Spectroscopy – Page 12 – David Bradley

Frogs legs and AMPs

Solid state NMR is unlocking the secrets of compounds found in natural membranes from frogs’ legs to human lungs that could lead to an entirely new class of antibiotic drugs. The compounds in question are antimicrobial peptides (AMPs) and they have been detected in every living creature studied so far. AMPs act as a first line chemical defence system in a huge range of organisms and could provide a novel approach to defeating drugs resistance in bacteria.

“Our overall mission is to use the kind of basic physical data we obtain from NMR to help interpret biological functions,” team leader Ayyalusamy Ramamoorthy of the University of Michigan explains. As with most discoveries of this nature, it will be several years before any clinical trials for specific health problems or diseases are complete. “How it works against viruses are under investigation in other labs,” Ramamoorthy told me.

You can find out more about AMPs as the front line defenders in the latest issue of SpectroscopyNOW.

Viruses Do Not Eat Spaghetti

The faint glow from a single molecule combined with a stretch from “magnetic tweezers” could help scientists get a grip on how viruses that infect bacteria, so-called bacteriophages pack up their DNA. The research could lead to a resurgence of interest in the West for a potent treatment for infection that uses bacteriophages instead of antibiotics to attack disease-causing bacteria. The treatment side-steps the problem of bacteria evolving resistance to antibiotics because the agent of bacterial death can evolve just as quickly to cope with any defences put up by the bacteria.

In the face of deadly emergent bacteria such as Escherichia coli O157, multiple-resistance Staphylococcus aureus (MRSA) and Clostridium difficile, there is renewed interest in this alternative to antibiotics. The same study might also lead to new insights into how to combat viruses that infect people too, including herpes and adenoma viruses.

Many viruses use a self-assembly stage in which a powerful molecular motor packs their genetic code into the viruses’ preformed protein shell, its capsid. Now, Carlos Bustamente and colleagues at the University of California, Berkeley, have demonstrated that the genetic code is not coiled up like so much spaghetti on a fork but is packed using a concertina type approach. You can find out more about the details of this work in the current news round-up on SpectroscopyNOW.com

Shadowy face recognition

Shadowy face Face recognition is the most obvious approach to identification but it suffers from a major drawback – shadows and bad lighting. If there is inconsistent lighting in a room or on a face then it becomes difficult to produce reproducible digital image of the face for face recognition algorithms to work with. Now, researchers in China have turned to near infra-red to help computers cope with variable lighting conditions and so recognize even the most shadowy of faces.

Face recognition is a key function of the human brain…let me put it another way, from a very, very early age we can all recognize faces, from the familiar view from mother’s knee to spotting a friend in a crowd. Computers too can process a digital image and compare it with a database entry to carry out simple face recognition. But only if the light is right. Throw in a few shadows, sunlight through a window, or a flickering overhead fluorescent light, and the computer usually cannot spot the difference between John Doe and Joe Bloggs. Stan Li believes the answer lies in the near infra red, you can find out more tomorrow in the latest issue of spectroscopynow.com or get an advance view here.

Does Traditional Chinese Medicine work

Gingko biloba Many of the health claims of herbal medicine bear fruit for the pharmaceutical industry, leading to new drugs that are more potent and more targeted than the original remedy. In Traditional Chinese medicine there are many health claims for the likes of Ginkgo biloba and many other remedies that might bear closer scrutiny. Now, pharmaceutical chemist David Barlow and colleagues Peter Hylands and Thomas Ehrman at King’s College London have undertaken the biggest study yet of the active ingredients in TCM and used an analytical system known as a multiple decision tree technique, called Random Forest, to unearth the root of the activity of the natural products in TCM.

Their study seems to vindicate many of the claims of TCM as well revealing several compounds that might be indicated for diseases and symptoms not treated with in the traditional system.

The team built a database containing well over 8000 compounds from 240 of the most commonly used TCM herbs and used a second database of almost 2600 known active plant chemicals and other natural products as a training set for the Random Forest computer algorithm. The team found that about 62% of the herbs they tested in silico against various drug targets (mostly enzymes associated with pathogens or problems in the body) contained candidate drug compounds that might be isolated for treating a single disease without the associated issues of a TCM approach. They also found that more than half of these compounds worked against at least two diseases and so might have multiple applications.

You can read more about this research today on SpectroscopyNOW news round up from David Bradley. I asked Barlow about the wider application of this research and he said it might be applied equally well to other databases. “The same methodology might also be applied in screening other similar databases, constructed, for example, with reference to herbs used in Ayurvedic medicine,” he said.

Identifying the Valentine’s Day murder weapon

Knife murder weapon

The air in the courtroom was so thick you could cut it with a…well…a knife, some broody dame was sobbing in the gallery, and the steno guy snuffled as he bashed the keys. It was a year ago today, Valentine’s Day, that the massacre took place. The investigating team was presenting its evidence, it was obvious to everyone but the judge, who’d stabbed the victim, the knife and the body had both been bagged. Trouble is, there was a thread hanging from the attorney’s Armani, but this was no slapdash haberdashery, this was the proverbial chink in the armour through which a guilty blade could easily slip. The wound was inflicted with the kind of blunt edged kitchen knife you can buy in any five and dime store so it was looking like our felon wasn’t gonna face the chair after all…

But wait, new evidence just in, a study of metal particles found in the valentines day wound reveals the presence of nickel and chromium atoms, exactly the same metallic blend on the accused’s kitchen dagger and in exactly the same ratio as the cutting edge of the knife itself. Crank up the juice Eugene, we got ourselves a fryer!

More cloak and dagger this week in David Bradley takes on Sam Spade, over on SpectroscopyNOW. You do know how to whistle, don’t you?

NearIR Nightly

Organic light-emitting diodes (OLEDs) are finding applications in a whole range of devices now not least because of their flexibility, in both the physical and viability sense, and their high energy efficiency. Until recently, however, OLED research was focused on visible emission. Now, US scientists have developed a near infra-red OLED, a NIR OLED. They reckon an NIR OLED could be used in future night-vision devices. NIR OLEDs might also one day find use in small-scale, portable NIR spectrometers or lab-on-a-chip systems for medical and environmental analysis, or potentially chemical and bio weapons detection.

Mark Thompson of the University of Southern California and colleagues at Princeton University, Steve Forrest’s group at the University of Michigan, and Julie Brown’s team at Universal Display Corporation have used a phosphorescent platinum-porphyrin complex as a doping agent to create the new class of NIR OLED.

You can read the full story in my SpectroscopyNOW column this week.

If anyone gets the allusion in this post title, drop me a line.

Singling out molecules

tip enhanced raman spectroscopy Swiss chemists have devised a new approach to the familiar analytical technique of Raman spectroscopy that allows them to investigate the structure of individual molecules.

The full story is available today in advance of publication on SpectroscopyNOW’s Raman channel for Sciencebase readers only.

According to research team leader Renato Zenobi, there are two potentially very important applications of this new high-gain Raman technique:

Molecular electronics – This is a field where individual molecules are being used as electronic elements (diodes, transistors, logic gates, etc.). One can, for example, imagine that a molecule would “switch” a current by a change in conformation (shape), which would of course be immediately reflected in a change of the Raman spectrum. Molecular diagnostic / analytical methods for this emerging field are largely missing so far. Here this methodology could make an important contribution, Zenobi told me.
Cataysis – In catalytic conversions, A -> (B) -> (C) ->D , where A is the reactant, B and C are intermediates and D is the product, reactions are accelerated by a catalyst, by activating the molecules. Usually this happens on the surfaces of finely dispersed metal on a support material, i.e., it is generally surface process. Catalysis is employed in many industrially important chemical reactions, but – surprisingly – often the exact course of the reaction / the nature of the intermediates is not known. Again, identification of small numbers of molecules in tight spaces (= the nanoscale metallic “active sites” on catalysts) could be achieved with our methodology.

Nuclear assured destruction

Radiation damage Advocates of nuclear power point to recent advances in waste storage materials that could allow the radioactive byproducts of the nuclear industry to be stored safely and indefinitely in ceramics rather than glass. Whereas those not in favour of splitting atoms to produce almost limitless energy point out that even vitrified nuclear waste will represent an ongoing problem for thousands of years.

Ceramics have come to the fore as an alternative storage medium. However, a recent study by researchers at Cambridge University and Pacific Northwest National Laboratory using NMR spectroscopy suggests that storing high-level nuclear waste (plutonium) without leakage over thousands of years might not be possible even with those materials. The NMR study reveals that alpha particles emitted by the plutonium, while only travelling a short distance through the ceramic wreak havoc with the ceramic’s structure and so could lead to long-term stability problems.

I spoke with Cambridge’s Ian Farnan about the research for the February 1 issue of the NMR channel on SpectroscopyNOW.com. He explained that silicon-29 NMR spin counting experiments on samples with activities greater than 4 GBq was used for the first time to demonstrate how decaying plutonium knocks atoms in the ceramic out of kilter. The findings do not preclude the use of zircon ceramics in the storage of radioactive waste but provides a stronger basis in long-term stability on which to make nuclear waste disposal decisions.

Ambiguous aspirin

Aspirin Two back-to-back papers in the well-known chemistry journal Angewandte Chemie recently could have potentially serious consequences for the pharmaceutical industry, because they reveal what the authors claim are inherent ambiguities in the crystalline forms of aspirin.

A team of scientists from Denmark, Germany, and India suggest that the recently reported form II of the ubiquitous pharmaceutical may indeed exist but the crystallographic evidence could just as readily be interpreted as being from a single crystal of form I. The findings could have implications for patent arguments over novel forms of the purportedly generic drug.

Even from the early days of crystal studies into aspirin, there were serious issues surrounding its structure. PJ Wheatley obtained the first crystal structure in 1964, but certainly not without a degree of ambiguity. “After Wheatley, Chick Wilson got very high R-factors in his neutron study of 2000,” Desiraju told SpectroscopyNOW.com, “this is what was nagging me throughout, why were these R-factors so high?” Desiraju and his colleagues suggest that the Zaworotko study does not represent much of an improvement on the precision of these earlier studies and moreover confounds attempts to define a new polymorphic form of aspirin.

Read the full story on SpectroscopyNOW.com

Antibiotics from green tea

Green tea antibiotic Researchers from Slovenia have used spectroscopy to home in on the active site of an essential bacterial enzyme, DNA gyrase. They say they now understand more clearly how a compound found in green tea, EGCG, which is a health-boosting antioxidant, works to kill bacteria.

The findings should allow researchers to design new, synthetic versions of EGCG that improve on its activity without side effects.

“I think that this direction is worth pursuing,” team leader Roman Jerala told me, “EGCG besides being unpatentable is not very stable in the body and has low bioavailability but this could be improved.” In their paper, the researchers discuss several possible research directions, however Jerala concedes that he and his colleagues lack the synthetic capabilities to pursue them. “We could only go in this direction with support from other labs,” he says, “Hopefully pharmaceutical companies will consider it.”

More…