Professor Shawn Collins of the University of Montreal visited us today as the external examiner at Ramsey Beveridge’s PhD defense (Ramsey is one of Rob Batey’s PhD students). The defense went really smoothly and it was great to hear about Ramsey’s accomplishments in the area of total synthesis of macrocyclic natural products. Shawn gave a really nice talk earlier in the day. Some of his lab’s methods tackle the challenge of ring-chain equilibrium in macrocycle synthesis. They bias reactions away from oligomers and polymers without relying on high-dilution. In order to do that, Shawn resorts to biphasic systems that sequester catalysts in a highly polar and/or hydrophilic phase through the use of hydrophilic ligands (http://pubs.acs.org/doi/abs/10.1021/ja208902t). Time and again, it was clear that polyethylene glycol (PEG) has been playing a major role in this research. Shawn’s talk reminded me of a discussion I had with Professor Frey at the University of Mainz last week where we were contemplating some of the mysteries of PEG. Seriously, what is the deal with all these linear PEG-like polyethers? PEG is widely used in areas that range from drug formulation to materials chemistry. The bizarre solvent properties of this and related polether polymers are perhaps best illustrated using a comparison shown below. It is intuitively clear that addition of a methyl group to PEG would increase hydrophobicity, which is the experimentally observed result with PPG (it becomes less water-soluble). However, removal of a methylene group from PEG leads to POM, which is not soluble in water at all (remember those clamps for holding flasks in fume hoods? They are made of POM…). There are models that aim to rationalize this difference in properties and one of them suggests that solvation of water accounts for the observed difference in properties.
amphoteros 
Definitely PEG is an amazing material. Even though it has been widely used for a long time and numerous PEG-focused papers has been published, the origin of its astonishing properties is still unclear and it is still being used as a ‘black box’. I have seen several papers trying to deal with the PEG hydration structure you mentioned, but the calculated number of water molecules per single PEG unit ranged from one to four.
I really enjoy your blog, keep on!
Thanks a lot for the comment. This is fascinating stuff. I would also note that PEG is the key ingredient in our protein crystallization work with SGC. Their standard procedures call for screening of various combinations of PEG and salts in efforts to cause proteins to crystallize.
I make functionalized PEGs from ethylene oxide on half-kilo scale all the time, we are using them as a starting material for bio-compatible polymeric detergents (PEG is the hydrophilic part, a random peptide from greasy L and D aminoacids is the hydrophobic part). I remember my boss explaining to me once this solubility paradox. PEG apparently can worm around and displace individual water molecules while not perturbing the structure of liquid water.
There is couple of unusual properties of PEGs: Pure PEGs in range 1-15 kDa, with narrow Mw dispersity, are highly crystalline and form several polymorphs, depending on the solvent system and temperature used for precipitation, and some solid forms of PEG are exceptionally fluffy (density 100g/liter) and static when dry – it is quite a fun to try to pack them into plastic bottles. The viscosity of PEGs in water solution is relatively low (compared to other polymers) and it further decreases with salinity, I have been filtering fairly concentrated 12kDa PEGs in nearly saturated brine (20% PEG solution in about 30% NaCl) through sub-micron size filters, to remove colloids from hydrogenation on Pd-C, and it filtered like water. The solubility of higher PEGs is contra-intuitive: They like benzene but are insoluble in ether and MTBE, and the solubility in alcohols (EtOH, iPrOH) is limited. And so on.
Well, what an enigma! Amazing stories.
one more thing: POM is paraformaldehyde capped with methyl groups at ends. Paraformaldehyde depolymerizes readily from its hemiacetal ends, capping it greatly improves stability… under neutral conditions. (I am working currently on inorganic chemistry of ruthenium complexes, the stuff is made in refluxing concentrated HCl at 80C, and those plastic Keck clips made from POM really despise it – they are cracked and done after single use)
Ha! This is pretty cool.
One more PEG-magic-trick, this time in solid state – conformational change of PEG single unit triggers single crystal transition:
http://onlinelibrary.wiley.com/doi/10.1002/anie.201402560/abstract
And definitely there are many more things to be discovered about PEG.
This is actually really interesting and perhaps suggests why PEG is so critical in protein crystallization experiments. I will read this paper carefully. Thanks!