Structure-properties relationships in thermoplastic polyurethane elastomer nanocomposites: Interactions between polymer phases and nanofillers

Polyurethane thermoplastic elastomer (TPU) nanocomposites were prepared by the incorporation of 1 wt% of high-structured carbon black (HSCB), carbon nanofibers (CNF), nanosilica (NS) and nanoclays (NC), following a proper high-shear blending procedure. The TPU nanofilled mechanical properties and morphology was assessed. The nanofillers interact mainly with the TPU hard segments (HS) domains, determining their glass transition temperature, and increasing their melting temperature and enthalpy. A significant improvement upon the modulus, sustained stress levels and deformation capabilities is evidenced. The relationships between the morphology and the nanofilled TPU properties are established, evidencing the role of HS domains on the mechanical response, regardless the nanofiller type.

Food Structure Design: Innovation in food structure-properties relationships

This Special Issue gathers selected contributions from the 1st Congress on Food Structure Design, covering most of the topics described above.

Antioxidant properties of hydroxycinnamic acids: a review of structure- activity relationships

Hydroxycinnamic acids (HCAs) are important phytochemicals possessing significant biological properties. Several investigators have studied in vitro antioxidant activity of HCAs in detail. In this review, we have gathered the studies focused on the structure-activity relationships (SARs) of these compounds that have used medicinal chemistry to generate more potent antioxidant molecules. Most of the reports indicated that the presence of an unsaturated bond on the side chain of HCAs is vital to their activity. The structural features that were reported to be of importance to the antioxidant activity were categorized as follows: modifications of the aromatic ring, which include alterations in the number and position of hydroxy groups and insertion of electron donating or withdrawing moieties as well as modifications of the carboxylic function that include esterification and amidation process. Furthermore, reports that have addressed the influence of physicochemical properties including redox potential, lipid solubility and dissociation constant on the antioxidant activity were also summarized. Finally, the pro-oxidant effect of HCAs in some test systems was addressed. Most of the investigations concluded that the presence of ortho-dihydroxy phenyl group (catechol moiety) is of significant importance to the antioxidant activity, while, the presence of three hydroxy groups does not necessarily improve the activity. Optimization of the structure of molecular leads is an important task of modern medicinal chemistry and its accomplishment relies on the careful assessment of SARs. SAR studies on HCAs can identify the most successful antioxidants that could be useful for management of oxidative stress-related diseases.

Solution enthalpies of 1,4-dioxane: Study of solvent effects through quantitative structure-property relationships

Solution enthalpies of 1,4-dioxane have been obtained in 15 protic and aprotic solvents at 298.15 K. Breaking the overall process through the use of Solomonov's methodology the cavity term was calculated and interaction enthalpies (Delta H-int) were determined. Main factors involved in the interaction enthalpy have been identified and quantified using a QSPR approach based on the TAKA model equation. The relevant descriptors were found to be pi* and beta, which showed, respectively, exothermic and endothermic contributions. The magnitude of pi* coefficient points toward non-specific solute-solvent interactions playing a major role in the solution process. The positive value of the beta coefficient reflects the endothermic character of the solvents' hydrogen bond acceptor (HBA) basicity contribution, indicating that solvent molecules engaged in hydrogen bonding preferentially interact with each other rather than with 1,4-dioxane. (C) 2013 Elsevier B.V. All rights reserved.

Structure-property relationships in polymer nanocomposites

Tese de Doutoramento em Ciência e Engenharia de Polímeros e Compósitos

Structure-function relationships of the alpha1b-adrenergic receptor.

The alpha1b-adrenergic receptor (AR) is a member of the large superfamily of seven transmembrane domain (TMD) G protein-coupled receptors (GPCR). Combining site-directed mutagenesis of the alpha1b-AR with computational simulations of receptor dynamics, we have explored the conformational changes underlying the process of receptor activation, i.e. the transition between the inactive and active states. Our findings suggest that the structural constraint stabilizing the alpha1b-AR in the inactive form is a network of H-bonding interactions amongst conserved residues forming a polar pocket and R143 of the DRY sequence at the end of TMDIII. We have recently reported that point mutations of D142, of the DRY sequence and of A293 in the distal portion of the third intracellular loop resulted in ligand-independent (constitutive) activation of the alpha1b-AR. These constitutively activating mutations could induce perturbations resulting in the shift of R143 out of the polar pocket. The main role of R143 may be to mediate receptor activation by triggering the exposure of several basic amino acids of the intracellular loops towards the G protein. Our investigation has been extended also to the biochemical events involved in the desensitization process of alpha1b-AR. Our results indicate that immediately following agonist-induced activation, the alpha1b-AR can undergo rapid agonist-induced phosphorylation and desensitization. Different members of the G protein coupled receptor kinase family can play a role in agonist-induced regulation of the alpha1b-AR. In addition, constitutively active alpha1b-AR mutants display different phosphorylation and internalization features. The future goal is to further elucidate the molecular mechanism underlying the complex equilibrium between activation and inactivation of the alpha1b-AR and its regulation by pharmacological substances. These findings can help to elucidate the mechanism of action of various agents displaying properties of agonists or inverse agonists at the adrenergic system.

Prediction of cross-recognition of peptide-HLA A2 by Melan-A-specific cytotoxic T lymphocytes using three-dimensional quantitative structure-activity relationships.

The cross-recognition of peptides by cytotoxic T lymphocytes is a key element in immunology and in particular in peptide based immunotherapy. Here we develop three-dimensional (3D) quantitative structure-activity relationships (QSARs) to predict cross-recognition by Melan-A-specific cytotoxic T lymphocytes of peptides bound to HLA A*0201 (hereafter referred to as HLA A2). First, we predict the structure of a set of self- and pathogen-derived peptides bound to HLA A2 using a previously developed ab initio structure prediction approach [Fagerberg et al., J. Mol. Biol., 521-46 (2006)]. Second, shape and electrostatic energy calculations are performed on a 3D grid to produce similarity matrices which are combined with a genetic neural network method [So et al., J. Med. Chem., 4347-59 (1997)] to generate 3D-QSAR models. The models are extensively validated using several different approaches. During the model generation, the leave-one-out cross-validated correlation coefficient (q (2)) is used as the fitness criterion and all obtained models are evaluated based on their q (2) values. Moreover, the best model obtained for a partitioned data set is evaluated by its correlation coefficient (r = 0.92 for the external test set). The physical relevance of all models is tested using a functional dependence analysis and the robustness of the models obtained for the entire data set is confirmed using y-randomization. Finally, the validated models are tested for their utility in the setting of rational peptide design: their ability to discriminate between peptides that only contain side chain substitutions in a single secondary anchor position is evaluated. In addition, the predicted cross-recognition of the mono-substituted peptides is confirmed experimentally in chromium-release assays. These results underline the utility of 3D-QSARs in peptide mimetic design and suggest that the properties of the unbound epitope are sufficient to capture most of the information to determine the cross-recognition.

The lipopolysaccharide of Aeromonas spp: structure-activity relationships.

Marine microorganisms, including Aeromonas, are a source of compounds for drug development that have generated great expectations in the last decades. Aeromonas infections produce septicaemia, and ulcerative and haemorrhagic diseases in fish. Among the pathogenic factors associated with Aeromonas, the lipopolysaccharides (LPS), a surface glyconconjugate unique to Gram-negative bacteria consisting of lipid A (lipid anchor of the molecule), core oligosaccharide and O-specific polysaccharide (O antigen), are key elicitors of innate immune responses. The chemical structure of these three parts has been characterized in Aeromonas. Based on the high variability of repeated units of O-polysaccharides, a total of 97 O-serogroups have been described in Aeromonas species, of which four of them (O:11; O:16; O:18 and O:34) account for more than 60% of the septicemia cases. The core of LPS is subdivided into two regions, the inner (highly conserved) and the outer core. The inner core of Aeromonas LPS is characterized by the presence of 3-deoxy-D-manno-oct-2-ulosonic (ketodeoxyoctonic) acid (Kdo) and L-glycero-D-manno-Heptoses (L,D-Hep), which are linked to the outer core, characterized by the presence of Glc, GlcN, Gal, and GalNAc (in Aeromonas salmonicida), D,D-Hep (in Aeromonas salmonicida), and L,D-Hep (in Aeromonas hydrophila). The biological relevance of these differences in the distal part of the outer core among these species has not been fully assessed to date. The inner core is attached to the lipid A, a highly conserved structure that confers endotoxic properties to the LPS when the molecule is released in blood from lysed bacteria, thus inducing a major systemic inflammatory response known as septic or endotoxic shock. In Aeromonas salmonicida subsp. salmonicida the Lipid A components contain three major lipid A molecules, differing in acylation patterns corresponding to tetra-, penta- and hexaacylated lipid A species and comprising of 4′-monophosphorylated β-2-amino-2-deoxy-D-glucopyranose-(1→6)-2-amino-2-deoxy-D-glucopyranose disaccharide. In the present review, we discuss the structure-activity relationships of Aeromonas LPS, focusing on its role in bacterial pathogenesis and its possible applications.

The lipopolysaccharide of Aeromonas spp: structure-activity relationships

Marine microorganisms, including Aeromonas, are a source of compds. for drug development that have generated great expectations in the last decades. Aeromonas infections produce septicemia, and ulcerative and haemorrhagic diseases in fish. Among the pathogenic factors assocd. with Aeromonas, the lipopolysaccharides (LPS)​, a surface glyconconjugate unique to Gram-​neg. bacteria consisting of lipid A (lipid anchor of the mol.)​, core oligosaccharide and O-​specific polysaccharide (O antigen)​, are key elicitors of innate immune responses. The chem. structure of these three parts has been characterized in Aeromonas. Based on the high variability of repeated units of O-​polysaccharides, a total of 97 O-​serogroups have been described in Aeromonas species, of which four of them (O:11; O:16; O:18 and O:34) account for more than 60​% of the septicemia cases. The core of LPS is subdivided into two regions, the inner (highly conserved) and the outer core. The inner core of Aeromonas LPS is characterized by the presence of 3-​deoxy-​d-​manno-​oct-​2-​ulosonic (ketodeoxyoctonic) acid (Kdo) and l-​glycero-​d-​manno-​Heptoses (l,​d-​Hep)​, which are linked to the outer core, characterized by the presence of Glc, GlcN, Gal, and GalNAc (in Aeromonas salmonicida)​, d,​d-​Hep (in Aeromonas salmonicida)​, and l,​d-​Hep (in Aeromonas hydrophila)​. The biol. relevance of these differences in the distal part of the outer core among these species has not been fully assessed to date. The inner core is attached to the lipid A, a highly conserved structure that confers endotoxic properties to the LPS when the mol. is released in blood from lysed bacteria, thus inducing a major systemic inflammatory response known as septic or endotoxic shock. In Aeromonas salmonicida subsp. salmonicida the Lipid A components contain three major lipid A mols., differing in acylation patterns corresponding to tetra-​, penta- and hexa-​acylated lipid A species and comprising of 4'-​monophosphorylated β-​2-​amino-​2-​deoxy-​d-​glucopyranose-​(1→6)​-​2-​amino-​2-​deoxy-​d-​glucopyranose disaccharide. In the present review, we discuss the structure-​activity relationships of Aeromonas LPS, focusing on its role in bacterial pathogenesis and its possible applications.

The lipopolysaccharide of Aeromonas spp: structure-activity relationships

Marine microorganisms, including Aeromonas, are a source of compds. for drug development that have generated great expectations in the last decades. Aeromonas infections produce septicemia, and ulcerative and haemorrhagic diseases in fish. Among the pathogenic factors assocd. with Aeromonas, the lipopolysaccharides (LPS)​, a surface glyconconjugate unique to Gram-​neg. bacteria consisting of lipid A (lipid anchor of the mol.)​, core oligosaccharide and O-​specific polysaccharide (O antigen)​, are key elicitors of innate immune responses. The chem. structure of these three parts has been characterized in Aeromonas. Based on the high variability of repeated units of O-​polysaccharides, a total of 97 O-​serogroups have been described in Aeromonas species, of which four of them (O:11; O:16; O:18 and O:34) account for more than 60​% of the septicemia cases. The core of LPS is subdivided into two regions, the inner (highly conserved) and the outer core. The inner core of Aeromonas LPS is characterized by the presence of 3-​deoxy-​d-​manno-​oct-​2-​ulosonic (ketodeoxyoctonic) acid (Kdo) and l-​glycero-​d-​manno-​Heptoses (l,​d-​Hep)​, which are linked to the outer core, characterized by the presence of Glc, GlcN, Gal, and GalNAc (in Aeromonas salmonicida)​, d,​d-​Hep (in Aeromonas salmonicida)​, and l,​d-​Hep (in Aeromonas hydrophila)​. The biol. relevance of these differences in the distal part of the outer core among these species has not been fully assessed to date. The inner core is attached to the lipid A, a highly conserved structure that confers endotoxic properties to the LPS when the mol. is released in blood from lysed bacteria, thus inducing a major systemic inflammatory response known as septic or endotoxic shock. In Aeromonas salmonicida subsp. salmonicida the Lipid A components contain three major lipid A mols., differing in acylation patterns corresponding to tetra-​, penta- and hexa-​acylated lipid A species and comprising of 4'-​monophosphorylated β-​2-​amino-​2-​deoxy-​d-​glucopyranose-​(1→6)​-​2-​amino-​2-​deoxy-​d-​glucopyranose disaccharide. In the present review, we discuss the structure-​activity relationships of Aeromonas LPS, focusing on its role in bacterial pathogenesis and its possible applications.

The physics of baking: rheological and polymer molecular structure-function relationships in breadmaking

Molecular size and structure of the gluten polymers that make up the major structural components of wheat are related to their rheological properties via modem polymer rheology concepts. Interactions between polymer chain entanglements and branching are seen to be the key mechanisms determining the rheology of HMW polymers. Recent work confirms the observation that dynamic shear plateau modulus is essentially independent of variations in MW amongst wheat varieties of varying baking performance and is not related to variations in baking performance, and that it is not the size of the soluble glutenin polymers, but the structural and rheological properties of the insoluble polymer fraction that are mainly responsible for variations in baking performance. The rheological properties of gas cell walls in bread doughs are considered to be important in relation to their stability and gas retention during proof and baking, in particular their extensional strain hardening properties. Large deformation rheological properties of gas cell walls were measured using biaxial extension for a number of doughs of varying breadmaking quality at constant strain rate and elevated temperatures in the range 25-60 degrees C. Strain hardening and failure strain of cell walls were both seen to decrease with temperature, with cell walls in good breadmaking doughs remaining stable and retaining their strain hardening properties to higher temperatures (60 degrees C), whilst the cell walls of poor breadmaking doughs became unstable at lower temperatures (45-50 degrees C) and had lower strain hardening. Strain hardening measured at 50 degrees C gave good correlations with baking volume, with the best correlations achieved between those rheological measurements and baking tests which used similar mixing conditions. As predicted by the Considere failure criterion, a strain hardening value of I defines a region below which gas cell walls become unstable, and discriminates well between the baking quality of a range of commercial flour blends of varying quality. This indicates that the stability of gas cell walls during baking is strongly related to their strain hardening properties, and that extensional rheological measurements can be used as predictors of baking quality. (C) 2004 Elsevier B.V. All rights reserved.

The physics of baking: rheological and polymer molecular structure-function relationships in breadmaking

Molecular size and structure of the gluten polymers that make up the major structural components of wheat are related to their rheological properties via modern polymer rheology concepts. Interactions between polymer chain entanglements and branching are seen to be the key mechanisms determining the rheology of HMW polymers. Recent work confirms the observation that dynamic shear plateau modulus is essentially independent of variations in MW amongst wheat varieties of varying baking performance and is not related to variations in baking performance, and that it is not the size of the soluble glutenin polymers, but the structural and rheological properties of the insoluble polymer fraction that are mainly responsible for variations in baking performance. The rheological properties of gas cell walls in bread doughs are considered to be important in relation to their stability and gas retention during proof and baking, in particular their extensional strain hardening properties. Large deformation rheological properties of gas cell walls were measured using biaxial extension for a number of doughs of varying breadmaking quality at constant strain rate and elevated temperatures in the range 25oC to 60oC. Strain hardening and failure strain of cell walls were both seen to decrease with temperature, with cell walls in good breadmaking doughs remaining stable and retaining their strain hardening properties to higher temperatures (60oC), whilst the cell walls of poor breadmaking doughs became unstable at lower temperatures (45oC to 50oC) and had lower strain hardening. Strain hardening measured at 50oC gave good correlations with baking volume, with the best correlations achieved between those rheological measurements and baking tests which used similar mixing conditions. As predicted by the Considere failure criterion, a strain hardening value of 1 defines a region below which gas cell walls become unstable, and discriminates well between the baking quality of a range of commercial flour blends of varying quality. This indicates that the stability of gas cell walls during baking is strongly related to their strain hardening properties, and that extensional rheological measurements can be used as predictors of baking quality.

Structure property relationships in electrically conducting copolymers formed from pyrrole and N-methyl pyrrole

A series of copolymers containing differing proportions of pyrrole and N-methyl pyrrole were prepared electrochemically at various temperatures using acetonitrile as the solvent. The resultant electrical conductivity decreases universally with increasing fraction of N-methyl pyrrole. Films prepared with p-toluene sulfonate as the dopant show a marked variation in structural anisotropy as revealed by X-ray scattering with apparent copolymer content. There is a clear trend between the variation in electrical conductivity and this structural anisotropy. Different patterns of behaviour are observed for films prepared using perchlorate as the dopant and this is attributed to the role of the dopant and final structure in determining the relative reactivities of the pyrrole and N-methyl pyrrole monomers. These observations support the concept that the introduction of methyl substituents into a polypyrrole chain results in a twisted chain conformation. The structure and properties of the resultant copolymer films are particularly sensitive to the preparation conditions.

Classical and fragment-based hologram structure-activity relationships for a series of analgesic cyclic imides

Cyclic imides have been widely employed in drug design research due to their multiple pharmacological and biological properties. In the present study, two-dimensional quantitative structure-activity relationship (2D QSAR) studies were conducted on a series of potent analgesic cyclic imides using both classical and hologram QSAR (HQSAR) methods, yielding significant statistical models (classical QSAR, q(2) = 0.80; HQSAR, q(2) = 0.84). The models were then used to evaluate an external data test, and the predicted values were in good agreement with the experimental results, indicating their consistency for untested compounds.

Structure-function relationships of the peptide Paulistine: A novel toxin from the venom of the social wasp Polybia paulista

Background: The peptide Paulistine was isolated from the venom of wasp Polybia paulista. This peptide exists under a natural equilibrium between the forms: oxidised - with an intra-molecular disulphide bridge; and reduced - in which the thiol groups of the cysteine residues do not form the disulphide bridge. The biological activities of both forms of the peptide are unknown up to now. Methods: Both forms of Paulistine were synthesised and the thiol groups of the reduced form were protected with the acetamidemethyl group [Acm-Paulistine] to prevent re-oxidation. The structure/activity relationships of the two forms were investigated, taking into account the importance of the disulphide bridge. Results: Paulistine has a more compact structure, while Acm-Paulistine has a more expanded conformation. Bioassays reported that Paulistine caused hyperalgesia by interacting with the receptors of lipid mediators involved in the cyclooxygenase type II pathway, while Acm-Paullistine also caused hyperalgesia, but mediated by receptors involved in the participation of prostanoids in the cyclooxygenase type II pathway. Conclusion: The acetamidemethylation of the thiol groups of cysteine residues caused small structural changes, which in turn may have affected some physicochemical properties of the Paulistine. Thus, the dissociation of the hyperalgesy from the edematogenic effect when the actions of Paulistine and Acm-Paulistine are compared to each other may be resulting from the influence of the introduction of Acm-group in the structure of Paulistine. General significance: The peptides Paulistine and Acm-Paulistine may be used as interesting tools to investigate the mechanisms of pain and inflammation in future studies. © 2013 Elsevier B.V.