The Old Days in Organic Chemistry
A look back at the way it used to be, courtesy of ChemTips. What did you do without NMR, without LC-mass spec? You tried all kinds of tricks to get solids that you could recrystallize, and liquids that you could distill. I missed out on that era of chemistry, and most readers here can say the same. But it's a good mental exercise to picture what things used to be like. (Source: In the Pipeline)
Source: In the Pipeline - November 22, 2013 Category: Chemists Tags: Chemical News Source Type: blogs
Things People Won't Listen To?
Here's a podcast interview I did recently for "Science For the People" (formerly known as "Skeptically Speaking", where they quizzed me about some of the "Things I Won't Work With" compounds. The whole show is worth listening to (there's Scicurious and ZeFrank in there, but I come in at about the 38 minutes mark. (Source: In the Pipeline)
Source: In the Pipeline - November 22, 2013 Category: Chemists Tags: Blog Housekeeping Source Type: blogs
A Place to Go For Scientific Whistleblowing
You've seen those "Call for papers" notices, from journals or conferences? Over at Synthetic Remarks, there's a call for whistleblowers. Reacting to the recent reports of scientific fraud, Fredrik von Kieseritzky is asking those who want to get the details of such things out safely to contact him. Swedish law is very protective of sources, and he's basically making that jurisdiction available to anyone for whom it would be in a position to help. He also has some sound advice on how to communicate such things (Tor, PGP, TrueCrypt), which are the sorts of tools that, apparently, the modern world is trying to make sure that e...
Source: In the Pipeline - November 22, 2013 Category: Chemists Tags: The Dark Side Source Type: blogs
Cesium, Uh, Trifluoride?
Here's a very surprising idea that looks like it can be put to an experimental test. Mao-Sheng Miao (of UCSB and the Beijing Computational Sciences Research Center) has published a paper suggesting that under high-pressure conditions, some elements could show chemical bonding behavior involving their inner-shell electrons. Specific predictions include high-pressure forms of cesium fluoride - not just your plain old CsF, but CsF3 and CsF5, and man, do I feel odd writing down those formulae.
These have completely different geometries, and should be readily identifiable should they actually form. I'm thinking of this as ces...
Source: In the Pipeline - November 21, 2013 Category: Chemists Tags: Chemical News Source Type: blogs
The Chemistry Book
I wanted to mention to readers here that I've agreed to write a book (for a general audience) on chemistry for Sterling Publishers (the publishing arm of Barnes and Noble). They've been putting out a series of books (Sterling Milestones) on various scientific topics, looking at 250 key concepts or historical events. There's a short essay on each of these, and an illustration on the facing page. Clifford Pickover did The Math Book, The Physics Book, and The Medical Book for them, and recently they've published The Drug Book, The Space Book, and The Psychology Book as well. So I'm doing The Chemistry Book, which occupies me ...
Source: In the Pipeline - November 21, 2013 Category: Chemists Tags: Book Recommendations Source Type: blogs
Fred Sanger, 1918-2013
Double Nobelist Frederick Sanger has died at 95. He is, of course, the pioneer in both protein and DNA sequencing, and he lived to see these techniques, revised and optimized beyond anyone's imagining, become foundations of modern biology.
When he and his team determined the amino acid sequence of insulin in the 1950s, no one was even sure if proteins had definite sequences or not. That work, though, established the concept for sure, and started off the era of modern protein structural studies, whose importance to biology, medicine, and biochemistry is completely impossible to overstate. The amount of work needed to seque...
Source: In the Pipeline - November 20, 2013 Category: Chemists Tags: Chemical News Source Type: blogs
A New Way to Get Protein Crystal Structures
We present a method, ‘MicroED’, for structure determination by electron crystallography. It should be widely applicable to both soluble and membrane proteins as long as small, well-ordered crystals can be obtained. We have shown that diffraction data at atomic resolution can be collected and a structure determined from crystals that are up to 6 orders of magnitude smaller in volume than those typically used for X-ray crystallography.
For difficult targets such as membrane proteins and multi-protein complexes, screening often produces microcrystals that require a great deal of optimization before reaching the size requ...
Source: In the Pipeline - November 20, 2013 Category: Chemists Tags: Analytical Chemistry Source Type: blogs
Phenotypic Screening Everywhere
The Journal of Biomolecular Screening has a new issue devoted to phenotypic and functional screening approaches, and there looks to be some interesting material in there. The next issue will be Part II (they got so many manuscripts that the intended single issue ran over), and it all seems to have been triggered by the 2011 article in Nature Reviews Drug Discovery that I blogged about here. The Society for Laboratory Automation and Screening set up a special interest group for phenotypic drug discovery after that paper came out, and according to the lead editorial in this new issue, it quickly grew to become the largest SI...
Source: In the Pipeline - November 19, 2013 Category: Chemists Tags: Drug Industry History Source Type: blogs
More on the Open Access Sting Article
I wrote here about the recent article by John Bohannon in Science, where he submitted a clearly substandard article to a long list of open-access publishers. (The results reflected poorly on many of them). Now here's a follow-up interview with Bohannon at The Scholarly Kitchen, where he addresses many of the critiques of the piece. Well worth a read if this issue interests you.
Q: What has been the response of editors and publishers? Have any journals ceased publication? Have any editors/editorial board members resigned in protest? Do any of them blame you, personally, for the outcomes? Have any threats (legal or otherwis...
Source: In the Pipeline - November 19, 2013 Category: Chemists Tags: The Scientific Literature Source Type: blogs
When the "c" in cLogP Stands For "Crazy" (Update: Fixed!)
I don't know how many readers out there use the cLogP function in ChemDraw, but you might want to take a look at the illustration here before you use it again. A reader alerted me to this glitch: drawing in explicit hydrogens sends it into an even stranger world of fantasy than most calculated logP values inhabit. There seems to be a limit, though, as that cyclopropane series illustrates. (Note that the "logP" function resists temptation).
PerkinElmer says that there are several logP calculating functions built in, but that cLogP is from BioByte. I don't think that they got their money's worth from them. Now, this isn't ...
Source: In the Pipeline - November 18, 2013 Category: Chemists Tags: In Silico Source Type: blogs
Cuts at Shire
I'm hearing reports of re-organization and worse at Shire's UK R&D today (Basingstoke). There had been reports in the press earlier this month, but things seem to be underway. The medicinal chemistry situation in the UK is surely the worst it's been in living memory. . . (Source: In the Pipeline)
Source: In the Pipeline - November 18, 2013 Category: Chemists Tags: Business and Markets Source Type: blogs
The Heirloom Chemistry Set
I wrote here about chemistry sets as gifts for science-minded youngsters, and at the time, the only recommendation I could make was the Thames and Kosmos line (which are definitely still worth a look). A reader sends along another possibility, though: the Heirloom Chemistry Set, a deliberate attempt to recreate the classic sets of 50 or 60 years ago. It's not cheap, but it certainly looks like the real deal. This part, though, is cause for concern:
Regarding equipment, while we have shipped custom chemistry sets (both chemicals and equipment) to customers in each of the 50 states for the past 10 years it needs to be noted...
Source: In the Pipeline - November 15, 2013 Category: Chemists Tags: Science Gifts Source Type: blogs
Zafgen's Epoxide Clears A Hurdle
I wrote here about Zafgen and their covalent Met-Ap2 inhibitor beloranib. Word is out today that the compound has passed its first Phase II trial handily, so score one for covalent epoxides as drug candidates.
Zafgen has followed up promising results from early-stage work on its weight drug beloranib with a stellar Phase II study that tracked rapid weight loss among the severely obese, with one group shedding an average of 22 pounds in 12 weeks. CEO Tom Hughes says the mid-stage success clears a path to a Phase IIb trial that can fine tune the dose while taking more time to gauge the longterm impact of its treatment on we...
Source: In the Pipeline - November 15, 2013 Category: Chemists Tags: Diabetes and Obesity Source Type: blogs
Nasty Odor as a Drug Side Effect
If you read the publications on the GSK compound (darapladib) that just failed in Phase III, you may notice something odd. These mention "odor" as a side effect in the clinical trial subjects. Say what?
If you look at the structure, there's a para-fluorobenzyl thioether in there, and I've heard that this is apparently not oxidized in vivo (a common fate for sulfides). That sends potentially smelly parent compound (and other metabolites?) into general circulation, where it can exit in urine and feces and even show up in things like sweat and breath. Off the top of my head, I can't think of another modern drug that has a se...
Source: In the Pipeline - November 14, 2013 Category: Chemists Tags: Clinical Trials Source Type: blogs
Layoffs and Personal Finance
A reader sent along a note about some of the recent layoffs we've been seeing across pharma/biotech companies. Different organizations have very different ways of handling things like stock units and options, and in a layoff one of the key variables is the vesting schedule. Remember, if you have compensation of this sort that hasn't vested, it isn't yours. It may show up in your statements (albeit under its own category), and you will have seen the announcements of it being awarded to you, but until this stuff vests that's all provisional.
I think that most people realize that part, although if you don't, it's going to co...
Source: In the Pipeline - November 14, 2013 Category: Chemists Tags: Business and Markets Source Type: blogs
