CrystEngComm Blog

Nano-sized crystals (or nanocrystals) have better solubilities and dissolution characteristics than larger crystals do.   Preparation of nanocrystals of drug molecules is therefore of interest to the pharmaceutical industry, particularly in cases where poor solubility is an issue.  However, preparation of crystals of the desired size and crucially, the correct polymorph, is not straightforward.  Problems include the long times required and the unwanted formation of amorphous material. One promising method of nanocrystal preparation  is to grow crystals in pores where the size of the pores limits the size of the crystals formed.

A recent paper in CrystEngComm by Myerson and co-workers reports the growth of three nanocrystals of pharmaceutical ingredients (APIs) – ibuprofen, fenofibrate and griseofulvin – using silica, where the pores of the silica structure provide so-called rigid confinement. The formation process is simple, involving loading of the API into the silica, washing to remove any API adhering to the surface (rather than inside the pores, see diagram below), crystallisation and drying. These steps can be varied to optimise the outcomes.

The nanocrystals exhibit enhanced solubilities and improved stabilities, due to the protection offered from e.g. moisture by the pores. The pores also limit possible reorganisations which would result in undesired crystal forms. The authors also highlight that the samples can be directly formulated into capsules without any additional steps, decreasing the formulation time significantly.

Read the full paper for more information:

Formation of organic molecular nanocrystals under rigid confinement with analysis by solid state NMR
X. Yang, T. C. Ong, V. K. Michaelis, S. Heng, J. Huang, R. G. Griffin and A. S. Myerson
CrystEngComm, 2014, DOI: 10.1039/C4CE01087F, Paper

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Gwenda Kyd has a PhD in metallocarborane chemistry from the University of Edinburgh. Other research work includes the spectroscopic study of the structure of glasses and organometallic electron-transfer reactions and the preparation of new inorganic phosphors. She has recently published a book on chemicals from plants.

The quality of protein crystals can sometimes make study of their structure by X-ray crystallography challenging.   Producing higher quality crystals could be facilitated by a better understanding of the crystal growth process.

One method of achieving this  involves inserting a small fluorescent dye into a protein (to form an F-protein) and adding this labelled protein to the crystallising protein.  The distribution, orientation and incorporation efficiency of the F-protein during the growth of the crystals can be studied optically using techniques including polarisation microscopy (see diagram below).

A new paper describes the use of three different F-proteins, each incorporating the dye DY-632-01 NHS ester, to study the crystallisation of the three unlabelled proteins.  This enabled visualisation of the crystal growth habits, symmetry and history as well as the distribution of the F-proteins.

In some cases, the F-proteins are preferentially incorporated into the growing crystal and can act as tracers.  Alternatively, they may not be incorporated at all and provide information about the biophysical factors which affect crystal growth (such as charge distribution and hydrophobicity).

As different F-proteins behave differently during the crystallisation of a given unlabelled protein, repeating the crystallisation experiment with different F-proteins can provide complementary information.

The distribution of F-proteins is not uniform throughout the crystal and authors conclude that that the diffraction quality of the crystal is position dependent. The incorporation of F-proteins may allow areas of higher diffraction quality to be identified.

For more information, read the full paper:

Illuminating protein crystal growth using fluorophore-labelled proteins
Alaa Adawy, Willem J. P. van Enckevort, Elisabeth S. Pierson, Willem J. de Grip and Elias Vlieg
CrystEngComm, 2014, DOI: 10.1039/C4CE01281J

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Gwenda Kyd has a PhD in metallocarborane chemistry from the University of Edinburgh. Other research work includes the spectroscopic study of the structure of glasses and organometallic electron-transfer reactions and the preparation of new inorganic phosphors

The use of fossil fuel-powered vapour compressors for the allocation of hot and cold air makes a significant contribution to global warming. A greener alternative involves reversible adsorption and desorption of a working fluid (often water) in adsorption heat pumps (AHPs) or adsorption chillers (ADCs), concepts originally devised by Michael Faraday in 1848.

The limiting factor when using MOF-based AHPs and ADCs is the rate of heat transfer. In this light, Al-based MOFs provide an attractive target as Al can not only provide a heat-conducting surface, but is also naturally abundant and of low toxicity.

MOFs for heat transfer

In their recent paper in CrystEngComm, de Lange, Gascon and co-workers evaluate a series Al-based MOFs for use in AHPs and ADCs. Of all the materials they tested, the most favourable characteristics were shown by the compound designated CAU-10-H, a material comprised of [Al–OH]²⁺ chains linked together by isophthalic acid, (CAU is Christian-Albrechts-Universität, where the compounds were first developed). 

In the presence of hydrochloric acid, CAU-10-H can be grown directly on to γ-alumina beads or metallic aluminium. These systems show good water adsorption and stability.  Up to 38kJ of heat can be withdrawn in the evaporator of an AHP/ADC per square metre of Al-coated surface, suggesting further study and development of Al-MOFs is worthwhile.

For more details, read the full paper:

Crystals for sustainability – structuring Al-based MOFs for the allocation of heat and cold
M. F. de Lange, C. P. Ottevanger, M. Wiegman, T. J. H. Vlugt, J. Gascon and F. Kapteijn
CrystEngComm, 2014, DOI: 10.1039/C4CE01073F

Gwenda Kyd has a PhD in metallocarborane chemistry from the University of Edinburgh. Other research work includes the spectroscopic study of the structure of glasses and organometallic electron-transfer reactions and the preparation of new inorganic phosphors

Zinc oxide (ZnO) is an important semiconductor material which can be used for gas sensing.  The sensing property relies on an oxidation-reduction reaction on the ZnO surface between the detected gas and surface oxygen molecules which causes the resistance of the sensor to change.  The nature of exposed facets on the sensor is crucial to its performance however, control of the growth, number, and morphology of these features has so far proved difficult.

In their recent paper in CrystEngComm, Xiang, Xu and co-workers report a simple synthesis of ZnO which allows for exposed facet control.  They discovered a two-step hydrothermal synthesis does not require use of any templates or surfactants but achieves structure control simply by adjusting pH.  In this way, hexagonal-pyramids, -prisms, -prismoids and -disks could be formed (see below)/

The authors tested the materials for gaseous ethanol sensing and the sensitivity was found to vary in the order disks > prismoids > prisms > pyramids.  They showed that the sensitivity of the sensors increased with exposure of (0001) crystal planes as these polar facets can provide more active sites for oxygen absorption than other facets, increasing the gas sensor response.   Their new findings are significant for the future development of high performance gas sensors.

For more information, read the full paper:

Evolution of ZnO microstructures from hexagonal disk to prismoid, prism and pyramid and their crystal facet-dependent gas sensing properties
Nan Qin, Qun Xiang, Hongbin Zhao, Jincang Zhang and Jiaqiang Xu
CrystEngComm, 2014, DOI: 10.1039/C4CE00637B

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Gwenda Kyd has a PhD in metallocarborane chemistry from the University of Edinburgh. Other research work includes the spectroscopic study of the structure of glasses and organometallic electron-transfer reactions and the preparation of new inorganic phosphors. She has recently published a book on chemicals from plants.

Cheap and effective storage of renewable energy is a key challenge for consumers in the future. Lithium ion batteries (LIBs) are one class of materials that meet the important requirements of high energy density, low cost, good power capacity and efficient cycling.

Recent research on LIB materials has focused on maximising their favourable properties to bring them closer to commerical use.

A new paper by Jun Liu and co-workers (Central South University, Changsha, China) describes the preparation and testing of a new anode material based on MoO₃ and graphene oxide (GO). The former material is naturally abundant, has good chemical stability and a high storage capability but also exhibits poor conductivity and lithium ion diffusion. GO has good conductivity, a large surface area and is highly stable, making it an attractive material for composite material formation.  

The authors prepared the new material by first synthesising GO and α-MoO₃ nanoribbons before modifying the surface of the latter to produce a positive charge. This allowed the MoO₃ material to assemble onto the GO.  They then applied heat to form the product, α-MoO₃@GNS (GNS refers to graphene nanosheet), and fabricated the material to form an anode.

These robust nanocomposites exhibit greatly enhanced Li transport efficiency compared to other MoO₃-based materials, as well as high electrical conductivity and good cycling efficiency.

The authors concluded that the two components work synergistically to produce the observed properties and suggested the composite as a potential anode material for high performance LIBs.

 To find out more, read the full article:

Graphene nanosheets encapsulated α-MoO₃ nanoribbons with ultrahigh lithium ion storage properties
Pei-Jie Lu, Ming Lei and Jun Liu
CrystEngComm, 2014, DOI: 10.1039/C4CE00252K

Gwenda Kyd has a PhD in metallocarborane chemistry from the University of Edinburgh. Other research work includes the spectroscopic study of the structure of glasses and organometallic electron-transfer reactions and the preparation of new inorganic phosphors.  She has recently published a book on chemicals from plants.

Human kidney stones contain over 200 components, most significantly, anhydrous uric acid (UA, below) and its dihydrate (UAD).  When UAD is present, UA is also, however the reverse isn’t always true. This  suggests the conversion of UAD to UA may be a significant step in the formation of kidney stones.  A deeper understanding of how the stones form could inform strategies to prevent their formation and to disperse them once formed.

A new paper in CrystEngComm looks at the relationship between UAD and UA under physiologically relevant conditions.  The authors studied the behaviour of UAD in aqueous solution at body temperature (37^oC), both at various pHs in the presence of a buffer and in an artificial urine solution. In aqueous solution at acidic pH values, the conversion of UAD occured via a slow dissolution, followed by recrystallization, to form UA over 42 hours. At neutral pH, the final product formed was uric acid monohydrate (UAM), which was obtained either directly or via a UA intermediate. In urine solution, UA formation was much faster (complete in 30 hours) and crystals were much smaller.

The rate limiting step is believed to be the dissolution of UAD, with the timescale of the UA formation explaining why UAD is rarely found in the absence of UA.  Future studies will look at how other urinary components and/or additives can affect UA formation.

For more information, see the full paper:

Solution-mediated phase transformation of uric acid dihydrate
Janeth B. Presores and Jennifer A. Swift
CrystEngComm, 2014, DOI: 10.1039/C4CE00574K

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Gwenda Kyd has a PhD in metallocarborane chemistry from the University of Edinburgh. Other research work includes the spectroscopic study of the structure of glasses and organometallic electron-transfer reactions and the preparation of new inorganic phosphors.  She has recently published a book on chemicals from plants.

Iron vanadate (FeV_xO_y) nanostructures have shown very good performance in sensors, lithium batteries and as catalysts.  Their properties are strongly related to the shape and surface area of the particles and this makes the controllable preparation of one dimensional (1D) nanostructures (i.e. nanowires or nanorods), with large surfaces areas, a target for scientists.

A new paper reports a simple hydrothermal technique which achieves this.   The length of the particles can be adjusted simply by varying the pH of the reaction mixture between pH 4 and pH 6, with longer wires favoured at higher pH, as shown in the diagram below.  Using this methodology, lengths from several micrometers to several millimetres can be obtained and the ratios of diameters to lengths can also be varied from 10 to over 1000. In addition, the pore sizes in the nanostructures can also be controlled using the same method of pH variation.

There are four steps in the  formation of the nanostructures – dissolution, anisotropic growth (i.e. growth in one direction), Ostwald ripening (a process where smaller particles dissolve and deposit on larger particles to achieve more thermodynamically stable particles) and, finally, pore formation by loss of water molecules.

A sample of one of the prepared nanostructures (FeVO₄ nanorods) was tested for use in selective catalytic reduction (SCR) of NO with NH₃ as the reduction of NOx emissions from diesel engines is important to reduce air pollution.  The nanorods proved stable and selective under typical reaction conditions and, in addition, were resistant against two major catalyst poisons present in exhaust fumes, H₂O and SO_2.

For more information, read the full paper using the link below:

Hydrothermal growth and characterization of length tunable porous iron vanadate one-dimensional nanostructures
Lei Huang, Liyi Shi, Xin Zhao, Jing Xu, Hongrui Li, Jianping Zhang and Dengsong Zhang
CrystEngComm, 2014, DOI: 10.1039/C3CE42608D

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Gwenda Kyd has a PhD in metallocarborane chemistry from the University of Edinburgh. Other research work includes the spectroscopic study of the structure of glasses and organometallic electron-transfer reactions and the preparation of new inorganic phosphors. Currently, she is writing a book on chemicals from plants

Furosemide is a loop diuretic (a ‘water pill’) used to treat congestive heart failure, oedema and sometimes hypertension.  It can also be used to reduce bleeding in horses during horseracing and is banned from use for this purpose in the UK. The bioavailability of the drug when taken orally is limited by the relatively low solubility. 

Formation of co-crystals with the co-formers caffeine or cytosine improves solubility (by 6 or 11 times) but the co-crystals suffer from low stability so are not suitable for pharmaceutical use.

A new paper takes a different approach, using salt formation as an alternative to co-crystal formation. Sodium and potassium salts of furosemide were prepared and their solubilities and stabilities assessed.  The solubility of the sodium salt (furo-Na-trihydrate) was over 4000 times higher than that of the free drug, while the potassium salt (furo-K-monohydrate) was over 10000 times more soluble.

Both salts show improved stability compared to the co-crystals – at 40 °C and 75% humidity furo-Na-trihydrate is stable for 2 weeks and furo-K-monohydrate is stable for 1 week.

The authors conclude that the low cost of preparation and the enhanced solubility and stability of the salts merits their consideration for use in oral drug formulations.

For more information see the paper:

High solubility crystalline hydrates of Na and K furosemide salts
U. B. Rao Khandavilli, Swarupa Gangavaram, N. Rajesh Goud, Suryanarayan Cherukuvada, S. Raghavender, Ashwini Nangia, Sulur G. Manjunatha, Sudhir Nambiar and Sharmistha Pal
CrystEngComm, 2014, DOI: 10.1039/C3CE42347F

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Gwenda Kyd has a PhD in metallocarborane chemistry from the University of Edinburgh. Other research work includes the spectroscopic study of the structure of glasses and organometallic electron-transfer reactions and the preparation of new inorganic phosphors. Currently, she is writing a book on chemicals from plants

Nanometer- or micrometer-sized particles, doped with a small quantity of rare-earth cations, exhibit two types of luminescence. Where the light absorbed is of higher energy than the light emitted (known as down-conversion or DC) the materials can be used in lighting and displays.  If the light absorbed is of lower energy than the light emitted (up-conversion or UC), the materials can be used in photonics and biological imaging.  The luminescence behaviour depends on the composition, size and shape of the particles and the rare-earth ion (or ions) used for doping.

Lanthanide oxyfluorides, such as YOF, are attractive candidates for the host particles, due to their high stability and good transparency.  These materials have been prepared with various particle sizes but using harsh conditions and complicated processes which can, crucially, leave behind traces of the organic molecules used to control morphology.  These can be detrimental to the physical and chemical properties of the final product.

A new paper shows how a simple hydrothermal method can be used to prepare YOF particles with controllable size and shape, determined by altering the pH of the reaction mixture and without the need for organic shape-directing reagents.   At pH 9 microrods form, while at pH 11 the particles form as nanospheres and at pH 14 there is a mixture of the two morphologies.  The UV luminescence properties of samples doped with the rare-earth cations Tm³⁺, Tb³⁺ or Eu³⁺show characteristic blue, green or red DC emissions. Samples doped with two different rare earth cations, under lower energy excitation,  show red, blue and green UC emissions for Yb³⁺/Er³⁺, Yb³⁺/Tm³⁺ and Yb³⁺/Ho³⁺ doped particles, respectively (see diagram below).

The emission intensities are related to the particle size and the number of surface defects (which lead to quenching of the luminescence).  Intensities are therefore highest for the microrods which are largest and have fewest defects.  Authors conclude that the YOF particles prepared are excellent host lattices for efficient luminescence which could find application in colour displays and anti-counterfeit labels.

For more details see the paper at:

YOF nano/micro-crystals: morphology controlled hydrothermal synthesis and luminescence properties

Yang Zhang, Xuejiao Li, Dongling Geng, Mengmeng Shang, Hongzhou Lian, Ziyong Cheng and Jun Lin

CrystEngComm, 2014, Advance Article
DOI: 10.1039/C3CE42323A, Paper

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Gwenda Kyd has a PhD in metallocarborane chemistry from the University of Edinburgh. Other research work includes the spectroscopic study of the structure of glasses and organometallic electron-transfer reactions and the preparation of new inorganic phosphors. Currently, she is writing a book on chemicals from plants

Successful use of pharmaceutical drugs depends on their delivery and controlled release so that their bioactivity can be harnessed.  This can mediate poor solubility, degradation and other properties of the drug which might otherwise be problematic.  One way to control delivery is to load the drug into a container which allows the compound to be transported to the desired location, to then be released over a suitable time period.  The behaviour of the container is dependent on both the size and the shape, so simple and reliable fabrication techniques are required.

In a recent CrystEngComm article, scientists from China show how such containers can be made which are shaped like lotus leaves and are nano/microsized.  The Co₃O₄ nano/microcontainers can be easily prepared from Co(NO₃)₂.6H₂O by evaporation of the acetone solvent followed by calcining (i.e. heating at below the melting point).   In this process, shown in the diagram below, the large amount of gas bubbles produced are key to determining the shape of the containers, with no other shape-directing agents required.  The size and density of the nano/microlotus-leaf arrays can be controlled by variation of the evaporation time and temperature.

The research team used fluorescein isothiocyanate (FITC) as a model drug to study the controlled drug delivery from the nano/microlotus-leaf arrays.  They found that it could be loaded and released more effectively than for comparable Co₃O₄ microspheres and showed that cells which were treated with the arrays retained over 80% viability even at high concentration — indicating that these microcontainers are a safe delivery vehicle of active compounds to cells.

For more details, see the paper:

Facile bubble-assisted evaporation-induced assembly of high-density arrays of Co₃O₄nano/microlotus leaves: fluorescent properties, drug delivery, and biocompatibility

 Gwenda Kyd has a PhD in metallocarborane chemistry from the University of Edinburgh. Other research work includes the spectroscopic study of the structure of glasses and organometallic electron-transfer reactions and the preparation of new inorganic phosphors. Currently, she is writing a book on chemicals from plants.