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Supramolecular cages for chemical weapons

The research of RSC Advances Chief Editor Mike Ward focussing on the development of supramolecular cages that trap chemical weapon stimulants, has been highlighted in Chemistry World.

Mike and his team at Sheffield University have developed new supramolecular cages that exploit the hydrophic effect and bind alkyl phosphonates inside. These phosphonates are very similar to organophosphorous chemical weapons. Cobalt or cadmium dications form the cage vertices and bis(pyrazolyl-pyridine) ligands run along each edge, forming a hydrophobic centre lined with CH groups. So, in water, the phosphonate hydrophobic alkyl tails are attracted to the inside of the cage. Whats more, the cage is luminescent and this luminescence reduces when alkyl phosphonate enters, meaning that the cages can also be used to signal the presence of chemical weapons.

The supramolecular structure

To find out more, read the full Chemistry World article based on this paper:

Binding of chemical warfare agent simulants as guests in a coordination cage: contributions to binding and a fluorescence-based response
Christopher G. P. Taylor, Jerico R. Piper and Michael D. Ward
Chem. Commun., 2016
DOI: 10.1039/C6CC02021F

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Modelling lung cancer: tumor cells on collagen scaffolds

Non-small-cell lung cancer (NSCLC) is among the leading causes of cancer-related deaths globally. Our understanding of the way tumors grow, spread and respond to therapy is driven largely by studies conducted on tumor cells growing as monolayers in plastic cell culture flasks in laboratories across the world. The ability to develop novel and more effective cancer-fighting drugs is dependent, in part, on developing cell culture systems that allow scientists to better observe how tumor cells grow in a three dimensional, physiologically relevant environment.

SEM images of the collagen meshwork and A549 cell aggregates (noted by the arrow head) formed during the
3D cultivation in vitro.

The tumor microenvironment (TM) is the area that immediately surrounds a tumor and includes non-cancer cells together with secreted proteins called the extracellular matrix (ECM), which supports tumor growth. Monolayer cell cultures, although utilized widely, cannot accurately mimic the TM. For instance, cell-cell and cell-ECM interactions that influence tumor growth cannot be observed in great detail with conventional monolayer cultures. Inspired by the up-and-coming field of tumor engineering, which aims to construct culture models that recapitulate aspects of the TM, a team of researchers led by Dr. Dan-Dan Wang at the Chinese Academy of Sciences developed a 3D culture system wherein A549 cells (immortal lung cancer cells of human origin) grow on a collagen hydrogel scaffold.

To demonstrate the utility of the 3D culture system, the study measured cell viability and showed that cells in the collagen hydrogel scaffold were alive for extended periods (>12 days) in vitro. The study also assessed the appearance of artificial A549 tumors growing on the hydrogel to demonstrate that 3D cultures more closely recapitulate the morphology of tumors growing within human tissues.

The proliferation of A549 cells is driven by the activation of a cell surface protein called Epidermal Growth Factor Receptor (EGFR), which in turn switches on genes that sustain cell growth and cell division. The team observed that Gefitinib, a drug known to disrupt growth-promoting signals arising at EGFR, was able to significantly constrain A549 cell proliferation in 3D cultures. Interestingly, the team reports that a higher concentration of Gefitinib was required to curb cell growth in 3D cultures compared to monolayers due to the complex architecture of the artificial tumors in 3D cultures.

Collectively, this study demonstrates an improved culture model of human lung cancer. Since collagen is an important component of the ECM, the study sets the stage for future efforts to better recapitulate the TM in vitro. The collagen hydrogel scaffold system could serve as in important tool in the discovery of targeted therapies for lung cancer.

Read the full article here:

Dan-Dan Wang,   Wei Liu,   Jing-Jie Chang,   Xu Cheng,   Xiu-Zhen Zhang,   Hong Xu,   Di Feng,   Li-Jun Yu and   Xiu-Li Wang
RSC Adv., 2016, 6, 24083-24090
DOI: 10.1039/C6RA00229C
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Hitching a ride: recombinant DNA delivery into mammalian cells via nanoparticle-based vehicles

Transfection is the process of introducing genetic material, typically DNA, into mammalian cells. This technique has proven indispensable in understanding signaling networks that govern cellular function. To better understand the function of a given protein, molecular biologists routinely transfect cells with DNA (i.e. recombinant DNA). This enters cells in culture and subsequently encodes the specific protein under study. The recombinant DNA is combined with a transfection reagent, typically Lipofectamine, to facilitate its entry into cells.

A study conducted by Neuhaus and colleagues, at the Inorganic Chemistry and Center for Nanointegration (CeNIDE) in Germany, utilizes calcium phosphate nanoparticles (CPNPs) as vehicles to deliver recombinant DNA into cells. CPNPs have previously been shown to spontaneously bind DNA, thus supporting the notion that they could be used as transfection agents. The approach requires that CPNPs first be mixed with a buffer containing recombinant DNA before being added to cultures containing actively growing mammalian cells.

Despite its simplistic approach, the transfection process in general has a few technical limitations. First, not all cells in culture uptake the recombinant DNA. This leads to reduced transfection efficiency. Second, the transfection efficiency is strongly influenced by the cell type (i.e. distinct cell forms within a species). And third, cells interpret recombinant DNA as ‘foreign’ genetic material and trigger alarms which culminate in cell death.

Images demonstrating the uptake of green flourescent nanoparticles by different cell types

To better assess the utility of CPNPs as transfection agents, the study’s authors first transfected ten different cell types with DNA. The DNA in their study encoded a protein that fluoresces green when excited at a specific wavelength. Using Lipofectamine as a comparator reagent, the study assessed the transfection efficiency of CPNPs by measuring the proportion of cells that glowed green under a fluorescent microscope. The study also highlighted the differences in transfection efficiencies between different cell types. The authors propose that CPNPs represent promising candidates as transfection agents and therefore warrant further study.

Clinical trials utilizing nucleotide-based targeted therapies for multiple human diseases are on the rise. CPNPs may represent the new breed of nucleotide-based drug delivery agents in the years to come.

Read the full article here:

Nanoparticles as transfection reagents: a comprehensive study with ten different cell lines
Bernhard Neuhaus,  Benjamin Tosun, Olga Rotan, Annika Frede, Astrid M. Westendorf and Matthias Epple
RSC Adv., 2016,6, 18102-18112
DOI: 10.1039/C5RA25333K

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Magnetic leathers

Leather is a natural, durable and flexible material that has been prepared and used by humans for millennia. Now, scientists in India have developed magnetic leathers that can make this material evermore versatile.

Made from animal hide, leather is largely made of a chromium-collagen matrix and is paramagnetic. Despite this, it does not interact effectively with magnetic fields. Introducing ferromagnetic properties to leather could enable this material to be used in smart or intelligent garments, electromagnetic interference shielding, adhesive-free wall covering and even in energy harvesting from human motion. As such, a team lead by Dr Krishbaraj Kaliappa at the Central Leather Institute in Chennai, added iron oxide nanoparticles to leather that show significant magnetic behaviour.

The team prepared leather samples using conventional finishing techniques. During this process, they applied a coating of  iron oxide nanoparticles produced by co-precipitation, or a commercially available magnetic pigment. The presence of Fe3O2 in both samples was confirmed by X-ray diffraction analysis. When compared to the paramagnetic control leather, magnetic hysteresis revealed considerable ferromagnetic behavior in the two samples. In addition, the leathers show significant response to permanent magnets. Further tests revealed that particle incorporation leaves other physical properties of the leather, largely unchanged.

Investigations in to the applications of these magnetic leathers have already shown them to be promising adhesive-free wall tiles. The team also demonstrate that their properties may also enable application in electromagnetic energy generation from human motion.

Digital images of the control leather , that with iron oxide nanoparticles and that with the commercially available magnetic pigment added during finishing.

Read the full article:

Magnetic leathers
P. Thanikaivelan, R. Murali and K. Krishnaraj
RSC Adv., 2016,6, 6496-6503 DOI: 10.1039/C5RA21909D

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Canine tea time

Researchers in China have manufactured dog food containing tea polyphenols. They have shown that when dogs are fed tea polyphenol containg food, antioxidant and antimicrobial effects, similar to those observed in humans, are demonstrated.

Fang Zhong and colleagues also wanted to test the foods palpability to find out if the dogs would actually enjoy eating it. Following a five day trial, it emerged that dogs actually preferred eating food that contained 0.5% tea polyphenols. The dogs’ diet was then restricted to either tea polyphenol containing food or the control food. Subsequent tests revealed higher levels of antioxidant activity in the dogs on the tea polyphenol diet, along with lower levels of fecal bacteria in their stool.

To find out more, read the full Chemistry World article.

Quantitative optimization and assessments of supplemented tea polyphenols in dry dog food considering palatability, levels of serum oxidative stress biomarkers and fecal pathogenic bacteria,
Maoshen Chen, Xuemei Chen, Wenli Cheng, Yue Li, Jianguo Ma and Fang Zhong
RSC Adv., 2016,6, 16802-16807
DOI: 10.1039/C5RA22790A

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Stencilling self-propulsion engines

Researchers in the US have designed and made millimetre-sized motors in the shape of fish that could be produced on an enormous scale and used to purify water.

Catalytic fish in action

Nano- and micro-sized machines that convert chemical reactions into motion have been on the drawing board for many years. However, they are complicated and expensive to make. Now, researchers led by Joseph Wang at the University of California San Diego have developed a simple way to print 2D millimetre-sized motors. The motors are shaped like fish, swim autonomously while performing specific functions and avoid the costs and complications of more traditional fabrication processes, such as electrodeposition, sputtering and lithography.

To read the full article please visit Chemistry World.

Self-propelled screen-printable catalytic swimmers
Rajan Kumar, Melek Kiristi, Fernando Soto, Jinxing Li, Virendra V. Singh and Joseph Wang �
RSC Adv., 2015,5, 78986-78993
DOI: 10.1039/C5RA16615B, Paper

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Smartphones develop a taste for red wine

Colormetric sensor array that can distinguish red wines by grape and oxidation state using principal component analysisYou can find me with great infrequency (ahem) pacing the wine, beers and spirit aisles of the supermarket trying to select the best wine for the occasion that I may be attending, be it dinner at friends or watching season four of Game of Thrones, alone, with a pizza. It may amaze you to know that, despite this penchant for the finer things in life, my wine tasting ability is a work in constant progress. Currently, my selection criterion for a bottle comprises two factors; 1) how pretty is the bottle and 2) how special is the special offer on it?

Finally, to save me from my ignorance, Tu San Park and co-workers have developed a paper microfluidic chip for red wine tasting. Their recent publication in RSC Advances details the development of a colormetric sensor array that can distinguish red wines by grape and oxidation state using principal component analysis. This isn’t just good news for me; This could be employed in the wine industry as a simple  and low cost quality control check, helping to minimise the variation inherent by employing taste panellists.

What is exciting about this assay is the room for development. The authors have been investigating the alignment of the assay with a smartphone application that would be able to image the areas of interest and measure the red, green and blue pixel intensities. This data would then be reduced for principal component analysis.

The benefits of this low cost, portable check are obvious, especially for small wineries and also, small wine drinkers, like myself.

To find out more, click below to read the full article in RSC Advances. It’s free to access for the next 4 weeks:

Paper microfluidics for red wine tasting, Tu San Park, Cayla Baynes, Seong-In Cho and Jeong-Yeol Yoon, RSC Adv., 2014, 4, 24356–24362 (DOI: 10.1039/C4RA01471E)


Sarah Brown Sarah Brown is a guest web-writer for RSC Advances. Sarah hung up her lab coat after finishing her PhD and post-doctorate in nanotechnology for diagnostics and therapeutics and now works in academic publishing. When not trying to explain science through ridiculous analogies, you can often find her crocheting, baking or climbing, but not all at once.

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Does size matter? Rational design of potent ice recrystallization inhibitors

Ice recrystallization inhibition (IRI) activity is a highly desirable property for an effective cryoprotectant. Cryopreservation is a very important process for regenerative medicine therapies, but ice recrystallization causes reduced post thaw cell viability. Although antifreeze proteins (AFPs) and antifreeze glycoproteins (AFGPs) were first investigated as cryoprotectants, their ability to bind and alter the ice crystals behaviour has encouraged researchers to look for further improvement in this field. This has led to the development of AFGP to AFGP analogues and further to the discovery of small carbohydrate-based IRIs with similar IRI activity to that of native AFGP-8.

In this review, Robert Ben and co-workers from the University of Ottawa, Canada, present recent developments of IRIs mainly focusing on novel small molecules that have emerged as potential cryoprotectants.

Designing ice recrystallization inhibitors: from antifreeze (glyco)proteins to small molecules

They begin with the molecular mechanism of the ice recrystallization phenomenon and it’s relation with IRI activities of biological antifreezes. The recent strategies for improving antifreeze compounds have been thoroughly discussed including large protein or peptide analogues, easily accessible synthetic polymers, simple mono- and disaccharide derivatives, truncated C-linked glycopeptides and carbohydrate or lysine-based surfactants/gelators. This review nicely highlights the importance of hydration index, relative orientation of hydrophilic groups and size of the linker of synthetic antifreeze compounds on their overall IRI activity.

In future these kinds of highly IRI active small molecules may replace the most widely used cytotoxic cryoprotectant DMSO and improve upon currently limited cryopreservation protocols.

Read the full review in RSC Advancesfree to access for 4 weeks:

Designing ice recrystallization inhibitors: from antifreeze (glyco)proteins to small molecules

Anna K. Balcerzak, Chantelle J. Capicciotti, Jennie G. Briard and Robert N. Ben,  RSC Adv., 2014, 4, 42682-42696

You may also be interested in these related articles:

The importance of hydrophobic moieties in ice recrystallization inhibitors

Anna K. Balcerzak, Michela Febbraro and Robert N. Ben,  RSC Adv., 2013, 3, 3232-3236

Developing highly active small molecule ice recrystallization inhibitors based upon C-linked antifreeze glycoprotein analogues

John F. Trant, Robyn A. Biggs, Chantelle J. Capicciotti and Robert N. Ben,  RSC Adv., 2013, 3, 26005-26009

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Supramolecular Chemistry Themed Collection now online

The latest RSC Advances web-collection on the topic of Supramolecular Chemistry is now available to view online!

The anion complexation properties of a fluorinated alcohol that is isosteric with a simple isophthalamide revealed that the alcohol can complex weakly basic anions with stability constants greater than those of the isophthalamide.The title of the collection is ‘Supramolecular chemistry: self-assembly and molecular recognition’ and is Guest Edited by Professor Mike Ward (University of Sheffield, UK). The articles presented here cover many aspects of the formation of, and molecular recognition with, non-covalent self-assembled systems. Systems studied span the range of supramolecular assemblies from MOFs to gels, and potential applications or functional behaviour that are on display here include host/guest chemistry, spin crossover, molecular sensors, and extraction/separation.  This collection of articles powerfully illustrates the diversity and increasing importance of supramolecular chemistry, and we hope you enjoy reading it.

Click here to view the full collection.

Some highlights from the collection include:

A ligand possessing two orthogonal metal binding sites is designed to bind three-fold and four-fold symmetric metal ions in such a way as to form a cage.An octahedral aluminium(III) complex as a three-fold node for supramolecular heterometallic self-assemblies: solution and solid state chemistry
Damien Simond, Sarah E. Clifford, Andreia F. Vieira, Céline Besnard and Alan F. Williams 
RSC Adv., 2014, 4, 16686-16693
DOI: 10.1039/C4RA00575A

Subtle backbone modifications control the interpenetration of dibenzosuberone-based coordination cages
Thorben R. Schulte, Marcel Krick, Carmen I. Asche, Sabrina Freye and Guido H. Clever 
RSC Adv., 2014, 4, 29724-29728
DOI: 10.1039/C4RA04679J

The versatility of “click” reactions: molecular recognition at interfaces
Thomas Heinrich, Christoph H.-H. Traulsen, Erik Darlatt, Sebastian Richter, Johannes Poppenberg, Nora L. Traulsen, Igor Linder, Andreas Lippitz, Paul M. Dietrich, Baha Dib, Wolfgang E. S. Unger and Christoph A. Schalley 
RSC Adv., 2014, 4, 17694-17702
DOI: 10.1039/C4RA01730G

Melting temperatures deduced from molar volumes: a consequence of the combination of enthalpy/entropy compensation with linear cohesive free-energy densities
Thibault Dutronc, Emmanuel Terazzi and Claude Piguet 
RSC Adv., 2014, 4, 15740-15748
DOI: 10.1039/C4RA00348A

Bis-triazolium containing macrocycles, pseudorotaxanes and interlocked structures for anion recognition
Nicholas G. White, Henry G. Lovett and Paul D. Beer 
RSC Adv., 2014, 4, 12133-12147
DOI: 10.1039/C4RA00615A

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Winning by an E-nose

By Sarah Brown, web writer for RSC Advances

Superhuman olfaction isn’t right up there on my list of desired super powers for a number of reasons that I won’t share here; however, an enhanced appreciation for the detection of various gases is underrated.

For example, the ability to detect toxic gases is of huge benefit, particularly at levels before they pose danger to humans. Electronic noses (E-noses) have been created from nanowire arrays as devices for sensing technology; however, most E-noses require operating temperatures of over 200 °C, which may be a limiting factor in their practical application.

Writing in RSC Advances, Chatchawal Wongchoosuk and co-workers describe the fabrication of a ZnO-based E-nose that operates at room temperature and can detect down to the ppb level. The ZnO nanowires were surface modified to include ZnO-ZnAl2O3 and ZnO-Zn2TiO4 core-shell nanowires, which formed electrical connections by self-assembly. Ultraviolet light, positioned above the sensors, was used to generate electron hole pairs and oxygen species, which, on reaction with a gas or gases could change the layer width of the nanowires and ultimately lead to the detection and characterisation of the substance.

The ability for the E-nose to operate sensitively at room temperature makes a lot of scents and these developments are not something to be sniffed at (groan!)

Read the full article by clicking the link below – free to access until 16th October:

Electronic nose for toxic gas detection based on photostimulated core–shell nanowires
Chatchawal Wongchoosuk, Kittitat Subannajui, Chunyu Wang, Yang Yang, Firat Güder, Teerakiat Kerdcharoen, Volker Cimalla and Margit Zacharias, RSC Adv., 2014, 4, 35084–35088, DOI: 10.1039/C4RA06143H


Sarah Brown Sarah Brown is a guest web-writer for RSC Advances. Sarah hung up her lab coat after finishing her PhD and post-doctorate in nanotechnology for diagnostics and therapeutics and now works in academic publishing. When not trying to explain science through ridiculous analogies, you can often find her crocheting, baking or climbing, but not all at once.

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