin (CUR) affects the fragmentation patterns in mass spectra, particularly for the disubstituted OH-terminated second generation derivative (labeled as 2C2), undergoing the cleavage of one of the aromatic rings. This fact may be related to the antioxidant capacity of 2C2, evaluated following its reaction with superoxide (O2•-) by cyclic voltammetry (CV). As opposed to CUR and the rest of its derivatives that react with O2•- via proton transfer reactions, 2C2 reacts with O2•- mainly by hydrogen atom transfer. 2C2 radical scavenging activity versus O2•- is higher than the one observed for CUR. From DFT calculations, independently of the substitution on CUR, the frontier molecular orbitals remain nearly unaltered as compared to CUR. On the other hand, when CUR is dendronized, the electric dipole moment notably changes as a function of the nature of the terminal groups.

Magnetic Nanoparticles in Medical Diagnostic Applications: Synthesis, Characterization and Proteins Conjugation

Background: Magnetic nanoparticles (NPs) used in biomedical applications should be discrete with small particle sizes, narrow size distribution and superparamagnetic. NPs can be tailored to target, through chemical bonds, specific organs, cells, or even molecular markers of different diseases in vivo, with suitable surface chemistry modification. Methods: Nanoparticles are synthesized by a low cost coprecipitation reaction of ferrous and ferric salts with alkaline solution. The characteristics of the NPs are modified by varying the addition rate of the alkaline solution. NPs surface is silica coated using a modified Stöbe method. The conversion of the surface hydroxyl groups into amino-groups is performed by two different alkoxysilanes and the silanization reaction is conducted either in Methanol – Glycerol environment at elevated temperature, or in water at room temperature. The surface amine groups of the NPs are further converted, either to aldehyde groups by glutaraldehyde, or to carboxyl groups using glutaric anhydride. Bovine Serum Albumin and Vena human natural immunoglobulin are used in order to study the protein conjugation capacity of the functionalized NPs. The amount of protein attached to the nanoparticles is determined by UV–Vis spectroscopy of the supernatant. Conjugation of synthesized nanoparticles to protein BSA is examined by FTIR spectroscopy. SDS-PAGE electrophoresis followed by protein immunoblotting is used to test the effect of nano-conjugation to the antibodies. Results: Superparamagnetic Fe3O4 nanoparticles with saturation magnetization 60emu/g, a mean diameter 8-12 nm and BET surface areas between 100-250 m2/gr are obtained with total time of addition of the base between 1-5 minutes. They are coated with a thin and nearly uniform silica (SiO2) layer with thickness 1-2 nm. The most appropriate source for surface functionalization with amino groups is 3-aminopropyltriethoxysilane (APTES), while the two silanization methods used, proved to be equally efficient. NPs with surface aldehyde groups display better conjugation capacity than NPs functionalized with carboxyl groups. The FTIR spectra of the protein conjugated NPs samples, contain the two main peaks, at 1529 cm-1 and 1661 cm-1, attributed to the amide bond of the protein, which confirms the conjugation of the protein to the NPs. During a SDS-PAGE electrophoresis - protein immunoblotting experiment, the antibodies, after being conjugated to the nanoparticles, are selectively attached to their antigen, which indicates of lack of significant conformation changes secondary to the conjugation process. Conclusion: The conjugation capacity of the optimized nanoparticles is higher for Ig antibody than for BSA protein, under similar reaction conditions. The conjugational efficacy and conformational stability and the effect on electrophoretic mobility of the antibodies conjugated to the nanoparticles are verified by protein immunoblotting. Keywords: Conjugation, magnetite, nanoparticles, proteins, silica coating, superparamagnetic.

Chemical composition and vascular and intestinal smooth muscle relaxant effects of the essential oil from Psidium guajava fruit

Context: Psidium guajava L. (Myrtaceae) is widely used in traditional medicine for the treatment of various ailments including cardiovascular and gastrointestinal disorders.Objectives: The current study investigated the chemical composition and cardiovascular and gastrointestinal effects of the essential oil of P. guajava.Materials and methods: The chemical composition of the essential oil was investigated using gas chromatography-mass spectrometry (GC-MS) technique. The biological activity of the essential oil was tested on rabbit aorta and jejunum. All changes in isometric tension were recorded through a force transducer coupled with a bridge amplifier data acquisition system.Results and discussion: GC-MS analysis showed the presence of butanoic acid methyl ester, 3-methyl glutaric anhydride, 1-butanol, 3-hexenal, cinnamyl alcohol, 1-hexanol and hexane as the major components. In isolated rabbit aorta preparations, the essential oil showed vasorelaxation at doses of 3-10 mg/mL against high K+ and phenylephrine pre-contractions with EC50 values of 5.52 (5–6.04) and 6.23 mg/mL (5.0–7.46). The essential oil inhibited spontaneous and high K+ induced contractions in isolated rabbit jejunum with EC50 values of 0.84 (0.3–1.38) and 0.71 mg/mL (0.3–1.12) and shifted Ca + 2 concentration curves to the right, similar to verapamil, suggesting spasmolytic activity mediated possibly through Ca + 2 channel blockade.Conclusions: In summary, the data indicated the presence of seven different phytoconstituents in the essential oil of P. guajava and calcium channel blocking activity, which provides a pharmacological base to the traditional use of P. guajava in cardiovascular and gastrointestinal disorders. Further studies are suggested to explore the molecular nature of these effects.

ChemInform Abstract: Current Diversity of Cyclic Anhydrides for the Castagnoli—Cushman‐Type Formal Cycloaddition Reactions: Prospects and Challenges

AbstractReview: [36 refs.

Adipic acid – glutaric anhydride – epoxidised linseed oil biobased thermosets with tunable properties

In this study, the preparation and characterization of biobased thermosets comprising epoxidized linseed oil (ELO), adipic acid and/or glutaric anhydride, initiated by N,N-4-dimethylaminopyridine (DMAP) is reported. By changing the ratio of adipic acid to glutaric anhydride, the obtained resins changed from soft and flexible to hard and brittle materials. The Young’s modulus varied from 25MPa to 1477MPa, tensile strength varied from 10.3MPa to 25.7MPa, and the elongation at break varied from 2.7% to 67.5%. The maximum toughness was found with the sample containing 20% glutaric anhydride and 80% adipic acid. With the increase of glutaric anhydride content, the total heat released during the curing reaction and the glass transition temperature (Tg) increased. This is the first paper that reports the combination of glutaric anhydride and adipic acid as curing agents for epoxidized plant oils to produce thermosets ranging from flexible to hard.

Release-Modulated Antioxidant Activity of a Composite Curcumin-Chitosan Polymer.

Curcumin is known to have immense therapeutic potential but is hindered by poor solubility and rapid degradation in solution. To overcome these shortcomings, curcumin has been conjugated to chitosan through a pendant glutaric anhydride linker using amide bond coupling chemistry. The hybrid polymer has been characterized by UV-visible, fluorescence, and infrared spectroscopies as well as zeta potential measurements and SEM imaging. The conjugation reactivity was confirmed through gel permeation chromatography and quantification of unconjugated curcumin. An analogous reaction of curcumin with glucosamine, a small molecule analogue for chitosan, was performed and the purified product characterized by mass spectrometry, UV-visible, fluorescence, and infrared spectroscopies. Conjugation of curcumin to chitosan has greatly improved curcumin aqueous solubility and stability, with no significant curcumin degradation detected after one month in solution. The absorbance and fluorescence properties of curcumin are minimally perturbed (λmax shifts of 2 and 5 nm, respectively) by the conjugation reaction. This conjugation strategy required use of one out of two curcumin phenols (one of the main antioxidant functional groups) for covalent linkage to chitosan, thus temporarily attenuating its antioxidant capacity. Hydrolysis-based release of curcumin from the polymer, however, is accompanied by full restoration of curcumin's antioxidant potential. Antioxidant assays show that curcumin radical scavenging potential is reduced by 40% after conjugation, but that full antioxidant potential is restored upon hydrolytic release from chitosan. Release studies show that curcumin is released over 19 days from the polymer and maintains a concentration of 0.23 ± 0.12 μM curcumin/mg polymer/mL solution based on 1% curcumin loading on the polymer. Release studies in the presence of carbonic anhydrase, an enzyme with known phenolic esterase activity, show no significant difference from nonenzymatic release studies, implying that simple ester hydrolysis is the dominant release mechanism. Conjugation of curcumin to chitosan through a phenol ester modification provides improved stability and solubility to curcumin, with ester hydrolysis restoring the full antioxidant potential of curcumin.

On the stability of adsorbed and grafted fibronectin coatings on fluorocarbon surfaces for cardiovascular applications

Event Abstract Back to Event On the stability of adsorbed and grafted fibronectin coatings on fluorocarbon surfaces for cardiovascular applications Vanessa Montano-Machado1, 2, Ludivine Hugoni1, 2, Sergio Díaz-Rodríguez1, Ranna Tolouei1, Pascale Chevallier1, Emmanuel Pauthe2 and Diego Mantovani1 1 CHU de Quebec, Research Center, Laval University, Lab. Biomaterials & Bioengineering CRC-I, Dept. Min-Met-Mater Eng, Canada 2 University of Cergy-Pontoise, ERRMECe, France Introduction: When a dispositive is implanted in the human body its clinical success is influenced by the first interactions its surface establishes with the surrounding biological tissues and fluids. In the case of cardiovascular applications, endothelialization is still the missed element. Although numerous surfaces modifications based on biomolecules coatings have been reported in the literature, the stability of the coatings is rarely assessed for blood applications involving circulation. This study focuses on the development of a long-term-stable fibronectin (FN) coating on fluorocarbon films (CFx) able to promote endothelial-cell response on cardiovascular devices. Materials and Methods: Cleaned stainless steel substrates were first coated by a plasma deposition process, leading to CFx films[1]. Afterwards, FN was added following two approaches: adsorption for 30 min at 37 ºC (FNa) or CFx film functionalization followed by FN grafting through glutaric anhydride (FNg)[2]. Deformation tests were performed in order to simulate cardiovascular stenting procedure. Samples were tested under static and dynamic conditions during 7 days in PBS solution[3]. Coating characterizations were performed through X-Ray Photoelectron Spectroscopy, Contact Angle (CA), Atomic Force Microscopy (AFM), Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) and immunostaining of FN with polyclonal and monoclonal antibodies. Haemolysis rate (40 min) and endothelial cell viability test (7 days) were completed. Results and Discussion: XPS survey analysis demonstrated the CFx deposition after plasma process, as well as the presence of both FN coatings (Table 1). Furthermore, high resolution of C1s evidenced that CF2 bonds from CFx were still detected on FNa whereas for FNg this contribution was no more detectable, but only the picks corresponding to the protein. The CA was very high for CFx film, 122.1 ± 4.2º, and it decreased to 104.2 ± 7.2º and 67.2 ± 3.6º for FNa and FNg respectively (Figure 1). These results evidenced differences in covering of the CFx film and/or in the protein conformation. However immunostaining assays showed a homogeneous coating for both FNa and FNg samples. Regarding AFM analysis, CFx film presented a Rq and Rsk values of 1 nm and 0.5 respectively, for FNa these values were 4 nm and -1.6, while for FNg were 4.5 nm and 0.6, respectively. ToF-SIMS imaging and depth profiling analysis showed denser coatings of FNg when compared to FNa. After stability tests, both FNa and FNg coatings showed high stability after the deformation process and after static tests. However, after 7 days of dynamic test, FNg presented a more homogeneous and denser coating mainly evidenced by the preservation of the CA, the chemical composition and a decrease of the Rq value. Regarding biological tests (Figure 2), significant improvement on cell viability was detected of both FNa and FNg coatings when compared to the CFx film. FNg showed better hemocompatibility properties than FNa coatings. Conclusions: Two FN coatings, either adsorbed (FNa) or grafted (FNg), have been characterized by using different techniques and submitted to several stability tests. FN grafted exhibited higher stability and denser coatings than FNa. The pertinence of FNg coating for cardiovascular applications was confirmed also by high endothelial cell viability and hemocompatibility properties. This work was partially funded by NSERC-Canada, FRQ-NT-Quebec, CFI-Canada, Québec/France Samuel de Champlain Program, Centre de Recherche sur les Matériaux Avancés CERMA-ULaval, Research Center of the CHU de Québec and Wallonie-Bruxelles International. VMM was awarded of a doctoral scholarship from CONACYT – National Council of Science and Technology, Mexico. ToF-SIMS analysis were performed by Céline Noël at the Research Centre in Physics of Matter and Radiation (PMR) in Namur University, Belgium. The authors would like to express their gratitude for their collaboration on the performance of experiments and/or their technical assistance to Laurent Houssiau, Jean-Jacques Pireaux and Stéphane Turgeon.

ChemInform Abstract: New Heterocyclic Product Space for the Castagnoli—Cushman Three‐Component Reaction.

AbstractThe use of heteroatom containing analogues of glutaric anhydride in the Castagnoli—Cushman type reaction with imines gives predominately the corresponding trans substituted heterocyclic products.

Synthesis of thiourethanes and poly(thiourethane)s bearing carboxylic groups by nucleophilic acylation using cyclic acid anhydrides

A mercapto group generated by addition of 5-phenoxymethyl-1,3-oxathiolane-2-thione and benzylamine could react with cyclic acid anhydrides to give the corresponding carboxylic acids. This method was applied to a polymer modification. Poly(thiourethane)s containing mercapto groups were prepared from difunctional five-membered cyclic dithiocarbonates and diamines could react with succinic or glutaric anhydride to give the corresponding poly(thiourethane)s bearing carboxyl group in the side chains in high yield. Thermal properties of the obtained polymers were examined by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). The obtained polymers showed 5 % weight loss temperatures (T d5) at 170 and 216 °C. These polymers exhibited glass transition temperatures (T g) at 52 and 57 °C, respectively. Furthermore, a cross-linked poly(thiourethane) was readily obtained using difunctional cyclic acid anhydride, 1,2,3,4-butanetetracarboxylic dianhydride as a cross linker.

Effect of a tetra functional epoxy monomer on the thermomechanical properties of shape-memory epoxy resin

The effect of a tetra functional epoxy monomer on thermomechanical properties and shape recovery performance of a shape-memory epoxy resin system was studied. The system is prepared using hydro-epoxy, tetra functional epoxy monomer (AG-80), and glutaric anhydride. The molecular structure of the shape-memory epoxy resin system can be changed by varying AG-80 content. Fundamental trends are established between the chemical structure, cross-link density, glass transition temperature (Tg), rubber modulus, bend strength, and shape-memory properties. The thermal and thermomechanical properties of shape-memory epoxy resin system are characterized by differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA), and the results indicate that the Tg and rubber modulus increase as AG-80 content increases. The room-temperature bend strength increases at first and then decreases with increasing AG-80 content. Shape memory properties are also studied using a U-type shape-memory test. Results show that full recovery is achieved after only several minutes when the temperature is equal to or above Tg. Shape recovery time decreases initially and then increases with increasing AG-80 content, thereby showing an extreme value for the system with 8.33 mol% AG-80 content. These results are attributed to the increase in AG-80 content.

New Heterocyclic Product Space for the Castagnoli-Cushman Three-Component Reaction.

Significant expansion of heterocyclic product space accessible by the Castagnoli-Cushman reaction (CCR) has been achieved via the use of glutaric anhydride analogues containing endocyclic substitutions with oxygen, nitrogen, and sulfur. Incorporation of these heteroatoms in the anhydride's backbone results in enhanced reactivity and generally lower temperatures that are required for the reactions to go to completion. These findings are particularly significant in light of the CCR recently recognized as an efficient tool for lead-oriented synthesis.

Bacteria-Targeting Conjugates Based on Antimicrobial Peptide for Bacteria Diagnosis and Therapy.

Chloramphenicol (CAP) is one of the most effective antimicrobial agents, but its therapeutic efficacy is greatly limited by its nonspecific distribution and consequent side effects in neutrophils. Targeting to the infection sites, and thus restricting CAP nonselective delivery, provides an alternative way to overcome this limitation. The antibacterial peptide fragment UBI29-41 was identified to have a high bacterial affinity. However, no research so far has been carried out to utilize UBI29-41 as a ligand for bacteria-targeting therapies. In this Article, we first labeled a near-infrared fluorescent dye (ICG02) with UBI29-41 to investigate its targeting capability in different bacteria (S. aureus, E. coli, and P. auruginosa) and bacteria-infected mouse models. Subsequently, UBI29-41 was conjugated with the typical antibiotic (CAP) through the linker glutaric anhydride to form the conjugate CAP-UBI29-41 for the bacteria-targeting therapy. In vitro studies demonstrated the enhanced antibacterial effects of CAP-UBI29-41 on S. aureus and E.coil. Meanwhile, the toxicity of CAP-UBI29-41 on normal cells decreased distinctly in comparison with CAP. Most importantly, CAP-UBI29-41 exhibited more favorable antibacterial efficacy than CAP in bacteria-bearing mouse models. All these results demonstrated that UBI29-41 is an ideal targeting ligand to construct antibacterial agents for bacteria-targeting therapy.

Protein covalent immobilization via its scarce thiol versus abundant amine groups: Effect on orientation, cell binding domain exposure and conformational lability

Quantity, orientation, conformation and covalent linkage of naturally cell adhesive proteins adsorbed or covalently linked to a surface, are known to influence the preservation of their subsequent long term cell adhesion properties and bioactivity. In the present work, we explore two different strategies for the covalent linking of plasma fibronectin (pFN) – used as a cell adhesive model protein, onto a polystyrene (PS) surface. One is aimed at tethering the protein to the surface in a semi-oriented fashion (via one of the 4 free thiol reactive groups on the protein) with a heterofunctional coupling agent (SSMPB method). The other aims to immobilize the protein in a more random fashion by reaction between the abundant pendant primary amine bearing amino acids of the pFN and activated carboxylic surface functions obtained after glutaric anhydride surface treatment (GA method). The overall goal will be to verify the hypothesis of a correlation between covalent immobilization of a model cell adhesive protein to a PS surface in a semi-oriented configuration (versus randomly oriented) with promotion of enhanced exposure of the protein's cell binding domain. This in turn would lead to enhanced cell adhesion. Ideally the goal is to elaborate substrates exhibiting a long term stable protein monolayer with preserved cell adhesive properties and bioactivity for biomaterial and/or cell adhesion commercial plate applications. However, the initial restrictive objective of this paper is to first quantitatively and qualitatively investigate the reversibly (merely adsorbed) versus covalently irreversibly bound protein to the surface after the immobilization procedure.Although immobilized surface amounts were similar (close to the monolayer range) for all immobilization approaches, covalent grafting showed improved retention and stronger “tethering” of the pFN protein to the surface (roughly 40%) after SDS rinsing compared to that for mere adsorption (0%) suggesting an added value to the covalent grafting immobilization methods. However no differences in exposure of the cell binding domains were observed (ELISA results) before SDS rinsing, suggesting that pFN protein grafting to the surface is initially kinetically driven be a stochastic random adsorption phenomenon. Covalent grafting acts in the final stage as a process that simply tethers and stabilizes (or freezes) the initial conformation/orientation of the adsorbed protein on the surface. In addition covalent linkage via the SSMPB approach is likely favored by surface-induce exposure of one of the normally hidden free thiol group pair, thus optimizing covalent linkage to the surface.However after SDS rinsing, this “tethering”/”freezing” effect was significantly more prominent for the GA grafting approach (due to greater number of potential covalent links between the protein and the surface) compared to that for the SSMPB approach. This hypothesis was buttressed by the improved resistance to denaturation (smaller conformational lability) for the GA compared to the SMPB approach and improved exposure of the cell binding domain for the former (>50%) even after SDS rinsing.These results are promising in that they suggest covalent tethering of fibronectin to PS substrate in a monolayer range, with significantly improved irreversible protein surface bonding via both approaches (compared to that for mere adsorption). The latter are likely applicable to a wide range of proteins.

Thermal properties of neryl long-chain esters obtained under microwave irradiation

Thermal properties of novel, neryl long-chain esters obtained through the esterification process of nerol, different chain lengths acidic components such as succinic anhydride, glutaric anhydride, adipic acid or sebacic acid and diol components such as ethylene glycol or diethylene glycol in solvent-free conditions under microwave irradiation were studied by TG/FTIR-coupled method. The studies confirmed that the use of microwave irradiation allowed obtaining flavor esters in absolutely shorter reaction time (only minutes) with high purity and yield compared to conventional method. The prepared novel, neryl long-chain esters were high thermal stable compounds and decomposed at three stages under air conditions including the breaking of ester bonds, oxidation and decarboxylation processes of formed intermediate products in a gaseous phase and thus the emission of various gaseous products. It was indicated on the same, complex and parallel decomposition mechanism under oxidative conditions for the present and previously studied long-chain esters of primary order terpene alcohols showing it independence on the type of alcohol used for their synthesis.

Influence of Chemical Conjugation Strategies on Fibronectin's Bioactivity

Since thirty years, efforts were put forward to engineer materials that could be used to build up biomedical devices that have to come in contact with human tissues. The first devices that were developed were designed to reproduce the basic functions of the tissue or organ that they were intended to replace. For example, the first designs of arterial prostheses were made from materials that can be formed as tubes with sufficient mechanical properties and chemical stability, to withstand the pulsatile blood pressure for many years without failure. Only few concerns were raised regarding the interaction between the material and the physiological environment. Nowadays, the common strategy consists in developing materials that are likely to proactively interact with their environment.For instance, one idea is to coat the surface of biomaterials with proteins of the extracellular matrix, therefore promoting cell adhesion and proliferation. Fibronectin is one of these proteins and has been the subject of several investigations as to its potential to be used to promote cell/material interaction once conjugated to the surface of biomaterials. In this context, the aim of this study was to compare two strategies of FN immobilization in regards to the amount of bound FN and its biological activity. Two heterobifunctional cross-linkers were used to conjugate FN to ammonia plasma-treated PTFE: glutaric anhydride (GA) and Sulfo-succinimidyl 4-[p-maleimidophenyl] butyrate (sulfo-SMPB). In addition, we have also investigated the influence of adding either a hydrophilic or hydrophobic spacer between the protein and the surface on the protein bioactivity. On one hand, our results demonstrated that fibronectin RGD sequences are more available when the protein is conjugated through its lysine moieties. On the other hand, an hydrophobic spacer between fibronectin and the biomaterial surface is also likely to promote the protein bioactivity.