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.

Contact lenses… more interesting than meets the eye?

So anyone who follows me on twitter might know that I have had some eye issues in the past. I have had blocked eye lid glands which were exacerbated by my repeated wearing of contact lenses and this got me to thinking…what the heck are my contact lenses made from and why were they making my eyes dry?

In 1936, polymethylmethacrylate (PMMA) was introduced and this led to the first commercial example of contact lenses. A big improvement in the industry came in the 1970s when Wichterle1 introduced the soft hydrogel, polymacon or polyHEMA (poly-2-hydroxyethyl methacrylate). HEMA is synthesised from methacrylic acid and ethylene or propylene oxide and then polymerised to give polyHEMA.

Polymacon (or Soflens by Bausch & Lomb) was quickly followed by a range of soft contact lenses made from hydrogels. It was swiftly understood that the cornea uses oxygen to maintain its function and obtains this oxygen from the air and with this knowledge in hand contact lenses rapidly improved. 2

Soft contact lenses worn by most people now are still made from hydrogels. A hydrogel is a network of hydrophilic polymer chains that is insoluble in water.  The main advantage of hydrogels is that they are very highly absorbent and may absorb up to thousands of times their dry weight in water. To be a hydrogel, water must constitute at least 10% of the total weight (or volume) of the polymer. When the content of water exceeds 95% of the total weight (or volume), the hydrogel is said to be super-absorbent. Have you ever noticed that when you leave your contact lens out of the solution it shrivels up and hardens but when you put it back in solution it becomes soft and flexible again? This is because it is a hydrogel.

Simply put, hydrogels work by highly electronegative atoms (from polar groups) in the polymer causing a charge asymmetry which favours hydrogen bonding with water. There are two types of hydrogels:3

Chemical/Permanent hydrogels

–      Covalently cross-linked

–      Absorb water until they reach equilibrium swelling

–      High stability in harsh environments (high temp, high/low pH)

Physical/Reversible hydrogels

–      Non-covalently cross-linked (e.g. electrostatic interactions)

–      Weaker and more reversible form of interaction

–      Respond to changes in temperature and pH

Contact lenses are required to do a lot: maintain a tear film for clear vision, sustain normal hydration, allow oxygen to permeate and be non-irritating and comfortable. The lens must have excellent surface characteristics being neither hydrophobic nor lipophilic (and there are many publications on the surface properties of contact lenses should you want to find out more). It is pretty amazing that they do all this work whilst allowing us to see properly. Interestingly, the reason we are supposed to only wear our contact lenses for only ~12 hours a day is because keeping them in too long can cause continuous corneal hypoxia. Hydrogel-based contact lenses are thought to reduce this as oxygen can diffuse through the lens. Contact lenses can be a made from a range of polymer hydrogels, many of which now contain silicone as these are thought to allow more oxygen to the eye and therefore lead to healthier eyes.

As the name suggests, hydrogels form sticky gel like materials which can be used in a wide variety of applications from drug delivery to tissue engineering.  There are some great reviews on hydrogels in biology and medicine by Pappas and Langer4 and Hoffmanand I highly recommend reading more because hydrogels really are interesting things!

I haven’t gone into the polymer chemistry involved in the synthesis of hydrogels but I hope you have learnt something about the gooey things we put in our eyes on a daily basis.

1     O. Wichterle, D. Lim, Nature, 1960, 185, 117-118.

2     P. C. Nicolson, J. Vogt, Biomaterials, 2001, 22, 3273-3283.

3     A. Hoffman, Adv. Drug Deliver. Rev., 2001, 944, 62-73

4     N. Peppas, J. Z. Hilt, A. Khademhosseini, R. Langer, J. Adv. Mater., 2006, 18, 1345.

5      I. Fatt I, R. St Helen, Am. J. Optom. Physiol. Opt., 1971, 48, 545

Chemistry at the hairdresser

So, very recently I spent four (yes, really) hours sat in my hairdresser’s chair. After having read all the trash about what all those celebrities were up to and what ridonculous items of clothing I should be wearing in this so called British summer, I got to thinking about chemistry, more specifically, what transformations were actually happening to me and my hair, other than me slowly but surely looking like an alien from the planet Foil.

So what chemical processes have my ~100000 strands of hair gone through?

Hair is mainly keratin, the same protein found in skin and fingernails. The natural colour of hair depends on the ratio and quantities of two proteins: eumelanin and pheomelanin. Eumelanin gives us the brown/black hair shades (my natural colour) whereas phaeomelanin is responsible for the red based colours. Conversely, the absence of either type of melanin protein produces white/gray hair. 1

Hair dyeing by oxidation been practiced for well over 100 years and came from the observation that colourless p-phenylenediamine (shown below) produces a coloured compound when subjected to oxidation, and that this reaction could be used to colour a variety of substrates. The first patent relating to oxidation dyeing of human hair was applied for in 1883 by Monnet (F.P. 158,558).2 More scientifically put, permanent hair colouring involves the in-fibre formation of indo-dyes from colourless precursors by oxidation with hydrogen peroxide, under alkaline conditions. The primary intermediates are p-phenylenediamines (shown below) or p-aminophenols which are easily oxidised by hydrogen peroxide to form p-benzoquinone imines. 3

The use of hydrogen peroxide to develop the colour also allows for bleaching of the natural pigment by one or two shades at the same  time as the synthetic  colour is being formed.

The mechanism of oxidation dyes involves three steps:

  • The first step shows the oxidation of p-phenylenediamine (or similar stuctures, below) to the quinonediimine derivative

  • The second step involves the attack of this quinonediimine on the coupler (with chosen colour properties) by electrophilic aromatic substitution.
  • In the third and final step, the product from the quinonediimine-coupler reaction oxidises to the final hair dye.

Hair can also be dyed by bleaching of the hair’s natural pigments only. Bleaching is simply the removal of colour from hair. Bleaching can be caused by the sun’s ultra violet rays breaking bonds in the pigment molecules but hair bleaching is most commonly achieved by using hydrogen peroxide. Typically, a low volume of peroxide (5-30%) is applied to hair and left until the required amount of colour is stripped from the hair, at which point it is rinsed out. Before the bleach can change the colour of the hair, however, it must first penetrate below the surface of the hair’s cuticle. This is achieved by mixing the peroxide bleach with an alkaline solution, most commonly ammonia. The ammonia swells the hair fibres causing the cuticles to separate and open allowing the bleach to penetrate the cortex of the hair. This cuticle opening effect is also important when colour is being added to or implanted into the hair.

Hydrogen peroxide reacts with the melanin within the hair and in an irreversible reaction, the peroxide oxidises the melanin which renders it colourless. Complete bleaching tends to leave hair a pale yellow colour rather than pure white, however.

A really good review on hair dye in the modern world has been written by Christie and Morel. Well worth a read if you want to know more about dyes.

1            J. F. Corbett, Dyes Pigments, 1999, 41, 127-136.

2            J. F. Corbett, J. Soc. Dyers Colour., 1976, 285-303.

3            C. Incorporated and A. Seminar, J. Soc. Cosmet. Chem., 1984, 310, 297-310.

4            O. J. X. Morel and R. M. Christie, Chem. Rev., 2011, 111, 2537-2561.

5            http://www.chem.shef.ac.uk/chm131-2003/cha02js/dye.html