Category: Sciencebase

We recently reported on how acetaminophen can slow bone growth. Now, researchers in the US are warning that consuming large amounts of caffeine while taking acetaminophen, the widely used painkiller, could potentially cause liver damage. The combination of painkiller and caffeine is a well-known “morning-after-the-night-before” concoction and is often used to deal with an alcohol hangover, which presumably could compound the potential liver damage still further.

A preliminary laboratory study published in the October 15 issue of Chemical Research in Toxicology explains how this toxic interaction might arise not only through drinking coffee and beverages with added caffeine while taking the painkiller but also from using large quantities of medications that combine caffeine and acetaminophen for the treatment of migraine headaches, menstrual discomfort and other conditions. The preliminary bit of this research refers to the fact that it’s only been demonstrated in bacteria engineered to express the appropriate liver enzymes, though.

Of course, health experts have warned for many years that excess alcohol coupled with acetaminophen could cause liver damage and in the worst-case scenario even death. This is the first time that a potentially harmful interaction with the painkiller and caffeine has been reported, and even if it has only been demonstrated to harmful to bacteria you might err on the side of caution and go cafe lite next time you’re popping those pills to quench a hangover.

Years ago, I wrote about the lab-on-a-CD concept (actually it was in the September 2001 issue of Reactive Reports). Now, it seems the use of CD-ROMs and DVDs and the hardware used to play these popular audio and video compact discs (CDs) is coming of age in terms of home health monitoring and laboratory-based testing. Spanish scientists say CD technology could be adapted for tests ranging from the measurement of environmental toxins to at-home disease diagnosis.

Angel Maquieira and colleagues at Valencia Polytechnic University, Spain, have developed a CD with an immunoassay surface coating that can detect three pesticides, 2,4,5-TP, chlorpyrifos, and metolachlor, when samples are placed on the disc. By spinning the disc in a CD player the standard laser light can “read” the chemistry of the bound pesticides and a computer interpret the changes in laser intensity to identify them.

“The obtained results show the enormous prospective of compact discs in combination with CD players for multiresidue and drug discovery applications,” the researchers say. They are now improving sensitivity and versatility.

More information in the journal Analytical Chemistry

Many years ago, I reported on the earliest synthesis of the analgesic compound epibatidine from the poison frog Epipedobates tricolor. You’ll notice I was careful to say poison frog, not poison dart frog. In the prestigious pages of Science in 1993 I wasn’t quite so careful and describes this creature as a poison dart frog.

It was a simple mistake to make as there were dozens of references in the literature to this species as the toxic secretions of this and other frogs as being used in poison darts. However for E tricolor, this wasn’t and isn’t the case. It’s a toxic frog most certainly, but no one has ever tipped their darts with its secretions. The venom in the deluge of letters from readers wishing to highlight and correct my error while I was still a cub reporter writing freelance for the journal via its Cambridge office was enough to make my toes curl.

Anyway, the analgesic properties of epibatidine became famous. Several hundred times more potent than morphine, but with none of the addictive properties of its fellow opiates, it seemed that its career as a new painkiller was set. It has, as you can see from the picture, a quite stupendous chemical structure, which took several attempts to yield a total synthesis. Efforts are still ongoing I see from a quick scan of the current literature. A paper in JOC this month, has Armstrong, Bhonoah, and Shanahan wrestling with an aza-prins-pinacol approach to the 7-azabicyclo[2.2.1]heptanes of which epibatidine and its close cousin epiboxidine are examples.

It still surprises me that so little work seems to have been done to bring this compound and its analogs into the pharmaceutical fold. For instance, only a limited number of analogs have actually been synthesized and evaluated in vitro and negligible numbers have been tested in vivo. Given the enormous market a non-addictive painkiller with opiate-like power might share, I wonder why. Any pharma readers care to enlighten us?

Not spiders, but bees. Researchers at the University of Illinois Urbana-Champaign have identified an odorant receptor that allows male bee drones to find a queen in flight. The receptor is present on the male antennae and can detect an available queen up to 60 metres away, which is quite a feat in chemical detection. This is the first time an odorant receptor has been linked to a specific pheromone in honey bees.

The “queen substance”, a pheromone, was first identified decades ago, but scientists have only recently begun to understand its structure and its role in hive life. The pheromone is a primary source of the queen’s authority. It is made up of eight components, one of which, 9-oxo-2-decenoic acid (9-ODA), attracts the drones during mating flights. It also draws workers to the queen and retards their reproductive growth.

More on this direct from Illinois

A press release just in announced that “Paracetamol, one of most used analgesics, could slow down bone growth”. In vitro tests apparently demonstrated that the compound slows bone regeneration in the proverbial test-tube.

The press release writer missed a serious trick in using the word paracetamol throughout and not mentioning some of the proprietary formulations of the analgesic, which include the far more familiar names Tylenol, Acetaminofen, Acetaminophen, and Amadil, it may be picked up by the US media with that name, but I suspect a headline mentioning Tylenol would be a far stronger grab.

Olga García Martínez of the Departamento de Enfermeria at the University of Granada and colleagues based their analysis on several clinical processes in which accelerating bone growth is required. “Certain anti-inflammatories such as paracetamol should be cautiously taken, especially in situations in which require a rapid bone tissue regeneration, such as after placement of a prosthesis or dental implant is needed,” she says. Other anti-inflammatories that have no such effect on bone growth should be used instead.

The research has not been confirmed in people yet, but somehow the tests on isolated osteoblasts are taken as definitive evidence that the drug will slow bone regeneration in vivo.

Diamonds almost as old as the Earth itself have been found locked in ancient crystals of zircon from the Jack Hills region of Western Australia, according to scientists writing in Nature this week. The diamonds could provide unique insights into the early evolution of our planet’s crust.

Zircons are tough and resist heat and some samples have been shown to be several billion years old. As such, they retain vital clues about the Earth’s geological evolution, at least as far as the crust and mantle are concerned. Recent studies of these ancient crystals have suggested that the Earth may have cooled much faster than previously thought, with the continental crust and oceans forming some 4.4 billion years ago.

Now, Martina Menneken and colleagues at the Westfaeische Wilhelms-Universitaet Muenster, in Germany, have investigated mineral inclusions within zircons and found that some of them contained small diamonds. The zircons have been dated using uranium and lead isotopes and found to be over four billion years old,” almost one billion years older than the previous oldest-known terrestrial diamonds, and present in material that crystallized within 300 million years of the formation of the Earth itself.

The authors suggest that these diamond inclusions formed under ultrahigh-pressure conditions, which implies that the Earth had a relatively thick continental crust and crust-mantle interaction at least 4.25 billion years ago. Diamonds are formed in the earths interior, where they are brought to the surface by volcanoes and it is known as one of the hardest materials on earth.

Steve Ley and his team (some 40 PhD students over the last two decades) have finally cracked the total synthesis of the natural insecticide azadirachtin. This hugely complex natural product extracted from the Indian neem tree put up quite a struggle from the year it was isolated (1968) till its structure was unequivocally elucidated (seventeen years later) till the publication of Ley’s paper in Angewandte Chemie outlining the 64-step strategy for making it from standard starting materials. Check out the Angewandte press site for a more detailed write-up and the paper itself for full details of the completion of these chemical odyssey.

A molecular Möbius strip that can flip between single-sided and double-sided modes has been synthesised by chemists in Poland without snapping the ring.

Lechoslaw Latos-Grazynski and his colleagues at the University of Wroclaw explain that for a molecule to be defined as aromatic it must exist as a near planar ring and have a pi electron system that allows for the free movement of electron pairs between alternating double and single bonds – the classic Hückel topology. Even rings that are twisted into a figure eight can have this topology. However, a molecule with a 180 degree twist has the Möbius topology and there is no distinction between the “upper and lower” pi electron cloud to give it the properties of aromaticity.

The team worked with an expanded porphyrin analogue – A,D-di-p-benzi[28]hexaphyrin(1.1.1.1.1.1) with a figure-of-eight shape having two phenylene six-membered carbon rings at the crossover point. Whether or not these rings are perpendicular or parallel dictates whether or not the molecule is Hückel or Möbius.

Finding molecules of this type are of fundamental importance to understanding molecular topology and aromaticity but the color change inherent in the flip might also allow the compound to be used as an indicator for the presence of other species in a solution, for instance.

You can read more about the study in the current issue of the SpectroscopyNOW.com ezine and see a blue-green morph of Prof Latos-Grazynski.

Atrazine, a herbicide, and some of its degradation products could seep into groundwater and impair water quality across the Florida Everglades, according to Scientists from the USDA-Agricultural Research Service (ARS) and University of Florida. The team reports details of its studies into specific groundwater risk from atrazine in the September issue of the Journal of Environmental Quality.

In the same report, Thomas Potter and colleagues also report how they may have discovered a solution to the potential problem – a herbaceous annual that grows to two meters: sunn hemp.

The studies focused on sweet corn production and investigated whether fields with a highly vigorous cover crop would reduce the impact of herbicide use on the environment. Sunn hemp planted during uncultivated summer periods was found to be effective in reducing weeds and leaching while at the same time enriching the soil. Sunn hemp, not to be confused with cannabis hemp, can be grown to prevent soil erosion, as high-protein forage. The older plants can be used to make cloth, twine, and rope.

InChI=1/C8H14ClN5/c1-4-10-7-12-6(9)13-8(14-7)11-5(2)3/h5H,4H2,1-3H3,(H2,10,11,12,13,14)/f/h10-11H

When nicotine binds to a neuron, how does the cell know to send the signal that announces a smoker’s high? A recently determined crystal structure of a key player in the process suggests that a sugar molecule has a simple mechanical role acting as a hinge to open a gate in the cell membrane. The research might one day lead to new treatments for drug addiction, depression, epilepsy, schizophrenia, and other disorders.

I discussed the issue with Lin Chen of the University of Southern California and you can read the full story in the X-ray crystallography channel on SpectroscopyNOW.com