Two journal cover articles in one month! (and another inside!)
This month, two publications which used results from work on SRS Station 9.8 were featured on the cover of Royal Society of Chemistry Journals (Dalton Transactions and New Journal of Chemistry). Arising from longstanding collaborations between the Station Scientist, John Warren, and Sofia Pascu (University of Oxford) and Scott Dalgarno (Heriot-Watt University), both papers reported on novel chemical structures solved using data obtained from tiny crystals that would be impossible on conventional sources. The first [1] was a biologically active metal complex synthesised by the group in Oxford to be used in both tomographic imaging and cellular-level fluorescence microscopy. In the second [2], researchers from Edinburgh and Columbia, USA describe the packing of self-assembled molecular systems which form some of the most extensive nanotubular arrays fabricated to date. These studies demonstrate the power of this single crystal diffraction facility to reveal structural details that are critical to fundamental understanding in diverse areas of science. Station 9.8 can thus be expected to contribute to front line research right up until it closes in July next year.
The front cover of the 21 November 2007 issue of Dalton Transactions shows an image taken from a report on recently synthesised complexes of M(II) bis(thiosemicarbazonato) (where M = Ni(II), Cu(II) and Zn(II)) featuring allyl groups (H2C=CH-CH2) at exocyclic nitrogens (i.e. nitrogens on the outside of benzene rings). The biological activity of such complexes, known for some time, has applications in tomographic imaging techniques used in vivo to follow their distribution in living cells. Their use has also become popular recently to monitor the uptake in vitro using fluorescence microscopy to obtain information at the cellular level on the mechanism for the biological activity and so follow the role of Cu(II) in biology in addition to the use of its radioactive isotopes in medical imaging. To improve the fluorescence it has been of interest to substitute other metals such as Zn(II) and to synthesise novel molecular structures to modify solubility and stability. Structural characterisation was undertaken by NMR spectroscopy in solution but X-ray diffraction studies were required to obtain a full description of the molecular structure. However, it was only possible to grow very small and weakly diffracting crystals so the qualities of synchrotron radiation had to be exploited and hence the role played by Station 9.8. The Zn(II) complex was found to be intrinsically fluorescent and soluble in biocompatible media. The uptake of this Zn(II) complex in HeLa, MCF-7 and IGROV cancer cells was monitored by fluorescence microscopies (by epi- and confocal-fluorescence imaging). The radiolabelling was performed by transmetallation from the corresponding Zn(II) species.
Epifluorescence image of HeLa cancer cells taken 60 minutes after loading with one of the complexes
[ 1 ] Designing Zn(II) and Cu(II) derivatives as probes for in vitro fluorescence imaging Sofia I. Pascu, Philip A. Waghorn, Timothy D. Conry, Helen M. Betts, Jonathan R. Dilworth, Grant C. Churchill, Tzveta Pokrovska, Martin Christlieb, Franklin I. Aigbirhio and John E. Warren,Dalton Trans., 2007, 43, 4988-4997
On the cover of the November issue of New Journal of Chemistry there is a view down the axis of a nanotubular assembly. Researchers undertook co-crystallisation studies with the intention of constructing an assembly featuring a large core diameter - a very rare feature - and the crystallisation of para-carboxylatocalix[4]arene from pyridine was successful in producing one with back-to-back packing of calixarenes (macrocyclic (see below) compounds that have hydrophobic cavities capable of holding smaller molecules or ions). The self-assembly of directional molecules is of great interest and has many applications. Tubular structures can be used as a supporting framework in which to form useful end products an example of which being the fabrication of ultrathin nanowires of silver. However, controlling the processes involved in assembling these structures is challenging. Generating large superstructures such as capsules or tubes on a nanometre scale has required experimenting with a range of crystallisation parameters which is costly in both time and materials. Characterisation of these materials is also difficult and largely relies on X-ray crystallography to provide an insight into the resulting self-assembled structures. The sheer size of supermolecules often gives rise to disorder in both the crystallising asymmetric unit (the basic building blocks of the crystal) and the relatively large quantity of solvent molecules retained, resulting in very weakly diffracting crystals. In this case, even using synchrotron radiation, relatively long exposures were required and data had to be collected from several crystals on Station 9.8.
A section through the non-covalent nanotubular array of para-carboxylatocalix[4]arene
The solvent channels are shown in blue
[ 2 ] Large diameter non-covalent nanotubes based on the self-assembly of para-carboxylatocalix[4]arene
Scott J. Dalgarno, John E. Warren, Jochen Antesberger, Timothy E. Glass and Jerry L. Atwood,
New J. Chem., 2007, 31, 1891-1894
A third paper [3], published in the same issue of Dalton Transactions, featured work completed on copper (II) complexes using SRS Station 7.1 by a team from the University of Hull and the Katholieke Universiteit of Leuven which included SRS Station Scientist Steven Fiddy. Macrocyclic compounds (molecules containing a ring of seven, fifteen, or any arbitrarily large number of atoms) such as this have a potential role in anti-HIV activity. The multidisciplinary research involved computational modelling using Density Functional Theory calculations of molecules in solution to determine the nature of potential binding interactions with surface protein aspartate residues (one of the 20 building blocks of proteins). The EXAFS study proved convincingly the metal-coordination sphere in solution to be identical to its solid state counterpart so no change occurs to the structure of the drug molecule on dissolution. Thus, Station 7.1 was contributing to leading research right up until its closure in April this year.
The calculated structures of the copper(II) N-methyl side-bridged cyclam complex in the (a) trans-I, (b) trans-IV and (c) trans-II configurations.
[ 3 ] Probing key coordination interactions: configurationally restricted metal activated CXCR4 antagonists
Graeme McRobbie, Gina C. Valks, Christopher J. Empson, Abid Khan, Jon D. Silversides, Christophe Pannecouque, Erik De Clercq, Steven G. Fiddy, Adam J. Bridgeman, Nigel A. Young and Stephen J. Archibald, Dalton Trans., 2007, 43, 5008-5018
