Hydrogen-deuterium exchange structures

Nazabal, A., Maddelein, M. L., Bonneu, M., Saupe, S. J., and Schmitter, J. M. (2005). Probing the structure of the infectious amyloid form of the prion-forming domain of HET-s using high resolution hydrogen/deuterium exchange monitored by mass spectrometry./ Biol. Chem. 280, 13220-13228. 

A. A. Kossiakoff, M. Ultsch, S. White, C. Eigenbrot, Neutron Structure of Subtilisin BPN Effects of Chemical Environment on Hydrogen-Bonding Geometries and the Pattern of Hydrogen-Deuterium Exchange in Secondary Structure Elements , Biochemistry 1991, 30, 1211-1221. 

Hamuro, Y. Coales, S.J. Southern, M.R. Nemeth-Cawley, J.F. Stranz, D.D. Rod, G.P. Rapid analysis of protein structure and dynamics by hydrogen/deuterium exchange mass spectrometry. J. Biomol. Tech. 2003,... 

Andersen M.D., Shaffer J., Jennings P.A., Adams J.A. Structural characterization of protein kinase A as a function of nucleotide binding. Hydrogen-deuterium exchange studies using matrix-assisted laser desorption ionization-time of flight mass spectrometry detection. J. Biol. Chem. 2001, 276, 14204-14211. 

Englander J., Del Mar C., Li W, Englander S., Kim J., Stranz D., Hamuro Y., Woods Jr. V. Protein structure change studied by hydrogen-deuterium exchange, functional labeling, and mass spectrometry. Proc. Natl Acad. Sci. USA 2003, 100, 7057-7062. 

The hydrogen/deuterium exchange has proven to be an extremely valuable tool for the analysis of gas-phase anion structures and reactivity184-187. The data which are reported in Table 25 suggest an absolute gas-phase basicity (AG°) of H2C=CH—S- is 341 ... 

Chen, G., Khusid, A., Daaro, I., Irish, P., and Pramanik, B. N. (2007). Structural identification of trace level enol tautomer impurity by on-line hydrogen/deuterium exchange HR-LC/MS in a LTQ-Orbitrap hybrid mass spectrometer. J. Mass Spectrom. 42 967-970. 

Recent experimental developments in coupling IR spectroscopy techniques with mass spectrometry, which allow the structural characterization of isolated and microsolvated protonated aromatic molecules in the gas phase have been summarized.64 Hydrogen-deuterium exchange has been observed at Ha in (59) and some closely related substrates when this ligand is complexed to Cu1 in [2Hg]acetone.65 The process is finely controlled by the precise coordination distance required to form agostic interaction between Cu(I) and the C-H bond and is believed to involve the enol form of [2H6]acetone and a reversible Cu(I) to Cu(III) interconversion. 

Many organic anions have been found to undergo hydrogen/deuterium exchange in the presence of deuterated reagents, such as p,0 and CH,OD. Such exchange reactions have proved to be a valuable method of probing mechanisms of ion/molecule reactions and structures of ions in the gas phase. 

In addition to the fact that hydrogen/deuterium exchange reactions can be helpful to probe ion structures as will be shown later, they can also reveal mechanistic details such as the site of reaction within ions. For example, the pentadienyl anion exchanges four protons rapidly, demonstrating, as shown in (12), that proton addition occurs more rapidly at the ends of the conjugated system than in the middle (Stewart et al., 1977 DePuy et al., 1978a). 

Interestingly, the hydrogen/deuterium exchange of both (M — H) ions with D20 is not observed to go to completion, but stops after a certain reaction time. Evidence has been presented that this phenomenon is due to an irreversible isomerization of the (M — H) ions to the enolate anion [13] of 3-methylbutanal, which also gives the same product ions in reactions with hexafluorobenzene (Peerboom et al., 1985). The results obtained clearly point to a complex mixture of interconverting ion structures as shown in (67a-e). 

It must be stressed, however, that the hydrogen-deuterium exchange reactions discussed earlier are extremely informative and most useful in assigning structures to a wide variety of anions. Although the specific examples of the (M — H) ions of 2,4- and 1,5-hexadiene, discussed above, cannot be distinguished by these reactions, the 1-phenylcyclopropyl and 2-phenylallyl anions are easily shown to be distinct, non-interconverting species by their differing reactions with D20 (Andrist et al., 1984 Squires et al., 1981). 

Hydrogen-deuterium exchange experiments have been used extensively to study both structural parameters and dynamic and mechanistic aspects. They are utilized in conjunction with both NMR and IR studies. Mass spectrometry, with its high sensitivity and resolution, is ideally suited for isotopic exchange studies. 

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