Seek and ye shall find

By: David Bradley

New imaging agents that seek out cancer cells could eventually lead to earlier tumour detection and so improve the prognosis of various cancers.
   Carolyn Bertozzi and her colleagues at the University of California, Berkeley, have found they can target cells with a magnetic resonance imaging (MRI) contrast agent by exploiting differences in cell surface proteins, antigens, without the need to resort to often poorly specific antibodies.
   Bertozzi reasoned she could use subtle differences in the way healthy cells and tumour cells metabolise carbohydrates expressed on their surfaces. She explains that tumour cells exhibit abnormal surface carbohydrates that are normally only expressed during foetal development. In many cancers - gastric, colon, pancreatic, liver, lung, prostate, and breast tissue, and in leukaemia these abnormal carbohydrate structures contain the monosaccharide sialic acid, which raises levels of this sugar on tumour cell surfaces.
 

Since healthy cells produce far fewer sialosides, their abundance might be used to distinguish normal cells from tumour cells. This difference could be used to target MRI contrast agents, which enhance cancer tissue images.
   The researchers knew that the enzymes producing sialosides could tolerate non-natural substrates well. They figured that by using a compound such as N-levulinoylmannosamine as the substrate they could produce sialosides on a tumour cell that would have a ketone group to act as a unique chemical handle for contrast reagents bearing an aminooxy or hydrazide side chain. The ketone should thus enhance tumour imaging.
   The team synthesised an aminooxy derivitised contrast reagent, (GdDTPA), and swapped the gadolinium ion for a fluorescent europium ion so they could detect its presence on cells. To test their idea, they cultured human T-cell lymphoma cells with N-levulinoylmannosamine as feedstock. Lymphoma cells are heavily sialylated so ketone expression should be high.
   They next added the Eu-based contrast reagent and measured fluorescence levels to see how well the agent bonds to the cancer cells. Control measurements without the aminooxy modification were also made. They found that tumour cell targeting depended strongly on the presence of the ketone on the cell surface and the reactive aminooxy group on the contrast agent.
   'We are only at the very early stages,' Bertozzi says, 'but we are doing some in vitro MRI work to establish the parameters of our reagent and depending on the outcome of these studies we might want to design second generation analogues with enhanced relaxivity for later in vivo experiments.'

J Am Chem Soc, 1999, JA984228M

Turning the armyworm

 

When beet armyworm caterpillars attack maize, volatile terpenoids are produced that attract parasitic wasps to kill the caterpillars. The possibility of a natural pesticide was immediately spotted. The trigger is a component of the caterpillar's saliva.
   Georg Pohnert and his colleagues at the Max Planck Institute in Jena have now devised a very short stereoselective synthetic route to the specific component  (17-hydroxylinolenoyl)-L-glutamine, volicitin, with support from

 

BASF and Bayer. Their method is based on a three-component Wittig reaction that efficiently converts a hexenediol into volicitin with its three alternating double bonds. This motif is common in other natural products so the scheme could be used to efficiently synthesise several other compounds too. Chem Commun, 1999, 1087

An entirely new method of changing the surface of a metal electrode has been developed by Japanese chemists. The technique, based on the self-assembly of monolayer and polymer films composed of a new tetrathiafulvalenyl-tetrathiol, could open up new tailored applications such as sensors and more specific catalytic electrodes.
   To date, chemists have had to rely on a straightforward adsorption process to add functional groups the surface of an electrode. Compounds containing an alkyl chain with a surface-active sulphur group, such as alkane-monothiols and n-alkyl disulphides can be used to make functionalised electrodes for various applications.
   Hisashi Fujihara, Hidetaka Nakai, Masakuni Yoshihara and Toshihisa Maeshima of Kinki University in Kowakae, Higashi-Osaka considered that alkane-polythiols might increase the electrode repertoire as well as allowing easier production. They began investigating a new class of surface-modification reagent, known as tetrathiafulvalenyl alkane-tetrathiols, with which they say they can produce 'remarkably stable' surface films on gold electrodes and tough polymer films on glassy carbon electrodes.
   Creating the films is simplicity itself. They dip a clean polycrystalline gold electrode in a dichloromethane solution of their new tetrathiol and warm it gently. The formation of bonds between thiolate and gold binds the tetrathiols to the electrode. Once they had given the electrode a good wash they could measure its anodic and cathodic properties and verify that the tetrathiafulvalenyl groups had been fully incorporated into the surface film. They compared their electrode with standard monothiol gold electrodes and found it to be much more stable to solvents and to electrochemical cycling.
   They spotted, however, that repeated electrochemical oxidation of the tetrathiol at moderate potential on a glassy carbon electrode gave polymer films. The team quickly recognised that this electropolymerisation might open up a new way to increase the functionality of the electrode.
   'This is the first example of the surface modification of electrodes with the same adsorbate molecule by the self-assembly method and electropolymerisation using the same starting material,' explains Fujihara. 'We will be able to compare the interfacial properties on the monolayer and polymer films containing tetrathiafulvalene,' he explains,' since electropolymerised films generally contain pyrrole or thiophene groups which appear in the cyclic voltammogram as the redox peak.'

Chem. Commun., 1999, 737

Coloured polystyrene

Adding colour to polystyrene could lead to novel catalysts for oxidising and so removing mercaptans from crude oil, antibacterials that produce singlet oxygen in light to kill bugs, optical materials for use in spectrometers and optoelectronics and optical limiters to protect eyes from laser damage, according to research at the University of Manchester.

Bringing colour to polystyrene with phthalocyanine

Neil McKeown and his team specialise in the chemistry of a group of highly coloured compounds known as phthalocyanines (Pc). These materials, related to porphyrins - the pigments that make leaves green and blood red, are widely used as industrial colourants and as photoconductors in laser printers and in compact discs.    The researchers can now incorporate Pcs into the side chains of polystyrene. 'The new materials have already proved to have excellent  processibility for the fabrication of non-scattering thin films for a wide range of optical studies,' says McKeown. McKeown was recently interviewed by DB for The Alchemist on www.ChemWeb.com Chem. Commun., 1999, 419

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