The other day I made an offhand comment that the chirality problem was nowhere being solved. Yellow Shark was nice enough to provide a link to new research published in November, 2008. Now I was referring to scenarios which could occur in nature, not in lab conditions, and so I contacted some friends to see what they thought and to see if the research was indeed relevant to OOL scenarios.
Noorduin WL, Izumi T, Millemaggi A, Leeman M, Meekes H, Van Enckevort WJP, Kellogg RM, Kaptein B, Vlieg E, Blackmond DG. 2008. Emergence of a Single Solid Chiral State from a Nearly Racemic Amino Acid Derivative. Journal of the American Chemical Society 130 (4):1158-1159 • DOI: 10.1021/ja7106349
Many carbon-based molecules, including most amino acids, exist in mirror image forms designated either R or S enantiomers. Individual amino acids incorporated into proteins are enantiomerically pure, although some bacteria modify them to the other enantiomer after translation. When amino acids are made outside of living things, they typically come in a racemate; a 50:50 ratio of the R and S forms. How did proteins composed of enantiomerically pure amino acids come to be? One Darwinian speculation posits that they were produced from an enantiomerically pure solution of amino acids.
Noorduin et al. http://pubs.acs.org/doi/pdfplus/10.1021/ja7106349 experimentally demonstrated a technique for producing enantiomerically pure crystals and proposed a mechanism. Does this mean that the problem chirality presents for chemical evolution has been solved? Read on and judge for yourself.
When enantiomers form crystals, the crystals have different geometries resulting in enantiomerically pure differently shaped crystals reflecting the different geometries of their R and S enantiomer subunits. This phenomenon allowed Louis Pasteur to discover different enantiomers of tartaric acid, contributing greatly to modern understanding of stereochemistry. The technique of Noorduin et al. takes advantage of the same phenomenon.
A mixture of R and S crystals of the imine of 2-methyl-benzaldehyde and phenylglycinamide (a large complex molecule with a chiral center) was partially dissolved in methanol or acetonitrile, and stirred vigorously until equilibrium between the dissolved and solid phases of the solution was reached. Then glass beads were added along with a slight excess of one enantiomer and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) – which catalyzes rapid conversation between the R and S enantiomers. Under these conditions, the original mixture of crystals converted over a matter of days to weeks to become purely which ever enantiomer was initially in slight excess. A similar result was achieved by seeding the solution with enantiomerically pure phenylglycine (Phg), possibly because it provided a chiral template for the larger and more complex molecules already in the solution.
What was so special about the glass beads? It seems they constantly abrading crystals resulting in faster dissolution of smaller abraded crystals while larger crystals tended to grow because they dissolved more slowly. The equilibrium was shifted in the direction of one enantiomer or the other by a dynamic process in which whatever crystal was present in the greatest abundance accrued new molecules in the configuration necessary to fit into the geometry of the crystal lattice while the other enantiomer in solution was constantly changed via DBU catalysis into the one that fit.
The authors propose that, while multiple artificial factors contributed to the rapid formation of enantiomerically pure crystals in this experiment, given eons of time a similar process could produce the enantiomerically pure solutions of amino acids that formed the first abiotically produced proteins.
That seems optimistic and untestable. Tellingly, simply stirring the solution without glass beads produced no enatiomeric excess and the other conditions used in this experiment do not reflect what could be realistically expected prior to life. On earth, the solvent would presumably be water, not methanol or acetonitrile, amino acids would need to be in such abundance that they precipitated, conversion between R and S enantiomers would presumably lack a catalyst and even if it didn’t, the production of proteins would have to occur in (or very close to) the solution of amino acids, not in the enantiomerically pure crystals. In other words, the solution of amino acids in this mechanism remains a racemate, which calls into question its utility as a starting point for enantiomerically pure proteins.
It is hard to conceive of where more favorable conditions could have existed in outer space if that is where biological molecules came from. Furthermore, the large molecules used by Noorduin et al. were not amino acids or other biologically abundant molecules.
Much as the Miller-Urey experiment demonstrated that it is possible to produce insignificant yields of a very few biologically important monomers in a laboratory device, Noorduin et al. demonstrated that chemists are capable of producing enantiomerically pure crystals under laboratory conditions. This laboratory technique fails to show a mechanism by which enatiomerically pure solutions of all 20 amino acids used in protein construction may have existed before the advent of life, not to mention the other chiral molecules found in living things. As a consequence, the chirality problem for chemical evolution remains unresolved by this technique.
Timothy G. Standish, PhD
Geoscience Research Institute
Loma Linda, California
Now Tim and another ID proponent had a conversation on this topic and they were nice enough to send me a copy.
The solvent issue was what struck me. I haven’t seen the crystallography data, but sometimes the solvent is part of the crystal structure or is at least a very important contributing factor – you want a crystallization solvent where the compound is soluble, but not too soluble so that it will promote crystal growth. Acetonitrile and methanol are not what I would expect on an early earth.
Tim: Yes, the solvent does seem relevant here. I’m assuming the solvent on a prebiotic earth would be water, but given the different solubility of different amino acids (not to mention other chiral molecules essential to life) how you would get anything like the conditions they used stretches the imagination. The idea that any amino acid would be present in such high concentrations that it was precipitating in water is incredible.
I question the validity of this experiment as an explanation of the early earth when a catalyst is used. Please correct me here if I’m wrong, but a catalyst only affects the kinetics of a reaction, and theoretically if this catalyst were not present then given enough time we would eventually get the same product. However, just because on paper the thermodynamic equations say this reaction is spontaneous, that doesn’t mean that the amount of time required to get this product is feasible, even on a large scale. And this might have been covered in the paper and I missed it, but how do we know that the product is the thermodynamic product and not the kinetic product? Since you’re using a catalyst, then how do we know that the reaction, left to itself over millions of years would produce this product at 100% of one enantiomer?
Tim: If a catalyst is present, it defeats the purpose of the experiment as it keeps the amino acids in solution a racemate. The proteins were not made from crystals, they were presumably made in a solution of amino acids. Here is how I can conceive of something working. Let’s say the D crystal is very insoluble for some reason and that it snaps up every D-amino acid that comes by, kind of like Maxwell’s demon. If the rate of conversion from L to D was very slow and the concentration of amino acids was high and there were lots of D crystals with lots of surface area, then you could get a fairly pure solution of an L-amino acid. Could anyone realistically believe conditions like that ever existed?
If conversion between D and L was slow (which I believe it is for most amino acids) and a mixture of crystals existed, it would take very special conditions to escape the crystals being destroyed before a significant enantiomeric excess had been achieved.
I haven’t looked up their experimental section, but I would be interested in seeing exactly how they grew their crystals. Crystallization can be a touchy process – did they heat and cool the vial?
Tim: No heating or anything special, just room temperature.
Did they just leave the reaction to react and crystals formed? How do the glass beads correspond to the early earth, or are they just another way to promote the kinetics of the reaction? They seem to play a more important role in the solubility of the product which is key to crystal growth; they seem to keep the smaller crystals (formed from one isomer) in solution while leaving the larger crystals (the other isomer). To get enantiomerically pure crystals, organic chemists will often exploit the slight solubility differences (if there are any) between the enantiomers so one recrystallizes while the other stays in solution. It sounds like they’re doing the same thing, but they are forcing one back into solution mechanically instead of chemically. That sounds like an essential function to the reaction, so how does it translate into an early earth scenario?
Tim: They don’t say.