Christmas rose and hellebrigenin

Structure of hellebrigenin

Members of the plant family Ranunculaceae are ever-popular at this time of year, especially in Europe, where the Christmas rose, Helleborus niger, is wheeled out as a natural decoration for countless households. Interesting then, that extracts of this plant have been used as a heart tonic in herbal medicine alongside the likes of digitalin (from foxglove) and strophanthin from the West African plant Strophanthus gratus.

H. niger contains various potent toxins in addition to cardiac glycosides helleborin, hellebrin and helleborein and saponosides and the ranunculoside derivative, protoanemonine. It was searching for information on the compound hellebrigenin (3-acetate) that brought one Sciencebase reader to this site, so here’s the structure of the molecule. This biologically active compound, which also goes by the name (3beta,5beta,14beta)-3,5,14-trihydroxy-19-oxobufa-20,22-dienolide, is a cardioactive steroid compound as well as having been demonstrated (in the 1960s) to have activity against tumour growth.

More on the Christmas Rose here.

Latest chemical discoveries

The latest bumper Xmas issue of Reactive Reports, actually the 61st issue I’ve produced for the site is now online. In this issue we cover:

photovoltaic power station 
Molecular Light Switch
– According to Nobel laureate Roald Hoffmann, “Nanotechnology is the result of the marriage of the synthetic talent of Chemists with a device-driven ingenuity.”

 Blood, Light, and Water – Two molecules that occur naturally in blood have been engineered by scientists from the UK and Japan to use sunlight to split water into hydrogen and oxygen.

stent and fastener Plastic Shape Shifter – Temperature-controlled “triple-shaped plastics” that can change shape from one form to another, then another, have been developed by researchers in Germany and the US.

Top Chemical Discoveries of 2006

My good friend Stu Borman and his colleagues at Chemical & Engineering News (C&EN) have come up with a fascinating mash up of the most important chemical discoveries of 2006.

First up, is the total synthesis of UCS1025A, this esoteric-sounding compound is actually a potential inhibitor of the enzyme telomerase, and the incredibly compact synthesis was achieved by Tristan Lambert and Samuel Danishefsky of the Sloan-Kettering Institute for Cancer Research and Columbia University (J. Am. Chem. Soc. 2006, 128, 426). Inhibiting this enzyme could retard the growth of tumours.

Another synthesis published in JACS is second in Stu’s list. The scheme comes from Elias J. Corey’s group at Harvard University and represents a cheaper and faster way to construct the flu drug oseltamivir phosphate, better known as Roche’s antiviral Tamiflu (J. Am. Chem. Soc. 2006, 128, 6310).

Another synthetic achievement this year is the construction of the compound 2-quinuclidone by Brian Stoltz and Kousuke Tani at California Institute of Technology (Nature 2006, 441, 731). A quick glance at this simple-seeming structure might have you reaching for your Merck Index thinking that surely it must have been synthesised decades ago. But, no, this is the first synthesis of this bicyclic. Their synthetic scheme may provide new insights into biological amide hydrolysis as well as representing a rather aesthetically pleasing synthesis.

You can read about the other syntheses picked out by Borman and his colleagues in C&EN.

Also on their list is research at the frontiers of carbohydrate chemistry, where researchers have developed a high-throughput technique for screening mutant glycosyltransferases (GTs) for biomedical activity. The work could lead to a new generation of designer sugars for a range of medical conditions. Advances in structural biology (chemistry by any other name) achieved Nobel status this year, and crystallography also produced some amazing results in revealing the structure of Dicer, an enzyme that initiates RNA interference (RNAi). Also in this field a new NMR technique, SAIL, on which I reported for SpectroscopyNOW earlier in the year, could revolutionize solution structure determination of proteins.

Molecular biology (also chemistry by another name) features in Borman’s round-up with researchers gaining important insights into the molecular mechanisms of cellular protein production, Alzheimer’s disease, and RNA interference.

In the field of analytical chemistry, a new approach to nanoscale secondary ion mass spectrometry (nanoSIMS) was developed for imaging lipid bilayers at below 100 nm resolution and computational chemistry produced a 3000-member family of artificial cytochrome P450 enzymes for studying how these enzymes metabolize drugs and toxins.

In inorganic chemistry, says Borman, researchers produced previously elusive molecules and atoms, such as P2. Nuclear, polymer, and space chemistry also feature in this year’s round-up as does nanotechnology, not surprisingly.

But, one highlight of the chemical year not mentioned in C&EN, but certainly on my list was the culmination of work at a small laboratory in Northern Ireland that has led to the maturation of work I first wrote about for New Scientist back in the early 1990s and that has now, in its teens, reached a level of application its detractors said could never be – AP de Silva’s research on molecular logic.

Bird flu non-news

Over on foreignpolicy.com they’re reporting the Top Ten non-News Stories of 2006. Among their picks is the non-story of bird flu, or avian influenza as it’s more correctly known. In case you missed it, we didn’t all die of bird flu again this year. However, there were a few people who, having got so scared of the tiny risk that they might catch the H5N1 strain of the disease began taking Tamiflu prophalactically. More fool them, it turned out. Here’s what the site had to say:

“In November, the Canadian health ministry issued a warning on Tamiflu after 10 Canadians taking the drug had died suspiciously. And the US Food and Drug Administration received more than 100 reports of injury and delirium among Tamiflu takers for a 10-month period in 2005 and 2006. That’s nearly as many cases as were logged over the drug’s five-year trial period. For now, the cure seems worse than the disease.”

Highly ironic that a drug taken for its protective effects against a disease that doesn’t really yet exist should have claimed so many victims. Unless we see a sudden spate of bird flu infections in the developed world, 2006 will remain another year in which none of the scaremongerees actually died of bird flu.

Marrying up lost chemistry and chemists

British-born Dick Lewin Wife followed a traditional educational path, receiving his chemistry first degree from the University of Leeds in 1969 and staying on to do an organic PhD with David W. Jones. Research fellowships then took him to London, New York, and finally California, after which he returned to a job in the UK with Shell in 1976, moving to The Netherlands with the company in 1979. He stayed with Shell until 1987 at which point he founded SPECS and BioSPECS BV, in The Netherlands. In 2005, he co-founded a new company, SORD, which aims to find “lost chemistry” and make it accessible to the scientific world.

Read the full story in the latest issue of Reactive Reports online now.

Sniffing out our sense of smell

How we smellOur sense of smell is much better than we give it credit for. A report in Nature Neuroscience puts paid to the notion that the human reputation for having a poor sense of smell compared to other animals.

Noam Sobel and colleagues laid down scent trails in a grassy field, and asked human subjects to find the trail and track it to the end. Subjects were blindfolded and wore thick gloves and earplugs to force them to rely exclusively on smell. Contrary to expectations, the volunteers exhibited some of the same tracking strategies used by dogs and were certainly capable of following the trail.

In follow-up experiments, the authors also demonstrated that this ability partially depends on comparisons of odour information in each nostril, it’s almost like smelling in stereo.

When subjects had one nostril plugged their tracking performance was much worse.

Admittedly, the volunteers were much slower than dogs at following the scent trail, but with practice they got quicker.

the findings raise the intriguing possibility that our sense of smell is far better than we think and that using it more effectively is simply a skill we don’t teach our children so it gives us the impression that we don’t have it.

For more on a provocative theory of how we smell check out this page from the Sciencebase archives.

Influenza’s long tail

A long protein tail found in all influenza A virus raises the possibility of novel drugs that can grab on to it and stop the virus in its tracks. The protein tail is present in common human influenza A which kills thousands of people every year as well as rare forms such as bird flu.

US scientists used crystallography to study the long flexible tail of the influenza virus’ nucleoprotein. They found that even seemingly insignificant changes to the structure of this protein tail prevent it from fulfilling a key role in viral replication. That is, they prevent them from linking together to form structural columns used by the virus to transmit copies of itself.

More…

WEEE regulations

Electrical goodsThe environmental costs of dealing with waste products from old electrical goods will have to be met by the device manufacturers in Europe from July 2007.

Laying the Waste Electrical and Electronic Equipment (WEEE) Regulations before Parliament, UK Science Minister Malcolm Wicks said:

“Electrical waste such as toasters, fridges and washing machines are a growing environmental problem here in the UK with over two million tonnes being dumped in landfill last year alone. There is currently no incentive for those that produce them to care about the life cycle of their products. These regulations will mean they can no longer shirk this responsibility.”

The new regulations were announced in the summer of 2006 to give businesses a decent run up to the deadline. Some producers are already factoring in recycling of their products into the design process, Wicks adds.

According to the DTI (Department of Trade & Industry), the regulations will:

  • Enable consumers to dispose of their electrical waste free of charge at accessible and appropriate places. Consumers will start to see changes from July 2007, with new signage at their local council refuse centres, in shops, and on new electrical products.
  • Give distributors the choice of how to meet their obligations under the Directive by either joining the Distributor Take-back Scheme (DTS) or by offering customers in-store take-back.
  • Allow existing relationships currently managing electrical waste to continue. This is consistent with the Government’s overall approach to regulation, which is to be as ‘light-touch’ as possible.
  • Enable any operator of a designated collection facility (DCF) to arrange with a producer compliance scheme (PCS) to have the electrical waste deposited at their site taken away for treatment and recycling by that PCS, free of charge.
  • Allow for and encourage the re-use of equipment after it has been discarded where possible.
  • Allows for the continued collection of old equipment at the same time of delivering new goods by retailers, and some producers.

Flu mechanics

With the holiday season almost upon us, that means only one thing, flu is also on its way and if the scaremongers are to be believed the long-forewarned bird flu epidemic might follow in its wake any time soon.

Now, US researchers have put to work the 15-ton 900 MHz NMR machine at Florida State U to help them figure out the mechanics of infection by influenza A virus. The common human form of the disease already kills several hundred thousand people every year, and forecasters predict the emergence of a human transmissible form of avian influenza could kill millions more.

“Using NMR helps us build a blueprint for a virus’s mechanics of survival,” explains FSU’s Tim Cross, “The more detailed the blueprint, the better our chances of developing drugs capable of destroying it.” The researchers have found that the virus’ protein coat contains channels that control various biochemical reactions crucial to viral infection and replication.

Read on…

Deafening toys

Thousands of children will receive toys this Christmas that could leave them deaf. That’s the message from UK national charity Deafness Research UK.

According to Brad Backus of University College London’s Ear Institute in a report commissioned by the charity, almost every noisy toy they tested produced noise levels above the recommended safety limit of 85dB(A) when held close to the ear. Prolonged exposure to noise levels above 85dB(A) can cause hearing loss. Half of the toys tested had levels above or very near recommended safety limits when measured at 25 cm – about an arm’s length away.

Not surprisingly, the most hazardous toys were toy guns. A mechanical toy machine gun, a plastic tommy gun, and a cap gun were tested and all were found to have noise levels that exceed recommended limits. It sounds like scaremongering and yet another nanny-ist intervention, but at these noise levels such toy guns could cause serious damage and even instant hearing loss.

Among the toys tested were Pixar Cars “Lightening McQueen”, Fireman Sam’s Action Jupiter and Tomy’s “Spin n’Sound” remote-controlled car. Only one toy, the VTECH mobile phone for babies, was found to have a noise level below the safety threshold although the Pixar toy too had a level just below the threshold at 82.5dB(A).

“Children’s toys clearly have the potential to do harm to their hearing so it’s important that people are aware of the dangers and what to do about them,” says Backus, “With most of the toys we tested, apart from the guns, there is a potential for harm but they’re safe if used sensibly. With most toys, your child will only damage their hearing if they use them too often and for too long a duration, or if they stick them in their ear.”

You can get more advice and help if you suspect your child has a hearing problem by contacting Deafness Research UK on 0808 808 2222.