Self-assembled morphologies of monotethered polyhedral oligomeric silsesquioxane nanocubes from computer simulation

Self-assembly of functionalized nanoscale building blocks is a promising strategy for "bottom-up" materials design. Recent experiments have demonstrated that the self-assembly of polyhedral oligomeric silsesquioxane (POSS) "nanocubes" functionalized with organic tethers can be utilized to synthesize novel materials with highly ordered, complex nanostructures. We have performed molecular simulations for a simplified model of monotethered POSS nanocubes to investigate systematically how the parameters that control the assembly process and the resulting equilibrium structures, including concentration, temperature, tether lengths, and solvent conditions, can be manipulated to achieve useful structures via self-assembly. We report conventional lamellar and cylindrical structures that are typically found in block copolymer and surfactant systems, including a thermotropic order-order transition, but with interesting stabilization of the lamellar phase caused by the bulkiness and cubic geometry of the POSS nanocubes.     

Invariance of the dissipative action at ultrahigh strain rates above the strong shock threshold

We have directly resolved shock structures in pure aluminum in the first few hundred picoseconds subsequent to a dynamic load at peak stresses up to 43 GPa and strain rates in excess of 10(10) s(-1). For strong shocks we obtain peak stresses, strain rates, and rise times. From these data, we directly validate the invariance of the dissipative action in the strong shock regime, and by comparing with data obtained at much lower strain rates show that this invariance is observed over at least 5 orders of magnitude in the strain rate. Over the same range, we similarly validate the fourth-power scaling of the strain rate with the peak stress (the Swegle-Grady relation).     

On the complexity of deciding whether the distinguishing chromatic number of a graph is at most two

In an article Cheng (2009) [3] published recently in this journal, it was shown that when k≥3, the problem of deciding whether the distinguishing chromatic number of a graph is at most k is NP-hard. We consider the problem when k=2. In regards to the issue of solvability in polynomial time, we show that the problem is at least as hard as graph automorphism, but no harder than graph isomorphism.     

Lipid-based nanoparticles as drug delivery system for paclitaxel in breast cancer treatment

Paclitaxel (PTX) is a well-known antitumor drug, widely utilized in the treatment of breast, ovarian, head, and neck tumors, among others. The low aqueous solubility (< 1.0 μg/mL; log P = 3.96) limits its use by intravenous route, and alternatives found for the marketed products are associated with high toxicity. Incorporation of PTX into lipid nanocarriers has been considered an interesting nontoxic alternative for this route, but drug loading is usually low. This study aimed to analyze the influence of the lipid composition and three different lipid nanosystems—solid lipid nanoparticles, nanostructured lipid carriers (NLCs), and nanoemulsion—in PTX encapsulation and its biological response. The three proposed systems were prepared by hot melt homogenization followed by ultrasonication. Among the blank formulations first prepared, NLC had the smallest size (74 ± 1 nm), with negative zeta potential (? 11.4 ± 0.1 mV). The incorporation of 0.10 mg/mL PTX into this NLC formulation yielded high and stable encapsulation (0.089 ± 0.003 mg/mL), also supported by polarized light microscopy and differential scanning calorimetry curves. NLC-PTX was very effective against MCF-7 (IC50 25.33 ± 3.17 nM) and MDA-MB-231 breast cancer cell lines (IC50 2.13 ± 0.21 nM), compared to free PTX (IC50 > 500 nM). In addition, no significant cytotoxicity was found against fibroblast cells. Taken together, these results demonstrated that PTX was successfully incorporated into NLC with appropriate physicochemical characteristics for intravenous administration, suggesting that the use of NLC as vehicle to incorporate PTX may be a promising strategy in the treatment of breast cancer.     

Thermal and structural characterization of SrTi1-xNdxO3

Sr(Ti,Nd)O₃ was synthesized in order to evaluate the influence of the amount of neodymium on the thermal and structural properties of SrTiO₃. The synthesis was carried out using the polymeric precursor method. A small mass gain was observed for the SrTiO₃ and SrTi_0.98Nd_0.02O₃ samples accompanied by an exothermic peak in the DTA curves. Other steps at higher temperatures are assigned to the combustion of the organic material and carbonate. Elimination of defects by previous calcination of the precursors is responsible by the short and long range ordering of the perovskite. Cubic phase was obtained for undoped and doped SrTiO₃.     

1,2,3-Triazolylidene based complexes via post-modification of pincer click ligands

Preparation of 1,2,3-triazolylidene metal complexes by simple alkylation of triazolyl based parent species was demonstrated for the first time. Based on this post-modification approach, unprecedented tridentate Pd and Pt complexes bearing a 1,2,3-triazolylidene core were synthesized.     

Protamine neutralisation of low molecular weight heparins and their oligosaccharide components

Protamine sulphate is an effective inhibitor of heparin and is used clinically to neutralise both low molecular weight heparins (LMWH) and unfractionated heparin (UFH). However, protamine sulphate does not fully counter the anti-Xa effect of LMWH, even in excess (>40 μg to 1 IU/ml). To investigate the molecular basis for this observation, the residual potencies in the presence and absence of plasma as well as the molecular weight profiles of commercial LMWH neutralised with increasing amounts of protamine were measured. Materials over 5000 Da are preferentially neutralised by protamine. To further investigate this molecular weight dependence, monodisperse oligosaccharides were prepared from three commercial LMWHs. The specific anti-Xa activity for the fractions increased with molecular weight, and was found to vary between the three preparations for oligosaccharides of the same molecular weight. Our results indicate that protamine sulphate neutralisation is largely dependent on molecular weight, leading to the implication that LMWHs containing a larger proportion of small oligosaccharides will not be as effectively neutralised. Protamine sulphate neutralisation of any given LMWH is also affected by the specific anticoagulant activities of its low molecular weight components, which varies between LMWH products, presumably with the method of manufacture.     

Antibacterial Thiopeptide GE2270-Congeners from Nonomuraea jiangxiensis

Thiopeptides are macrocyclic natural products with potent bioactivity. Nine new natural thiopeptides (1–9) were obtained from a Nonomuraea jiangxiensis isolated from a terrestrial soil sample collected in Singapore. Even though some of these compounds were previously synthesized or isolated from engineered strains, herein we report the unprecedented isolation of these thiopeptides from a native Nonomuraea jiangxiensis. A comparison with the literature and a detailed analysis of the NMR and HRMS of compounds 1–9 was conducted to assign their chemical structures. The structures of all new compounds were highly related to the thiopeptide antibiotics GE2270, with variations in the substituents on the thiazole and amino acid moieties. Thiopeptides 1–9 exhibited a potent antimicrobial activity against the Gram-positive bacteria, Staphylococcus aureus with MIC₉₀ values ranging from 2 µM to 11 µM. In addition, all compounds were investigated for their cytotoxicity against the human cancer cell line A549, none of the compounds were cytotoxic.     

Synthesis, photophysical properties and in vitro photodynamic activity of axially substituted subphthalocyanines

A new series of subphthalocyanines substituted axially with an oligoethylene glycol chain [SPcB(OCH(2)CH(2))(n)OH, n = 3 (2) or 4 (3)] or a p-phenoxy oligoethylene glycol methyl ether chain [SPcBOC(6)H(4)(OCH(2)CH(2))(n)OCH(3), n = 2 (4) or 3 (5)] have been synthesised by substitution reactions of boron subphthalocyanine chloride SPcBCl (1) with the corresponding oligoethylene glycols, and characterised with various spectroscopic methods and elemental analysis. The molecular structure of one of these compounds (subphthalocyanine 4) has also been determined. As revealed by absorption spectroscopy, these compounds are essentially non-aggregated in DMF. The low aggregation tendency of these compounds results in a strong fluorescence emission and high efficiency to generate singlet oxygen. All these subphthalocyanines, being formulated with Cremophor EL, function as efficient photosensitisers and exhibit a high photocytotoxicity against HepG2 human hepatocarcinoma and HT29 human colon adenocarcinoma cells. The phenoxy analogues 4 and 5 show a relatively high photostability and are particularly potent towards these cell lines, with IC(50) values down to 0.02 microM.