Shape memory polymers based on uniform aliphatic urethane networks

Aliphatic urethane polymers have been synthesized and characterized, using monomers with high molecular symmetry, to form amorphous networks with very uniform supermolecular structures, which can be used as photo‐thermally actuable shape memory polymers (SMPs). The monomers used include hexamethylene diisocyanate (HDI), trimethylhexamethylenediamine (TMHDI), N,N,N′,N′‐tetrakis(hydroxypropyl)ethylenediamine (HPED), triethanolamine (TEA), and 1,3‐butanediol (BD). The new polymers were characterized by solvent extraction, NMR, XPS, UV/VIS, DSC, DMTA, and tensile testing. The resulting polymers were found to be single phase amorphous networks with very high gel fraction, excellent optical clarity, and extremely sharp single glass transitions in the range of 34–153°C. Thermomechanical testing of these materials confirms their excellent shape memory behavior, high recovery force, and low mechanical hysteresis (especially on multiple cycles), effectively behaving as ideal elastomers above T_g. We believe these materials represent a new and potentially important class of SMPs, and should be especially useful in applications such as biomedical microdevices. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Synthesis and evaluation of an intercalator-polyamide hairpin designed to target the inverted CCAAT box 2 in the topoisomerase IIalpha promoter

The synthesis and DNA-binding properties of a novel naphthalimide-polyamide hairpin (3) designed to target the inverted CCAAT box 2 (ICB2) site on the topoisomerase IIalpha (topoIIalpha) promoter are described. The polyamide component of 3 was derived from the minor-groove binder, 2, and tailored to bind to the 5'-TTGGT sequence found in and flanking ICB2. The propensity of mitonafide 4 to intercalate between G-C base pairs was exploited by the incorporation of a naphthalimide moiety at the N terminus of 2. Hybrid 3 targeted 5'-CGATTGGT and covered eight contiguous base pairs, which included the underlined ICB2 site. DNase I footprinting analysis with the topoIIalpha promoter sequence demonstrated that 3 bound selectively to the ICB2 and ICB3 sites. Thermal-denaturation studies confirmed these results, and the highest degree of stabilization was found for ICB2 and -3 in preference to ICB1 (4.1, 4.6, and 0.6 degrees C, respectively). CD studies confirmed minor-groove binding and suggested a 1:1 binding stoichiometry. Emission-titration experiments established intercalative binding. Surface plasmon resonance results showed strong binding to ICB2 (2.5x10(7) M(-1)) with no observable binding to ICB1. Furthermore, the binding constant of 3 to ICB2 was larger than that of the parent polyamide 2. The increased binding affinity was primarily due to a reduction in the dissociation-rate constant of the polyamide-DNA complex, which can be attributed to the N-terminal naphthalimide moiety. In addition, the binding site of 3 was larger than that of 2, which innately improved sequence selectivity. We conclude that the polyamide-naphthalimide 3 selectively binds to the ICB2 site by simultaneous intercalation and minor-groove binding, and warrants further investigation as a model compound for the regulation of topoIIalpha gene expression.     

Microstructures formed by spray freezing of food fats

The spray-freezing of two food fats, tripalmitin (PPP) and cocoa butter (CB) and mixtures thereof, has been modeled experimentally using a novel single droplet freezing apparatus configured so that temperature profiles or samples for microstructure analysis can be obtained. For 2 mm diameter droplets suspended in a cold air flow at temperatures around 2–15°C, initial cooling rates were on the order of 10 K s⁻¹ and the temperature profiles could be correlated directly to DSC data collected at 20 K min⁻¹, indicating that minimal supercooling of the materials occurred in the droplet form. Microstructure analysis confirmed that PPP crystallized preferentially in mixtures, and that the surface structure was very sensitive to storage conditions. The bulk structure was much less sensitive, and the internal microstructure of the PPP droplets revealed distinct nucleation sites, which were absent from the CB: These persisted in the mixtures up to 50 wt%. X-ray analysis indicated that the fats crystallized in their more stable forms, namely, β for PPP and Form V/V1 in CB.     

Analytic Model of Laminar‐Turbulent Transition for Bingham Plastics

It is often desirable to operate industrial pipelines transporting non‐Newtonian materials near the transition from laminar to turbulent flow. For the commonly used Bingham plastic model, the Hedström technique overestimates turbulent flow friction losses because it does not take account of viscous‐layer thickening. In the present paper, the Wilson‐Thomas model is applied to predict the transition point for Bingham plastics. Laminar and turbulent friction losses are calculated to show that conditions at transition depend only on the Hedström number. The results are approximated by simplified fit functions. Comparison with existing empirical correlations and experimental data from various sources shows satisfactory agreement.     

Small‐Molecule Proteomimetic Inhibitors of the HIF‐1α–p300 Protein–Protein Interaction

The therapeutically relevant hypoxia inducible factor HIF‐1α–p300 protein–protein interaction can be orthosterically inhibited with α‐helix mimetics based on an oligoamide scaffold that recapitulates essential features of the C‐terminal helix of the HIF‐1α C‐TAD (C‐terminal transactivation domain). Preliminary SAR studies demonstrated the important role of side‐chain size and hydrophobicity/hydrophilicity in determining potency. These small molecules represent the first biophysically characterised HIF‐1α–p300 PPI inhibitors and the first examples of small‐molecule aromatic oligoamide helix mimetics to be shown to have a selective binding profile. Although the compounds were less potent than HIF‐1α, the result is still remarkable in that the mimetic reproduces only three residues from the 42‐residue HIF‐1α C‐TAD from which it is derived.     

Anti‐HIV Small‐Molecule Binding in the Peptide Subpocket of the CXCR4:CVX15 Crystal Structure

The CXC chemokine receptor 4 (CXCR4) is involved in chemotaxis and serves as a coreceptor for T‐tropic HIV‐1 viral entry, thus making this receptor an attractive drug target. Recently, crystal structures of CXCR4 were reported as complexes with the small molecule IT1t and the CVX15 peptide. Follow‐up efforts to model different antagonists into the small molecule CXCR4:IT1t crystal structure did not generate poses consistent with either the X‐ray crystal structure or site‐directed mutagenesis (SDM). Here, we compare the binding pockets of the two CXCR4 crystal structures, revealing differences in helices IV, V, VI, and VII, with major differences for the His203 residue buried in the binding pocket. The small molecule antagonist AMD11070 was docked into both CXCR4 crystal structures. An AMD11070 pose identified from the CXCR4:CVX15 model presented interactions with Asp171, Glu288, Trp94, and Asp97, consistent with published SDM data, thus suggesting it is the bioactive pose. A CXCR4 receptor model was optimized around this pose of AMD11070, and the resulting model correlated HIV‐1 inhibition with MM‐GBSA docking scores for a congeneric AMD11070‐like series. Subsequent NAMFIS NMR results successfully linked the proposed binding pose to an independent experimental structure. These results strongly suggest that not all small molecules will bind to CXCR4 in a similar manner as IT1t. Instead, the CXCR4:CVX15 crystal structure may provide a binding locus for small organic molecules that is more suitable than the secondary IT1t site. This work is expected to provide modeling insights useful for future CXCR4 antagonist and X4‐tropic HIV‐1 based drug design efforts.     

Using gamma-ray emission to measure areal density of inertial confinement fusion capsules

Fusion neutrons streaming from a burning inertial confinement fusion capsule generate gamma rays via inelastic nuclear scattering in the ablator of the capsule. The intensity of gamma-ray emission is proportional to the product of the ablator areal density (ρR) and the yield of fusion neutrons, so by detecting the gamma rays we can infer the ablator areal density, provided we also have a measurement of the capsule's total neutron yield. In plastic-shell capsules, for example, (12)C nuclei emit gamma rays at 4.44 MeV after excitation by 14.1 MeV neutrons from D+T fusion. These gamma rays can be measured by a new gamma-ray detector under development. Analysis of predicted signals is in progress, with results to date indicating that the method promises to be useful for diagnosing imploded capsules.     

Surface separation and contact resistance considering sinusoidal elastic–plastic multi-scale rough surface contact

The current work considers the multi-scale nature of surface roughness in a new model that predicts the real area of contact and surface separation as functions of load. This work is based upon a previous rough surface multi-scale contact model which used stacked elastic–plastic spheres to model the multiple scales of roughness. Instead, this work uses stacked 3D sinusoids to represent the asperities in contact at each scale of the surface. By summing the distance between the two surfaces at all scales, a model of surface separation as a function of dimensionless load is obtained. Since the model makes predictions for the real area of contact, it is also able to make predictions for thermal and electrical contact resistance. In accordance with concerns in previous works that the iterative calculation of the real contact area in multi-scale methods does not converge, this work not only tests but also gives conditions required for convergence in these techniques. The results are also compared to other existing rough surface contact models.     

Achieving precision and reproducibility for writing patterns of n-alkanethiol self-assembled monolayers with automated nanografting

Nanografting is a high-precision approach for scanning probe lithography, which provides unique advantages and capabilities for rapidly writing arrays of nanopatterns of thiol self-assembled monolayers (SAMs). Nanografting is accomplished by force- induced displacement of molecules of a matrix SAM, followed immediately by the self-assembly of n-alkanethiol ink molecules from solution. The feedback loop used to control the atomic force microscope tip position and displacement enables exquisite control of forces applied to the surface, ranging from pico to nanonewtons. To achieve high-resolution writing at the nanoscale, the writing speed, direction, and applied force need to be optimized. There are strategies for programing the tip translation, which will improve the uniformity, alignment, and geometries of nanopatterns written using open-loop feedback control. This article addresses the mechanics of automated nanografting and demonstrates results for various writing strategies when nanografting patterns of n-alkanethiol SAMs.