Noteworthy Chemistry

January 17, 2011

Synthesize and colorize poly(lactic acid) in one step. Poly(lactic acid) (PLA) is a linear thermoplastic polyester derived from natural, renewable sources. It is compostable, generating CO2, water, biomass, humus, and other natural substances.

PLA is prepared by condensing lactic acid or by ring-opening polymerization (ROP) catalyzed by aluminum alkoxides. Dyeing PLA uses strongly alkaline conditions and large volumes of water; it often forms aromatic amines from the azo dyes as byproducts.

P. C. McGowan and coauthors at the University of Leeds (UK) and DyeCat (Leeds) developed new ROP catalysts that incorporate chromophores. The catalysts simultaneously control the polymerization and incorporate dyes in the polymer backbones to achieve high color strength without exposing the fibers to harsh conditions.

The authors prepared aluminum precatalysts 1 and 2, which react with an initiator (e.g., benzyl alcohol) to give catalytically active species such as 3. When the initiator contains a chromophore, the result is a colored polymer. Analysis of the PLA product showed that the initiator is incorporated at the end of the polymer chain. Fibers and plastics made from it deteriorate only slightly upon processing.

Commercially available dyes such as azo compounds 4 and 5 can be used as initiators. UV-responsive polymers can be obtained by using a fluorescent dye. The black PLA obtained from yellow and purple dyes was used as a fiber that was woven into to a black dress, which is on display at the Science Museum in London.

The amount of dye required for this technique is 0.5–0.7% of the mass of polymer. This is significantly lower than the amounts used in conventional dyeing. The process has several environmental advantages over the traditional fiber production process: It eliminates fiber wet-processing stages, wasted dye, and colored wastewater treatment. Developments such as this may help replace poly(ethylene terephthalate) in commercial polyesters. (Angew. Chem., Int. Ed. 2011, 50, 291–294; JosÉ C. Barros, Sally Peng Li)

A cationic hybrid copolymer is an efficient gene delivery vector. Cationic organic polymers, such as poly(ethylenimine) (PEI) and poly[(2-dimethylamino)ethyl methacrylate] (PDMAEMA), have high gene transfection efficiency. Unfortunately, the polymers are cytotoxic, which limits the scope of their biomedical applications. X. J. Loh, J. Li, and coauthors at the Institute of Materials Research and Engineering (Singapore) and the National University of Singapore developed an organic–inorganic hybrid system that is efficient for gene delivery and benign to living cells.

The hybrid is a star-shaped copolymer consisting of a hydrophobic inorganic core of polyhedral oligomeric silsesquioxane and multiple hydrophilic organic coronas of PDMAEMA chains. Because it is amphiphilic, the copolymer forms micelles into which hydrophobic drugs such as paclitaxel are readily encapsulated. The drug-encapsulated micelles are less toxic than PDMAEMA and PEI. Paclitaxel-loaded polyplexes show better gene transfection efficiency than their unloaded counterparts. (J. Mater. Chem. 2010, 20, 10634–10642; Ben Zhong Tang)

New shape memory materials have biodegradable components. L. Wu*, C. Jin, and X. Sun at Zhejiang University (Hangzhou, China) synthesized segmented polyurethanes derived from biodegradable blocks [poly(L,L-lactide) (PLLA) and poly(ε-caprolactone) (PCL)] and photoresponsive N,N-bis(2-hydroxyethyl)cinnamamide (BHECA) pendant groups (1) for biomedical shape memory applications. These microphase-segregated poly(ester urethane)s with PCL–BHECA soft segments and chain-extended PLLA hard domains have good mechanical properties-and are soluble in several organic casting solvents.

Attaching the bulky BHECA as pendant units reduces the degree of ordering of the PCL continuous domain and affects the organization or crystallinity of the PLLA hard phase. The materials have several mechanical properties that depend on the structural composition.

Because cross-linking the cinnamamide to form a cyclobutane ring structure (2) is photoreversible, ~73% of the shape memory behavior can be recovered. The authors show that an exposure time of 60–90 min and moderate elongations (<50%) are ideal for shape memory in these poly(ester urethane)s. They also report slow (12–25 wt% in 32 weeks) hydrolytic degradation of the materials in a phosphate buffer. (Biomacromolecules 2011, 12, 235–241; LaShanda Korley)

Reap the benefits of microwave-mediated drying. N. A. Pinchukova, L. A. Hulshof, and coauthors at the National Academy of Sciences of Ukraine (Kharkiv) and Eindhoven University of Technology (The Netherlands) studied the drying behavior of three thermolabile compounds: (S)-N-acetylindoline-2-carboxylic acid, N-acetyl-(S)-phenylalanine, and cocarboxylase hydrochloride. They compared conventional heating with microwave heating, both under vacuum.

In all cases, the use of microwave heating reduced drying times. For cocarboxylase hydrochloride, drying times were as short as 10% of those for conventional heating (8 h compared with 80 h). The authors believe that the shorter drying times are the result of the influence of microwaves on the diffusion rate of moisture through the sample. (Org. Process Res. Dev. 2010, 14, 1130–1139; Will Watson)

Oxazoloquinoline-based drugs have analgesic properties. The transient receptor potential vanilloid-1 (TRPV1) receptor is one of several ion channel targets believed to be involved in pain transmission;, it is activated by several pain-related stimuli. TRPV1 antagonists have shown promising analgesic efficacy according to models of inflammatory and neuropathic pain.

Previous studies showed that indazoleurea compounds such as 1 have potential value as TRPV1 antagonists. E. A. Voight*, J. F. Daanen, and M. E. Kort at Abbott Laboratories (Abbott Park, IL) modified this type of structure to form a group of compounds based on the oxazolo[4,5-c]quinoline scaffold. They describe an efficient three-step, one-pot synthesis of these compounds; compound 2 is the optimized product.

The synthesis begins with the reaction of quinoline derivative 3 with chiral isothiocyanate 4 to form thiourea 5. Variants of 3 are commercially available or easily prepared, and 4 is readily available in four steps. Carbodiimide-mediated cyclization of 5 produces oxazoloquinoline 6. The final acidification step removes the TBS protecting group to give desired structure 2. (TBS is tert-butyldimethylsilyl; EDC is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide.)

Structure–activity studies identified 2 as a potent, selective TRPV1 antagonist. It has an IC50 of 5 nM and >100-fold selectivity over other transient receptor potential channels. (IC50 is the drug concentration needed to inhibit a biological process by 50%.) (J. Org. Chem. 2010, 75, 8713–8715; W. Jerry Patterson)

These nanofiber scaffolds release antimicrobials quickly. X. Yu* and colleagues at Stevens Institute of Technology (Hoboken, NJ) and the University Medical Center Groningen and University of Groningen (The Netherlands) prepared cell scaffolds derived from electrospun poly(ε-caprolactone) (PCL) mats that contained antimicrobial, oxygen-producing CaO2 and ascorbic acid for cell preservation. The PCL–CaO2–ascorbic acid mats consisted of ~800 nm diam nanofibers that were reduced to ~400 nm diam without disrupting the mat integrity by leaching in deionized water.

The burst-release profile during leaching for 10% CaO2 on day 1 suggested that the antimicrobial was incorporated on or near the surfaces of the PCL nanofibers. The inhibition of Gram-positive and Gram-negative bacterial growth, coupled with the burst release of CaO2, is promising for a variety of biomaterial applications. Although these materials showed significant cell cytotoxicity during the initial burst period, cytotoxicity was minimal at longer cell incubation periods (day 4).

Including ascorbic acid in the nanofibers improved cell viability and shape when the cells were cultured on the electrospun scaffolds during initial burst release, particularly at the 10% CaO2dose level. At day 4, however, cell viability improved even without the ascorbic acid, suggesting that cell damage was transient and recoverable. (ACS Appl. Mater. Interfaces 2011, 3, Article ASAP DOI: 10.1021/am100862h; LaShanda Korley)

Synthesize fully soluble ladder-type poly(p-phenylene)s. The rigid, planar main chains of laddered conjugated polymers give useful electronic properties, including high carrier mobility and high luminescence intensity. Z. Bo and coworkers at Beijing Normal University describe a route to this type of polymer in which carbazole-based monomers are used to form azomethine-bridged ladder-type conjugated poly(p-phenylene)s. (According to the authors, this is the first report of this type of fully soluble polymer systems.)

Monomer synthesis starts with dibromocarbazole 1, which is easily converted to N-alkylated derivative 2. Standard nitration of 2 is followed by reduction to the corresponding amine and then treatment with an acid chloride to give key bisamide structure 3. The amide groups provide the reactivity needed to form the azomethine bridges later.

Suzuki–Miyaura–Schluter polycondensation of 3 with boron ester comonomer 4 creates the initial single stranded poly(p-phenylene) structure 5. Under optimized Bischler–Napieralski reaction conditions, 5 is converted to the corresponding azomethine-bridged double-stranded ladder polymer 6. Spectroscopic studies confirmed the completion of the ring-closure reaction leading to 6. The five long alkyl chains on each polymer repeat unit assure full solubility in common solvents such as CHCl3 and THF.

The molecular weights (Mw and Mn) measured for 6 were 23 and 16 kDa, respectively. Gel permeation chromatography used in this study, however, is not a good molecular weight measurement method for rodlike polymers.

The authors note that 6 has an alternating donor–acceptor structure along its main chain. They observed a well-resolved photoluminescence spectrum with an emission maximum at 496 nm. They note significant bathochromic shifting of the absorption and emission spectra of 6, which suggests that the effective conjugation length of this ladder polymer is longer than that of single-stranded polymer 5.

Notably, the nitrogen atom on the ladder polymer backbone can be easily and reversibly protonated and deprotonated, which indicates that structures such as 6 are promising protic acid–sensitive materials. This feature may lead to using them as pH sensors. (Macromolecules 2010, 43, 10216–10220; W. Jerry Patterson)

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