Chemical Science Blog

Regan Thomson’s group from Northwestern University, Illinois, present the first total synthesis of propolisbenzofuran B. The synthesis has been completed in 17 steps, starting from the phenolic aldehyde, vanillin.

In the natural world propolis is a resin made by bees and used in their hives to preserve a sterile environment. It encases waste and carcasses to prevent the decomposition of proteins and therefore decay.

The beneficial health effects of honeybee products have been hypothesised since ancient Roman times. More recently it has been determined that propolis has many biological and pharmacological properties including antibacterial, antibiotic, anti-oxidant, anti-fungal, anti-cancer and anti-inflammatory activities.

Propolisbenzofuran B is a natural product found in Brazilian propolis, first isolated in 2000 by Banskota and co-workers. Initial biological testing determined that the compound had a cytotoxic effect on murine colon 26-L5 carcinoma and human HT-1080 fibrosarcoma cells.

It was not only the promising range of biological activity which drew the authors’ attention to this particular compound; propolisbenzofuran B has a unique core with an unusual ring-system. The development of an efficient synthesis for this core opens the door to further biological evaluation and possible modifications to the compound.

Highlights of the synthesis include a silicon-tether controlled oxidative ketone-ketone cross-coupling as well as a novel and efficient benzofuran cascade. The cascade was discovered to be induced rapidly with the addition of trimethylsilyl triflate to the 1,4-diketone precursor. The authors believe this methodology will be useful in the synthesis of other complex molecules containing benzofuran groups.

To download the full article for free* click the link below:

Total synthesis of propolisbenzofuran B
Brian T. Jones, Christopher T. Avetta and Regan J. Thomson
DOI: 10.1039/c4sc00356j

*Access is free untill 13.06.14 through a registered RSC account – click here to register

We live in the technological age, surrounded by gadgets and gizmos with computer chips inside. They make our lives easier (mostly) and their speed just seems to keep increasing. But the computations only use binary code, zeros and ones and the speed at which they can be carried out will ultimately be limited by the size that the silicon circuits can be reduced to. What if computations could be done on a single molecule, which has been shown before, but also with the use of more than just two numbers? How about adding two and three to the available list of numbers? This is what Skrollan Stockinger and Oliver Trapp from the Ruprecht-Karls-Universitat Heidelberg detail in their recent Chemical Science paper.

They report a ternary/quaternary logic system based on a mixture of benzonitrile oxide with iron(III) ions and zinc ions which changes colour depending on the inputs. Using photographic recording and analysis of the Red/Green/Blue (RGB) values they can read out four different states: colourless, yellow, deep purple and a solution with precipitate present. This creates a system that gives the user a higher information processing density.

Two molecular logic systems with two independent input factors resulting in a continuous system and a system with a quaternary basis.

Does information processing really have to be restricted to zeros and ones? Using sodium thiocyanate ions rather than zinc ions the authors have created a continuous system. The sodium thiocynate creates a red complex and analysis of the RGB channels allow a range of concentrations to be detected which could be split up into any number of states for computation, rapidly increasing the information processing density. Therefore this continuous system could extend multi-valued logic beyond the ternary and quaternary systems described in the literature and the current paper.

Both systems show very good long-term stability and could find uses as a high potential storage medium with high data processing ability.

To find out the details of this work read the Chem. Sci. paper in full for free* today:

A Continuous and Multi Valued System as Molecular Answer for Data Processing and Data Storage

Skrollan Stockinger and Oliver Trapp

Scientists in China have designed a velcro-like material held together by non-covalent interactions that can be unfastened by electrical means and refastened again under pressure.

The velcro is ‘stuck’ together by compressing a flexible, conductive poly(ionic liquid) membrane (PIL) functionalised with ferrocene (Fc) with a PIL functionalised with β-cyclodextrin (β-CD). The strong binding of the Fc groups within the β-CD cavities causes the layers to adhere together tightly. Oxidation of the Fc moieties to ferrocenium ions (Fc⁺) by chemical or electrochemical means causes the layers to come unstuck, as the charged Fc⁺ is not bound inside the hydrophobic β-CD cavity. A reducing potential and further pressing reassembles the material.

A hook-and-loop strategy fastens the layers together but these links can be unfastened by an electric current

Read the full article in Chemistry World»

Read the original journal article in Chemical Science – it’s free to download until 19th June:
Flexible and Voltage-Switchable Polymer Velcro Constructed by Host−Guest Recognition Between Poly(ionic liquid) Strips
Jiangna Guo, Chao Yuan, Mingyu Guo, Lei Wang and Feng Yan  
Chem. Sci., 2014, Accepted Manuscript
DOI: 10.1039/C4SC00864B, Edge Article

Aristotle’s saying “the whole is more than the sum of its parts” is often well-exemplified in supramolecular chemistry – the result of non-covalent interactions present in a complex assembly of simple building blocks often generate novel properties that would not otherwise be present in a simple mixture of the components. The design of systems that exhibit these emergent phenomena is therefore an aim of many supramolecular chemists, including researchers from India who have achieved the control of supramolecular helicity in a bistable artificial self-assembled system through the addition of either a chiral or achiral component. This example of allosteric regulation in a synthetic system is an interesting analogue of that which occurs in biological systems, and offers an attractive approach to inducing not only conformational change in a pre-formed assembly, but also new chemical properties that could not otherwise be observed.

In biological systems, allosteric regulation, the binding of a secondary molecule to an enzyme, is employed to modulate the conformation of the active site and thus the effectiveness of an enzyme. This feature allows for communication between remote sites in a cell by providing a control loop in enzymes. It is therefore of interest to scientists to apply this allosteric regulation synthetically as a way of introducing a dynamic component to a molecular system.

Mohit Kumar and Subi George at the Jawaharlal Nehru Centre for Advanced Scientific Research[EB1] (JNCASR) in India have begun to experiment with the use of allostery in synthetic system[EB2] in order to induce [EB3] helicity in a polymeric supramolecular assembly comprised of a perylene bisimide functionalised at either end by a Zinc(II) motif that is known to bind phosphate ligands. In the “off” state this assembly exists as linear stacks of the molecule, such that overall the assembly is achiral. Upon the binding of 0.5 equivalents of chiral adenine trisphospate (ATP), a supramolecular reorganization is observed to form the helically dormant H1 state, which, upon the addition of further equivalents of ATP, results in a second conformational change to the helical H2, whereby the linear stacks are now twisted in nature and exhibit chirality. This example of chiral induction, in which a single molecule can turn “on” its chirality, exemplifies homotropic allosteric regulation. Furthermore, upon the addition of a second achiral pyrophosphate ligand (PPi) to H1, a different helical H2 state is induced in the assembly. The introduction of two chemically different molecules that interact with the assembly in different ways is an example of heterotropic allosteric regulation.

This use of supramolecular chemistry to post-synthetically elicit a change in a molecular assembly is an exciting way of mimicking the allostery observed in biology. Even more remarkable, is the ability of one system to respond in two different ways.

Read this HOT ChemSci article in full for free*!

Homotropic and heterotropic allosteric regulation of supramolecular chirality
Mohit Kumar and Subi B. George
DOI: 10.1039/C4SC00813H

About the Writer

Anthea Blackburn is a guest web writer for Chemical Science. Anthea is a graduate student hailing from New Zealand, studying at Northwestern University in the US under the tutelage of Prof. Fraser Stoddart (a Scot), where she is exploiting supramolecular chemistry to develop multidimensional systems and study the emergent properties that arise in these superstructures. When time and money allow, she is ambitiously attempting to visit all 50 US states before graduation.

*Access is free untill 06.06.14 through a registered RSC account – click here to register

All of the referee-recommended articles below are free to access until 2nd June 2014

Functionalised staple linkages for modulating the cellular activity of stapled peptides
Yu Heng Lau, Peterson de Andrade, Soo-Tng Quah, Maxim Rossmann, Luca Laraia, Niklas Sköld, Tze Jing Sum, Pamela J. E. Rowling, Thomas L. Joseph, Chandra Verma, Marko Hyvönen, Laura S. Itzhaki, Ashok R. Venkitaraman, Christopher J. Brown, David P. Lane and David R. Spring  
Chem. Sci., 2014, 5, 1804-1809
DOI: 10.1039/C4SC00045E, Edge Article

Single molecule analysis of light-regulated RNA:spiropyran interactions
Xing Zhang, Junji Zhang, Yi-Lun Ying, He Tian and Yi-Tao Long  
Chem. Sci., 2014, Advance Article
DOI: 10.1039/C4SC00134F, Edge Article

Imine-Based Chiroptical Sensing for Analysis of Chiral Amines: From Method Design to Synthetic Application
Leo A Joyce, Edward Sherer and Christopher J Welch  
Chem. Sci., 2014, Accepted Manuscript
DOI: 10.1039/C4SC01006J, Edge Article

Decoding the infrared signatures of pyramidal carbons in graphenic molecular nanostructures of interstellar origin
Héctor Álvaro Galué  
Chem. Sci., 2014, Advance Article
DOI: 10.1039/C4SC00890A, Edge Article

Chinese chemists have created an epoxy that can be rapidly hardened and reshaped by shining a light on it. Unlike traditional epoxies which are cured using heat, this approach uses carbon nanotubes to translate light energy into localised heat to set the epoxy. Shining additional light on the set polymer initiates self-healing and reshaping.

Read the full article in Chemistry World»

Read the original journal article in Chemical Science – it’s free to access until 17th June:
Carbon nanotube-Vitrimer composite for facile and efficient photo-welding of epoxy
Yang Yang, Zhiqiang Pei, Xiqi Zhang, lei tao, yen wei and Yan Ji  
Chem. Sci., 2014, Accepted Manuscript, DOI: 10.1039/C4SC00543K, Edge Article

At the mention of DNA most people think of the storage of genetic information, but due to its biocompatibility and the ease with which it can be manipulated, it is becoming increasingly common for DNA to be used as a building material in nanotechnology.

DNA cages have attracted interest in the world of drug delivery as they can encapsulate small molecule drugs and are easily taken up by cells. The precision with which the size and shape of the cages can be controlled is another attractive aspect. Past studies have established that DNA cages can target cells, deliver encapsulated cargo and have a cytotoxic effect in cancer cells. However, specific control of the cellular delivery profile of DNA cages has not yet been achieved.

Sleinman and co-workers, from McGill University based in Montréal, Canada, have created dynamic DNA cubes which ‘unzip’ in a specific cellular environment. The cages are assembled from six DNA strands which make up the six sides of the cube and only disassemble in the presence of a trigger found in prostate cancer cells. The authors tested the uptake and disassembly, or ‘unzipping’, of their DNA cubes in vitro using three different mammalian cell lines.

Hydrophobic and hydrophilic dendritic chains were added to the cube after initial testing. It was determined that these chains coat the exterior of the cube and have a significant effect on the uptake of the structure. While the addition of hydrophobic chains to the cube increase uptake, addition of hydrophilic chains increase the stability of the cube in cellular environments.

One of the exciting aspects about this work is the scope for adaptation; the cubes could potentially be designed to respond to any nucleic acid sequence found specifically in diseased cells. Future work in the group will also look at encapsulating and delivering cargo, such as oligonucleotide drugs, using this new delivery system.

To download the full article for free* click the link below:

Sequence-responsive unzipping DNA cubes with tunable cellular uptake profiles

Katherine E. Bujold, Johans Fakhoury, Thomas G. W. Edwardson, Karina M. M. Carneiro, Joel Neves Briard, Antoine G. Godin, Lilian Amrein, Graham D. Hamblin, Lawrence C. Panasci, Paul W. Wiseman and Hanadi F. Sleiman
DOI: 10.1039/C4SC00646A

*Access is free until 02/06/2014 through a registered RSC account – click here to register

For over 20 years the infrared spectra of many astronomical objects have been interpreted as flat two-dimensional polycyclic aromatic hydrocarbons (PAHs) that are also thought to be the source of organic matter on our own planet. More recently the detection of molecules such as fullerenes – molecules composed entirely of carbon, including the spherical C₆₀ – has revealed a more complicated picture of carbon in space. The links between these different molecules have been rather unclear but new research from Héctor Alvaro Galué at VU University of Amsterdam, in the Netherlands, has taken a fresh approach to this long-standing puzzle.

Energetic particles in interstellar space induce strain and re-hybridisation within flat carbon structures. Background image: © NASA, ESA, M Robberto (Space Telescope Science Institute/ESA) and the Hubble Space Telescope Orion Treasury Project Team

Read the full article in Chemistry World»

Read the original journal article in Chemical Science – it’s free to download until 6th June:
Decoding the infrared signatures of pyramidal carbons in graphenic molecular nanostructures of interstellar origin
Hector Alvaro Galue  
Chem. Sci., 2014, Accepted Manuscript, DOI: 10.1039/C4SC00890A, Edge Article