Anthea Blackburn, Web Science Writer – Chemical Communications Blog

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Fluorescently finding a specific disease marker needle in a biological haystack

01 Apr 2016

The early detection and monitoring of disease is a somewhat recent advancement in healthcare that offers the significant advantage of being able to treat an illness in its initial stages, rather than once it has already manifested itself in the patient. Such a feat requires, however, the ability to see very specific and characteristic disease markers in situ, not unlike the search for a needle in a haystack.

Luckily, with the advent of fluorescence (and other) imaging techniques, methods have been developed whereby, in combination with contrast agents that are able to interact with specific molecules in the body, cell chemistry and function can be observed with high sensitivity, and, more importantly, abnormalities in these processes noticed in real time.

The art and ultimate success of this fluorescence imaging comes from the design of the contrast agent employed – the probe should be able to selectively recognise and target the relevant disease marker reversibly and under biological conditions. A number of approaches currently exist that meet these requirements, one of which is the boronic acid recognition motif that is able to act as a molecular receptor for the 1,2- and 1,3-diols commonly expressed in carbohydrates and complex glycoproteins. Tony James and his team from the University of Bath, whose own research focuses on such use of boronic acid receptors in the detection of carbohydrates, have summarised the recent and exciting advances in this particular field of selective biological imaging.

The well-known and strong affinity of boronic acids for carbohydrates offers a convenient means of detecting commonly expressed markers in diseases including some cancers, as well as Alzheimer’s, autoimmune, and heart diseases. As such, the attachment of this relatively simple chemical moiety to fluorescent small molecular, polymeric or benzoxaborale-based probes offers a diagnostic tool that is able to detect, monitor, and aid in the personalised treatment of such significant and life-changing diseases.

This Feature Article convincingly highlights the impact that boronic acid-based fluorescence imaging will ultimately have on a range of important clinical and theranostic practices and their successes.

Read this hot ChemComm article in full:

Boronic acids for fluorescence imaging of carbohydrates

X. Sun, W. Zhai, J. S. Fossey and T. D. James

Chem. Commun., 2016, 52, 3456–3469

DOI: 10.1039/C5CC08633G

About the Writer:

Anthea Blackburn is a guest Web Writer for Chemical Communications. Anthea hails from New Zealand, carried out her graduate studies in mechanostereochemistry under the guidance of Prof. Fraser Stoddart in the US, and has recently relocated to live in London. She is a recent addition to the Econic Technologies team, where she is working on the development of new catalysts for the environmentally beneficial preparation of polycarbonates from CO₂.

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Coordinating nature and photochemistry to create hydrogen

28 Aug 2015

When we look to our future energy resources, the need to realise new means of renewable energy is immediately obvious. Much research is being carried out around the world into the development of systems that can generate energy – from H₂ to biofuels to solar fuels – all of which place great importance on high efficiency and sustainability.

Looking at the world around us for inspiration, the obvious candidate is the photosynthetic process, where visible light is employed to convert CO₂ and H₂O into chemical energy. This process involves the transport of electrons through a complex series of intricately aligned porphyrin-related and protein biomolecules. We can explore the development of a system that mimics the behaviour of natural systems, with respect to the relay of electrons along a series of molecules, or, alternatively, we can take the components in these systems and exploit their properties in combination with other electronically-active but non-natural molecules.

Upon photoexcitation of [Ru(bpy)3]2+, electron transfer through a ferredoxin scaffold to a cobaloxime catalyst facilitates the production of hydrogen. It is the latter approach which Lisa Utschig and her team from Argonne National Laboratory, near Chicago in the US, employed to generate a molecular system capable of photocatalysing the production of hydrogen. In their biohybrid system, the photosensitiser ruthenium(II) tris(bipyridine), ferredoxin (a water-soluble electron transfer protein), and cobaloxime (a cobalt(II)-based catalyst), were combined to generate a miniature reaction center that mimics those which occur in biological systems. However, the Utschig group’s system has a smaller molecular weight, which allows for characterisation of the electronic processes that occur in the system.

Lisa and her colleagues found that the presence of ferredoxin in the catalytic system acted as a scaffold to stabilise the charge-separated state necessary for electron transfer and the desired production of H_2.They also observed that the catalytic behaviour of the Ru(II)–Co(II) pair was only possible in the presence of ferredoxin, which acted to extend the lifetime of the otherwise transient Co(I), allowing the desired reaction to occur.

In order to fully understand and enhance the properties of the molecular systems developed to fulfil the increasing need for energy alternatives, we need to be able to probe the structure and processes that occur in the molecule; the use of smaller analogs to those that exist in nature offers a means by which to achieve this goal. The photoactivated catalyst discussed in this work is an important step forward in the development of an optimized system for use in solar fuel production.

Read this hot ChemComm article in full:
Aqueous light driven hydrogen production by a Ru–ferredoxin–Co biohybrid
S. R. Soltau, J. Niklas, P. D. Dahlberg, O. G. Poluektov, D. M. Tiede, K. L. Lulfort and L. M. Utschig
Chem. Commun., 2015, 51, 10628–10631
DOI: 10.1039/C5CC03006D

Biography

Anthea Blackburn is a guest web writer for Chemical Science. She hails originally from New Zealand, and is a recent graduate student of Northwestern University in the US, where she studied under the tutelage of Prof. Fraser Stoddart (a Scot. There, she exploited 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.

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Capturing C60 in a Crystalline Copolymer Chain

12 Nov 2014

Since its structural realisation in 1985, C₆₀ has garnered much attention in the chemical world for not only its spherical shape, but also its stability, electronic properties and the ability to do chemistry on its surface.

One such avenue that has proven popular in recent times is the incorporation of C₆₀ into one-, two- and three-dimensional arrays, either covalently or non-covalently, in attempts to control the distribution of the molecules in the solid- or solution-phase. One problem that arises in the synthesis of these extended frameworks, however, is that there often a large amount of disorder and void space in the structure, so it can be difficult to ascertain with much degree of certainty how these C₆₀ molecules are oriented. This uncertainty can consequentially result in the properties and behaviours of the new materials remaining unidentified.

Now, researchers from the University of California, Davis – Marilyn Olmstead and Alan Balch – have shown that coordination chemistry can be used to not only generate polymers that covalently link molecules of functionalised C₆₀ in such a manner that can they can be studied crystallographically, but also that these polymers can be used to capture free C₆₀ and C₇₀.

Initially, polymers of C₆₀ were synthesised through the mono-functionalisation of C₆₀ with a piperazyl group, which, on account of its two tertiary amines, can coordinate in a linear fashion with transition metal ions, in this case rhodium(II) acetate. Upon the combination of these two components, a linear one-dimensional polymer was formed, in which it could be seen crystallographically that the C₆₀ moieties were positioned on alternating sides of the polymer chain. These polymer chains were further found to extend into two dimensions through the interdigitation of neighbouring chains in a zipper-like fashion. C60-Rh(II) polymers can capture free C60

Perhaps more interestingly is that when these polymer chains were synthesised in the presence of either C₆₀ or C₇₀, free molecules of C₆₀ or C₇₀ were seen to occupy the void spaces between the C₆₀ molecules of the polymer. Additionally, if a mixture of C₆₀ and C₇₀ was present in the polymer synthesis, it was observed that only C₆₀ was captured by the polymer, most likely as a result of a better geometric match between the polymer and the spherical C₆₀ in preference to the more elongated shape of C₇₀.

This work elegantly demonstrates the generation of not only a self-assembling C₆₀-containing polymer that can be characterised structurally in the solid state, but of one that can entrap free molecules of C₆₀ selectively over molecules of C₇₀. Based on the properties of free C₆₀ and transition metal complexes, the electronic and chromophoric properties of such a crystalline system could also be expected to offer some noteworthy results.

Read this HOT ChemComm article in full!

Zipping up fullerenes into polymers using rhodium(II) acetate dimer and N(CH₂CH₂)₂NC₆₀ as building blocks
Amineh Aghabali, Marilyn M. Olmstead and Alan L. Balch
Chem. Commun., 2014, Advance Article.
DOI: 10.1039/C4CC06995A

Biography

Anthea Blackburn is a guest web writer for Chemical Communications. 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.

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Inducing β-Peptide Structures from the Inside Out

22 Aug 2014

The synthesis of tailor-made peptide chains represents a powerful tool for tuning the structure and properties of peptides, allowing for the development of analogues for medical, technological and synthetic purposes.

For example, the β-peptide is a synthetic peptide, which, in contrast to its naturally-occurring α-peptide analogue, is bonded through the β-carbon rather than the α-carbon. As a result of this seemingly small structural change, alterations in the peptide’s secondary structure and thermodynamic stability are observed.

Adding fluoride groups to peptide chains represents another way to alter and stabilise the folding structure through the presence of stronger hydrogen bonds and the introduction of fluorophilicity. This approach is generally employed for the addition of fluoride groups at ‘remote positions,’ spaced two or more methylene units from the peptide backbone. However, this method has less of an effect on the conformation of the peptide itself, and instead primarily influences the tertiary and quaternary self-aggregation of peptide chains, as a result of the fluorophilic effect of the functionalised peptide chains.

Much less commonly studied is the effect of incorporating fluorine groups in ‘direct proximity’ to the peptide chain, that is, directly attached to the β-carbon, where it is proposed that the intramolecular hydrogen bonding will be directly affected, and consequently, so too will the secondary structure of the peptide chain.

Yasuhiro Ishida and co-workers from the RIKEN Center for Emergent Matter Science have shown that this ‘direct’ fluorination of β-peptides can, in fact, affect the higher order structures of these peptide chains. Specifically, a hexameric β-peptide was designed, which consisted of cyclohexane-based β-amino acids in the 1-,3-,4- and 6-positions and L-alanine derivatives in the 2- and 5-positions, where the L-alanine methyl groups were either native or perfluorinated.

Irrespective of the degree of perfluorination in the β-peptide, it was found that the chains were arranged in the same left-handed 14-helix structure, with the NH-amide of the second and fifth residues participating in stabilising intramolecular H-bonding interactions. Moreover, it was found that although the presence of fluoride groups did not noticeably alter the overall secondary structure of the β-peptide chains, the stability of these structures was dramatically enhanced, showing the significant effect that fluoride groups can have on the hydrogen-bond donating ability of NH-amides.

This new approach of modifying peptide chains offers an interesting method for influencing the secondary, and higher order, structures of the compounds, as well as their kinetic and thermodynamic properties. The effect of these structural modifications offers the possibility of tuning the chemical and biological properties of these peptide chains for use in new types of antibiotics and synthetic systems.

Read this HOT ChemComm article in full!

Stabilization of β-peptide helices by direct attachment of trifluoromethyl groups to peptide backbones
Joonil Cho, Kyohei Sawaki, Shinya Hanashima, Yoshiki Yamaguchi, Motoo Shiro, Kazuhiko Saigo and Yasuhiro Ishida
Chem. Commun., 2014, 50, 9855–9858.

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Chemical Communications Blog

Author Archive

Fluorescently finding a specific disease marker needle in a biological haystack

Coordinating nature and photochemistry to create hydrogen

Capturing C60 in a Crystalline Copolymer Chain

Inducing β-Peptide Structures from the Inside Out

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