Metal Ion Guest Responsive Benzoxazine Dimers and Inclusion Phenomena of Cyclic Derivatives

This study was carried out with the aim to optimize the dissolution propertiesof diclofenac (DIC) – a non-steroidal anti-inflammatory drug sparingly solublein water – through association -with -cyclodextrin (CD). Theeffect of CD on the aqueous solubility of DIC was evaluated by thephase solubility method. The amount of DIC dissolved increased linearly withthe addition of CD according to an AL type plot and without precipitationof the complex. The apparent stability constant of the complex, calculated supposinga 1:1 stoichiometry, was 295 M^-1; this value was confirmed by circulardichroism analysis. DIC/CD interactions were also studied in water by¹H and ¹³C NMR spectroscopy. Equimolar DIC/CD solid systems were prepared by physical-mixing, kneading, co-evaporation andfreeze-drying, and their properties in the solid state studied by DifferentialScanning Calorimetry, X-ray powder diffractometry and Fourier-TransformInfrared analysis. For sake of comparison, the mixture of DIC and CDseparately lyophilized was investigated too. The results demonstrated that thefreeze-dried product had the highest degree of amorphization and they were inagreement with the existence of an inclusion complex in the solid state. Thedissolution profiles of the drug from each solid system were affected by its physico-chemical properties, the freeze-dried being the most rapidly dissolvingforms.     

Investigation of structural changes related to temperature: An understanding of H-bond based proton transfer in 4(5)-vinylimidazole and acrylic acid copolymer membrane

An attempt to understand how proton transfer proceeds in poly (acrylic acid-co-4(5)-vinylimidazole) has been carried out based on the temperature dependent characterization techniques, i.e., Fourier transform infrared spectroscopy (FTIR), wide angle X-ray diffraction (WAXD), Raman spectroscopy, including the atomic distance calculations. Systematical studies are achieved from a series of poly (acrylic acid-co-4(5)-vinylimidazole) with different acrylic acid content. When the copolymer is almost an ideal in equimolar ratio of an alternating structure, the hydrogen bond between carboxylic acid and imidazole is maintained and initiates the proton conductivity even at 120 °C. Whereas when the copolymer is carboxylic acid rich, the dehydration to form anhydride proceeds resulting in the decrease in proton conductivity at high temperature. The radial distribution function (RDF) calculated from the WAXD pattern shows that the inter-atomic distances reflect how the increase in temperature induces a favorable packing structure under the hydrogen bond network and the chain mobility to enhance the proton transfer at high temperature, especially in the case of the copolymer with an ideal alternating structure.     

Control of block copolymer morphology: An example of selective morphology induced by self‐assembly formation condition

An example case of selective morphology by simply varying pH and heating profile based on a diblock copolymer, i.e., poly(N‐isopropylacrylamide) (PNIPAAM) and poly[2‐(dimethylamino)ethyl acrylate] (PDMAEA) is reported. A variation of pH induces an aggregation of the block copolymers in either micelles or vesicles. In a subsequent step, temperature variation triggers the formation of vesicular structures. This demonstrates not only the temperature but also the heating rate that tunes the nanostructures from micelles to vesicles. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2009     

[1+1] and [2+2] crown ethers derived from N,N-bis(2-hydroxyalkylbenzyl)alkylamine and their inclusion phenomena with metal ions

N,N-bis(2-hydroxyalkylbenzyl)alkylamine (HBA) is a derivative obtained from a single time ring opening of benzoxazines. For HBA with methyl group at ortho and para positions, and at N atom, the reaction between this derivative and ditosylated compound gives [1+1] dibenzo-monoaza-crowns. For HBA without methyl group at ortho position, the compound gives [2+2] macrocyclic ethers. The studies on inclusion phenomena using Pedersen’s and molar ratio techniques clarify the alkali metal ion guest inclusion to be 2:1 for [2+2] and 5:2 for [1+1] macrocycles.     

Incorporation methods for cholic acid chitosan-g-mPEG self-assembly micellar system containing camptothecin

A water-insoluble anticancer agent, camptothecin (CPT) was incorporated to a polymeric micelle carrier system preparing from cholic acid chitosan-grafted poly (ethylene glycol) methyl ether (CS-mPEG-CA). CS-mPEG-CA formed a core–shell micellar structure with a critical micelle concentration (CMC) of 7.08 μg/ml. Incorporation efficiency was investigated by varying physical incorporation method and initial drug loading. Among three incorporation methods (dialysis, emulsion and evaporation methods), an emulsion method showed the highest CPT incorporation efficiency. Increasing the initial CPT loading from 5 to 40%, the incorporation efficiency decreased. In all examined CPT-loaded CS-mPEG-CA micelles, 5% initial drug loading showed the highest drug incorporation efficiency. Release of CPT from the micelles was sustained when increasing the initial CPT loading. This indicates the importance of incorporation method and the initial drug loading to obtain the optimum particle size with high drug loading and sustained drug release. When compared to the unprotected CPT, CPT-loaded CS-mPEG-CA micelles were able to prevent the hydrolysis of the lactone group of the drug. This novel CS-mPEG-CA polymer presents considerable potential interest in the further development of CPT carrier.     

Chitosan‐Hydroxybenzotriazole Aqueous Solution: A Novel Water‐Based System for Chitosan Functionalization

Summary: A chitosan‐hydroxybenzotriazole (HOBt) aqueous solution prepared by simply mixing chitosan and HOBt in water provides an effective system to functionalize chitosan in an aqueous environment. This aqueous solution in combination with water‐soluble carbodiimide (WSC) allows the conjugation of functional groups onto chitosan under mild conditions without requiring any organic solvents or acid and heat. In this contribution, a series of model reactions that use a novel water‐based system of chitosan to functionalize the polymer with boc‐L ‐phenylalanine, poly(ethylene glycol) methyl ether, and dicarboxylated poly(ethylene glycol) is demonstrated.

Chitosan‐HOBt is effectively conjugated with R‐COOH via a water‐soluble carbodiimide (WSC) conjugating agent.     

Electrospinning as a new technique to control the crystal morphology and molecular orientation of polyoxymethylene nanofibers

Electrospinning is widely accepted as a simple and versatile technique for producing nanofibers. The present work, however, introduces a new concept of the electrospinning method for controlling the crystal morphology and molecular orientation of the nanofibers through an illustration of a case study of polyoxymethylene (POM) nanofibers. Isotropic and anisotropic electrospun POM nanofibers are successfully prepared by using a stationary collector and a rotating disk collector. By controlling the voltage and the take-up velocity of the disk rotator, the morphology changes between an extended chain crystal (ECC) and a folded chain crystal (FCC) as clarified by a detailed analysis of the X-ray diffraction and polarized infrared spectra of the POM nanofibers. Herman's orientation function and dichroic ratio lead us to a schematic conclusion--that (i) molecular orientation is parallel to the fiber axis in both isotropic and anisotropic POM nanofibers, (ii) a single nanofiber consists of a nanofibril assembly with a size of 60-70 A and tilting at a certain degree, and (iii) the higher the take-up velocity, the smaller the nanofibril under the (9/5) helical structure of the POM chains. It should be emphasized here that the electrospinning method is no longer a single nanofiber producer but that it can be applied as a new instrument to control the morphology and chain orientation characteristics of polymer materials, opening a new research field in polymer science where we can understand the relationship between structure at the molecular level and the properties and performance at the macroscopic level.     

Camptothecin-incorporating N-phthaloylchitosan-g-mPEG self-assembly micellar system: effect of degree of deacetylation

Amphiphilic grafted copolymers, N-phthaloylchitosan-grafted poly (ethylene glycol) methyl ether (PLC-g-mPEG), were synthesized from chitosan with different degree of deacetylation (DD=80%, 85%, 90% and 95%). Due to their amphiphilic characteristic, these copolymers could form micelle-like nanoparticles. The critical micelle concentration (CMC) of these nanoparticles with different DD in water was similar (28microg/ml). Under transmission electron microscope (TEM), the nanoparticles exhibited a regular spherical shape with core-shell structure. The particle sizes determined by dynamic light scattering were in the range of 100-250nm, and increased as the %DD of chitosan increased. The cytotoxicity of phthaloylchitosans (PLC) and PLC-g-mPEG in Hela cells line were evaluated. The results showed that cytotoxicity of PLC and PLC-g-mPEG increased with increasing %DD of chitosan. The cytotoxicity of PLC-g-mPEG was significantly lower than that of PLC. Camptothecin as a model drug was loaded into the inner core of the micelles by dialysis method. It was found that %DD of chitosan, corresponding to the N-phthaloyl groups in the inner core of the nanoparticle obtained, was a key factor in controlling %yield, stability of the drug-loaded micelles, and drug release behavior. As the %DD increased, the CPT-loaded micelles stability increased. Release of CPT from the micelles was dependent on the %DD and a sustained release was obtained in high %DD.     

Investigating the proton transferring route in a heteroaromatic compound part I: a trial to develop di- and trifunctional benzimidazole model compounds inducing the molecular packing structure with a hydrogen bond network

Di- and trifunctional benzimidazole molecules, 1 and 2, have been synthesized as the model compounds to identify their molecular packing structure and hydrogen bond network, which is possibly involved in the proton transfer system belonging to its heteroaromatic functional groups. By carrying out the simple reaction between acid chloride and diamine, the desired benzimidazole model compounds are obtained with high yield above 60%. The comparison studies between the model compounds and benzimidazole reveal that the model compounds show well-packing structure with intermolecular hydrogen bonds similar to those observed in benzimidazole. The presence of solvent with 2 leads to the unique intermolecular hydrogen bonds between one molecule of 2 and six molecules of solvent (i.e., 2-propanol) resulting in the solvent-assisted intramolecular hydrogen bond network among benzimidazole functional groups. The comparative studies of the effect of temperature on the packing structure and hydrogen bond in the model compounds indicate that the development of the benzimidazole unit from monofunctional to difunctional and finally trifunctional enhances the intermolecular interaction between the molecules and results in the stronger molecular packing structure of the compounds. A study on proton conductivity by preparing the sulfonated poly(ether ether ketone) (SPEEK) membranes with benzimidazole, 1, and 2 for 15 phr equivalent to benzimidazole group clarifies (i) incorporation of benzimidazole compounds improves the proton conductivity of SPEEK in dry condition and (ii) the increase in proton conductivity is relevant to the number of benzimidazole group on molecule.