Elemental Discoveries, October 1999
Clean air act by David Bradley
A room temperature catalyst for efficiently converting carbon monoxide into the less innocuous carbon dioxide has been developed by UK chemists. The catalyst could be used in more effective and cheaper to run air purifiers at industrial sites, in mining and for deep sea and space exploration to avoid carbon monoxide poisoning.
Catalysts are crucial components of most gas filtering systems but are costly to run requiring a raised temperature to operate. Common catalysts do not provide 100% respiratory protection for workers.
Graham Hutchings and Stuart Taylor of Cardiff University working with Ali Mirzaei at the Leverhulme Centre for Innovative Catalysis at the University of Liverpool have now developed the first room temperature catalyst based on copper zinc oxide for oxidising carbon monoxide. Taylor says the catalyst is far more effective than the commonly used hopcalite - mixed manganese copper oxide - catalyst, although its structure must now be
optimised.
The team prepared their catalyst using co-precipitation under different gases - air, nitrogen, hydrogen and carbon dioxide. Each preparation effectively mixes copper (II) oxide and zinc oxide to form a highly dispersed mineral containing what Taylor and Hutchings describes as a solid solution phase. Composition depends on preparation gas the ageing between preparation and filtering the solid from the liquid.
The catalysts were tested for CO oxidation power at 20 celsius under a steady flow of CO. Hutchings says all the copper zinc oxides were highly active but the most active were those prepared in air and aged for one hour. Taylor told CiB, 'We are still really trying to unravel the relationship, and unfortunately cannot really expand.' While X-ray diffraction revealed different structures between the aged catalysts before calcination (blasting in a furnace in air to decompose the carbonates to oxides), after calcination was complete the materials were effectively mixed CuO and ZnO but with subtle differences revealed by electron microscopy.
The team is now studying the mechanism of oxidation more closely with a view to optimising the preparation conditions. Taylor admits they have no immediate plans to commercialise the catalysts, 'We will wait and see what commercial interest is generated.'
(Chemical Communications 1999, 1373)
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Copper compounds that selectively damage RNA at picomolar concentrations could one day lead to safe antiviral agents for treating numerous diseases, including AIDS, according to James Cowan and colleagues at Ohio State University in Columbus.
There are no cellular repair mechanisms for RNA so finding compounds that degrade it without interfering with DNA could lead to new antiviral agents without the side-effects associated with DNA damage. Aminoglycoside antibiotics, such as gentamicin and neamine, have been shown to block protein production in HIV by attaching themselves to viral RNA.
Cowan and his team hoped to take this approach one step further by developing an inorganic compound that would not only interfere with protein translation by RNA but degrade it too. Previous efforts to destroy RNA with conventional drug types have required high temperatures, acid conditions and many hours at high concentration - hardly the ideal drug candidate.
By complexing the aminoglycosides neomycin B and kanamycin A with copper ion, Cowan and his team hoped to be able to degrade RNA under much gentler, and ideally, physiological conditions. In a preliminary investigation the team chose an RNA segment, which they knew binds well to neomycin B. They treated it with the copper complexes of the two antibiotics at picomolar concentration, physiological pH and body temperature for about an hour. The products were then separated by gel electrophoresis.
NMR analysis of the RNA aptamer with neomycin B shows the aminoglycoside to bind in the stem loop region. Autoradiography of the products resulting from cleavage by the copper complexes demonstrated specific cleavage points corresponding to the sites predicted by the NMR solution structure. They also found that the addition of ascorbic acid to the reaction mixture boosted the effectiveness of the cleavage process. They did not see any degradation of the RNA with copper ions alone or with just the antibiotics.
The copper complex does not interact randomly with non-viral RNA nor DNA so they expect it to be a well targeted low dosage antiviral. Cowan says the new drug candidates could provide a useful and effective alternative to antisense drugs which attempt to disrupt DNA and RNA by binding but without degrading. Tests to demonstrate efficacy of the copper complexes against various viral RNA's, such as HIV and Dengue, are in progress.
(Chemical Communications, 1999, 1147)
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Mass spectrometry can now be used to quickly and easily measure the excess of one enantiomer over another in a compound library generated by combinatorial chemistry techniques, according to US chemists.
M. G. Finn and colleagues at the Scripps Research Institute in La Jolla, California have found they can determine the enantiomeric content of tiny product samples of chiral alcohols and amines - two common groups produced by putative synthetic catalysts. They simply use chiral acylating agents tagged with two different groups to convert the alcohol or amine group into its ester or amide form and then determine the electrospray ionisation mass spectrum for the samples, which need only be a few
nanomoles.
According to Finn, writing in Angewandte Chemie (1999, 38, 1755), the mass of the tagged ester or amide is correlated directly with absolute configuration of the original members of the library but because the technique requires only a very low selectivity in the acylation step it is generally applicable to a wide variety of structures.
The analytical steps in combinatorial chemistry have tended to be the rate-limiting ones. But, by using mass spectrometry in this way, the process of combinatorial chemistry could be speeded up by providing a high throughput method for measuring the effectiveness of stereoselective catalysts in generating an enantiomeric excess.
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The hunt for so-called 'natural' antioxidants for the food industry has led to a need for a quick and easy way to assess how potent a particular substance is at inhibiting oxidation. Saverio Mannino and his colleagues at Milan University have developed a technique for analysing 'total antioxidant power' of one of the most promising natural ingredient - olive oil. Indeed, waste water from olive oil processing is already being used as a food preservative
(Journal of Agricultural & Food Chemistry, 1999, ASAP).
Mannino and his team have used a flow injection analysis system with electrochemical detection to avoid some of the problems of standard techniques and say they can simply and easily process ninety samples an hour at lower concentration than possible with the common Rancimat method.
Oxidative rancidity is the critical factor affecting shelf-life of many foods according to Mannino with the autoxidation of fatty acids leading to foul smells and tastes and rendering the food unfit to eat. Various additives have been used for decades to inhibit oxidation and so keep processed food fresh for longer but consumer pressure applied to the industry has led to a need to find alternative 'natural' ingredients and to avoid synthetic antioxidants, despite several of these simply being manufactured vitamins.
Olive oils are well known as having antioxidant components, and this property has been used to explain some of the role they are thought to play in reducing cardiovascular disease. Various polar phenolic compounds such as tocopherols, phenolic derivatives of cinnamic and benzoic acid, and oily (oleosidic) versions of tyrosol and its derivatives are present in olive oil. Each component may have a role to play in reducing oxidation but assessing the overall effectiveness of the oil has, says Mannino, relied on questionable methods.
The standard tests usually apply oxidative conditions to food samples with light or metal catalysis, high-temperature oxygen 'bombs' and active oxidation. These methods are rather severe in their oxidation and do not represent the normal autooxidation of foods. The electrochemical method developed by the Milan team avoids the severity of oxidation so provides a much more representative method of assessing antioxidant power.
(The Analyst, 1999, 124, 1115).
'I hope the technique will be quickly adopted by the industry,' Mannino told CiB, 'the apparatus is simple but at present I am not in the position to commercialise it.'
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Methicillin-resistant Staphylococcus aureus (MRSA) often defeats even vancomycin the last resort antibiotic. Japanese researchers have now come up with a multi-valent vancomycin polymer with enhanced activity that could lead to a new approach for antibiotic drug development.
MRSA emerged as a serious problem in hospitals in the 1980s, having evolved resistance to common antibiotics, worldwide. Until recently, vancomycin remained a last defence against the superbug but recently resistance even to this potent antibiotic has been reported.
Attempts to keep MRSA under control have focused on modifying vancomycin itself to produce better drugs. Vancomycin binds to an amino acid residue, D-Ala-D-Ala, in a bacterial cell wall peptide precursor - the binding process halts construction work and the bacterium dies. There are several clues as to how vancomycin binds to the growing bacterium but importantly researchers know that five hydrogen bonds are involved and that a single change in the peptide residue to D-Ala-D-Lac in resistant bugs stops these H-bonds forming.
Hirokazu Arimoto and his colleagues at Shizuoka University, the National Institute of Infectious Diseases in Tokyo and Nagoya University figured that if they could increase the number of anchor points for vancomycin the subtle change in amino acid sequence would not be enough to stop binding so vancomycin could still halt cell wall construction. The team modified vancomycin using a ruthenium catalyst to link several together with a norbornene unit that would activate the polymerisation process. The process resulted in two polymeric versions of vancomycin, which they could then test against resistant bacteria.
They compared the activity of the two polymers with the common monomeric vancomycin and found that one of them was sixty times more effective against vancomycin-resistant bacteria. 'We have no firm evidence for precise mode of action but are currently investigating the structural parameters, such as, degree of polymerisation, length of linker between polymer chain and vancomycin, which may provide an insight,' explains Arimoto. The multiple bonding points in the polymer are thought to strengthen the association of biologically active ligands and receptor molecules, when the spatial arrangements are right, he adds, making the polymer a promising drug lead.
(Chemical Communications, 1999, 1361).