Synthesis and phase behaviour of a homologous series of polymethacrylate-based side-chain liquid crystal polymers

The homologous series of side chain liquid crystal polymers, the poly[x-(4-methoxyazobenzene- 40-oxy)alkyl methacrylate]s, has been prepared in which the length of the flexible alkyl spacer has been varied from 3 to 11 methylene units. All the polymers exhibit liquid crystalline behaviour. The propyl and butyl members show exclusively nematic behaviour. The pentyl, hexyl, octyl and decyl members show a nematic and a smectic A phase while the heptyl, nonyl and undecyl homologues exhibit only a smectic A phase. The smectic A phase has been studied using X-ray diffraction and assigned as a smectic A1 phase in which the side chains are fully overlapped and the backbones are confined to lie between the smectic layers. For the nonyl member an incommensurate smectic phase is observed. The dependence of the transition temperatures on the length of the flexible spacer is understood in terms of the average shapes of the side chains.

Effects of Side-Chain and Electron Exchange Correlation on the Band Structure of Perylene Diimide Liquid Crystals: A Density Functional Study

The structural and electronic properties of perylene diimide liquid crystal PPEEB are studied using ab initio methods based on the density functional theory (I)FT). Using available experimental crystallographic data as a guide, we propose a detailed structural model for the packing of solid PPEEB. We find that due to the localized nature of the band edge wave function, theoretical approaches beyond the standard method, such as hybrid functional (PBE0), are required to correctly characterize the band structure of this material. Moreover, unlike previous assumptions, we observe the formation of hydrogen bonds between the side chains of different molecules, which leads to a dispersion of the energy levels. This result indicates that the side chains of the molecular crystal not only are responsible for its structural conformation but also can be used for tuning the electronic and optical properties of these materials.

Optical VOCs detection using poly(3-alkylthiophenes) with different side-chain lengths

The use of conjugated polymers in the gas and volatile organic compounds (VOCs) detections represents an advance in the development of the electronic noses. Polythiophenes show good thermal and environmental stability, are easily synthesized and they have been studied as gas and VOCs sensors using different principles or transduction techniques. Among these techniques, optical sensing has been attracted attention, mainly due to its versatility. However, conjugated polymer-based optical sensors are still less studied. This paper describes the use of two poly(3-alkylthiophenes) for VOCs optical detection. The sensing measurements were carried out using visible spectroscopy. Both polymers showed good sensitivity to the VOCs, showing fast and reversible responses with some hysteresis, and were unable to detect hydroxylated samples. Furthermore, it was demonstrated that the thickness of polymer films influences the intensity of the optical response. Although there is similarity in the superficial composition of the polymers films, demonstrated by their surface energies, they showed significant differences in their optical properties upon exposure to the VOCs. (c) 2009 Elsevier B.V. All rights reserved.

Manipulation of anchoring strength in an azo-dye side chain polymer by photoisomerization

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

EPR investigation of the influence of side chain protecting groups on peptide-resin solvation of the Asx and Glx model containing peptides

In spite of all progressive efforts aiming to optimize SPPS, serious problems mainly affecting the assembly of aggregating sequences have persisted. Following the study intended to unravel the complex solvation phenomenon of peptide-resin beads, the XING and XAAAA model aggregating segments were labeled with a paramagnetic probe and studied via EPR spectroscopy. Low and high substituted resins were also comparatively used, with the X residue being Asx or Glx containing the main protecting groups used in the SPPS. Notably, the cyclo-hexyl group used for Asp and Glu residues in Boc-chemistry induced greater chain immobilization than its tert-butyl partner-protecting group of the Fmoc strategy. Otherwise, the most impressive peptide chain immobilization occurred when the large trytil group was used for Asn and Gln protection in Fmoc-chemistry. These surprising results thus seem to stress the possibility of the relevant influence of the amino-acid side chain protecting groups in the overall peptide synthesis yield. (C) 2007 Elsevier Ltd. All rights reserved.

Chromophore relaxation in a side-chain methacrylate copolymer functionalized with 4-[N-ethyl-N-(2-hydroxyethyl)]amino-2 '-chloro-4 '-nitroazobenzene

A side-chain methacrylate copolymer functionalized with the nonlinear optical chromophore 4-[N-ethyl-N-(2-hydroxyethyl)]amino-2'-chloro-4'-nitroazobenzene, disperse red-13, was prepared and characterized. The chromophore relaxation was investigated measuring the decay of the electrooptic coefficient r(13) and the complex dielectric constant at different temperatures. Results obtained below and above T-g were analyzed using the Kohlrausch-Williams-Watts(KWW) equation, through the study of the temperature dependence of the KWW parameters. Above T-g the relaxation time experimental data were fitted to the Williams-Landel-Ferry (WLF) equation and its parameters determined. Chromophore relaxation leading to the decrease of electrooptic properties was found associated with a primary alpha relaxation. The obtained WLF equation parameters were introduced into the Adam-Gibbs-Tool-Narayanaswamy-Moynihan equation, and the overall relaxation time temperature dependence was successfully obtained in terms of the fictive temperature, accounting for the sample thermal treatment and allowing optimized thermal treatment to be found. The copolymer KWW stretching parameter at the glass transition temperature lies close to the limit value for short-range interactions, i.e., 0.6, suggesting that the chromophore group is participating in primary a relaxation.

Self-Assembly of Poly(4-vynil-N-alkylpyridinium) Bromide onto Silica: Effect of Side-Chain Length on Structural Aspects at a Molecular Level

Self-assembly of poly(4-vynil-N-alkyl)pyridinium bromide with alkyl side chains of 2, 5, 7, 10, or 16 carbons from ethanolic solutions onto flat silica surfaces was studied by means of ellipsometry, atomic force microscopy (AFM), contact angle measurements, and sum-frequency generation (SFG) vibrational spectroscopy in the CH3 and CH2 stretch region. Ab initio quantum-chemical calculations on the N-alkylpyridinium side-group with restricted Hartree-Fock (RHF) method and 6-311G (d,p) basis set were C one to estimate the charge distribution along the pyridinium ring and the alkyl side-chain. SFG results showed that longer side chains promote the disorientation of the alkyl groups at the surface, corroborating with the contact angle values. AFM images revealed film homogeneity, regardless the alkyl side group. However, after 24 h contact with water, ringlike structures appeared on the film surfaces, when the polycation alkyl side chain had 7 or less carbons, and as the alkyl chain increased to 10 or 16 carbons, the films dewetted because the hydrophobic interactions prevailed over the electrostatic interactions between the pyridinium charged groups and the negatively charged SiO2 surface. Under acid conditions (HCl 0.1 mol.L-1), the film mean thickness values decreased up to 50% of original values when the alkyl side chains were ethyl or pentyl groups due to ion-pair disruption, but for longer groups they remained unchanged. Quantum-chemical optimization and Mulliken electron population showed that (i) from C2 to C15 the positive charge at the headgroup (HG) decreased 0.025, while the charge at combined HG + alpha-CH2 increased 0.037; and (ii) for C6 or longer, the alkyl side group presents a tilt in the geometry, moving away from the plane. Such effects summed up over the whole polymer chain give support to suggest that when the side chains are longer than 7 carbons, the hydrophobic interaction decreases film stability and increases acid resistance.

The binding mode of side chain- and C3-modified epothilones to tubulin

The tubulin-binding mode of C3- and C15-modified analogues of epothilone A (Epo A) was determined by NMR spectroscopy and computational methods and compared with the existing structural models of tubulin-bound natural Epo A. Only minor differences were observed in the conformation of the macrocycle between Epo A and the C3-modified analogues investigated. In particular, 3-deoxy- (compound 2) and 3-deoxy-2,3-didehydro-Epo A (3) were found to adopt similar conformations in the tubulin-binding cleft as Epo A, thus indicating that the 3-OH group is not essential for epothilones to assume their bioactive conformation. None of the available models of the tubulin-epothilone complex is able to fully recapitulate the differences in tubulin-polymerizing activity and microtubule-binding affinity between C20-modified epothilones 6 (C20-propyl), 7 (C20-butyl), and 8 (C20-hydroxypropyl). Based on the results of transferred NOE experiments in the presence of tubulin, the isomeric C15 quinoline-based Epo B analogues 4 and 5 show very similar orientations of the side chain, irrespective of the position of the nitrogen atom in the quinoline ring. The quinoline side chain stacks on the imidazole moiety of beta-His227 with equal efficiency in both cases, thus suggesting that the aromatic side chain moiety in epothilones contributes to tubulin binding through strong van der Waals interactions with the protein rather than hydrogen bonding involving the heteroaromatic nitrogen atom. These conclusions are in line with existing tubulin polymerization and microtubule-binding data for 4, 5, and Epo B.

Stereoselective synthesis of 12,13-cyclopropyl-epothilone B and side-chain-modified variants

A general strategy has been devised for the stereoselective synthesis of 12,13-cyclopropyl-epothilone B and side-chain-modified variants thereof, which relies on late stage introduction of the heterocycle through Wittig olefination of ketone 14. Formation of the macrocycle was achieved through RCM-based ring closure and introduction of the cyclopropane moiety involved a highly selective Charette cyclopropanation of allylic alcohol 7.

The stereochemistry of the amino acid side chain influences the inflammatory potential of muramyl dipeptide in experimental meningitis

Intrathecal injections of 50 to 100 micro g of (N-acetylmuramyl-L-alanyl-D-isoglutamine) muramyl dipeptide (MDP)/rabbit dose-dependently triggered tumor necrosis factor alpha (TNF-alpha) secretion (12 to 40,000 pg/ml) preceding the influx of leukocytes in the subarachnoid space of rabbits. Intrathecal instillation of heat-killed unencapsulated R6 pneumococci produced a comparable leukocyte influx but only a minimal level of preceding TNF-alpha secretion. The stereochemistry of the first amino acid (L-alanine) of the MDP played a crucial role with regard to its inflammatory potential. Isomers harboring D-alanine in first position did not induce TNF-alpha secretion and influx of leukocytes. This stereospecificity of MDPs was also confirmed by measuring TNF-alpha release from human peripheral mononuclear blood cells stimulated in vitro. These data show that the inflammatory potential of MDPs depends on the stereochemistry of the first amino acid of the peptide side chain and suggest that intact pneumococci and MDPs induce inflammation by different pathways.

Infantile hypophosphatasia due to a new compound heterozygous TNSALP mutation - functional evidence for a hydrophobic side-chain?

BACKGROUND: Infantile hypophosphatasia (IH) is an inherited disorder characterized by defective bone mineralization and a deficiency of alkaline phosphatase activity. OBJECTIVE/DESIGN: The aim of the study was to evaluate a new compound heterozygous TNSALP mutation for its residual enzyme activity and localization of the comprised amino acid residues in a 3D-modeling. PATIENT: We report on a 4-week old girl with craniotabes, severe defects of ossification, and failure to thrive. Typical clinical features as low serum alkaline phosphatase, high serum calcium concentration, increased urinary calcium excretion, and nephrocalcinosis were observed. Vitamin D was withdrawn and the patient was started on calcitonin and hydrochlorothiazide. Nonetheless, the girl died at the age of 5 months from respiratory failure. RESULTS: Sequence analysis of the patient's TNSALP gene revealed two heterozygous mutations [c.653T>C (I201T), c.1171C>T (R374C)]. Transfection studies of the unique I201T variant in COS-7 cells yielded a mutant TNSALP protein with only a residual enzyme activity (3.7%) compared with wild-type, whereas the R374C variant was previously shown to reduce normal activity to 10.3%. 3D-modeling of the mutated enzyme showed that I201T resides in a region that does not belong to any known functional site. CONCLUSION: We note that I201, which has been conserved during evolution, is buried in a hydrophobic pocket and, therefore, the I>T-change should affect its functional properties. Residue R374C is located in the interface between monomers and it has been previously suggested that this mutation affects dimerization. These findings explain the patient's clinical picture and severe course.

The Hydroxyl Side Chain of a Highly Conserved Serine Residue Is Required for Cation Selectivity and Substrate Transport in the Glial Glutamate Transporter GLT-1/SLC1A2

Glutamate transporters maintain synaptic concentration of the excitatory neurotransmitter below neurotoxic levels. Their transport cycle consists of cotransport of glutamate with three sodium ions and one proton, followed by countertransport of potassium. Structural studies proposed that a highly conserved serine located in the binding pocket of the homologous GltPh coordinates l-aspartate as well as the sodium ion Na1. To experimentally validate these findings, we generated and characterized several mutants of the corresponding serine residue, Ser-364, of human glutamate transporter SLC1A2 (solute carrier family 1 member 2), also known as glutamate transporter GLT-1 and excitatory amino acid transporter EAAT2. S364T, S364A, S364C, S364N, and S364D were expressed in HEK cells and Xenopus laevis oocytes to measure radioactive substrate transport and transport currents, respectively. All mutants exhibited similar plasma membrane expression when compared with WT SLC1A2, but substitutions of serine by aspartate or asparagine completely abolished substrate transport. On the other hand, the threonine mutant, which is a more conservative mutation, exhibited similar substrate selectivity, substrate and sodium affinities as WT but a lower selectivity for Na(+) over Li(+). S364A and S364C exhibited drastically reduced affinities for each substrate and enhanced selectivity for l-aspartate over d-aspartate and l-glutamate, and lost their selectivity for Na(+) over Li(+). Furthermore, we extended the analysis of our experimental observations using molecular dynamics simulations. Altogether, our findings confirm a pivotal role of the serine 364, and more precisely its hydroxyl group, in coupling sodium and substrate fluxes.

Involvement of a cytosine side chain in proton transfer in the rate-determining step of ribozyme self-cleavage

Ribozymes of hepatitis delta virus have been proposed to use an active-site cytosine as an acid-base catalyst in the self-cleavage reaction. In this study, we have examined the role of cytosine in more detail with the antigenomic ribozyme. Evidence that proton transfer in the rate-determining step involved cytosine 76 (C76) was obtained from examining cleavage activity of the wild-type and imidazole buffer-rescued C76-deleted (C76Δ) ribozymes in D2O and H2O. In both reactions, a similar kinetic isotope effect and shift in the apparent pKa indicate that the buffer is functionally substituting for the side chain in proton transfer. Proton inventory of the wild-type reaction supported a mechanism of a single proton transfer at the transition state. This proton transfer step was further characterized by exogenous base rescue of a C76Δ mutant with cytosine and imidazole analogues. For the imidazole analogues that rescued activity, the apparent pKa of the rescue reaction, measured under kcat/KM conditions, correlated with the pKa of the base. From these data a Brønsted coefficient (β) of 0.51 was determined for the base-rescued reaction of C76Δ. This value is consistent with that expected for proton transfer in the transition state. Together, these data provide strong support for a mechanism where an RNA side chain participates directly in general acid or general base catalysis of the wild-type ribozyme to facilitate RNA cleavage.