|A Surprising Path for Proton Transfer Without Hydrogen Bonds|
Hydrogen bonds are found everywhere in chemistry and biology and are critical in DNA and RNA. A hydrogen bond results from the attractive dipolar interaction of a chemical group containing a hydrogen atom with a group containing an electronegative atom, such as nitrogen, oxygen, or fluorine, in the same or a different molecule. Conventional wisdom has it that proton transfer from one molecule to another can only happen via hydrogen bonds. Recently, a team of Berkeley Lab and University of Southern California researchers, using the ALS, discovered to their surprise that in some cases, protons can find ways to transfer even when hydrogen bonds are blocked.
To understand how bases are bonded in staircase-like molecules such as DNA and RNA, the USC group made computer models of paired, ring-shaped uracil molecules and investigated what might happen to these dimers when they were ionized. Uracil is one of the four nucleobases of RNA. The group modeled the uracil dimer 1,3-dimethyluracil. The purpose was to block hydrogen bonding of the two identical monomers of the dimer by attaching a methyl group to each; methyl groups are poison to hydrogen bonds.
The uracils could still bond in the vertical direction by means of π bonds, which are perpendicular to the usual plane of bonding among the flat rings of uracil and other nucleobases. So called "π stacking" is important in the configuration of DNA and RNA, in protein folding, and in other chemical structures as well, and π stacking was what interested the USC researchers. They brought their theoretical calculations to Berkeley Lab for experimental testing at the ALS's Chemical Dynamics Beamline 9.0.2.
To examine how the molecules were bonded, the team first created a gaseous molecular beam of methylated uracil monomers and dimers, then ionized them with vacuum ultraviolet light from the ALS. The resulting species were analyzed in a mass spectrometer. What the collaboration expected to see was that if the monomers were bonded, they would be stacked on top of each other. Instead, they found that when ionized, some uracil dimers had fallen apart into monomers, some of which carried an extra proton, i.e., proton transfer had occurred.
To test the hypothesis that the source of the proton was the methyl group, the researchers invited colleagues from Berkeley Lab's Molecular Foundry to join the collaboration. They created methyl groups in which the hydrogen atoms were replaced by deuterium atoms. The molecular beam experiment was repeated with deuterium-containing uracil, and once again some of the methylated uracil dimers fell apart into monomers upon ionization, but this time they were deuterated. This proved that, indeed, the transferred protons came from the methyl groups.
Just as important, proton transfer was seen to follow a very different route from the usual hydrogen bond pathway, following instead one that involved significant rearrangements of the two uracil dimer fragments to allow protons from hydrogen atoms in the methyl group on one monomer to move closer to an oxygen atom in the other.
This result means there could be unsuspected pathways for proton transfer in RNA and DNA and other biological processes upon ionization, especially those that involve π-stacking, as well as in environmental chemistry and in purely chemical processes like catalysis. The next step is a series of experiments to directly map proton transfer rates and gain structural insight into the transfer mechanism, with the goal of visualizing these unexpected new pathways for proton transfer.
Research conducted by: A. Golan and S.R. Leone (Berkeley Lab and University of California, Berkeley); K.B. Bravaya and A.I. Krylov (University of Southern California); and R. Kudirka, O. Kostko, and M. Ahmed (Berkeley Lab).
Funding: U.S. Department of Energy, Office of Basic Energy Sciences (BES); Defense Threat Reduction Agency; and the National Science Foundation. Operation of the ALS is supported by BES.
Publication about this research: A. Golan, K.B. Bravaya, R. Kudirka, O. Kostko, S.R. Leone, A.I. Krylov, and M. Ahmed, "Ionization of dimethyluracil dimers leads to facile proton transfer in the absence of H-bonds," Nature Chem. 4, 323 (2012).
ALS Science Highlight #252