Thursday, 25 April 2013

Chemistry Classics: X-Ray Diffraction

#RealTimeChem week has passed the halfway point, and we've reached the penutlimate post in my series of five classic chemistry papers. These are meant to be quick coffee-break reads covering classic papers from across chemistry; we've covered flash chromatography, NMR spectroscopy, and prebiotic synthesis.

2013 is a significant year indeed. This year we may well have seen history in the making, as Fujita and co-workers published a method of obtaining x-ray structures without the need for crystals. Appropriately enough, this year is also the 100th anniversary of the publication of Bragg's law, an equation which is at the foundation of this technique and won the Nobel Prize a mere two years after publication! Unfortunately, I can't find a copy of Bragg's original paper, "The Diffraction of Short Electromagnetic Waves by a Crystal", anywhere.

And so we turn to a classic application of crystallography, for today is another anniversary: the 60th anniversary of the publication of the crystal structure of DNA.

James D. Watson and Francis H. C. Crick, "Molecular Structure Of Nucleic Acids: A Structure For Deoxyribose Nucleic Acid", Nature, 1953, 171, 737-738.

The story of this discovery is well-known to most people. The centrality of DNA to inheritance had been realised, but its structure and the mechanism of information transmission were both unknown. Using data provided by Rosalind Franklin (who died before the Nobel was awarded, and only relatively recently has started to receive due credit) they determined that DNA has the famous double-helical structure. Another stroke of luck came from a visit of Chargaff to Cambridge; one version of this story goes that, over a formal dinner, he gave Watson and Crick a lesson in tautomerism of nucleobases, prompting them both to rush in their gowns from the table to build models of the now-famous Watson-Crick base pairing.

This classic paper is written in a wonderful, understated fashion.It is brief and contains only two figures. It opens by informing us that their proposed structure "has novel features which are of considerable biological interest", before giving us an overview of the other structures that had been proposed. Notably, the triple-helix proposed by chemistry legends E. J. Corey and Linus Pauling is mentioned. This structure put the hydrophilic backbone at the axis of the helix, and the relatively hydrophobic residues on the outside, protruding into the solution. Their discussion is quietly withering; another triple helix proposed by Fraser is dismissed as "rather ill-defined".

Following this is the now-textbook description of their model of DNA, complete with inter-residue distances, turn angles, and strand diameter. What makes this structure "radically different" is their key innovation of base-pairing, which is described succinctly in three short paragraphs. They then come to their evidence: stereochemical arguments; Chargaff's rule, supporting the necessary ratios of nucleobases; and their new crystallographic data.

Despite hedging somewhat - "it must be regarded as unproved until it has been checked against more exact results" - they scatter tantalising hints of things to come throughout the paper. They predict that RNA will not adopt this structure due to its extra hydroxyl group; that dehydrated DNA will adopt more compact structures (A-DNA); and most famously, they state that "it has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material".

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