Acidity of Organic Compounds and Small Peptides in Solution and in the Gas-Phase
Poster Number
6A
Introduction/Abstract
Acidities of organic compounds and small peptides are an important parameter gauging their reactivity and regulating their applications. The degree of acidity changes upon changing the environment where the compounds residing. Organic compounds used as pharmaceuticals and preservatives, including ibuprofen, methylparaben, and triclosan, have been shown to be harmful to human health and to the environment. Aspartic acid-containing polyproline peptides serve as models for small peptides. Polyproline is selected because of its ability to switch between two helical conformations, which can be used to design molecular scaffolds.
Purpose
This work focuses on studying the influence of solvent polarity on the pKa values of organic compounds and small peptides, as well as comparing the acidities measured in solution and in the gas-phase.
Method
pKa values were determined by potentiometric titrations with an 8220 BNWP ROSS micro pH electrode, and by UV-Vis spectrophotometric titrations with a Perkin/Elmer Lambda 35 spectrophotometer. Gas-phase acidities were measured using a tandem quadrupole and a linear ion trap mass spectrometers with an ESI source. The pKa values were determined in mixed solvents of methanol-water and acetonitrile-water with varying proportions of the organic to aqueous component. The gas-phase acidities were determined by using the bracketing experiments as well as the extended kinetic method.
Results
The acidity of three organic compounds and four peptides has been measured in mixed solvents as well as in the gas-phase. The organic compounds were observed to be more acidic in the mixed solvent of MeOH/H2O than they were in that of MeCN/H2O. For instance, at 50% MeOH to H2O, the pKa values of ibuprofen, methylparaben, and triclosan were measured to be 5.64, 8.98, and 8.95, respectively, but in 50% MeCN to H2O, they were measured to be 6.17, 9.57, and 9.57. The pKa values increased (the acidity decreased) with increasing proportion of the organic solvent. For instance, the pKa of methylparaben in 0%, 25%, 50% and 75% MeOH to H2O were 8.23, 8.43, 8.98, and 9.65. In 0%, 25%, 50% and 60% MeCN to H2O, the values were 8.23, 8.88, 9.57, and 9.84. The relative solution phase acidity of the three organic compounds is in the order of ibuprofen > triclosan > methylparaben. The acidity trend appears to be reversed in the gas-phase, such that triclosan > methylparaben > ibuprofen. The peptides were amidated at the C-terminus, and therefore, the side-chain of the aspartic acid is the acidic site for deprotonation. The peptides were observed to be more acidic when aspartic acid was positioned at the C-terminus compared to when it was at the N-terminal position. This trend was seen both in solution and in gas phase, indicating that the C-terminal anion is intrinsically more stable than the N-terminal anion. In solution, it was only possible to measure the acetylated peptides, and the pKa values of Ac-DPP and Ac-PPD were 5.21 and 5.01. In the gas phase, the acidity trend was Ac-PPD > PPD > Ac-DPP > DPP. Acetylation increases the acidity of the peptide, but the position of the aspartic acid has a much stronger effect.
Location
Library and Learning Center, 3601 Pacific Ave., Stockton, CA 95211
Format
Poster Presentation
Acidity of Organic Compounds and Small Peptides in Solution and in the Gas-Phase
Library and Learning Center, 3601 Pacific Ave., Stockton, CA 95211
Acidities of organic compounds and small peptides are an important parameter gauging their reactivity and regulating their applications. The degree of acidity changes upon changing the environment where the compounds residing. Organic compounds used as pharmaceuticals and preservatives, including ibuprofen, methylparaben, and triclosan, have been shown to be harmful to human health and to the environment. Aspartic acid-containing polyproline peptides serve as models for small peptides. Polyproline is selected because of its ability to switch between two helical conformations, which can be used to design molecular scaffolds.
