Gas phase acidity and proton affinity studies of organic species using mass spectrometry
Creators: name: Liu, Min
Publisher: name: No Publisher Supplied
Year: 2011

description: DNA bases can be chemically or photochemically damaged from a variety of endogenous and exogenous sources. Such damaged bases are linked to carcinogenesis, aging and cell death. One of our main focuses is to examine the intrinsic reactivity of normal and damaged nucleobases in order to find out how damaged bases are different from normal bases. Particularly in this thesis we are interested in the thermochemical properties (acidity and proton affinity) of damaged bases 1,N6-ethenoadenine (eA) and O6-methylguanine (OMG). eA is one of the damaged nucleobases which can be excised by  alkyladenine DNA glycosylase (AAG) in humans. We find that the N9-H of eA is more acidic than adenine and guanine, which might indicate that AAG may cleave certain damaged nucleobases as anions and deprotonated damaged bases are better leaving groups than normal adenine and guanine. Also the active site may take advantage of a nonpolar environment to favor deprotonated eA as a better leaving group than adenine and guanine. In addition we find the N9-H of OMG is less acidic than adenine and guanine. This result is consistent with the fact that OMG is not one of the substrates of AAG. Besides the damaged bases, we also studied the thermochemical properties and tautomerism of normal pyrimidine bases cytosine and thymine, because the first step to understand how damaged bases differ from normal bases is to characterize the naturally occurring normal compounds.  One of our focuses is gas phase acidity studies of organic silanols and some known hydrogen-bonding organocatalysts. This project is in collaboration with Professor Annaliese Franz at UC Davis, who develops a series of organic silanols used as a new class of hydrogen bonding catalysts for enantioselective carbon-carbon bond forming reactions. It is generally accepted that silanols are more acidic than their carbon analogs, but we have found the theoretical carbon diol analogs are actually more acidic than silicon diols depending on substitution and structure. Also polarizability versus induction, gas phase versus solution phase, catalysis and molecular recognition are discussed.   We are also interested in the proton affinity and reactivity of N-heterocyclic carbenes (NHCs). Stable NHCs are widely used as novel ligands for transition-metal-catalyzed reactions such as the Grubbs ruthenium olefin metathesis catalysis, palladium-catalyzed cross-coupling reactions and nickel-catalyzed cycloadditions. The dialkylimidazolium salts (protonated carbenes) are also an important class of ionic liquids, which are used as “green” nonvolatile solvents in organic synthesis. It has been found that the second generation of Grubbs metathesis catalyst comprising NHC is more active than the first generation catalyst containing tricyclohexyl phosphine (PCy3) only. More basic carbenes presumably will be more effective ligands. Therefore we are interested in the proton affinity of carbenes versus PCy3. By using the Cooks kinetic method we find both di-methyl carbene and ethyl methyl carbene have similar proton affinities to PCy3. However bracketing experiments conducted on a modified LCQ show that di-methyl carbene and ethyl methyl carbene are more basic than PCy3. This inconsistence is probably due to a technical problem with the Cooks method or ethylene elimination for the ethyl methyl carbene and PCy3 system during the Cooks experiments. Proton-bound dimers of carbenes and PCy3 are also found to exhibit interesting reactivity involving ethylene elimination, phosphine alkylation and/or cyclohexene elimination.