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New way to make 2-arylphenols – used in sensors and biologically active substances

18 Oct 2012

A new way to make 2-arylphenols, which are found in organocatalysts, sensors, phosphite ligands, and biologically active substances has been devised by scientists in the US.

Simple and cheap aryl chlorides can be used to directly arylate unprotected phenols without transition metals. This is the first general, regioselective intermolecular phenol ortho-arylation process that uses aryl chlorides as one of the coupling components. It is the most direct synthetic pathway to 2-arylphenols – no protecting group manipulations are required.

The team also made arylated binaphthol derivatives. Additionally, they have presented the shortest pathway to date for the synthesis of helicenes – one step from commercially available reagents.

Read this ‘HOT’ Chemical Science article today:

Divergent Reaction Pathways for Phenol Arylation by Arynes: Synthesis of Helicenes and 2-Arylphenols
T Truong and O Daugulis
Chem. Sci., 2012, DOI: 10.1039/c2sc21288a

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New coating for anticancer compounds improves generation of cancer-killing singlet oxygen

16 Oct 2012

Phthalocyanines (Pcs) have excellent electronic and optical properties, which make them promising as a photosensitisers (PSs) for photodynamic therapy (PDT). Since Pcs strongly and selectively absorb light in the range of 600-800nm, they allow high penetration depth of light in normal tissue while minimising the risk and complications such as burning. But Pcs are highly hydrophobic and tend to form aggregates in aqueous media, which reduces their therapeutic activity.

Various types of nanocarriers, such as micelles, liposomes and nanoparticles, have been used to overcome this problem, and to prepare a stable dispersion of Pc in aqueous solution. However, most of them still suffer from shortcomings such as poor loading of Pc (small weight % of Pc in nanocarriers), risk of payload leaking before reaching target cells, and laborious, time-consuming fabrication and encapsulation processes.

Scientists in the Republic of Korea have made ZnPc nanospheres in one pot without using any templates or emulsifiers. They can be post-synthetically modified to improve their dispersibility in aqueous solution without altering their morphology or properties. They show higher singlet oxygen generation efficiency and in vitro phototoxicity than monomeric Pc molecules, suggesting that they are potentially useful as a photosensitiser for photodynamic therapy.

Targeting ligands could be introduced to deliver the nanospheres to specific target sites, anticipate the researchers. And if therapeutic agents were encapsulated, they could perform dual chemo- and photodynamic therapy.

Read this ‘HOT’ Chemical Science article:

Self-assembled, covalently linked, hollow phthalocyanine nanospheres
Raghunandan Hota, Kangkyun Baek, Gyeongwon Yun, Youngkook Kim, Hyuntae Jung, Kyeng Min Park, Eunjin Yoon, Taiha Joo, Juseok Kang, Chan Gyung Park, Su Mi Bae, Woong Shick Ahn and Kimoon Kim
Chem. Sci., 2012, DOI: 10.1039/C2SC21254D

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Super imaging of living cells

15 Oct 2012

A new method of introducing single-molecule-quality fluorophores into live bacterial cells for superresolution imaging studies has been developed by researchers in the US.

Superresolution imaging can image structures with a spatial resolution 5 to 10 times smaller than the diffraction limit of about 200nm for visible wavelengths. In contrast to previous ideas, the team allows a permeable dye molecule (the substrate) to enter the cell in a fluorescently deactivated state.

Subsequent photoactivation by reaction with the enzyme nitroreductase produces fluorescent products whose concentration is controlled by the level of substrate uptake. Importantly, fluorophores can enter living cells fairly easily because they are neutral, and they emit at long wavelengths to avoid autofluorescence.

Read this ‘HOT’ Chemical Science article today:

Enzymatic Activation of Nitro-Aryl Fluorogens in Live Bacterial Cells for Enzymatic Turnover-Activated Localization Microscopy
Marissa K. Lee, Jarrod Williams, Robert Twieg, Jianghong Rao and W.E. Moerner
Chem. Sci., 2012, DOI: 10.1039/C2SC21074F

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Investigating protein interactions with anticancer drugs

16 Aug 2012

You can have too much of a good thing, in a manner of speaking. Cisplatin, a platinum-based anticancer drug, has been hugely successful in treating a range of cancers but severe side-effects require its administration to be dose-limited. Analogues, such as carboplatin and nedaplatin have been developed to overcome these problems; carboplatin can be administered at 20 times the dosage of cisplatin. These drugs, however, have their own problems and exhibit inherent and acquired toxicity.

Investigation into the uptake of platinum anticancer drugs has highlighted that the regulation of transport using carriers/ channel-mediated systems may be one of the key factors for drug resistance. In particular, copper transporters and chaperones have been identified as participating in the uptake, transport and efflux of these drugs.

mechanism of in vivo activation of platinum anticancer compounds

The interactions of the N-terminus of hCTR1 with carboplatin

Hongzhe Sun and co-workers have advanced on previous work in which they employed NMR to study metallodrug-biomolecule interactions. They identified that the methionine residues in the N-terminus of human CTR1 (hCTR1_N), a copper transporter, were essential to allow binding to cisplatin, potentially activating the drug.

Looking at carboplatin and nedaplatin as well as cisplatin’s clinically ineffective isomer, transplatin, the research team extended their studies to further understand the interaction between platinum compounds with hCTR1_N and compare their findings with cisplatin.

The NMR studies revealed that carboplatin and nedaplatin both bound to the methionine residues of the transporter, although when compared to cisplatin, less was activated. Interestingly, they are more stable than cisplatin, potentially due to shielding effects of their ligands. Transplatin was also found to bind to methionine residues at a much higher rate than its isomer. This sophisticated investigation into the kinetics and speciation of platinum-based drugs gives greater understanding into drug-binding and insights into their distinct biological roles.

Read more about this research in Sun’s Chemical Science Edge article, free to access for a limited period.

Posted on behalf of Sarah Brown, Chemical Science web writer.

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Calix[6]arenes as models of enzymes?

22 Nov 2011

When it comes to supramolecular chemistry in water, the best lessons are learnt from nature. Enzymes and antibodies use non-covalent interactions, including hydrogen bonding, coordination to a metal centre and hydrophobic effects, to bind guests extremely strongly. Olivia Reinaud’s group are following suit with their water-soluble funnel calix[6]arene receptor that complexes both Zn²⁺ cations and primary amines in aqueous solution.

In the presence of both Zn²⁺ and primary amines, a complex is formed in which the Zn²⁺ cation is bound by the imidazole groups. The amine is bound to the Zn²⁺ with favourable hydrophobic interactions between the cavity of the calixarene and the alkyl chain. Interestingly, the calixarene does not complex either of these guests individually, showing that the binding is highly cooperative. This type of complex only forms with primary amines. Considering this selectivity and the type of interactions used, plus the fact that the complex forms in water near pH 7 and a pseudo pK_a shift of the bound amine, the authors point out that the complex formation is highly reminiscent of the binding mode of Zn-based enzymes.

This is one of only a few examples of selective encapsulation of primary amines in water, and an inspiring step towards emulating the function of natural metalloenzymes.

Keen to read more? Download Reinaud’s Chemical Science Edge article.

Posted on behalf of Cally Haynes, Chemical Science web writer.

Also of interest:
RSC Macrocyclic and Supramolecular Chemistry Meeting – 19-20 December 2011
Solvent responsive cage: inducing a pronounced reorganisation of a metallasupramolecular cage complex with a conservative change in solvent polarity

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Mechanically locked capsule captures oppositely charged guests

06 Oct 2011

By combining hydrogen bonding and mechanical bonding, scientists in Spain have made a mechanically locked capsule that can encapsulate two oppositely charged ions.

Pablo Ballester and Marco Chas, at the Institute of Chemical Research of Catalonia, Tarragona, made the capsule’s two hemispheres out of a calix[4]pyrrole and a calix[4]arene. The calix[4]pyrrole uses hydrogen bond interactions to recognise anions or N-oxide guests while the calix[4]arene provides efficient cation-π and CH-π interactions for co-encapsulated guests. The capsule can fit two neutral or oppositely charged guests and the encapsulation is reversible.

If this has captured your attention, download Ballester’s Chemical Science Edge article for free and read more.

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The next generation of foldamers

05 Sep 2011

Scientists in Germany have reported a novel foldamer structure based on perylene bisimide (PBI) dyes and rigid oligophenylene ethynylene (OPE) backbones. The work was born out of the desire to create a well-defined macromolecular framework with predictable geometries. The group, from the University of Würzburg and lead by Frank Würthner, designed an OPE-fused PBI oligomer in which the π-π interactions between the molecules of PBI direct the folding geometry.

Graphical abstract: Foldamer with a spiral perylene bisimide staircase aggregate structure While the influence of π-π interactions on systems which fold into highly ordered structures, or foldamers, has been previously studied, the system designed by Würthner and his team is unique in that the rigid OPE backbone played no part in directing the folding geometry; π-π interactions in the PBI units were the sole influence on the backbone conformation and lead to the final geometry.

A typical OPE-fused PBI oligomer was found to contain between 8 and 9 PBI units, as determined by gel permeation chromatography and diffusion NMR. Further studies using MALDI-TOF ruled out impurities or side production in the oligomer. With this structural data in hand, they used UV-vis spectroscopy to prove that only the PBI, not the OPE, units participated in π-π stacking; a feature that is unique to their oligomer system. The authors then proved, through a series of elegant UV-vis analyses in chloroform and methylcyclohexane, that the oligomer was able to fold and unfold with changes in solvent polarity. These conclusions were also supported by molecular modeling studies.

The PBI oligomer reported in this work, in which the OPE backbone does not play a role in π-π stacking, resembles interactions in nucleic acids. Therefore, this system could be an ideal mimic for functional biological systems such as DNA or may also prove to have very interesting photophysical properties.

Find out more by downloading Würthner’s Edge article.

Posted on behalf of Patricia Pantos, Chemical Science web writer.

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‘Dial a molecule’ approach controls antibiotic production

11 Aug 2011

UK scientists have used genetic methods to control the chemical structures of pacidamycin antibiotics produced in bacteria. Their approach allows them to ‘dial into’ particular molecules, and to generate new pacidamycins.

The pacidamycins are uridyl peptide antibiotics with specific activity against Pseudomonas aeruginosa, a common cause of hospital infections. They target a protein in the bug’s cell wall. Around 20 pacidamycins are produced naturally by Streptomyces coeruleorubidus, although they have never been used clinically.

Telephone As with many natural products, purifying one from a suite of similar compounds can be tricky. But Rebecca Goss and colleagues at the University of East Anglia say their approach allows them to steer production in the direction they choose. ‘We’ve been able to introduce the genes into an organism that doesn’t naturally produce pacidamycin and rather than it making a whole forest of different peaks – of different antibiotics – which would be a separation nightmare, we’ve been able to bolt in the genes to make the different members of the family,’ explains Goss. ‘So we’ve been able to “dial a molecule” within the bug.’

Find out more in Chemistry World and download Goss’ Chemical Science Edge article for free.

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How polar are ionic liquids?

02 Jun 2011

Ionic liquids interact with dissolved salts to give solutions that are completely different to salt solutions in traditional organic solvents or water, say UK scientists.

Ionic liquids are of great interest as green solvents but the way they solvate solutes isn’t well understood. Scientists studying their polarity have produced contradictory results – in some cases they are reported to be highly polar, in others non-polar.

Now Tom Welton and colleagues at Imperial College London say they’ve resolved this contradiction and have revealed a completely new solvent paradigm for salt solutions in ionic liquids.

In contrast to molecular solvents, where the solute cation and anion need to stay close to each other to preserve charge neutrality, ionic liquids solvate individual solute ions, explains Welton. This completely divorces the cations and anions from each other but the ionic liquid itself is capable of preserving the charge neutrality.

The polarity of ionic liquids depends on when you ask, adds Welton. Polarity measurements that record snapshots of the ionic liquid on a short timescale (such as measuring the position of the absorption maximum) ‘freeze out’ ionic movement and so the ionic liquid appears non-polar. Absorptivity measurements involve a longer timescale, allowing ion movement to dominate solvation, yielding a much higher polarity.

Read more in ‘Salts dissolved in salts‘ in Chemical Science.

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Studying reaction mechanisms in the solid state

19 May 2011

Photochemical reactions in crystals can show excellent selectivity, thanks to the rigid environment. But the development and applications of reactions in crystals has suffered due to a lack of mechanistic insight.

Now Miguel Garcia-Garibay, at the University of California, Los Angeles, US, and colleagues have published the first report addressing the absolute reaction kinetics of a reaction taking place in the crystalline solid state, using conventional pump-probe methods with excitation in the nanosecond and femtosecond time domains.

Graphical abstract: Steady state and transient kinetics in crystalline solids: the photochemistry of nanocrystalline 1,1,3-triphenyl-3-hydroxy-2-indanone

They studied the Norrish type I decarbonylation of a 2-indanone in solution and as a nanocrystalline suspension and, for the first time, detected the radical intermediates involved in the reaction.

To find out more, download the group’s Chemical Science Edge article for free.

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