2-methyl-2,4-pentanediol (MPD) is commonly used in the crystalization of oligonucleotides. We present our results of computational studies indicating that the reduction of C5-C6 bonds of pyrimidines by MPD is thermodynamically favorable. At the B3LYP/cc-pVDZ level, stabilization increases in the order U > T > C > 5-metC.  However,  the stabilization of U or T in a  W-C pair with A is lowered, whereas the stabilization of C and 5-metC in a W-C pair with G increases upon reduction. Computations for a CpG step with the M05-2X and M06-2X functionals and the 6-31+G(d,p) basis set indicate that the stabilization per C:G pair, due to C5-C6 bond hydrogenation, increases further with the formation of a base pair step.While the reduction of pyrimidine nucleotides, or small oligonucleotides in a solution should be kinetically forbidden, in the large ordered structures of oligonucleotides in crystals it may become feasible. We leave it to experimentalists to definitively confirm or rebuff our computational prediction.

Does 2-methyl-2,4-pentanediol reduce pyrimidines in the process
of crystallization of oligonucleotides?

239th National Meeting (2010)

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Does 2-methyl-2,4-pentanediol reduce pyrimidines in the process of crystallization of oligonucleotides?