Monthly Archives: July 2009

Handy Chart for the 2008 Top 200 Drugs

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I ran across this handy pdf file from the website of Prof. Njardason at Cornell. It is a graphic compilation of the top selling drugs (in the USA?). Just click on the image and a pdf will download.  The site has compilations for the last several years as well.

A few of the drugs on the list are protected under patents that will expire in the next few years- Lipitor, Crestor, Lexapro, Advair, Singulair, Plavix, etc. Hours after the license to print money expires, the generic barbarians and visigoths will storm the gates and unceremoniously slaughter these cash cows. The horror, the horror.

Bruker’s New 1 Gigahertz NMR Spectrometer

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June 1, 2009, Bruker announced the release of the AVANCE 1000 NMR Spectrometer. This 1000 MHz (1 GHz) instrument features a standard 54 mm bore within a 23.5 Tesla superconducting magnet. The magnet technology offers subcooling (below the bp of He) in the magnet, which Bruker claims to be necessary for the stability of the magnetic field. Bruker also offers nitrogen-free magnets that are able to keep the helium boil-off rates to a minimum. While it would be nice to avoid having to manage two cryogenic liquids, I wonder what the pay-back time is for the chiller equipment?

Imagine the hassles, begging, and incredulous stares that the users will have to contend with to to get some 1 GHz NMR time? I wonder if anyone will do 1-D experiments with it?

The AVANCE  1 GHz instrument is priced at a cryogenic ~$16,000,000 per copy with an 18-24 month lead time. I’ll have to stick with Anasazi Instruments for a while at least.

Separately, a link at the Bruker website will take you to the University of York where a site dedicated to one groups NMR work with parahydrogen is detailed. A technique called SABRE, Signal Amplification by Reversable Exchange, is described. The exposure of an NMR sample to parahydrogen (singlet H2) results in the transfer of polarization to the sample and subsequent increase in sensitivity.

The workers describe the operation of a device used for the conversion of triplet orthohydrogen to singlet parahydrogen as a ready source of this peculiar “isomer” of dihydrogen. Parahydrogen is the dominant form at 20 K, but drops to 25 % abundance at room temperature. Exposure of a mixture of ortho and parahydrogen to a paramagnetic catalyst does the conversion to achieve enriched singlet H2.

According to one on-line source, the conversion of ortho- to parahydrogen evolves 527 kJ/kg. I’d watch out.

July Lenticular Clouds

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Warmer weather in Colorado brings cloud formations that are characteristic to the summer season. Summer in the Colorado front range typically brings convective activity that boils up cumuloform clouds, some of which accelerate into anvil shaped storm cells that bring rain and hail.

What are not often seen in the summer, at least for a hack weather observer like Th’ Gaussling, are lenticular clouds. These are characteristic of the cooler seasons. Indeed, since I have been following weather here (late 1970’s), I have never witnessed lenticular clouds in July, at least until yesterday. Very curious.

HR 2868- Good intentions gone sour

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There is a fine line between good sense and paranoia and HR 2868 has definitely crossed over into deep paranoia. This resolution, sponsored by Rep. Thompson (Mississippi), Rep. Waxman of CA, Rep. Jackson-Lee of TX, Rep. Markey of CA, and reps Clarke and Pascrell, is an amendment to the Homeland Security Act of 2002.  Its purpose is

“to extend, modify, and recodify the authority of the Secretary of Homeland Security to enhance security and protect against acts of terrorism against chemical facilities, and for other purposes.”

Well, how could anyone be against such a noble sounding piece of code? The sponsors are struggling to protect the homeland against attack on chemical facilities. Facilities whose hazardous material inventories could be maliciously released to cause harm to the surrounding neighborhoods of innocent and helpless citizens.

Sec. 2102 (a) (1) allows the Secretary to designate any chemical substance as a “substance of concern” and establish a threshold quantity for each substance of concern.

There are many goodies and zingers in this bill. Sec. 2115 (a) (1) (A) requires that the Secretary issue regulations for substantial background checks to establish personnel surety in covered chemical facilities. The security check will be deep and will serve as a reservoir of information collected by company on citizen employees and subject to inspection on demand by the Secretary.

Sec. 2116 (a) (1) states that any person may commence a civil suit against any person “who is alleged to be in violation of any standard, regulation, condition, requirement, prohibition, or order which has become effective pursuant to this title; or … “.  This citizen lawsuit provision will open the floodgates to lawsuits on companies running chemical plants and in so doing, under the rules of discovery, break through the IP protection afforded by trade secrecy.

This proposed law also provides for close oversight by the Secretary of Homeland Security as well as civil penalties (Sec. 2107 (b) (1)) of up to $50,000 per day of violation.

OK. Nobody wants acts of terrorism to happen and especially not on the site of a chemical plant. But to legislate the transformation of chemical plants into a “Fort Apache” scenario in the absence of a history of attacks on US plants is to invite needless cost and complication to an industry that is already heavily regulated. This is plainly the result of irrational fearfulness on the part of congressional sponsors. And Congressmen are in a position to convert their fears into law.

Compliance with this law will require considerable effort and expense to be carried by industry. The downside to being out of compliance is too expensive. Over time companies may opt out of processes that use chemicals of concern simply to reduce the risk of noncompliance as determined by government audit.

The chemical industry uses hazardous chemicals of many varieties. Hazardous chemicals are often reactive chemicals. And reactive chemicals are useful chemicals.

The entire chemical industry is built around the exploitation of reactive attributes in order to cause a desired change in chemical composition. The unintended consequence of this legislation is that useful but reactive chemicals may be inherently prone to identification as chemicals of concern. The effect would then be that key substances at the core of a given technology platform would be regulated on the basis of what a terrorist could do with it rather than its value to technology and to civilization.

What constitutes adequate security? Who is to say what security measures are satisfactory? The security industry seems to attract the paranoid who see threats behind every shrub. To have such people deciding what chemical is acceptable for use in manufacturing is unacceptable.

Palin to run for President of Confederacy

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July 3, 2009, Wasilla, Alaska.  Governor Sarah Palin announced her intent to resign from the office of Governor of Alaska. The governor took great care to explain that her continued presence in office was costing taxpayers considerable tax money as well as time lost as she responds to inquiries into her personal affairs.

Standing with her family by her side Gov. Palin said at the outdoor press conference that her family had unanimously voted in agreement that she should stand down from her position as Alaska Governor eighteen months ahead of her term limit. Governor Palin then announced that she would be meeting with leaders of the GOP over so-called articles of confederation. 

When  asked to clarify what she meant by “articles of confederation”, the Governor declined to elaborate.

In response to repeated inquiries, R. Eric Lee, a spokesman for the RNC, held a short phone conference and denied any knowledge of  “articles of confederation” or any movement toward a confederacy “by or on behalf of the GOP”.  

“Anyway,” Mr. Lee continued, ” Speaker Newt Gingrich advises that the word ‘confederation’ is inaccurate and obsolete.”  Lee refused to answer any further questions and promptly halted the interview.

Cyclic Endo Dig

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Several times a week a few of us take a morning bike ride 12 miles out into the countryside. Being exceptionally clever, I decided to take a shortcut through the weeds to avoid a busy intersection. This morning, while bombing through the brush, I plowed into an irrigation ditch and flew over handlebars and landed ass-over-teakettle. Of course, chemists will recognize this as an example of a cyclic endo dig.  Naturally, when something like this happens, the first thing you do is look around to see if anyone witnessed the crash.

Robustness Challenge Tests

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I and my assistant have spent the last month devising experiments that are meant to chart out the stability or robustness of a small set of compounds whose manufacture has been problematic. This has been a kind of a process development activity wherein we are trying to understand what the specific sensitivities of this molecule are and how they might impact process stability.

My job these days is reactive hazards analysis and process safety. We have been trying to dream up experiments that tease out particular weaknesses a compound may have in normal or plausible off-normal conditions. While the compounds in question do not have apparent issues with reactive hazards, the skill set needed to find reactive hazards is useful in finding economic hazards as well.

An economic hazard would be something that threatens the profitability of a process. A production instability is simply a low threshold for a transition to off-normal processing conditions. Sometimes a process instability is physically dangerous and sometimes it is only an economic threat.

I have to say that this has been very enlightening so far.