Design of a new foldamer turn-linker-turn in acyclic hexapeptides and formation of channels through self-assembly

Single crystal X-ray diffraction studies and solvent dependent NMR titration reveal that the designed pepticles I and 11, Boc-Xx(1)-Aib(2)-Yy(3)-NH(CH2)(2)NH-Yy(3)-Aib(2)-Xx(1)-Boc, where Xx and Yy are lie and Leu in peptide I and Leu and Val in peptide 11, respectively, fold into a turn-linker-turn (T-L-T) conformation both in the solid state and in solution. In the crystalline state the T-L-T foldamers; of peptide I and II self-assemble to form a three-dimensional framework of channels. The insides of the channels are hydrophilic and found to contain solvent CHCl3 hydrogen bonded to exposed C=O of Aib located at the turn regions. (c) 2008 Elsevier B.V. All rights reserved.

Ordering in thin films of block copolymers: fundamentals to potential applications

The ordering of block copolymers in thin films is reviewed, starting, from the fundamental principles and extending to recent promising developments as templates for nanolithography which may find important applications in the semiconductor industry. Ordering in supported thin films of symmetric and asymmetric AB diblock and ABA triblock copolymers is discussed, along with that of more complex materials such as ABC triblocks and liquid crystalline block copolymers Techniques to prepare thin films, and to characterise ordering within them, are summarized. Several methods to align Hock copolymer nanostructures, important in several applications are outlined A number of potential applications in nanolithography, production of porous materials, templating. and patterning of organic and inorganic materials are then presented. The influence of crystallization on the morphology of a block copolymer film is briefly discussed, as are structures in grafted block copolymer films. (C) 2009 Elsevier Ltd All rights reserved.

Overlapping double turn conformations adopted by tetrapeptides containing non-coded alpha-Amino Isobutyric Acid (AIB) and formation of tape-like structures through supramolecular helix mediated self-assembly

Single crystal X-ray diffraction studies and solvent dependent H-1 NMR titrations reveal that a set of four tetrapeptides with general formula Boc-Xx(1)-Aib(2)-Yy(3)-Zz(4)-OMe, where Xx, Yy and Zz are coded L- amino acids, adopt equivalent conformations that can be described as overlapping double turn conformations stabilized by two 4 -> 1 intramolecular hydrogen bonds between Yy(3)-NH and Boc C=O and Zz(4)-NH and Xx(1)C=O. In the crystalline state, the double turn structures are packed in head-to-tail fashion through intermolecular hydrogen bonds to create supramolecular helical structures. Field emission scanning electron microscopic (FE-SEM) images of the tetrapeptides in the solid state reveal that they can form flat tape-like structures. The results establish that synthetic Aib containing supramolecular helices can form highly ordered self-aggregated amyloid plaque like human amylin.

Effect of sequence distribution on the morphology, crystallization, melting, and biodegradation of poly(epsilon-caprolactone-co-epsilon-caprolactam) copolymers

Two types of poly(epsilon-caprolactone (CLo)-co-poly(epsilon-caprolactam (CLa)) copolymers were prepared by catalyzed hydrolytic ring-opening polymerization. Both cyclic comonomers were added simultaneously in the reaction medium for the First type or materials where copolymers have a random distribution of counits, as evidenced by H-1 and C-13 NMR. For the second type of copolymers, the cyclic comonomers were added sequentially, yielding diblock poly(ester-amides). The materials were characterized by differential scanning calorimetry (DSC), wide- and small-angle X-ray scattering (WAXS and SAXS), and transmission and scanning electron microscopies (TEM and SEM). Their biodegradation in compost was also studied. All copolymers were found to be miscible by the absence of structure in the melt. TEM revealed that all samples exhibited a crystalline lamellar morphology. DSC and WAXS showed that in a wide composition range (CLo contents from 6 to 55%) only the CLa units were capable of crystallization in the random copolymers. The block copolymer samples only experience a small reduction of crystallization and melting temperature with composition, and this was attributed to a dilution effect caused by the miscible noncrystalline CLo units. The comparison between block and random copolymers provided a unique opportunity to distinguish the dilution effect of the CLo units on the crystallization and melting of the polyamide phase from the chemical composition effect in the random copolymers case, where the CLa sequences are interrupted statistically by the CLo units, making the crystallization of the polyamide strongly composition dependent. Finally, the enzymatic degradation of the copolymers in composted soil indicate a synergistic behavior where much faster degradation was obtained for random copolymers witha CLo content larger than 30% than for neat PCL.

Discovery of three polymorphs of 7-fluoroisatin reveals challenges in using computational crystal structure prediction as a complement to experimental screening

A combined computational and experimental polymorph search was undertaken to establish the crystal forms of 7-fluoroisatin, a simple molecule with no reported crystal structures, to evaluate the value of crystal structure prediction studies as an aid to solid form discovery. Three polymorphs were found in a manual crystallisation screen, as well as two solvates. Form I ( P2(1)/c, Z0 1), found from the majority of solvent evaporation experiments, corresponded to the most stable form in the computational search of Z0 1 structures. Form III ( P21/ a, Z0 2) is probably a metastable form, which was only found concomitantly with form I, and has the same dimeric R2 2( 8) hydrogen bonding motif as form I and the majority of the computed low energy structures. However, the most thermodynamically stable polymorph, form II ( P1 , Z0 2), has an expanded four molecule R 4 4( 18) hydrogen bonding motif, which could not have been found within the routine computational study. The computed relative energies of the three forms are not in accord with experimental results. Thus, the experimental finding of three crystalline polymorphs of 7- fluoroisatin illustrates the many challenges for computational screening to be a tool for the experimental crystal engineer, in contrast to the results for an analogous investigation of 5- fluoroisatin.

First report of structurally characterized dimorph of an oxovanadium(V)-hydrazonato complex containing, VO3+ core

The orthorhombic crystalline variety (with Pbca space group) of the title complex [V2O3(L)(2)], incorporating the doubly deprotonated tridentate benzoyl hydrazone of 2-hydroxy-5-methylacetophenone has been synthesized from the decomposition of [(VO)-O-IV(L)(bipy)] complex in CH2Cl2 and structurally characterized in contrast to its recently reported monoclinic variety (with C2/c space group) obtained from the reaction of [VO(acac)(2)] with H2L in acetone.

A short water-soluble self-assembling peptide forms amyloid-like fibrils

A water-soluble tripeptide Val-Ile-Ala (VIA) 1, bearing sequence identity with the C-terminal portion of the Alzheimer A beta-peptide (A beta(40-42)), self-assembles, in crystalline form, to produce an intermolecularly hydrogen bonded supramolecular beta-sheet structure which self-associates to form straight, unbranched nanofibrils exhibiting amyloid-like behavior; in contrast, the synthetic tripeptide Ala-Val-Ile (AVI) 2 self-assembles to produce a beta-sheet structure that forms branched nanofibrils which do not show any characteristic features of amyloid-like fibrils.

Synthesis and characterization of packed mesoporous tungsteno-silicates: application to the catalytic dehydrogenation of 2-propanol

The synthesis of highly ordered mesoporous tungsteno-silicas in which a high percentage of tungsten is introduced into a silica framework is reported hereafter. Powder XRD and TEM have been used to characterize the materials synthesized at room temperature. The materials are shown to be homogeneous as there is no evidence for any crystalline species other than the silica framework. The pore diameter and the surface area of the materials, evaluated from the nitrogen adsorption isotherms and unit cell parameter indicate a pore diameter of about 2 nm and a surface area of 1400 m(2) g(-1) for a content of 10% tungsten. Catalyzed dehydration of 2-propanol has been investigated and the activity of the materials synthesized is significant, even for low tungsten content W-MCM-41 materials. (C) 2003 Elsevier B.V. All rights reserved.

Synthesis and fabrication of a thin film containing silica-encapsulated face-centered tetragonal FePt nanoparticles

Self-assembly of monodisperse, silica-encapsulated, face-centered tetragonal FePt nanoparticles forms closely packed 2D arrays (see figure). Placing monodisperse FePt nanoparticles in silica nanocapsules allows the transition from a disordered face-centered cubic phase to a ferromagnetic crystalline face-centered tetragonal structure at elevated temperature without severe sintering. These materials are potential candidates for the generation of ultrahigh-density magnetic recording media.

Effects of resistant starch type III polymorphs on human colon microbiota and short chain fatty acids in human gut models

This study probed the possible effects of type III resistant starch (RS) crystalline polymorphism on RS fermentability by human gut microbiota and the short chain fatty acids production in vitro. Human fecal pH-controlled batch cultures showed RS induces an ecological shift in the colonic microbiota with polymorph B inducing Bifidobacterium spp. and polymorph A inducing Atopobium spp. Interestingly, polymorph B also induced higher butyrate production to levels of 0.79 mM. In addition, human gut simulation demonstrated that polymorph B promotes the growth of bifidobacteria in the proximal part of the colon and double their relative proportion in the microbiota in the distal colon. These findings suggest that RS polymorph B may promote large bowel health. While the findings are limited by study constraints, they do raise the possibility of using different thermal processing to delineate differences in the prebiotic capabilities of RS, especially its butryrogenicity in the human colon.

Polymer-mediated disruption of drug crystallinity

Ibuprofen (IB), a BCS Class II compound, is a highly crystalline substance with poor solubility properties. Here we report on the disruption of this crystalline structure upon intimate contact with the polymeric carrier cross-linked polyvinylpyrrolidone (PVP-CL) facilitated by low energy simple mixing. Whilst strong molecular interactions between APIs and carriers within delivery systems would be expected on melting or through solvent depositions, this is not the case with less energetic mixing. Simple mixing of the two compounds resulted in a significant decrease in the differential scanning calorimetry (DSC) melting enthalpy for IB, indicating that approximately 30% of the crystalline content was disordered. This structural change was confirmed by broadening and intensity diminution of characteristic IB X-ray powder diffractometry (PXRD) peaks. Unexpectedly, the crystalline content of the drug continued to decrease upon storage under ambient conditions. The molecular environment of the mixture was further investigated using Fourier transform infrared (FT-IR) and Fourier transform Raman (FT-Raman) spectroscopy. These data suggest that the primary interaction between these components of the physical mix is hydrogen bonding, with a secondary mechanism involving electrostatic/hydrophobic interactions through the IB benzene ring. Such interactions and subsequent loss of crystallinity could confer a dissolution rate advantage for IB. (C) 2006 Elsevier B.V. All rights reserved.

Accurate molecular structures of chlorothiazide and hydrochlorothiazide by joint refinement against powder neutron and X-ray diffraction data

The compounds chlorothiazide and hydrochlorothiazide (crystalline form II) have been studied in their fully hydrogenous forms by powder neutron diffraction on the GEM diffractometer. The results of joint Rietveld refinement of the structures against multi-bank neutron and single-bank X-ray powder data are reported and show that accurate and precise structural information can be obtained from polycrystalline molecular organic materials by this route.

Solvent influences on metastable polymorph lifetimes: real-time interconversions using energy dispersive X-ray diffractometry

Solvent influences on the crystallization of polymorph and hydrate forms of the nootropic drug piracetam (2-oxo-pyrrolidineacetamide) were investigated from water, methanol, 2-propanol, isobutanol, and nitromethane. Crystal growth profiles of piracetam polymorphs were constructed using time-resolved diffraction snapshots collected for each solvent system. Measurements were performed by in situ energy dispersive X-ray diffraction recorded in Station 16.4 at the synchrotron radiation source (SRS) at Daresbury Laboratory, CCLRC UK. Crystallizations from methanol, 2-propanol, isobutanol, and nitromethane progressed in a similar fashion with the initial formation of form I which then converted relatively quickly to form II with form III being generated upon further cooling. However, considerable differences were observed for the polymorphs lifetime and both the rate and temperature of conversion using the different solvents. The thermodynamically unstable form I was kinetically favored in isobutanol and nitromethane where traces of this polymorph were observed below 10 degrees C. In contrast, the transformation of form II and subsequent growth of form III were inhibited in 2-propanol and nitromethane solutions. Aqueous solutions produced hydrate forms of piracetam which are different from the reported monohydrate; this crystallization evolved through successive generation of transient structures which transformed upon exchange of intramolecular water between the liquid and crystalline phases. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96:1069-1078, 2007.

Stochiometrically governed molecular interactions in drug: Poloxamer solid dispersions

This study probes the molecular interactions between model drugs and poloxamers that facilitate dissolution rate improvements using solid dispersions. Ibuprofen and ketoprofen solid dispersions were prepared at different mole ratios using poloxamers 407 and 188. The carbonyl stretching vibration of the ibuprofen dimer shifted to higher wavenumber in the infrared spectra of 2:1 drug:carrier mole ratio solid dispersions, indicating disruption of the ibuprofen dimer concomitant with hydrogen bond formation between the drug and carrier. Solid dispersions with mole ratios >2:1 drug:carrier (up to 29:1) showed both ibuprofen hydrogen-bonded to the poloxamer, and excess drug present as dimers. X-ray diffraction studies confirmed these findings with no evidence of crystalline drug in 2:1 mole ratio systems whereas higher drug loadings retained crystalline ibuprofen. Similar results were found with ketoprofen-poloxamer solid dispersions. Thermal analysis of ibuprofen-poloxamer 407 solid dispersions and their resultant phase diagram suggested solid solutions and a eutectic system were formed, depending on drug loading. Dissolution studies showed fastest release from the solid solutions; dissolution rates from solid solutions were 12-fold greater than the dissolution of ibuprofen powder whereas the eutectic system gave a 6-fold improvement over the powder. When designing solid dispersions to improve the delivery of poorly-water soluble drugs, the nature of drug:carrier interactions, which are governed by the stochiometry of the composition, can affect the dissolution rate improvement.

Mechanistic insights into a gas–solid reaction in molecular crystals: the role of hydrogen bonding

Reactions in (molecular) organic crystalline solids have been shown to be important for exerting control that is unattainable over chemical transformations in solution. Such control has also been achieved for reactions within metal– organic cages. In these examples, the reactants are already in place within the crystals following the original crystal growth. The post-synthetic modification of metal–organic frameworks (MOFs and indeed reactions and catalysis within MOFs have been recently demonstrated; in these cases the reactants enter the crystals through permanent channels. Another growing area of interest within molecular solid-state chemistry is synthesis by mechanical co-grinding of solid reactants—often referred to as mechanochemistry. Finally, in a small number of reported examples, molecules also have been shown to enter nonporous crystals directly from the gas or vapor phase, but in only a few of these examples does a change in covalent bonding result, which indicates that a reaction occurs within the nonporous crystals. It is this latter type of highly uncommon reaction that is the focus of the present study.