Werner_Heisenberg_Log

Werner Heisenberg's Log:

23rd September, 2010: Considering researching into cancer-related topics. Maybe in relation to a specific chemical, like Coumadin, for therapy purposes. Alternatively, maybe a look into the HPV vaccine's efficacy in preventing prostate cancer in men.

30th September, 2010: Coumadin is a brand name for Warfarin, an anti-coagulant. Possible secondary sources: http://chestjournal.chestpubs.org/content/126/3_suppl/204S.full (via Wikipedia) http://www.chemspider.com/Chemical-Structure.10442445.html

The CHEST journal presented a possible topic for the research project, relating patient's warfarin therapy to levels of vitamin K: "Subjects receiving long-term warfarin therapy are sensitive to fluctuating levels of dietary vitamin K,[|64][|65] which is derived predominantly from phylloquinones in plant material.[|65] The phylloquinone content of a wide range of foodstuffs has been listed by Sadowski and associates.[|66]"

7th October, 2010: Decided on the last two properties, and discovered a nice resource: http://zusammen.metamolecular.com/2009/03/09/sixty-four-free-chemistry-databases-serialized Hunted down a few more sources for Warfarin properties.

14th October, 2010: Re-evaluating links to remove non-primary sources, to insure links still correctly point, and to neatly format links. Also need to replace molecular weight, as it's a computed quantity, not a measured one. Density?

10th November 2010: Interesting [|article] on the history and discovery of warfarin. May summarize that for the class.
 * [good choice JCB]**

11th November 2010: Finished 5 properties, and summarized the article mentioned on 10th November.

__**5 Properties of Warfarin**__ LD50 in Rats (Oral): melting point: molecular weight: Solubility (in water) Stability:
 * 135 mg/kg ([|Knovel])
 * 3 mg/kg to 186 mg/kg ([|Oxford])
 * 10 mg/kg ([|InChem])
 * 3 mg/kg ([|Cornell])
 * 3.0 mg/kg ([|Journal of Toxicology and Applied Pharmacology])
 * 161-162 °C ([|Oxford])
 * 197.13 °C (predicted) ([|ChemSpider])
 * 161°C ([|InChem])
 * 162-164 °C ([|Chemical Book])
 * 161 °C ([|Knovel])
 * 308.35g/mol ([|Knovel])
 * 308.33 g/mol ([|Sigma Aldrich])
 * 308.3 g/mol ([|SDPS])
 * 308.328 g/mol ([|Wolfram Alpha])
 * 308.33 g/mol ([|Chemical Book])
 * 1.7 mg/100 ml @ 20 ° C ([|DrugBank])
 * none ([|NIOSH])
 * 1.7mg/100 ml @ 20 ° C ([|Oxford])
 * 5.427mg/100 ml @25 ° C ([|ChemSpider])
 * 1.28 × 10−5 M @25 ° C ([|Journal of Pharmaceutical Sciences])
 * Stable. Incompatible with strong oxidizing agents ([|Oxford])
 * Low volatility. It is practically insoluble in water. The rate of degradation is relatively slow ([|InChem])
 * Evaporation at 20°C is negligible. Reacts violently with strong oxidants causing fire and explosion hazard ([|NIOSH])
 * Contact with strong oxidizers may cause fires and explosions ([|Chemical Book])
 * When heated to decomposition, emits toxic fumes of K2O([|Knovel])

__**Article Summary**__ [|article]
 * [Full marks - but email me your name so I can assign grades JCB]**
 * In the early 1920s, healthy cattle grazing on wet sweet clover hay in Canada and the northern United States began dying with no apparent cause. As livestock was a pivotal industry, and the Great Depression had economically stretched North America, two veterinary surgeons, Schofield and Roderick, concluded that 'sweet clover disease' was a coagulation disorder caused by plasma prothrombin defect; reversible if blood were transfused into the bleeding cattle.
 * Ed Carlson, an exasperated Wisconsin farmer, brought his dying cow 200 miles through a blizzard to an agricultural experiment station, where he brought a can of the dying animal's blood to Karl Link and Wilhelm Schoeffel. Link and Schoeffel began isolating the active component responsible for sweet clover disease, as only the source of the disease was known at that time.
 * Using an //in vitro// clotting assay, and 6 years of work, 3,3′-methylene-bis[4-hyfroxycoumarin] was crystallized. In the moldy hay, the coumarin was oxidized, causing the clotting disorder when ingested. Funding for the work was provided by the Wisconsin Alumni Research Foundation (WARF), and large-scale isolation was accomplished by Mark Stahmann.
 * in 1945, Link had the idea of using oxidized coumarin as rat poison, and the 42nd variant became known as warfarin, after the supporting foundation. In 1948, warfarin was marketed as a rodentcide.
 * The transition of coumarin from rodentcide to clinical applications was made under the name Coumadin, and administered orally, making it a more viable option than heparin-based anti-coagulants. The most important difference between heparin and Coumadin was the ability to reverse Coumarin's effects with vitamin K.
 * When President Eisenhower suffered a heart attack, Coumarin was administered to treat the clotting. The success of it's use prompted wider clinical usage.
 * Dosage control of warfarin became a problem as the measure of clotting time, the prothrombin time, varied greatly depending on the sensitivity of the thrombroplasins used to measure the PT. Different sensitivities in the UK and US versions prompted the World Health Organization to create an international standard for anticoagulant control.
 * in 1960, the first randomized clinical trials for warfarin were performed on patients with pulmonary embolisms between heparin and a control, than heparin and acencoumorol. Heparin with acencoumorol resulted in none of the 60 patients extending their condition. No matter what combination was administered, patients who received the proper dosage within the first 24 hours saw an almost 10-fold decrease in recurrence rate.
 * Differences in practice between the US and UK dosage practices resulted in controversy that was not resolved until the WHO standardized procedures.
 * As heparin use developed, lower molecular-weight heparins were preferred, as the clotting time was much more predictable. The predictable nature of the low MW heparin also allowed for dosages to be calculated based on body weight, without adjusting the dosage based on patient response.


 * [you might find [|this] of interest too JCB]**