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Sierpinski triangle made easy

20 September 2014 - Fractals

pierkinski triangle Newkome 2014.PNGOne step beyond a dendrimer is a Sierpinski triangle. Imagine a first-generation dendrimer with each extending unit having three arms and then close the edges. Synthesizing a molecule based on this concept may seem a mission impossible but the George R. Newkome team (of dendrimer fame) has reported they pulled it off (Sarkar et al. DOI). Even in a one-step reaction by self-assembly.

The precise procedure involved reacting a 1:1 mixture of two particular terpyridine units, one K-shaped and one V-shaped, in a methanol solution of a cadmium salt. Adding hexafluorophosphate after 30 minutes made sure the cadmium ions are countered by PF6-. Yield 95%. As evidence for the purity the methoxy groups showed up at the expected places in the correct ratio in NMR. Furthermore the blobs visible on the TEM image have the correct dimensions and even hint at triangles. Sierpinski triangles made easy!

Melamine detection at 20 ppm

16 September 2014 - Food safety

melamine in milk detection.PNGMelamine and milk share a connection ever since the 2008 Chinese milk scandal. You are not supposed to find the compound in it and detection methods have been discussed here ranging from the expensive to the cumbersome. There is always a market for new analytical chemistry and a group of Chinese researchers report on a novel idea here featuring a certain peptide and cyanuric acid.

The peptide is known to self-assemble into nanofibers in plain water or milk. Cyanuric acid units attached to the peptide will end up at the outer surface of the fibers. With a sufficient concentration of melamine, melamine cyanurate adducts will cross-link the fibers causing the formation of a hydrogel. Laboratory testing does not ignore theory and gelling can be visibly detected in milk containing 0.5% (w/w) of the peptide and 20 ppm of melamine after 30 minutes.

Well, not entirely new: cyanuric acid involvement is featured in this 2009 report here. The method will also fail if the milk adulteration is caused by melamine cyanurate in the first place.

Tramadol is not a natural product

13 September 2014 - Pharma

Last year a French - Cameroonian - Swiss team reported they had isolated the compound tramadol (0.4% by weight) from the root bark of the Cameroonian medicinal plant Nauclea latifolia (Boumendjel et al. DOI). This is unexpected because tramadol was until then only known as a synthetic pain-killer as a simplified morphine derivative.

The finding was also somewhat expected because in Cameroon the root bark is used in traditional medicine in pain relief. With hindsight, the finding that the compound was isolated as a racemate just like synthetic tramadol should be a warning sign. On the other hand the researchers did make an effort to exclude the possibility of contamination by synthetic tramadol by isotope analysis.

Brand new research by a German - Cameroonian team now expresses serious doubt (Kusari et al. DOI). Their interest in the Boumendjel work was triggered by the isotope results and on re-examination with fresh samples they found: 1] much less tramadol (up to 0.0000017% by weight) in samples from one region and 2] no tramadol at all in samples from another region. Another finding explains it all: in the first region, local farmers were found to deploy synthetic tramadol as stamina enhancers for themselves and for their cattle when used as draft animals. In region number two this practice was unknown.

The team then went on to isolate tramadol from ground samples and water samples in general and were then confident to conclude that the tramadol found in the plant sample had originated from from synthetic tramadol passed through the urine of humans and cattle.

Note added: removed comment on enantiomeric composition

Nicolaou on drug development

06 September 2014 - Pharma

It would be a disappointment if someone like K.C. Nicolaou would write an essay on the present and the future of drug development along the lines that everything that is being done is simply fantastic. The opening line of his essay on this very topic in the Angewandte then is not an encouragement: The recent successes of the pharmaceutical enterprise are undeniable and extraordinary (DOI). K.C. Nicolaou does not read blogs. Luckily the text is not devoid of quotable segments.

On strategies : It is particularly disappointing that the human genome project has not as yet had the expected impact on drug discovery, Disappointingly, other developments that started in the 1990s, such as the combinatorial chemistry and high throughput screening of random compound libraries, also failed to impact dramatically the drug discovery and development process.

On conservative and non-innovative organic chemists: it is surprising that so many of the essential experimental techniques employed in laboratories of organic synthesis today are very similar, if not the same, as those employed one or even two generations ago, in contrast to the rather dramatic increase of useful reactions for molecular construction and improvements in analytical instrumentation in the same period.

What does not always work: Several important and long-lasting drugs of natural origin such as Taxol, amphotericin B, and vancomycin, for example, lie outside the rule of five and, in that respect, they are inspiring

And what may work: Interestingly, the first drugs to be approved for use against new targets in recent times are those emerging from research directed toward orphan or rare diseases