Development of Photorefractive Polymers: Evaluation of Photoconducting and Electro-optic Properties

This Thesis discussed molecules suitable for photorefractive effect. Out of the molecules studied, only one system was used to make photorefractive polymers system. Other molecules, especially, the electro-optic polymer, Poly(3-methacrloyl-1-(4'-nitro-4-azo-1'-phenyl)phenylalanine-co- methyl methacrylate) can be subjected to more detailed studies to explore the possibilities of using them for electro-optic applications. Though not included in the thesis, the efficient photoconductor, Poly(6-tert-butyl-3- phenyl-3,4-dihydro-2H-1,3-benzoxazine) sensitized with C60, which was described in Chapter 3 showed a low magnitude photovoltaic effect. This hints at the possibility of using this system for organic solar cells also. The thesis presented the initial observation of photorefractive effect in a polybenzoxazine based polymer system. A detailed analysis of the effect of C60, ECZ and DR1 can be carried out to check for the possibility of a high efficiency photorefractive system.

Provenance, Isolation and Characterisation of Organic Matter in the Cochin Estuarine Sediment-“a Diagenetic Amino Acid Marker Scenario

Cochin estuarine system is among the most productive aquatic environment along the Southwest coast of India, exhibits unique ecological features and possess greater socioeconomic relevance. Serious investigations carried out during the past decades on the hydro biogeochemical variables pointed out variations in the health and ecological functioning of this ecosystem. Characterisation of organic matter in the estuary has been attempted in many investigations. But detailed studies covering the degradation state of organic matter using molecular level approach is not attempted. The thesis entitled Provenance, Isolation and Characterisation of Organic Matter in the Cochin Estuarine Sediment-“ A Diagenetic Amino Acid Marker Scenario” is an integrated approach to evaluate the source, quantity, quality, and degradation state of the organic matter in the surface sediments of Cochin estuarine system with the combined application of bulk and molecular level tools. Sediment and water samples from nine stations situated at Cochin estuary were collected in five seasonal sampling campaigns, for the biogeochemical assessment and their distribution pattern of sedimentary organic matter. The sampling seasons were described and abbreviated as follows: April- 2009 (pre monsoon: PRM09), August-2009 (monsoon: MON09), January-2010 (post monsoon: POM09), April-2010 (pre monsoon: PRM10) and September- 2012 (monsoon: MON12). In order to evaluate the general environmental conditions of the estuary, water samples were analysed for water quality parameters, chlorophyll pigments and nutrients by standard methods. Investigations suggested the fact that hydrographical variables and nutrients in Cochin estuary supports diverse species of flora and fauna. Moreover the sedimentary variables such as pH, Eh, texture, TOC, fractions of nitrogen and phosphorous were determined to assess the general geochemical setting as well as redox status. The periodically fluctuating oxic/ anoxic conditions and texture serve as the most significant variables controlling other variables of the aquatic environment. The organic matter in estuary comprise of a complex mixture of autochthonous as well as allochthonous materials. Autochthonous input is limited or enhanced by the nutrient elements like N and P (in their various fractions), used as a tool to evaluate their bioavailability. Bulk parameter approach like biochemical composition, stoichiometric elemental ratios and stable carbon isotope ratio was also employed to assess the quality and quantity of sedimentary organic matter in the study area. Molecular level charactersation of free sugars and amino acids were carried out by liquid chromatographic techniques. Carbohydrates are the products of primary production and their occurrence in sediments as free sugars can provide information on the estuarine productivity. Amino acid biogeochemistry provided implications on the system productivity, nature of organic matter as well as degradation status of the sedimentary organic matter in the study area. The predominance of carbohydrates over protein indicated faster mineralisation of proteinaceous organic matter in sediments and the estuary behaves as a detrital trap for the accumulation of aged organic matter. The higher lipid content and LPD/CHO ratio pointed towards the better food quality that supports benthic fauna and better accumulation of lipid compounds in the sedimentary environment. Allochthonous addition of carbohydrates via terrestrial run off was responsible for the lower PRT/CHO ratio estimated in thesediments and the lower ratios also denoted a detrital heterotrophic environment. Biopolymeric carbon and the algal contribution to BPC provided important information on the better understanding the trophic state of the estuarine system and the higher values of chlorophyll-a to phaeophytin ratio indicated deposition of phytoplankton to sediment at a rapid rate. The estimated TOC/TN ratios implied the combined input of both terrestrial and autochthonous organic matter to sedimentsAmong the free sugars, depleted levels of glucose in sediments in most of the stations and abundance of mannose at station S5 was observed during the present investigation. Among aldohexoses, concentration of galactose was found to be higher in most of the stationsRelative abundance of AAs in the estuarine sediments based on seasons followed the trend: PRM09-Leucine > Phenylalanine > Argine > Lysine, MON09-Lysine > Aspartic acid > Histidine > Tyrosine > Phenylalanine, POM09-Lysine > Histadine > Phenyalanine > Leucine > Methionine > Serine > Proline > Aspartic acid, PRM10-Valine > Aspartic acid > Histidine > Phenylalanine > Serine > Proline, MON12-Lysine > Phenylalanine > Aspartic acid > Histidine > Valine > Tyrsine > MethionineThe classification of study area into three zones based on salinity was employed in the present study for the sake of simplicity and generalized interpretations. The distribution of AAs in the three zones followed the trend: Fresh water zone (S1, S2):- Phenylalanine > Lysine > Aspartic acid > Methionine > Valine ῀ Leucine > Proline > Histidine > Glycine > Serine > Glutamic acid > Tyrosine > Arginine > Alanine > Threonine > Cysteine > Isoleucine. Estuarine zone (S3, S4, S5, S6):- Lysine > Aspartic acid > Phenylalanine > Leucine > Valine > Histidine > Methionine > Tyrosine > Serine > Glutamic acid > Proline > Glycine > Arginine > Alanine > Isoleucine > Cysteine > Threonine. Riverine /Industrial zone (S7, S8, S9):- Phenylalanine > Lysine > Aspartic acid > Histidine > Serine > Arginine > Tyrosine > Leucine > Methionine > Glutamic acid > Alanine > Glycine > Cysteine > Proline > Isoleucine > Threonine > Valine. The abundance of AAs like glutamic acid, aspartic acid, isoleucine, valine, tyrosine, and phenylalanine in sediments of the study area indicated freshly derived organic matter.

Aproximacions a la síntesi estereoselectiva de noves heteroarilglicines

L'objectiu principal de la present tesi doctoral ha consistit fonamentalment en la síntesi de noves heteroarilglicines òpticament pures. Amb aquesta idea s'han desenvolupat dues estratègies diferents: síntesi estereoselectiva utilitzant auxiliars quirals i síntesi estereocontrolada utilitzant aldehids quirals derivats d' L-serina com a "building-blocks". Així doncs, per a la primera estratègia s'han dissenyat i sintetitzat els dos nous auxiliars quirals del tipus imidazolidin-2-ona 111 i 135 utilitzant L-fenilalanina i L-serina respectivament com a materials de partida òpticament purs. Davant els problemes detectats en la síntesi d'a-aminoàdics mitjançant síntesi asimètric, s'ha canviat d'estratègia i s'ha utilitzat una síntesi estereocontrolada utilitzant aldehids quirals obtinguts a partir d'L-serina.

Pèptids biarílics a partir de 4-iodofenilalanina o 3-iodotirosina per borilació i reacció de Suzuki-Miyaura en fase sòlida. Avaluació de l'activitat antimicrobiana

En aquesta tesi doctoral es va estudiar la preparació de pèptids biarílics en fase sòlida. En primer lloc, es varen borilar residus de fenilalanina o tirosina presents a la seqüència peptídica a través d’una reacció de Miyaura. A continuació, es varen arilar els boronats resultants a través d’una reacció de Suzuki-Miyaura sota irradiació de microones, utilitzant diversos halurs d’aril i haloaminoàcids. La metodologia trobada es va estendre a la preparació de pèptids biarílics cíclics. Aquesta aproximació presenta l’avantatge d’evitar la síntesi en dissolució i la purificació del boronoaminoàcid. A més, permet la preparació d’una àmplia diversitat de pèptids biarílics a partir d’un únic boronopèptid. L’avaluació de l’activitat biològica dels pèptids sintetitzats va permetre idenficar seqüències actives enfront dels bacteris Erwinia amylovora, Xanthomonas vesicatoria, i Pseudomonas syringae, que són responsables de malalties greus en plantes d’interès econòmic com pereres i pomeres, i que varen resultar ser molt poc tòxics enfront cèl•lules eucariotes.

Síntesi, caracterització química i estudi de l'activitat biològica de nous complexos de Pt(II) amb lligands de tipus diaminocarboxílic i els respectius ésters i derivats peptídics

El cisplatí, PtCl2(NH3)2, ha estat una de les drogues més utilitzades en la quimioteràpia del càncer des del descobriment de la seva activitat. Però degut a la seva alta toxicitat i greus efectes secundaris, s'han sintetitzat nous compostos amb la finalitat de reduir aquests inconvenients. En aquest sentit, el treball desenvolupat en aquesta tesi doctoral ha estat la síntesi i caracterització de tretze complexos de Pt(II) amb la finalitat d'estudiar llur activitat antitumoral. Aquests complexos presenten unes característiques estructurals comunes: geometria cis, dos lligands làbils de tipus clorur i un lligand diaminoquelatant derivat dels àcids d,l-2,3-diaminopropiònic (Hdap) i d,l-2,4-diaminobutíric (Hdab). S'han dissenyat unes estratègies sintètiques a partir de les quals els lligands han estat funcionalitzats amb diferents grups de tipus éster, aminoàcid i peptídic: Etdap·2HCl, Etdab·2HCl, [(dap-Metala)·2CF3COOH], [(dab-Metala)·2CF3COOH], [(dap-phe)·2CF3COOH], [(dab-phe)·2CF3COOH], [(dap-Mettrp)·2CF3COOH], [(dab-Mettrp)·2CF3COOH], [(dap-ASTTTNYT-NH2)·2CF3COOH], essent Metala= éster metílic de L-alanina, phe= L-fenilalanina, Mettrp= éster metílic del L-triptofà. Aquests lligands diaminoquelatants s'han utilitzat per sintetitzar els corresponents complexos de Pt(II): PtCl2(Hdap), PtCl2(Hdab), PtCl2(Etdap), PtCl2(Etdab), PtCl2(dap-Metala), PtCl2(dab-Metala), PtCl2(dap-ala), PtCl2(dab-ala), PtCl2(dap-phe), PtCl2(dab-phe), PtCl2(dap-Mettrp), PtCl2(dab-Mettrp), PtCl2(dap-ASTTTNYT-NH2). A través de diferents tècniques i assaigs biològics (dicroisme circular, electroforesi en gel d'agarosa, microscopia de forces atòmiques, citometria de flux, assaigs de proliferació cel·lular) s'ha pogut demostrar l'activitat antitumoral d'aquests compostos. A través de la tècnica de dicroisme circular (DC) s'ha pogut demostrar que els lligands lliures no interaccionen covalentment amb el DNA de Calf Thymus i no modifiquen l'estructura secundària de la doble hèlix. En canvi, els respectius complexos han demostrat tenir capacitat per interaccionar amb el DNA i modificar la seva estructura secundària. Els complexos PtCl2(Hdap), PtCl2(Hdab) i PtCl2(dab-phe) mostren un comportament similar al cisplatí, generant adductes cis-bifuncionals que distorcionen la doble hèlix de forma no desnaturalitzant amb obertura de la doble cadena. Els complexos PtCl2(Etdap), PtCl2(Etdab), PtCl2(dap-ala), PtCl2(dab-ala), PtCl2(dap-Metala), PtCl2(dab-Metala), PtCl2(dap-phe), PtCl2(dap-ASTTTNYT-NH2) quan interaccionen amb el DNA generen un canvi en la conformació del DNA de la forma B a la forma C, produint-se un augment de la curvatura de l'hèlix per rotació de les bases nitrogenades. En aquests estudis s'ha comprovat que l'estructura del complex influeix en l'efecte generat sobre l'estructura secundària de l'àcid nucleic. En primer lloc, existeix una diferència en el comportament en funció del tamany del lligand diaminoquelatant, de manera que els complexos amb el lligand (dab) provoquen un efecte més remarcable. També s'observa aquest canvi de comportament al passar dels complexos que tenen el grup funcional esterificat als que el tenen protonat. D'aquesta manera, s'observa un major efecte sobre l'estructura secundària del DNA en aquells complexos que tenen el lligand diaminoquelatant de tres metilens (dab) i amb el grup carboxilat terminal protonat. Per tal de modelitzar la interacció d'aquests complexos amb el DNA, s'ha estudiat la interacció d'aquests compostos de Pt(II) amb 5'-GMP a través de RMN-1H, observant la variació dels senyals corresponents al H8 de 5'-GMP. Així s'ha pogut demostrar que aquests compostos interaccionen amb la 5'-GMP a través d'un enllaç covalent Pt-N7, de la mateixa manera a com interacciona el cisplatí. A través d'electroforesi en gel d'agarosa i microscopia de forces atòmiques (AFM) s'ha pogut determinar l'efecte que generen els lligands lliures i els respectius complexos de Pt(II) sobre l'estructura terciària del plasmidi pBR322. Els lligands provoquen un augment de l'agregació de les molècules de DNA i un lleuger augment de la compactació de l'estructura terciària. Aquests resultats s'atribueixen a la capacitat d'aquests compostos a interaccionar per pont d'hidrogen amb el DNA. Els corresponents complexos de Pt(II) provoquen un augment de l'agregació i una important compactació, degut per una banda a la capacitat de l'àtom de Pt a interaccionar covalentment amb el DNA, i per altra banda, a la capacitat del lligand a interaccionar per pont d'hidrogen amb l'àcid nucleic. Finalment s'ha estudiat l'activitat citotòxica d'aquests complexos de Pt(II) en diferents línies cel·lulars: A431 (línia de carcinoma epidermoide), HeLa (línia de carcinoma de coll d'úter) i HL-60 (línia promielocítica de leucèmia). Els complexos moderadament solubles en aigua, PtCl2(Hdap), PtCl2(Hdab), PtCl2(dap-ala), PtCl2(dab-ala), PtCl2(dap-phe) i PtCl2(dab-phe), han demostrat ser actius. L'activitat depèn de la concentració de complex, del temps d'incubació i de la línia cel·lular. Per temps d'incubació alts i concentracions de complex elevades s'observa la màxima activitat. Els complexos de l'alanina, PtCl2(dap-ala) i PtCl2(dab-ala), són els que mostren més activitat, mentre que els compostos de la fenilalanina són els menys actius, degut probablement a la voluminositat del lligand, la qual pot impedir o dificultar el transport del compost a través de la membrana cel·lular. L'activitat citotòxica dels complexos insolubles en aigua, PtCl2(Etdap) i PtCl2(Etdab), queda bloquejada per l'elevada concentració de DMSO (12%) necessària per solubilitzar els compostos. Aquests resultats permeten deduir que la presència d'un 12% de DMSO anul·la l'activitat d'aquests complexos, ja que el DMSO pot coordinar-se amb el Pt ocupant les posicions làbils del complex i evitant que es pugui coordinar amb el DNA. Els assaigs de proliferació cel·lular del complex PtCl2(dap-ASTTTNYT-NH2) i del pèptid lliure ASTTTNYT-NH2 han demostrat que ambdós compostos són actius. Tot i això, l'activitat del complex és superior a la del pèptid lliure, ja que el Pt pot interaccionar covalentment amb el DNA i augmentar l'efecte citotòxic. Per tant, el complex presenta un lligand portador biològicament actiu que pot transportar el metall a través de la membrana cel·lular i facilitar així la seva interacció amb el DNA. A través de la tècnica de citometria de flux s'ha comprovat que en tots els casos la mort cel·lular produïda pels complexos ha estat per apoptosi. Per últim, s'ha sintetitzat i caracteritzat un complex trinuclear de Pt(II), {[Pt(Me2Bpy)2][PtCl2(Me2Bpy)]2}, essent Me2Bpy= 4,4'-dimetil-2,2'-dipiridil. La resolució de la seva estructura per difracció de Raig-X ha permès determinar l'existència d'una interacció intramolecular Pt-Pt de 3.474 Å.

Mechanism of action of cyclic antimicrobial peptides

This PhD thesis is the result of the combination of experimental and computational techniques with the aim of understanding the mechanism of action of de novo cyclic decapeptides with high antimicrobial activity. By experimental techniques the influence of the replacement of the phenylalanine for tryptophan residue in their antimicrobial activity was tested and the stability in human serum was also analyzed, in order to evaluate their potential therapeutic application as antitumor agents. On the other hand, the interaction amongst the peptide BPC194 c(KKLKKFKKLQ), the best candidate from the whole library of cyclic peptides, and a model anionic membrane was simulated. The results showed a structure-function relationship derived from the stable conformation of the peptides involved in the membrane permeabilization. As a result, a rational design was performed being BPC490 the peptide with best antimicrobial activity compared with the best active peptide from the original library.

An integrative model of amino acid metabolism in the liver of the lactating dairy cow

The objective of this work was to construct a dynamic model of hepatic amino acid metabolism in the lactating dairy cow that could be parameterized using net flow data from in vivo experiments. The model considers 22 amino acids, ammonia, urea, and 13 energetic metabolites, and was parameterized using a steady-state balance model and two in vivo, net flow experiments conducted with mid-lactation dairy cows. Extracellular flows were derived directly from the observed data. An optimization routine was used to derive nine intracellular flows. The resulting dynamic model was found to be stable across a range of inputs suggesting that it can be perturbed and applied to other physiological states. Although nitrogen was generally in balance, leucine was in slight deficit compared to predicted needs for export protein synthesis, suggesting that an alternative source of leucine (e.g. peptides) was utilized. Simulations of varying glucagon concentrations indicated that an additional 5 mol/d of glucose could be synthesized at the reference substrate concentrations and blood flows. The increased glucose production was supported by increased removal from blood of lactate, glutamate, aspartate, alanine, asparagine, and glutamine. As glucose Output increased, ketone body and acetate release increased while CO2 release declined. The pattern of amino acids appearing in hepatic vein blood was affected by changes in amino acid concentration in portal vein blood, portal blood flow rate and glucagon concentration, with methionine and phenylalanine being the most affected of essential amino acids. Experimental evidence is insufficient to determine whether essential amino acids are affected by varying gluconeogenic demands. (C) 2004 Published by Elsevier Ltd.

Effect of plasma insulin and branched-chain amino acids on skeletal muscle protein synthesis in fasted lambs

The increase in fractional rate of protein synthesis (K-s) in the skeletal muscle of growing rats during the transition from fasted to fed state has been explained by the synergistic action of a rise in plasma insulin and branched-chain amino acids (BCAA). Since growing lambs Also exhibit an increase in K-s with level of feed intake, the objective of the present study was to determine if this synergistic relationship between insulin and BCAA also occurs in ruminant animals. Six 30 kg fasted (72 h) lambs (8 months of age) received each of four treatments, which were based on continuous infusion into the jugular vein for 6 h of: (1) saline (155 mmol NaCl/l); (2) a mixture of BCAA (0.778 mumol leucine, 0.640 mumol isoleucine and 0.693 mumol valine/min.kg); (3) 18.7 mumol glucose/min.kg (to induce endogenous insulin secretion): (4) co-infusion of BCAA and glucose. Within each period all animals received the same isotope of phenylalanine, (Phe) as follows: (1) L-[1-C-13]Phe; (2) L-phenyl-[ring H-2(5)]-alanine; (3) L-[N-15]Phe; (4) L-[ring 2,6-H-3]Phe. Blood was sampled serially during infusions to measure plasma concentrations of insulin, glucose and amino acids, and plasma free Phe isotopic activity; biopsies were taken 6 h after the beginning of infusions to determine K-s in in. longissimus dorsi and vastus muscle. Compared with control (saline-infused) lambs, K-s was increased by an average of 40% at the end of glucose infusion, but this effect was not statistically significant in either of the muscles sampled. BCAA infusion, alone or in combination with glucose, also had no significant effect on K-s compared with control sheep. K-s was approximately 60% greater for vastus muscle than for m. longissimus dorsi (P<0.01), regardless of treatment. It is concluded that there are signals other than insulin and BCAA that are responsible for the feed-induced increase in K-s in muscle of growing ruminant animals.

Microbe-associated molecular pattern (MAMP) signatures, synergy, size and charge: influences on perception or mobility and host defence responses

Triggering of defences by microbes has mainly been investigated using single elicitors or microbe-associated molecular patterns (MAMPs), but MAMPs are released in planta as complex mixtures together with endogenous oligogalacturonan (OGA) elicitor. We investigated the early responses in Arabidopsis of calcium influx and oxidative burst induced by non-saturating concentrations of bacterial MAMPs, used singly and in combination: flagellin peptide (flg22), elongation factor peptide (elf18), peptidoglycan (PGN) and component muropeptides, lipo-oligosaccharide (LOS) and core oligosaccharides. This revealed that some MAMPs have additive (e.g. flg22 with elf18) and even synergistic (flg22 and LOS) effects, whereas others mutually interfere (flg22 with OGA). OGA suppression of flg22-induced defences was not a result of the interference with the binding of flg22 to its receptor flagellin-sensitive 2 (FLS2). MAMPs induce different calcium influx signatures, but these are concentration dependent and unlikely to explain the differential induction of defence genes [pathogenesis-related gene 1 (PR1), plant defensin gene 1.2 (PDF1.2) and phenylalanine ammonia lyase gene 1 (PAL1)] by flg22, elf18 and OGA. The peptide MAMPs are potent elicitors at subnanomolar levels, whereas PGN and LOS at high concentrations induce low and late host responses. This difference might be a result of the restricted access by plant cell walls of MAMPs to their putative cellular receptors. flg22 is restricted by ionic effects, yet rapidly permeates a cell wall matrix, whereas LOS, which forms supramolecular aggregates, is severely constrained, presumably by molecular sieving. Thus, MAMPs can interact with each other, whether directly or indirectly, and with the host wall matrix. These phenomena, which have not been considered in detail previously, are likely to influence the speed, magnitude, versatility and composition of plant defences.

Domain swapping in the human histamine H-1 receptor

G-protein-coupled receptors (GPCRs) represent the largest family of receptors involved in transmembrane signaling. Although these receptors were generally believed to be monomeric entities, accumulating evidence supports the presence of GPCRs in multimeric forms. Here, using immunoprecipitation as well as time-resolved fluorescence resonance energy transfer to assess protein-protein interactions in living cells, we unambiguously demonstrate the occurrence of dimerization of the human histamine H-1 receptor. We also show the presence of domain-swapped H-1 receptor dimers in which there is the reciprocal exchange of transmembrane domain TM domains 6 and 7 between the receptors present in the dimer. Mutation of aspartate(107) in transmembrane (TM) 3 or phenylalanine(432) in TM6 to alanine results in two radioligand-binding-deficient mutant H-1 receptors. Coexpression of H-1 D(107)A and H-1 F(432)A, however, results in a reconstituted radioligand binding site that exhibits a pharmacological profile that corresponds to the wildtype H-1 receptor. Interestingly, the H-1 receptor radioligands [H-3] mepyramine and [H-3]-(-)- trans-1-phenyl-3-N, N-dimethylamino-1,2,3,4-tetrahydronaphthalene show differential saturation binding values (B-max) for wild-type H-1 receptors but not for the radioligand binding site that is formed upon coexpression of H-1 D(107)A and H-1 F(432)A receptors, suggesting the presence of different H-1 receptor populations.

A new molecular scaffold for the formation of supramolecular peptide double helices: the crystallographic insight

A series of water-soluble synthetic dipeptides (1-3) with an N-terminally located beta-alanine residue, beta-alanyl-L-valine (1), beta-alanyl-L-isoleucine (2), and beta-alanyl-L-phenylalanine (3, form hydrogen-bonded supramolecular double helices with a pitch length of 1 nm, whereas the C-terminally positioned beta-alanine containing dipeptide (4), L-phenylalanyl-beta-alanine, does not form a supramolecular double helical structure. beta-Ala-Xaa (Xaa = Val/Ile/Phe) can be regarded as a new motif for the formation of supramolecular double helical structures in the solid state.

Nematic and columnar ordering of a PEG-peptide conjugate in aqueous solution

The self-assembly in aqueous solution of a PEG-peptide conjugate is studied by spectroscopy, electron microscopy, rheology and small-angle Xray and neutron scattering (SAXS and SANS). The peptide fragment, FFKLVFF is based on fragment KLVFF of the amyloid beta-peptide, A beta(16-20), extended by two hydrophobic phenylalanine units. This is conjugated to PEG which confers water solubility and leads to distinct self-assembled structures. Small-angle scattering reveals the formation of cylindrical fibrils comprising a peptide core and PEG corona. This constrained structure leads to a model parallel beta-sheet self-assembled structure with a radial arrangement of beta sheets. Oil increasing concentration, successively nematic and hexagonal columnar phases are formed. The flow-induced alignment of both structures was studied in situ by SANS using a Couette cell. Shear-induced alignment is responsible for the shear thinning behaviour observed by dynamic shear rheometry. Incomplete recovery of moduli after cessation of shear is consistent with the observation from SANS of retained orientation in the sample.

Self-assembly of peptide nanotubes in an organic solvent

The self-assembly of a modified fragment of the amyloid beta peptide, based on sequence A beta(16-20), KLVFF, extended to give AAKLVFF is studied in methanol. Self-assembly into peptide nanotubes is observed, as confirmed by electron microscopy and small-angle X-ray scattering. The secondary structure of the peptide is probed by FTIR and circular dichroism, and UV/visible spectroscopy provides evidence for the important role of aromatic interactions between phenylalanine residues in driving beta-sheet self-assembly. The beta-sheets wrap helically to form the nanotubes, the nanotube wall comprising four wrapped beta-sheets. At higher concentration, the peptide nanotubes form a nematic phase that exhibits spontaneous flow alignment as observed by small-angle neutron scattering.

The effect of PEG crystallization on the morphology of PEG/peptide block copolymers containing amyloid beta-peptide fragments

Ordered nanostructures are observed in the melt and solid state for a series of three peptide/PEG conjugates containing fragments of amyloid beta-peptides. These are conjugated to PEG with (M) over bar (n) = 3 300 g.mol(-1) and a melting temperature T-m = 45-50 degrees C. The morphology at room temperature is examined by AFM and POM. This shows spherulite formation for the weakly fibrillizing KLVFF-PEG sample but fibril formation for FFKLVFF-PEG. The fibrillization tendency of the latter is enhanced by multiple phenylalanine residues. Simultaneous SAXS and WAXS was used to investigate the morphology as a function of temperature. The secondary structure is probed by FTIR.

Development of novel brush-type chiral stationary phases based on terpenoid selectors: HPLC evaluation and theoretical investigation of enantioselective binding interactions

The terpenoid chiral selectors dehydroabietic acid, 12,14-dinitrodehydroabietic acid and friedelin have been covalently linked to silica gel yielding three chiral stationary phases CSP 1, CSP 2 and CSP 3, respectively. The enantiodiscriminating capability of each one of these phases was evaluated by HPLC with four families of chiral aromatic compounds composed of alcohols, amines, phenylalanine and tryptophan amino acid derivatives and beta-lactams. The CSP 3 phase, containing a selector with a large friedelane backbone is particularly suitable for resolving free alcohols and their derivatives bearing fluorine substituents, while CSP 2 with a dehydroabietic architecture is the only phase that efficiently discriminates 1, 1'-binaphthol atropisomers. CSP 3 also gives efficient resolution of the free amines. All three phases resolve well the racemates of N-trifluoracetyl and N-3,5-dinitrobenzoyl phenylalanine amino acid ester derivatives. Good enantioseparation of beta-lactams and N-benzoyl tryptophan amino acid derivatives was achieved on CSP 1. In order to understand the structural factors that govern the chiral molecular recognition ability of these phases, molecular dynamics simulations were carried out in the gas phase with binary diastereomeric complexes formed by the selectors of CSP 1 and CSP 2 and several amino acid derivatives. Decomposition of molecular mechanics energies shows that van der Waals interactions dominate the formation of the diastereomeric transient complexes while the electrostatic binding interactions are primarily responsible for the enantioselective binding of the (R)- and (S)-analytes. Analysis of the hydrogen bonds shows that electrostatic interactions are mainly associated with the formation of N-(HO)-O-...=C enantio selective hydrogen bonds between the amide binding sites from the selectors and the carbonyl groups of the analytes. The role of mobile phase polarity, a mixture of n-hexane and propan-2-ol in different ratios, was also evaluated through molecular dynamics simulations in explicit solvent. (c) 2006 Elsevier Ltd. All rights reserved.