Steven R. Kass

Does Electrospray Ionization Produce Gas-Phase or Liquid-Phase Structures?

Electrospray ionization of tyrosine from a 3:1 (v:v) CH3OH/H2O solution is found to afford an M - H ion which is a 70:30 mixture of phenoxide and carboxylate ions. This corresponds to the gas-phase equilibrium composition and not the liquid-phase proportions. In contrast, the carboxylate is produced as the dominant ion (approximately 95%) from anhydrous CH3CN and CH3CN/H2O mixtures. The addition of small amounts of CH3OH to the solvent, however, convert the M - H ion back into the gas-phase isomeric ratio. The isomeric structure therefore depends on the solvent system from which an ion is sprayed.

Gas‐Phase versus Liquid‐Phase Structures by Electrospray Ionization Mass Spectrometry

Preferred protonation: Does electrospray ionization mass spectrometry produce gas-phase or liquid-phase structures? The preferred protonation site in p-aminobenzoic acid depends upon the medium, and the structure of its conjugate acid varies with the solvent used during spraying.

Are Carboxyl Groups the Most Acidic Sites in Amino Acids? Gas-Phase Acidities, Photoelectron Spectra, and Computations on Tyrosine, p-Hydroxybenzoic Acid, and Their Conjugate Bases

Deprotonation of tyrosine in the gas phase was found to occur preferentially at the phenolic site, and the conjugate base consists of a 70:30 mixture of phenoxide and carboxylate anions at equilibrium. This result was established by developing a chemical probe for differentiating these two isomers, and the presence of both ions was confirmed by photoelectron spectroscopy. Equilibrium acidity measurements on tyrosine indicated that deltaG(acid)(o) = 332.5 +/- 1.5 kcal mol(-1) and deltaH(acid)(o) = 340.7 +/- 1.5 kcal mol(-1). Photoelectron spectra yielded adiabatic electron detachment energies of 2.70 +/- 0.05 and 3.55 +/- 0.10 eV for the phenoxide and carboxylate anions, respectively. The H/D exchange behavior of deprotonated tyrosine was examined using three different alcohols (CF3CH2OD, C6H5CH2OD, and CH3CH2OD), and incorporation of up to three deuterium atoms was observed. Two pathways are proposed to account for these results, and all of the experimental findings are supplemented with B3LYP/aug-cc-pVDZ and G3B3 calculations. In addition, it was found that electrospray ionization of tyrosine from a 3:1 (v/v) CH3OH/H2O solution using a commercial source produces a deprotonated [M-H]- anion with the gas-phase equilibrium composition rather than the structure of the ion that exists in aqueous media. Electrospray ionization from acetonitrile, however, leads largely to the liquid-phase (carboxylate) structure. A control molecule, p-hydroxybenzoic acid, was found to behave in a similar manner. Thus, the electrospray conditions that are employed for the analysis of a compound can alter the isomeric composition of the resulting anion.

Infrared multiphoton dissociation spectroscopy study of protonated p-aminobenzoic acid: does electrospray ionization afford the amino- or carboxy-protonated ion?

Infrared multiphoton dissociation spectra of protonated p-aminobenzoic acid generated by electrospray ionization (ESI) from aqueous methanol and acetonitrile solutions were recorded in the gas phase from 2800-4000 cm(-1). The O-protonated ion is more stable than the N-protonated structure in the gas phase, whereas the opposite is true in both solutions. When CH(3)OH/H(2)O was used as the ESI solvent, only the O-protonated ion was observed. In contrast, a 70:30 mixture of the O- and N-protonated species were produced from CH(3)CN/H(2)O. These structural assignments are based on an assortment of experimental data (action spectra, photofragments, photofragmentation kinetics, and H/D exchange) and are fully supported by extensive computations. This work shows that ESI can lead to isomerization and that the ionization site may be varied by changing the solvent from which the substrate is analyzed.

Effect of hydrogen bonds on pKa values: importance of networking.

The pK(a) of an acyclic aliphatic heptaol ((HOCH(2)CH(2)CH(OH)CH(2))(3)COH) was measured in DMSO, and its gas-phase acidity is reported as well. This tertiary alcohol was found to be 10(21) times more acidic than tert-butyl alcohol in DMSO and an order of magnitude more acidic than acetic acid (i.e., pK(a) = 11.4 vs 12.3). This can be attributed to a 21.9 kcal mol(-1) stabilization of the charged oxygen center in the conjugate base by three hydrogen bonds and another 6.3 kcal mol(-1) stabilization resulting from an additional three hydrogen bonds between the uncharged primary and secondary hydroxyl groups. Charge delocalization by both the first and second solvation shells may be used to facilitate enzymatic reactions. Acidity constants of a series of polyols were also computed, and the combination of hydrogen-bonding and electron-withdrawing substituents was found to afford acids that are predicted to be extremely acidic in DMSO (i.e., pK(a) < 0). These hydrogen bond enhanced acids represent an attractive class of Brønsted acid catalysts.

Single-Centered Hydrogen-Bonded Enhanced Acidity (SHEA) Acids: A New Class of Brønsted Acids

Hydrogen bonds are the dominant motif for organizing the three-dimensional structures of biomolecules such as carbohydrates, nucleic acids, and proteins, and serve as templates for proton transfer reactions. Computations, gas-phase acidity measurements, and pK(a) determinations in dimethyl sulfoxide on a series of polyols indicate that multiple hydrogen bonds to a single charged center lead to greatly enhanced acidities. A new class of Brønsted acids, consequently, is proposed.

Hydrogen bonded arrays: The power of multiple hydrogen bonds

Hydrogen bond interactions in small covalent model compounds (i.e., deprotonated polyhydroxy alcohols) were measured by negative ion photoelectron spectroscopy. The experimentally determined vertical and adiabatic electron detachment energies for (HOCH(2)CH(2))(2)CHO(-)(2a), (HOCH(2)CH(2))(3)CO(-) (3a), and (HOCH(2)CH(2)CH(OH)CH(2))(3)CO(-) (4a)reveal that hydrogen-bonded networks can provide enormous stabilizations and that a single charge center not only can be stabilized by up to three hydrogen bonds but also can increase the interaction energy between noncharged OH groups by 5.8 kcal mol(-1) or more per hydrogen bond. This can lead to pK(a) values that are very different from those in water and can provide some of the impetus for catalytic processes.

Three Hydrogen Bond Donor Catalysts: Oxyanion Hole Mimics and Transition State Analogues

Enzymes and their mimics use hydrogen bonds to catalyze chemical transformations. Small-molecule transition state analogues of oxyanion holes have been characterized by computations, gas-phase IR and photoelectron spectroscopy, and determination of their binding constants in acetonitrile. A new class of hydrogen bond catalysts is proposed (donors that can contribute three hydrogen bonds to a single functional group) and demonstrated in a Friedel-Crafts reaction. The employed catalyst was observed to react 100 times faster than its rotamer that can employ only two hydrogen bonds. The former compound also binds anions more tightly and was found to have a thermodynamic advantage.

Electron-Withdrawing Trifluoromethyl Groups in Combination with Hydrogen Bonds in Polyols: Brønsted Acids, Hydrogen-Bond Catalysts, and Anion Receptors

Electron-withdrawing trifluoromethyl groups were characterized in combination with hydrogen-bond interactions in three polyols (i.e., CF3CH(OH)CH2CH(OH)CF3, 1; (CF3)2C(OH)C(OH)(CF3)2, 2; ((CF3)2C(OH)CH2)2CHOH, 3) by pKa measurements in DMSO and H2O, negative ion photoelectron spectroscopy and binding constant determinations with Cl(-). Their catalytic behavior in several reactions were also examined and compared to a Brønsted acid (HOAc) and a commonly employed thiourea ((3,5-(CF3)2C6H3NH)2CS). The combination of inductive stabilization and hydrogen bonds was found to afford potent acids which are effective catalysts. It also appears that hydrogen bonds can transmit the inductive effect over distance even in an aqueous environment, and this has far reaching implications.

Experimental determination of the α and β C—H bond dissociation energies in naphthalene

The acidities of the two different sites in naphthalene (1alpha and 1beta) and the electron affinities of the alpha- and beta-naphthyl radicals were measured using a Fourier transform mass spectrometer. Both carbon-hydrogen bond dissociation energies for naphthalene also were obtained, in this case via the application of a thermodynamic cycle. The final results are DeltaH(o)acid (1alpha) = 394.2+/-1.2 kcal mol(-1), DeltaH(o)acid (1beta) = 395.5+/-1.3 kcal mol(-1), EA(alpha) = 31.6+/-0.5 kcal mol(-1), EA(beta) = 31.6+/-0.5 kcal mol(-1), BDE(1alpha) = 112.2+/-1.3 kcal mol(-1) and BDE(1alpha) = 111.9+/-1.4 kcal mol(-1), and they are compared to benzene and phenyl radical as well as ab initio and density functional theory (B3LYP) calculations.