Plastic Blood?

I’m a little behind on my ‘interesting papers’ at the moment, but when this story hit the headlines this morning I wanted to talk further about the concepts[1,2].  The RSC was ahead of the curve with their chemical science article last year[3].

The background is that Lance Twyman, (University of Sheffield) has developed a polymer-porphyrin system with potential for acting as synthetic hemoglobin[4,5]. Hemoglobin is the oxygen carrying protein in blood and has a porphyrin unit.  Porphyrin with Fe (II) can bind oxygen reversibly.  The protein structure of hemoglobin protects the oxygen at the active site, isolating the porphyrin and protecting against deactivation.  Synthetic molecules that mimic the properties of hemoglobin must have a mechanism to protect the oxygen species whilst retaining reversible binding.  Twyman uses a hyperbranced polymer based on 3,5-diacetoxybenzoic acid, starting with tetrakis(4-acetoxyphenyl)porphyrin as the core.  The advantage of this system over (for example) a dendritic system with similar structure is that the polymer can be made in one step, eliminating the growth-activation strategy that normally plagues dendrimer chemists.  There are several examples of dendritic hemoglobin mimics but none have as elegant a synthetic method as this one.

The polymer branch, and the porphyrin core. 

 

Blood is made of many different components, of which hemoglobin is just one. Artificial blood must perform a variety of functions including carrying oxygen around the body, but critically the viscosity of blood must also be maintained.  Ideally replacing lost blood should be done with a liquid of similar viscosity to maintain correct cardiac function.   One reason this polymeric porphyrin may be additionally useful is that the polymeric component may be sufficient to increase the viscosity of any solution.

 

The drawbacks of such a system are touched upon briefly by Twyman in the Guardian article [2].  Twyman believes that the polymer will be ignored by the body’s immune system but the experiments to date have been in vitro.  Any polymeric material for human use must meet stringent criteria.  The polymer and any potential breakdown materials must not be toxic.  The polymer can be biocompatible, bioinert, biodegradeable, but close attention must be paid to the ultimate fate of the polymer within the body.  Which organs would it accumulate in?  How and where and when will it breakdown?  These are all questions that must be answered before this system can be applied in medicine, but don’t detract in anyway from the potential life saving usefulness of this discovery.

 

My only concern regarding the articles I’ve seen to day is the use of the term ‘plastic blood’.  I appreciate that it is important to convey concepts to the public but do we really want people associating grocery bags and non-biodegradable landfill disasters with a blood substitute?  I think polymer is a better, although less understood term, in this application.  Plastic is a little too simplified. 

[1] http://news.bbc.co.uk/2/hi/uk_news/england/north_yorkshire/6645923.stm

[2] http://technology.guardian.co.uk/weekly/story/0,,2075544,00.html

[3] http://www.rsc.org/Publishing/ChemScience/Volume/2006/05/artificial_blood.asp

[4] http://www.rsc.org/delivery/_ArticleLinking/DisplayArticleForFree.cfm?doi=b600831n&JournalCode=CC

[5] http://www.shef.ac.uk/chemistry/staff/profiles/twyman.html

   Vanillin

Metric Mental

It seems that it is insufficient merely to obtain funding and produce publications as an academic scientist.  One’s greatness must be somehow assessed, conjuring images of an early scene in Dead Poet’s Society where the greatness of a poem is obtained from a graph.  The Hirsch Index (h-index) was discussed when it was unveiled a while ago on many a blog and internet site.  The RSC has recently publicised a listing of 2000 living chemists based on this calculation.[1]

Hirsch Index calculations for the uninitiated:

A scientist has index h if h of his N_p papers have at least h citations each, and the other (N_p – h) papers have at most h citations each.[2]

So if h=100, we can expect a scientist to have 100 papers with 100 or more citations, and the remainder with less than 100 citations.  Previous metrics have involved quantifying the number of citations or publications only, this gives some measure of relative merit of papers.  There is a web program [3] available to calculate h indices if you feel so inclined.  It also allows distinction between scientists with a couple of great, highly cited papers in their careers, and those who have made broader impact with many well cited papers.

So who is on the chemistry list?[4]  Unsurprisingly the top three are:

1.  E. J. Corey, h = 132, Organic Chemistry
2.  G. M. Whitesides, h=131, Organic Chemistry
3.  M. Karplus, h=127, Theoretical

The list is a work in progress (only 2000 chemists so far, but is interesting reading).  Particularly due to the distribution of Nobel Laureates throughout the list…

 References
[1] Royal Society of Chemistry, Chemistry World News Article, Chemistry World Blog Article
[2] Wikipedia Article on h-index; Nature Article on h-index
[3] Web Program
[4] PDF of Chemistry List (from RSC Website)

Vanillin

Stinky Lab Stuff

Following on from Dylan Style’s theme – chemicals and lab stuff that smells bad.

• “Off” DMF
• t-butyl mercaptan (skunk juice)
• THF (loathsome)
• Benzoic acid (cloying, evil smell)
• Autoclaved stuff
• Someone elses success (ha!)
• Ion exchange resin (cat pee)
• Pentenoyl chloride (cat vomit anyone?)
• Bullshit (mainly in group meetings)

–Cryogen

Square Propellers

Polyhedral Oligomeric Silsesquioxanes are silicon-oxygen cage or ladder molecules.  The cubic form R8Si8O12 has silicons on the corners, bridged by oxygen atoms (making up the edges).  Each corner can be functionalised by a variety of groups – H, vinyl, allyl, aminopropyl etc. 

 

Vinyl Silsesquioxane (these things are hard to draw!)

Bromo-pyrene

JACS ASAP had  a very cool paper this week using octavinylsilsesquioxane and 1-bromopyrene.  Octavinylsilsesquioxane is commercaially available and was coupled to 1-bromopyrene using Heck conditions (palladium catalyst)*.  Varying the ratio of pyrene to cube created 8 to 16 subsituted molecules fo application in organic light emitting diodes.   For monosubsitution at each corner the 8-pyrene form was most abundant, for disubstitution, 14 pyrenes were most abudant, probably due to steric considerations.  Putting so many pyrene derivatives around a small silsesquioxane is hard work.

 When I printed this paper out, I was mesmerized for a few minutes – these molecules are beautiful. They have very high symmetry due to the cube structure and the 14 pyrene molecule is just elegant.  I’m not going to attempt to draw the final products. 

OLEDs were prepared using the 8- and 14- pyrene vinyl silsequioxanes.  The fluorescent efficiency was found to be good, and possibly the highest achieved to date for silsequioxane based emitters.  14-pyrene vinyl silsequioxane gave lower efficiency, probably due to the higher density of pyrene groups and subsequent quenching in the solid state.

Lo et al., JACS 2007; ASAP 

Vanillin 

*Heck reactions are palladium -catalyzed carbon carbon couplings betwene aryl or vinyl halides and alkenes, with base.

Awakenings

Crystals are the ultimate reward for hours of work synthesising new stuff.  Chemists wait with eager anticipation for the sparkling solids that may have been deposited in their flasks.  More often that not, things turn out semicrystalline – a mixture of near perfection and amorphous murk.  What is this blog about?  Well, we wanted to try this science writing/blogging thing.  We have an unhealthy fascination with both crystalline and gooey stuff.  We like the extreme ends of that spectrum, so this is our attempt to meet in the middle, find some common ground and write about stuff that is, to us, semicrystalline.