I am the captain of Team Fluorine

So..I thought it about time I joined in with #ToxicCarnival since I spent 3.5 years of my life playing with oh so scary elemental fluorine for my PhD.

According to gospel Wikipedia “above a concentration of 25 ppm, fluorine causes significant irritation while attacking the eyes, respiratory tract, lungs, liver and kidneys. At a concentration of 100 ppm, human eyes and noses are seriously damaged”. The MSDS of fluorine also states that fluorine gas is corrosive to exposed tissues and to the upper and lower respiratory tracts.  Fluorine penetrates deeply into body tissues and will continue to exert toxic effects unless neutralized.  Workers should have 2.5% calcium gluconate gel on hand before work with fluorine begins. Fluorine also reacts violently and decomposes to hydrofluoric acid (which has previously been described as part of #ToxicCarnival) on contact with moisture.  Fluorine is the most powerful oxidiser known.  It reacts with virtually all inorganic and organic substances.  Fluorine ignites in contact with ammonia, ceramic materials, phosphorus, sulfur, copper wire, acetone and many other organic and inorganic compounds.

As you can tell, it is pretty darn unpleasant. Thankfully, the very pungent odour is detectable at concentrations as low as 20 ppb so you have time to escape, should you come across a fluorine leak.

A little history lesson… Fluorine was isolated successfully over a century ago by Moissan (Ann. Chim. Phys., 1891, 19, 272.) who gained a Nobel Prize in 1906 for his achievement. He produced fluorine by electrolysing a solution of potassium hydrogen difluoride in non-conducting liquid anhydrous HF. The electrolytic cell was constructed from platinum/iridium electrodes in a platinum holder and the apparatus was cooled to -50 °C. Today, fluorine is still manufactured using this electrochemical process.

The first large-scale production of fluorine was actually associated with the Manhattan Project during World War II, where uranium hexafluoride (UF6) was used to allow separation of the 235U and 238U isotopes. The radioactive uranium was used for the construction of the first atomic bombs in 1945 and uranium refining for nuclear energy is still one of the major uses for elemental fluorine.

So..so far you have learnt that fluorine is scary stuff and can be used to make atomic bombs. Now I am going to tell you why we should all love fluorine a little more.

Organo-fluorine compounds are almost non-existent as natural products but these days 20–25 % of pharmaceuticals contain at least one fluorine atom with these drugs treating a huge variety of diseases. One of the earliest synthetic fluorinated drugs was the anti-neoplastic agent 5-fluorouracil, an anti-metabolite first synthesised in 1957 (Nature, 1957, 179, 663-666). It shows high anticancer activity by inhibiting the enzyme thymidylate synthase, thereby preventing the cellular synthesis of thymidine. Since 5-fluorouracil, fluorine substitution is commonly used in med. chem. to improve metabolic stability, bioavailability and protein–ligand interactions amongst other things. An increasing number of related fluorinated anti-tumour agents have now becoming available as cancer treatments, including 5-fluoro-2’- deoxyuridine and its derivatives (Frontiers Biosci., 2004, 9, 2484-2494).

5-Fluorouracil is synthesised by bubbling fluorine through a solution  of uracil in a high di-electric constant solvent. If used correctly and safely fluorine can be a cheap and easy reagent, especially in large scale synthesis. EASY PEASY! Other fluorinating agents (mainly N-F) are seen to be an easier and safer alternative but these reagents can be expensive and wasteful. Using elemental fluorine is really all about knowing how to use it, for example it is best when the reaction is carried out at around -10C as a low concentration mixture in nitrogen. The key is to stop the competing radical reaction and promote the electrophilic process by polarising the F-F bond.

So what have we learnt?

1) fluorine is toxic and smells bad

2) fluorine can be used to make life-saving drugs (cheaply and easily if the infrastructure is in place)

3) I love fluorine a little too much.

If you want to know more about elemental fluorine in synthesis then check out publications by R. D. Chambers, G. Sandford and S. Rozen. All legends in their own right.

If you want to know more about fluorine, then just get in touch. I may or may not know the answer but I will probably be able to point you in the right direction.

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4 thoughts on “I am the captain of Team Fluorine

  1. Other resources for fluorine fans:

    http://www.rsc.org/periodic-table/element/9/fluorine
    http://www.rsc.org/chemistryworld/podcast/element.asp?atomicnumber=9

    And for a little more info on 5-fluorouracil, and 5-fluoro-2’-deoxyuridine:

    http://www.chemspider.com/Chemical-Structure.3268.html
    http://www.chemspider.com/Chemical-Structure.5586.html

    And for a completely different application of fluorous compounds I’d point people to the work of Prof. Dennis Curran http://radical.chem.pitt.edu/Projects/Projects.html who does really cool thing with fluorous tagging, reagents and separations.

  2. Pingback: Toxic Carnival: Day Four | ScienceGeist

  3. you would be amazed – there are several families of tropical plants in Australia and Africa that are insidiously deadly-poisonous because they contain fluoroacetic acid, of all things. The metabolic pathway is bizarre too, it uses C5 of sugar unit of AMP to create C-F bond, if I remember correctly

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