Determination of Gas-Phase Acidity for Biologically Active Organic Compounds
Poster Number
33
Introduction/Abstract
The thermodynamics of biologically active organic molecules gives insight into the intrinsic nature of the compounds. Many of these compounds have not been comprehensively studied, preventing consumers from properly deciding on a product’s use and the extent of its usage.
Purpose
We are interested in establishing the intrinsic thermochemical properties of a library of biologically active organic compounds. Three compounds of interest have been studied, triclosan, ibuprofen, and methylparaben.
Method
Measurements were carried out using an ESI tandem quadrupole mass spectrometer (Varian 320 LC-MS). Extended Cooks’ kinetic method was applied to determine the gas-phase acidities. A heterodimer competitively dissociates using collision induced dissociation (CID). CID was performed at five different collision energies to determine the gas-phase deprotonation enthalpy (∆Hacid) and other related thermochemical quantities. Conformational analysis was performed using Spartan 08 at MMFF force field. The lowest two to seven energy conformations were optimized using Gaussian 03W software. Geometry, frequency, and energetic calculations of each analyte and reference acid were performed using the density functional theory (DFT) at the B3LYP/6-31+G(d,p) level. The resulting electronic enthalpies were used to calculate the theoretical gas-phase deprotonation enthalpy using the isodesmic proton transfer reaction.
Results
The gas-phase acidity (GA), deprotonation enthalpy (∆acidH) and deprotonation entropy (∆acidS) of triclosan was determined to be 320.4 kcal mol-1, 329.2 kcal/mol-1, and 29.5 cal mol-1 K-1, respectively. The computational ∆acidH for triclosan was determined to be 329.6 kcal mol-1. Triclosan and its ionic form display a difference in its conformation. The neutral form of triclosan has the hydroxyl group oriented away from the neighboring aryl group and this can be attributed to the electronic repulsion. However, the anionic form has the aryl group oriented toward the deprotonated oxygen; the change in conformation is a result of the electronic repulsion of the delocalized charge present in the aryl ring. The gas-phase acidity (GA), deprotonation enthalpy (∆acidH) and deprotonation entropy (∆acidS) of ibuprofen was determined to be 337.1 kcal mol-1, 343.1 kcal mol-1, and 20.2 cal mol-1 K-1, respectively. The calculated ∆acidH was determined to be 341.7 kcal mol-1. Ibuprofen and its anion do not exhibit a difference in conformation. Both compounds have agreeable experimental and computational values for the deprotonation enthalpy. The third compound methylparaben has gas-phase acidity (GA), deprotonation enthalpy (∆acidH) and deprotonation entropy (∆acidS) of 331.8 kcal mol-1, 338.9 kcal mol-1, 23.9 cal mol-1 K-1. The calculated ∆acidH of methylparaben was 339.3 kcal mol-1. Computational results do not exhibit a difference in conformation for the methylparaben and its anion.
Significance
The work has established gas-phase properties for ubiquitous biologically active compounds. The thermodynamic properties provide a numerical value for the intrinsic nature of the three mentioned compounds.
Location
DeRosa University Center, Stockton campus, University of the Pacific
Format
Poster Presentation
Determination of Gas-Phase Acidity for Biologically Active Organic Compounds
DeRosa University Center, Stockton campus, University of the Pacific
The thermodynamics of biologically active organic molecules gives insight into the intrinsic nature of the compounds. Many of these compounds have not been comprehensively studied, preventing consumers from properly deciding on a product’s use and the extent of its usage.
