Formation of crystalline macrocyclic phases during electrophilic precipitation-polycondensation syntheses of poly(arylene ether ketone)s

Elongated crystalline particles formed as by-products during poly(arylene ether ketone) synthesis by electrophilic precipitation-polycondensation of 4,4'-diphenoxybenzophenone with terephthaloyl chloride or isophthaloyl chloride, thought previously to be polymer-whiskers, have now been identified as macrocyclic phases. Single crystal X-ray analysis of the needle-like particles formed in the reaction with terephthaloyl chloride, using the microdiffraction technique with synchrotron radiation, revealed that they consist of a macrocylic compound containing ten phenylene units, i.e. the [2 + 2] cyclic dimer. An analogous structure has also been demonstrated for the corresponding macrocycle derived from the reaction of 4,4-diphenoxybenzophenone with isophthaloyl chloride. Chloroform extraction of the products of the two polycondensations dissolved the macrocyclic material (but not the linear polymer), and analysis of the extracts by MALDI-TOF mass spectrometry demonstrated the presence in both cases of homologous families of macrocyclic products. Higher yields of macrocycles were obtained under pseudo-high dilution conditions, enabling the [2 + 2] cyclodimers from reactions of 4,4'-diphenoxybenzophenone with both terephthaloyl and isophthaloyl chloride to be isolated as pure compounds and fully characterised. (C) 2003 Published by Elsevier Ltd.

pH-mediated interactions between poly(acrylic acid) and methylcellulose in the formation of ultrathin multilayered hydrogels and spherical nanoparticles

Poly(acrylic acid) forms insoluble hydrogen-bonded interpolymer complexes with methylcellulose in aqueous solutions under acidic conditions. In this work the reaction heats and binding constants were determined for the complexation between poly(acrylic acid) and methylcellulose by isothermal titration calorimetry at different pH and findings are correlated with the aggregation processes occurring in this system. The principal contribution to the complexation heat results from primary polycomplex particle aggregation. Transmission electron microscopy of nanoparticles produced at pH 1.4 and 2.4 demonstrated that they are spherical and dense structures. The nanoparticles ranged from 80 to 200 nm, whereas particles formed at pH 3.2 were 20-30 nm and were stabilized against aggregation by a network of uncomplexed macromolecules. For the first time, multilayered materials were developed on the basis of hydrogen-bonded complexes of poly(acrylic acid) and methylcellulose using layer-by-layer deposition on a glass surface. The thickness of these films was a linear function of the number of deposition cycles. The materials were subsequently cross-linked by thermal treatment, resulting in ultrathin hydrogels which detached from the glass substrate upon swelling. The swelling capacity of ultrathin hydrogels differed from the swelling of the thicker films of a similar chemical composition.

Hydrogen-bonding-driven self-assembly of PEGylated organosilica nanoparticles with poly(acrylic acid) in aqueous solutions and in layer-by-layer deposition at solid surfaces

PEGylated organosilica nanoparticles have been synthesized through self-condensation of (3-mercaptopropyl)trimethoxysilane in dimethyl sulfoxide into thiolated nanoparticles with their subsequent reaction with methoxypoly(ethylene glycol) maleimide. The PEGylated nanoparticles showed excellent colloidal stability over a wide range of pH in contrast to the parent thiolated nanoparticles, which have a tendency to aggregate irreversibly under acidic conditions (pH < 3.0). Due to the presence of a poly(ethylene glycol)-based corona, the PEGylated nanoparticles are capable of forming hydrogen-bonded interpolymer complexes with poly(acrylic acid) in aqueous solutions under acidic conditions, resulting in larger aggregates. The use of hydrogen-bonding interactions allows more efficient attachment of the nanoparticles to surfaces. The alternating deposition of PEGylated nanoparticles and poly(acrylic acid) on silicon wafer surfaces in a layer-by-layer fashion leads to multilayered coatings. The self-assembly of PEGylated nanoparticles with poly(acrylic acid) in aqueous solutions and at solid surfaces was compared to the behavior of linear poly(ethylene glycol). The nanoparticle system creates thicker layers than the poly(ethylene glycol), and a thicker layer is obtained on a poly(acrylic acid) surface than on a silica surface, because of the effects of hydrogen bonding. Some implications of these hydrogen-bonding-driven interactions between PEGylated nanoparticles and poly(acrylic acid) for pharmaceutical formulations are discussed.

Structural variations in self-assembled coordination complexes of Zn(II) with hexamethylenetetramine and isomeric 2-, 3- and 4-nitrobenzoates

Three new zinc(II)-hexamethylenetetramine (hmt) complexes [Zn-2(4-nbz)(4)(mu(2)-hmt)(OH2)(hmt)] (1). [Zn-2(2-nbz)(4)(mu(2)-hmt)(2)](n) (2) and [Zn-3(3-nbz)(4)(mu(2)-hmt)(mu(2)-OH)(mu(3)-OH)](n) (3) with three isomeric nitrobenzoate, [4-nbz = 4-nitrobenzoate, 2-nbz = 2-nitrobenzoate and 3-nbz = 3-nitrobenzoate] have been synthesized and structurally characterized by X-ray crystallography. Their identities have also been established by elemental analysis: IR, NMR, UV-Vis and mass spectral studies. 1 is a dinuclear complex formed by bridging hmt with mu(2) coordinating mode. The geometry around the Zn centers in 1 is distorted tetrahedral. Paddle-wheel centrosymmetric Zn-2(2-nbz)(4) units of complex 2 are interconnected by mu(2)-hmt forming a one-dimensional chain with square-pyramidal geometries around the Zn centers. Compound 3 contains a mu(2)/mu(3)-hydroxido and mu(2)-hmt bridged 1D chain. In this complex, varied geometries around the Zn centers are observed viz, tetrahedral, square pyramidal and trigonal bipyramidal. Various weak forces, i.e. lone pair-pi, pi-pi and CH-pi interactions, play a key role in stabilizing the observed structures for complexes 1,2 and 3. This series of complexes demonstrates that although the nitro group does not coordinate to the metal center, its presence at the 2-, 3- or 4-position of the phenyl ring has a striking effect on the dimensionality as well as the structure of the resulted coordination polymers, probably due to the participation of the nitro group in 1.p.center dot center dot center dot pi and/or C-H center dot center dot center dot pi interactions.

Bacillus subtilis natto: a non-toxic source of poly-γ-glutamic acid that could be used as a cryoprotectant for probiotic bacteria

It is common practice to freeze dry probiotic bacteria to improve their shelf life. However, the freeze drying process itself can be detrimental to their viability. The viability of probiotics could be maintained if they are administered within a microbially produced biodegradable polymer - poly-γ-glutamic acid (γ-PGA) - matrix. Although the antifreeze activity of γ-PGA is well known, it has not been used for maintaining the viability of probiotic bacteria during freeze drying. The aim of this study was to test the effect of γ-PGA (produced by B. subtilis natto ATCC 15245) on the viability of probiotic bacteria during freeze drying and to test the toxigenic potential of B. subtilis natto. 10% γ-PGA was found to protect Lactobacillus paracasei significantly better than 10% sucrose, whereas it showed comparable cryoprotectant activity to sucrose when it was used to protect Bifidobacterium breve and Bifidobacterium longum. Although γ-PGA is known to be non-toxic, it is crucial to ascertain the toxigenic potential of its source, B. subtilis natto. Presence of six genes that are known to encode for toxins were investigated: three component hemolysin (hbl D/A), three component non-haemolytic enterotoxin (nheB), B. cereus enterotoxin T (bceT), enterotoxin FM (entFM), sphingomyelinase (sph) and phosphatidylcholine-specific phospholipase (piplc). From our investigations, none of these six genes were present in B. subtilis natto. Moreover, haemolytic and lecithinase activities were found to be absent. Our work contributes a biodegradable polymer from a non-toxic source for the cryoprotection of probiotic bacteria, thus improving their survival during the manufacturing process.

Hollow capsules formed in a single stage via interfacial hydrogen-bonded complexation of methylcellulose with poly(acrylic acid) and tannic acid

Hollow capsules can be prepared in a single stage by the interfacial complexation of methylcellulose (MC) with poly(acrylic acid) (PAA) or tannic acid (TA) via hydrogen bonding in aqueous solutions. The formation of capsules is observed when viscous solution of methylcellulose is added drop-wise to diluted solutions of polyacids under acidic conditions. The optimal parameters such as polymer concentration and solution pH for the formation of these capsules were established in this work. It was found that tannic acid forms capsules in a broader range of concentrations and pHs compared to poly(acrylic acid). The TA/MC capsules exhibited better stability compared to PAA/MC in response to increase in pH: the dissolution of TA/MC capsules observed at pH > 9.5; whereas PAA/MC capsules dissolved at pH > 3.8. The interfacial complexation can be considered as a potential single stage alternative to the formation of capsules using multistage layer-by-layer deposition method.

Hydrogen-bonded complexes and blends of poly(acrylic acid) and methylcellulose: nanoparticles and mucoadhesive films for Ocular Delivery of Riboflavin

Poly(acrylic acid) (PAA) and methylcellulose (MC) are able to form hydrogen-bonded interpolymer complexes (IPCs) in aqueous solutions. In this study, the complexation between PAA andMC is explored in dilute aqueous solutions under acidic conditions. The formation of stable nanoparticles is established,whose size and colloidal stability are greatly dependent on solution pH and polymers ratio in the mixture. Poly(acrylic acid) and methylcellulose are also used to prepare polymeric films by casting from aqueous solutions. It is established that uniform films can be prepared by casting from polymer mixture solutions at pH 3.4–4.5. At lower pHs (pH<3.0) the films have inhomogeneous morphology resulting from strong interpolymer complexation and precipitation of polycomplexes, whereas at higher pHs (pH 8.3) the polymers form fully immiscible blends because of the lack of interpolymer hydrogen-bonding. The PAA/MC films cast at pH 4 are shown to be non-irritant to mucosal surfaces. These films provide a platform for ocular formulation of riboflavin, a drug used for corneal crosslinking in the treatment of keratoconus. An in vitro release of riboflavin as well as an in vivo retention of the films on corneal surfaces can be controlled by adjusting PAA/MC ratio in the formulations.

Cocrystalline copolyimides of poly(ethylene 2,6-naphthalate)

Copolycondensation of N,N′-bis(2-hydroxyethyl)-biphenyl-3,4,3′,4′-tetracarboxylic diimide (5–25 mol %) with bis(2-hydroxyethyl)-2,6-naphthalate affords a series of cocrystalline, poly(ethylene 2,6-naphthalate) (PEN)-based poly(ester imide)s. The glass transition temperature rises with the level of comonomer, from 118 °C for PEN itself to 148 °C for the 25% diimide copolymer. X-ray powder and fiber diffraction studies show that, when 5 mol % or more of diimide is present, the α-PEN crystal structure is replaced by a new crystalline phase arising from isomorphic substitution of biphenyldiimide for PEN residues in the polymer crystal lattice. This new phase is provisionally identified as monoclinic, C2/m, with two chains per unit cell, a = 10.56, b = 6.74, c = 13.25 Å, and β = 143.0°.

Improving survival of probiotic bacteria using bacterial poly-γ-glutamic acid

A major hurdle in producing a useful probiotic food product is bacterial survival during storage and ingestion. The aim of this study was to test the effect of γ-PGA immobilisation on the survival of probiotic bacteria when stored in acidic fruit juice. Fruit juices provide an alternative means of probiotic delivery, especially to lactose intolerant individuals. In addition, the survival of γ-PGA-immobilised cells in simulated gastric juice was also assessed. Bifidobacteria strains (B. longum, B. breve), immobilised on 2.5 % γ-PGA, survived significantly better (P < 0.05) in orange and pomegranate juice for 39 and 11 days respectively, compared to free cells. However, cells survived significantly better (P < 0.05) when stored in orange juice compared to pomegranate juice. Moreover, both strains, when protected with 2.5 % γ-PGA, survived in simulated gastric juice (pH 2.0) with a marginal reduction (<0.47 log CFU/ml) or no significant reduction in viable cells after four hours, whereas free cells died within two hours. In conclusion, this research indicates that γ-PGA can be used to protect Bifidobacteria cells in fruit juice, and could also help improve the survival of cells as they pass through the harsh conditions of the gastrointestinal tract (GIT). Following our previous report on the use of γ-PGA as a cryoprotectant for probiotic bacteria, this research further suggests that γ-PGA could be used to improve probiotic survival during the various stages of preparation, storage and ingestion of probiotic cells.

Mesomorphic behaviour in copoly(ester-imide)s of poly(butylene-2,6-naphthalate) (PBN)

Copolycondensation of N,N’-bis(4-hydroxybutyl)-biphenyl-3,4,3',4'-tetracarboxylic diimide at 20 and 25 mol% with bis(4-hydroxybutyl)-2,6-naphthalate produces PBN-based copoly(ester-imide)s that not only crystallise but also form a (smectic) mesophase upon cooling from the melt. Incorporation of 25 mol% imide in PBN causes the glass transition temperature (measured by DSC) to rise from 51 to 74 °C, a significant increase relative to PBN. Furthermore, increased storage- (G'), loss- (G'') and elastic (E) moduli are observed for both copoly(ester-imide)s when compared to PBN itself. Structural analysis of the 20 mol% copolymer by X-ray powder and fibre diffraction, interfaced to computational modelling, suggests a crystal structure related to that of α-PBN, in space group P-1, with cell dimensions a = 4.74, b = 6.38, c = 14.45 Å, α = 106.1, β = 122.1, γ = 97.3°, ρ = 1.37 g cm-3.

Redox- and glucose-responsive hydrogels from poly(vinyl alcohol) and 4-mercaptophenylboronic acid

Novel redox- and glucose-responsive hydrogels have been synthesized by simple mixing of poly(vinyl alcohol) (PVA) and 4-mercaptophenylboronic acid (MPBA) in aqueous solutions (pH > 9) in an oxidative aqueous media. These hydrogels are produced through the formation of disulfide linkages between MPBA molecules in an oxidative environment (oxygen dissolved in solution or hydrogen peroxide added to the reaction mixture) and complexation via dynamic covalent bonds between PVA and MPBA dimer. These hydrogels show degradation in solutions of l-glutathione and d-glucose.

Controlled variation of monomer sequence-distribution in the synthesis of aromatic poly(ether ketone)s

The effects of varying the alkali metal cation in the high-temperature nucleophilic synthesis of a semi-crystalline, aromatic poly(ether ketone) have been systematically investigated, and striking variations in the sequence-distributions and thermal characteristics of the resulting polymers were found. Polycondensation of 4,4'-dihydroxybenzophenone with 1,3-bis(4-fluorobenzoyl)benzene in diphenylsulfone as solvent, in the presence of an alkali metal carbonate M2CO3 (M= Li, Na, K, or Rb) as base, affords a range of different polymers that vary in the distribution pattern of 2-ring and 3-ring monomer units along the chain. Lithium carbonate gives an essentially alternating and highly crystalline polymer, but the degree of sequence-randomisation increases progressively as the alkali metal series is descended, with rubidium carbonate giving a fully random and non-thermally-crystallisable polymer. Randomisation during polycondensation is shown to result from reversible cleavage of the ether linkages in the polymer by fluoride ions, and an isolated sample of alternating-sequence polymer is thus converted to a fully randomised material on heating with rubidium fluoride.

Self-assembly of telechelic tyrosine end-capped PEO and poly(alanine) polymers in aqueous solution

The self-assembly in aqueous solution of three novel telechelic conjugates comprising a central hydrophilic polymer and short (trimeric or pentameric) tyrosine end-caps has been investigated. Two of the conjugates have a central poly(oxyethylene) (polyethylene oxide, PEO) central block with different molar masses. The other conjugate has a central poly(l-alanine) (PAla) sequence in a purely amino-acid based conjugate. All three conjugates self-assemble into β-sheet based fibrillar structures, although the fibrillar morphology revealed by cryogenic-TEM is distinct for the three polymers—in particular the Tyr5-PEO6k-Tyr5 forms a population of short straight fibrils in contrast to the more diffuse fibril aggregates observed for Tyr5-PEO2k-Tyr5 and Tyr3-PAla-Tyr3. Hydrogel formation was not observed for these samples (in contrast to prior work on related systems) up to quite high concentrations, showing that it is possible to prepare solutions of peptide–polymer-peptide conjugates with hydrophobic end-caps without conformational constraints associated with hydrogelation. The Tyr5-PEO6k-Tyr5 shows significant PEO crystallization upon drying in contrast to the Tyr5-PEO2k-Tyr5 conjugate. Our findings point to the remarkable ability of short hydrophobic peptide end groups to modulate the self-assembly properties of polymers in solution in model peptide-capped “associative polymers”. Retention of fluidity at high conjugate concentration may be valuable in potential future applications of these conjugates as bioresponsive or biocompatible materials, for example exploiting the enzyme-responsiveness of the tyrosine end-groups

Evaluation of in vitro resistance of titanium and resorbable (poly-L-DL-lactic acid) fixation systems on the mandibular angle fracture

The purpose of this study was to compare, by mechanical in vitro testing, a 2.0-mm system made with poly-L-DL-lactide acid with an analogue titanium-based system. Mandible replicas were used as a substrate and uniformly sectioned on the left mandibular angle. The 4-hole plates were adapted and stabilized passively in the same site in both groups using four screws, 6.0 mm long. During the resistance-to-load test, the force was applied perpendicular to the occlusal plane at three different points: first molar at the plated side; first molar at the contralateral side; and between the central incisors. At 1 mm of displacement, no statistically significant difference was found. At 2 mm displacement, a statistically significant difference was observed when an unfavourable fracture was simulated and the load was applied in the contralateral first molar and when a favourable fracture was simulated and the load was applied between the central incisors. At the failure displacement, a statistically significant difference was observed only when the favourable fracture was simulated and the load was applied on the first molar at the plated side. In conclusion, despite more failure, the poly-L-DL-lactic acid-based system was effective.