Chemical Science Blog

Glutathione is an antioxidant enzyme and the most abundant biothiol in human cells. It plays a crucial role in protecting cells against oxidative damage from various toxins that the body produces. However, abnormal levels of glutathione can lead to oxidative stress, which in turn can lead to premature aging and conditions such as Alzheimer’s or Parkinson’s disease. 

There is, therefore, a need for the selective detection of glutathione, so that its role in biological systems can be better understood. However, it is challenging to design a selective fluorescent probe for a specific biothiol due to the structural and reactivity similarities with other biothiols. This is the challenge that David Churchill and team from the Department of Chemistry at the Korea Advanced Institute of Science and Technology set out to meet.

Fluorescence response seen in Hep3B cells treated with the probe molecule

The team has previously explored the use of fluorescent probes containing selenium as the reactive centre and they have taken a similar approach with this challenge, using a phenylselenide group. The images below show the phenylselenide probe reacting with cellular glutathione, which fluoresces green in the images. The intensity of the fluorescence was around a hundred times greater than for cysteine or homocysteine, which are closely related to glutathione.

Until now, there has been no probe that can selectively detect glutathione in real time, so it will be interesting to see what future results come from this advance.

To read the details, download the Chemical Science article and read it in full – it’s open access:
Exceptional time response, stability and selectivity in doubly-activated phenyl selenium-based glutathione-selective platform
Youngsam Kim, Sandip V. Mulay, Minsuk Choi, Seungyoon B Yu, Sangyong Jon and David G Churchill
Chem. Sci., 2015, 6, Advance Article
DOI: 10.1039/C5SC02090E 

The ability to select which common building blocks of a mixture react, producing different products on demand, holds great promise for chemical synthesis. Think about systems where you have to add a great deal of additional components to prevent one reaction route and initiate another; wouldn’t it be simpler if you could add just one component that switches the chemical transformation?

This is what David Leigh and his team from the School of Chemistry at The University of Manchester have done. They have created a rotaxane with two different activation sites which promote different reactions and thus different products in the same mixture. The macrocycle position within the rotaxane is controlled and leads to one of the active sites being blocked while the other is active.

Switchable Rotaxane Organocatalyst – the position of the macrocycle either blocks or reveals one of the catalytic sites, leading to different products being formed from the same mixture of building blocks

The developed system promotes Michael addition reactions through iminium ion or hydrogen-bond-activated catalysis. The switch between these modes is provided by acid-base control of the position of the rotaxane macrocycle and leads to different products being formed.

This elegant catalytical switch approach holds great promise for chemical transformation and organic synthesis generally. To read the details of the transformations and, more importantly, how to make the rotaxane, read the Chemical Science paper today!

Read this Open Access Chem Sci article in full:
Selecting Reactions and Reactants using a Switchable Rotaxane Organocatalyst with Two Different Active Sites
David A Leigh, Jack Beswick, Victor Blanco, Guillaume De Bo, Urszula Lewandowska, Bartosz Lewandowski and Kenji Mishiro
Chem. Sci., 2014, Accepted Manuscript
DOI: 10.1039/C4SC03279A, Edge Article

Anthony White from the Department of Pathology, University of Melbourne and team have investigated the use of X-ray Fluorescence Microscopy to investigate subcellular biometal homeostasis in a mouse model of the childhood neurodegenerative disorder – Batten disease. This is a particularly nasty disease that causes progressive blindness and motor impairment leading to premature death. The team have previously highlighted the redistribution of brain zinc in diseased samples using subcellular fractionation techniques. However, the lack of a rapid, specific and sensitive technique to provide quantitative subcellular information in situ on biometal distributions is severely limiting the understanding of the effect that the changes in biometals distributions can have in neurodegenerative diseases.

Intracellular zinc and calcium distributions mapped by x-ray fluorescence microscopy.

In their Chemical Science paper the team have utilised the advances in data collection speed of X-ray fluorescence detectors to map the zinc and calcium distributions in a statistically relevant number of cells. Despite a lack of global changes in biometal levels this approach revealed the perturbed trafficking of zinc and the significantly altered subcellular calcium distributions. The restorative properties of a therapeutic zinc-complex were also shown using this technique.

Techniques and methodology reported in the Chemical Science paper can be applied to other neurodegenerative diseases and importantly can provide insights to the mechanism of action of novel therapeutics at the single cell level.

Read the Chem. Sci. paper in full today for free* and see if this technique could be applied to a disease you are studying!

X-ray fluorescence imaging reveals subcellular biometal disturbances in a childhood neurodegenerative disorder
A. Grubman, S.A. James, J. James, C. Duncan, I. Volitakis, J.L. Hickey, P.J. Crouch, P.S. Donnelly, K.M. Kanninen, J.R. Liddell, S.L. Cotman, M.D. de Jonge and A.R. White*
DOI: 10.1039/C4SC00316K

*Access is free until 20.06.14 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

When most people read a book they don’t remember every word. They compress the story down to the main points and remember those. The reverse is also true – given a few facts most people can embellish a story to a suitably lengthy tale of adventure and mystery.

These data compression/decompression processes are called logic operations and are a central theme in information theory. They are also replicated in biological systems where scaffolding proteins within the regulatory cellular networks carry out the operations. However, there has been no synthetic DNA-based system that can carry out this data compression/decompression process, until now.

Logic circuit showing how 4 inputs (I) can be compressed to one output (S)

Itamar Willner from the Hebrew University of Jerusalem and colleagues have developed such a system based on Mg²⁺-dependent DNAzyme subunits. Unlike previous approaches where the demonstration is done using two inputs and one output the team have investigated enhanced multiplexing in the compression process with four inputs producing one output.

Additionally they have also demonstrated the expansion of a single input to produce two outputs. Having such systems based on nucleic acids also raises the possibility of resetting the computational module. This means you could reconfigure and change its operation in situ by the addition of suitable complementary nucleic acid strands.

This article details important advances in DNA based logic networking and raises the potential to compress information held within genes into a single output. It also raises challenges for the future that must be overcome before these synthetic biomolecular computational systems can control natural intracellular processes.

For more, read the Chemical Science Edge article in full:

DNAzyme-Based 2:1 and 4:1 Multiplexers and 1:2 Demultiplexer
Ron Orbach, Francoise Remacle, R. D. Levine and Itamar Willner*
Chem. Sci., 2013, Accepted Article
DOI: 10.1039/C3SC52752B

Iain Larmour is a guest web writer for Chemical Science. He has researched a wide variety of topics during his years in the lab including nanostructured surfaces for water repellency and developing nanoparticle systems for bioanalysis by surface enhanced optical spectroscopies. He currently works in science management with a focus on responses to climate change.  In his spare time he enjoys reading, photography, art and inventing.

Water is essential for life as we know it and we are all familiar with the sight of water in the atmosphere and on the surface of the earth.  But where is the water deep down, beyond the crust?

The mantle (the part of the earth between the crust and the core) is primarily composed of iron-bearing magnesium silicates which undergo a number of phase transitions with depth. At the transition between the upper and lower mantle, olivine transforms into wadsleyite and this mineral has received interest due to its potential for hosting hydrogen, which is termed water in the realm of the inner-Earth. If fully hydrated the amount of hydrogen potentially stored in this mineral is four times the amount present in the oceans and the atmosphere.

When a hydrogen atom is incorporated into the mineral it is balanced by the removal of a magnesium cation, this produces several possible locations for the incorporation of the hydrogen in the vacancy, as well as different possible ordering of the vacancy in the structure. To solve this complex problem Stephen Wimperis and Sharon Ashbrook have teamed up and used the developments of high-field NMR and sophisticated experimental methods to study the ‘difficult’ NMR nuclei of ²⁵Mg and ¹⁷O within hydrated wadsleyite. In addition to the experimental approach, they have also carried out extensive DFT calculations.

Anhydrous (left) and one of the hypothetical ordered structures for fully-hydrated wadsleyite (right).

Most of the hydrogen was found to be located on the O1 site with the substitution charge balanced by Mg3 cation vacancies. A smaller amount of hydrogen was also found to be present in slightly higher energy defect sites with different proton arrangements or centred at different cation vacancies.

This study demonstrates the benefits of using a combined computational and experimental approach to reveal the location of hydrogen within wadsleyite. The use of this multinuclear NMR approach can be used to investigate a wide range of other silicate phases which should lead to a better understanding of the locations and distribution of hydrogen in the Earth’s mantle.

For more, read this ‘HOT’ Chemical Science article in full:

Water in the Earth’s Mantle: A Solid-State NMR Study of Hydrous Wadsleyite

John M. Griffin, Andrew J. Berry, Daniel J. Frost, Stephen Wimperis and Sharon E. Ashbrook
Chem. Sci., 2013, Advance Article
DOI: 10.1039/C3SC21892A

Potential energy surfaces of reactions are usually measured in the gas phase. However the vast majority of chemical reactions in the laboratory are conducted in solvent. What effect do these solvent molecules have on the potential energy surfaces that have been measured in the gas phase? Andrew Orr-Ewing and colleagues have been finding out.

They have used ultrafast time-resolved broadband infra-red absorption spectroscopy to study the reaction of chlorine atoms with hydrocarbons in chlorinated solvent.

Two timescales were found, which corresponded to prompt reaction of the chlorine atom with the hydrocarbon, which was most likely located in the immediate solvent shell, and a slower reaction following diffusion into the bulk solvent. The presence of solvent molecules also partially suppresses the presence of vibrationally excited products that occur when the exothermic reaction is sufficient to form vibrationally hot products.

This work extends previous experiments conducted with cyanide radicals in solvent and general conclusions on the effect of solvent molecules on the potential energy surface are now emerging.

To find out more, download the Chemical Science article today (free to access until the 7th of December 2012).