Noteworthy Chemistry

May 23, 2011

Nanodiamond provides enhanced nanocomposite properties. Research on polymer nanocomposites has produced some remarkable mechanical and structural properties, based primarily on the enhanced interactions of nanoscale filler materials with the polymer matrix.

T. Nishino and coauthors at Kobe University (Japan) and Bando Chemical Industries (Kobe) elaborated this technology by incorporating a nanodiamond-based filler into poly(vinyl alcohol) (PVA) to enhance the mechanical properties of the resulting nanocomposite. Nanodiamond typically is obtained by detonating explosive compounds. It forms as a diamond cubic lattice structure, although it is structurally imperfect. A representation is shown in the figure.

The nanodiamond source in this study was a commercially available 2.75 wt% aqueous suspension. The suspension is ultrasonicated for 1 h, and then treated with PVA powder, which dissolves in the aqueous medium. The resulting mixture is cast onto glass to provide films of ~100-μm thickness.

The authors measured various mechanical properties of the test films against those of unfilled PVA films. The stress–strain data indicate that tensile strength and Young’s modulus increase considerably above those of the control with increasing nanodiamond content. The nanocomposite reached a modulus value of 9.7 GPa with only 1 wt% nanodiamond loading, and its tensile strength increased by 30% compared with the control at 5 wt% loading.

The authors suggest that these reinforcing properties are a function of the extremely small particle size and high surface area of nanodiamond, which cause it to disperse efficiently within the polymer matrix. The observed modulus for the 1 wt% nanodiamond–based nanocomposite was the highest value among the carbon-based nanocomposites studied, which included single-wall nanotube and graphene oxide fillers. The nanodiamond-based composites were >90% transparent across the visible light region.

Nanodiamond nanoparticles should be attractive alternatives to conventional carbon-based fillers in a variety of polymer composites. (Macromolecules 2011, 44, Article ASAP DOI: 10.1021/ma200176r; W. Jerry Patterson)

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Proteases mediate endomorphin-1 production. Endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) is a tetrapeptide isolated from the bovine brain; it has high affinity for the μ-opioid receptor. This compound’s potency is comparable with that of morphine, making it a candidate for new analgesic drugs. Current syntheses of endomorphin-1 are chemical methods that require sequential protections and deprotections and enzymatic methods that give low yields.

B. He and co-workers at Nanjing University of Technology (China) developed a new chemoenzymatic process to prepare endomorphin-1. Their method uses two solvent-stable proteases to catalyze peptide coupling reactions, as shown in the figure.

The researchers previously had shown that proteases WQ9-2 and PT121 catalyze couplings of aromatic and acidic residues, respectively. In this sequence, using protease WQ9-2 in 20% aq MeOH solvent, the product Boc-Trp-Phe-NH2 crystallizes in 90% yield. The tert-butoxycarbonyl (Boc) protecting group is removed in the usual way.

The second building block for endomorphin-1, Boc-Tyr-Pro-OH, is obtained by using the classical mixed carbonic anhydride method. Using protease PT121 and a biphasic EtOAc–H2O solvent system to drive the reaction equilibrium, the authors produced Boc-Tyr-Pro-Trp-Phe-NH2 in 84.5% yield from the two dipeptides. After deprotection and purification with high-speed countercurrent chromatography, endomorphin-1 was obtained in 91% yield and 99.8% purity.

This process is green, easy to perform, and readily scalable; and it can be used to synthesize other polypeptides. (Green Chem. 2011, 13, Advance Article DOI: 10.1039/c1gc15042a; José C. Barros)

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Monitor your nails for exposure to fluorinated surfactants. Fluorinated surfactants are synthetic organic compounds that have multiple fluorine atoms along the carbon backbone. As surfactants, they are stable and useful under harsh conditions because of their inert C–F bonds. The downside of their stability is that they are persistent in the environment and may be toxic to humans.

Three widely used surfactants are perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA). They bind to proteins in the body, and they are routinely detected in serum samples. Y. H. Jin and coauthors at Dalian University of Technology (China), the Research Institute for Environmental Sciences and Public Health of Iwate Prefecture (Morioka, Japan), and Iwate University (Morioka) discovered that the concentrations of fluorinated surfactants in human nails reflect their occurrence in other parts of the body.

Further study was carried out on the assumption that these fluorinated compounds attack keratin and accumulate during nail growth. Twenty-eight healthy adult volunteers with no occupational exposure to fluorinated surfactants provided blood, fingernail, and toenail samples at time intervals commensurate with the lag times expected between detection in the blood serum and the nails.

PFOS had the highest level in nails, followed by PFNA and PFOA. These results are consistent with those from blood serum. The concentrations of most fluorinated surfactants fluctuated little between fingernails and toenails. Based on this research, the authors recommend human nails as alternative indicators of fluorinated surfactant exposure. (Environ. Sci. Technol. 2011, 45, Article ASAP DOI: 10.1021/es1036207; Sally Peng Li)

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Immune response can be mediated by nanostructured scaffolds. L. Visai and colleagues at the University of Pavia (Italy), the University of Bologna (Italy), the Center for Tissue Engineering (Pavia), and the Salvatore Maugeri Foundation (Pavia) explored the relationship between alignment and diameter of electrospun poly(L-lactic acid) (PLLA) fiber mats on macrophage immune response. The electrospinning solution concentration and take-up roll speed were used to control fiber diameter (micro- to nanometer size) and degree of alignment, respectively.

The authors compared four PLLA electrospun scaffolds—random, ~1.53 µm; aligned, ~1.60 µm; random, ~0.61 µm; and aligned, ~0.55 µm—with smooth PLLA films (see figure). Regardless of degree of alignment, activated, elongated, viable macrophages were usually observed after 7 days, longer than the 24-h activation on the smooth films. Fiber alignment produced only slightly more macrophage attachment than smooth films or random fibers.

 

Temporal cytokine secretion studies showed that the nanostructured fiber surfaces decrease the inflammatory response and that smaller fiber diameters are more biocompatible. These preliminary studies offer clues toward developing new nanostructured biomaterial scaffolds. (Biomacromolecules 2011, 12, 1900–1911; LaShanda Korley)

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Change a bioresolution substrate to improve the whole sequence. In early work on the development of a route to (S)-allysine ethylene acetal, C. J. Cobley, M. C. Lloyd, and coauthors at Dr. Reddy’s Laboratories (EU) (Cambridge, UK) and Nantong Cellulose Fibers (Jiangsu, China) prepared the racemic N-acetylallysine ethylene acetal from the racemic amino acid and used it as the substrate for bioresolution with an acylase. But the separation of the desired product caused by the high water solubility of the unreacted (R)-N-acetyl compound led to a search for an alternative substrate.

The N-benzoyl substrate is a crystalline intermediate that allows easier isolation and improves yields of the racemic N-benzoylallysine ethylene acetal. After optimization, bioresolution of the new substrate can be carried out at lower enzyme loadings and gives a much cleaner separation of product from unreacted (R)-N-benzoyl material. The separation may allow racemization and recycle via an azlactone intermediate. (Org. Process Res. Dev. 2011, 15, 284–290; Will Watson)

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Conjugation with NO donors enhances doxorubicin cytotoxicity. The efficacy of many cancer chemotherapeutic agents, including doxorubicin (1), is limited by the capacity of cancer cells to efflux these anticancer drugs. This form of multidrug resistance (MDR) subsequently limits cellular accumulation and therefore cytotoxicity of the drug. In some doxorubicin-resistant epithelial human colon cell lines, however, NO donors can reduce the efflux of 1 from the colon cells.

R. Fruttero, A. Bosia, and co-workers at the University of Turin (Italy) used this fact to develop a strategy for enhancing the efficacy of 1 by converting it to conjugates with NO donor capability. Conjugates 2 and 3 were formed by linking 1 via an ester with structures containing 3-phenylsulfonylfuroxan or nitrooxy moieties. Both structures release NO, although by different mechanisms.

The authors used several methods to compare 2 and 3 with 1 as cancer chemotherapeutic agents. They incubated the doxorubicin-resistant human colon cell line HT29-dx with the three compounds and observed that 2 and 3 accumulate in the cells in a concentration-dependent manner and are highly cytotoxic. In contrast, the intracellular concentration of 1 did not increase significantly except at the highest concentration. The accumulation and cytotoxicity effects are stronger for 3 than for 2.

The accumulation of 2 and 3 is also rapid: The elevation of intracellular content of 5 μM of the drugs is significant after 1–3 h, but it was never significant between 1 and 24 h for 1.

Measurements of the intracellular transport of the three drugs showed that efflux of 2 and 3 decreases dramatically compared with that of unconjugated drug 1. The efflux reduction resulted in toxicities of 2 and 3 that are definitively higher than that of 1, although this toxicity is reduced by the presence of NO scavengers such as red blood cells.

The results of the study suggest a promising strategy for hybrid NO donor antitumor drugs to address the problem of MDR in cancer therapy. (ACS Med. Chem. Lett. 2011, 2, Article ASAP DOI: 10.1021/ml100302t; W. Jerry Patterson)

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Triazole fluorophores emit ultraviolet and blue light efficiently. Fluorophores with short-wavelength light emission are useful for making full-color optical displays and fluorescence energy transfer systems. This type of emitter, however, is rare. X. Shi and coauthors at West Virginia University (Morgantown), Jilin University (Changchun, China), and Shandong University (Jinan, China) developed triazole-based fluorophores that emit efficiently in the UV and blue spectral regions.

The researchers prepared a series of 1,2,3-triazole derivatives with substituents at the 2-, 4-, and 5-positions (1) and studied their steric and electronic effects. With appropriate combinations of substituents, the researchers developed fluorophores with emission maxima in the short wavelength region (350–400 nm), high fluorescence quantum yields (up to 76%), and large Stokes shifts (up to 93 nm). (Chem.—Eur. J. 2011, 17, 5011–5018; Ben Zhong Tang)

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