„Protonenschwamm”︁‐Verbindungen und die Geometrie von Wasserstoffbrücken: Aromatische Stickstoffbasen mit ungewöhnlicher Basizität

112

Electrospray ionization mass spectrometry (ESI-MS) is a valuable tool in structural biology for investigating globular proteins and their biomolecular interactions. During the electrospray ionization process, proteins become desolvated and multiply charged, which may influence their structure. Reducing the net charge obtained during the electrospray process may be relevant for studying globular proteins. In this report we demonstrate the effect of a series of inorganic and organic gas-phase bases on the number of charges that proteins and protein complexes attain. Solution additives with very strong gas-phase basicities (GB) were identified among the so-called "proton sponges". The gas-phase proton affinities (PA) of the compounds that were added to the aqueous protein solutions ranged from 700 to 1050 kJ mol(-1). Circular dichroism studies showed that in these solutions the proteins retain their globular structures. The size of the proteins investigated ranged from the 14.3 kDa lysozyme up to the 800 kDa tetradecameric chaperone complex GroEL. Decharging of the proteins in the electrospray process by up to 60 % could be achieved by adding the most basic compounds rather than the more commonly used ammonium acetate additive. This decharging process probably results from proton competition events between the multiply protonated protein ions and the basic additives just prior to the final desolvation. We hypothesize that such globular protein species, which attain relatively few charges during the ionization event, obtain a gas-phase structure that more closely resembles their solution-phase structure. Thus, these basic additives can be useful in the study of the biologically relevant properties of globular proteins by using mass spectrometry.

Section: Introductionmentioning

confidence: 97%

Decharging of Globular Proteins and Protein Complexes in Electrospray

Catalina

Heuvel

Duijn

et al. 2005

112

“…[26] gem-Diamines present high pK a values and have been named as proton sponges. [27] On account of their strong basicity they have been used as organocatalysts for reactions such as Knoevenagel and aldol condensations. [28,29] We have recently shown that by anchoring the gem-diamine proton sponge 1,8-bis(dimethylamino)naphthalene (DMAN) on a carrier containing mildly acidic sites, a bifunctional catalyst containing acid and base sites is formed that enhances the rate of the Knoevenagel condensation between benzaldehyde and methylene active compounds.…”

Section: Introductionmentioning

confidence: 99%

Bifunctional Acid–Base Ionic Liquid Organocatalysts with a Controlled Distance Between Acid and Base Sites

Boronat

Climent

Corma

et al. 2010

Bifunctional acid-base ionic liquid organocatalysts with different distances between the two sites have been synthesised, and their activity for the Knoevenagel condensation has been tested. As has been found to be the case with enzymes, the distance between the acidic and basic sites determines the activity of the bifunctional organocatalyst, and at the optimal distance the reaction rate increases by two orders of magnitude with respect to the purely acidic or basic counterpart organocatalysts. The experimental results have been rationalised through the study of the reaction mechanism of the Knoevenagel condensation between malononitrile and benzaldehyde by means of DFT calculations. It has been found that it consists of two consecutive steps. First, deprotonation of malononitrile on the basic site to obtain a methylene carbanion intermediate takes place, and second, co-adsorption and activation of benzaldehyde on the acid centre of this intermediate followed by the C-C bond-formation reaction. The calculations and the kinetic study indicate that there is an inversion of the rate-controlling step when the distance between the acidic and the basic sites is modified, with a direct implication on the reaction rate.

“…[5] The HB energies are roughly coherent with the HB lengths, but as found previously for different systems containing intramolecular HBs, there is no quantitative relationship between the energetic and geometrical parameters of the HB. [7,42] It is important to mention that the quantity (HB + SE) Table 2). Indeed, as shown in Table 2 these two quantities, although of different computational origin, are in good agreement, which indirectly validates the used isodesmic reactions approach.…”

mentioning

confidence: 99%

Brønsted Basicities of Diamines in the Gas Phase, Acetonitrile, and Tetrahydrofuran

Rõõm

Kütt

Kaljurand

et al. 2007

A comprehensive basicity study of alpha,omega-alkanediamines and related bases has been carried out. Basicities in acetonitrile (AN, pK(a) values), tetrahydrofuran (THF, pK(alpha) values), and gas phase (GP, GB values), were measured for 16, 14, and 9 diamine bases and for several related monoamines. In addition the gas-phase basicities and equilibrium geometries were computed for 19 diamino bases and several related monoamines at the DFT B3LYP 6-311+G** level. The effects of the different factors (intrinsic basicity of the amino groups, formation of intramolecular hydrogen bonds, and molecular strain) determining the diamine basicities were estimated by using the method of isodesmic reactions. The results are discussed in terms of molecular structure and solvation effects. The GP basicity is determined by the molecular size and polarizability, the extent of alkylation, and the energy effect of intramolecular hydrogen bond formation in the protonated base. The basicity trends in the solvents differ very much from those in GP: 1) The solvents severely compress the basicity range of the bases studied (3.5 times for the 1,3-propanediamine family in AN, and 7 times in THF), and 2) while stepwise alkylation of the basicity center leads to a steady basicity increase in the gas phase, the picture is complex in the solvents. Significant differences are also evident between THF and AN. The high hydrogen bond acceptor strength of THF leads to this solvent favoring the bases with "naked" protonation centers. In particular, the basicity order of N-methylated 1,3-propanediamines is practically inverse to that in the gas phase. The picture in AN is intermediate between that of GP and THF.