Free energies of hydration from thermodynamic integration: Comparison of molecular mechanics force fields and evaluation of calculation accuracy

Four commonly used molecular mechanics force fields, CHARMM22, OPLS, CVFF, and GROMOS87, are compared for their ability to reproduce experimental free energies of hydration (ΔG_hydr) from molecular dynamics (MD) simulations for a set of small nonpolar and polar organic molecules: propane, cyclopropane, dimethylether, and acetone. ΔG_hydr values were calculated by multiconfiguration thermodynamic integration for each of the different force fields with three different sets of partial atomic charges: full charges from an electrostatic potential fit (ESP), and ESP charges scaled by 0.8 and 0.6. All force fields, except for GROMOS87, give reasonable results for ΔG_hydr · if partial atomic charges of appropriate magnitude are assigned. For GROMOS87, the agreement with experiment for hydrocarbons (propane and ethane) was improved considerably by modifying the repulsive part of the carbon-water oxygen Lennard-Jones potential. The small molecules studied are related to the chemical moieties constituting camphor (C₁₀H_l6O). By invoking force-field transferability, we calculated the ΔG_hydr for camphor. With the modified GROMOS force field, a ΔG_hydr within 4 kJ/mol of the experimental value of −14.8 kJ/mol was obtained. Camphor is one of the largest molecules for which an absolute hydration free energy has been calculated by molecular simulation. The accuracy and reliability of the thermodynamic integration calculations were analyzed in detail and we found that, for ΔG_hydr calculations for the set of small molecules in aqueous solution, molecular dynamics simulations of 0.8–1.0 ns in length give an upper statistical error bound of 1.5 kJ/mol, whereas shorter simulations of 0.25 nm in length given an upper statistical error bound of 3.5 kJ/mol. © 1997 by John Wiley & Sons, Inc.     

Determination of Diaryliodonium Species by Reverse Iodometric Titration with Ascorbic Acid

Diaryliodonium salts are used in organic chemistry, materials science and pharmaceutical chemistry. For the quantitative analysis of diaryliodonium salts, only instrumentally demanding techniques requiring highly skilled operators are available. Surprisingly, no titration method taking advantage of the oxidising ability of diaryliodonium is available in the literature. In the present work, a titration method for the determination of diaryliodonium salts is presented. It is based on the reaction of diaryliodonium species with ascorbic acid, whose excess is subsequently determined by means of iodometric potentiometric titration. Application of the protocol to various diaryliodonium salts revealed the scope and limitations of the method.