Related Experiment Video
Updated: Jun 10, 2026
Realistic Membrane Modeling Using Complex Lipid Mixtures in Simulation Studies
Published on: September 1, 2023
Nonadditive empirical force fields for short-chain linear alcohols: methanol to butanol. Hydration free energetics
1Department of Chemistry and Biochemistry, 238 Brown Lab, University of Delaware, Newark, Delaware 19716, USA.
Abstract:
Building upon the nonadditive electrostatic force field for alcohols based on the CHARMM charge equilibration (CHEQ) formalism, we introduce atom-pair specific solute-solvent Lennard-Jones (LJ) parameters for alcohol-water interaction force fields targeting improved agreement with experimental hydration free energies of a series of small molecule linear alcohols as well as ab initio water-alcohol geometries and energetics. We consider short-chain, linear alcohols from methanol to butanol as they are canonical small-molecule organic model compounds to represent the hydroxyl chemical functionality for parametrizing biomolecular force fields for proteins. We discuss molecular dynamics simulations of dilute aqueous solutions of methanol and ethanol in TIP4P-FQ water, with particular discussion of solution densities, structure defined in radial distribution functions, electrostatic properties (dipole moment distributions), hydrogen bonding patterns of water, as well as a Kirkwood-Buff (KB) integral analysis. Calculation of the latter provides an assessment of how well classical force fields parametrized to at least semiquantitatively match experimental hydration free energies capture the microscopic structures of dilute alcohol solutions; the latter translate into macroscopic thermodynamic properties through the application of KB analysis. We find that the CHEQ alcohol force fields of this work semiquantitatively match experimental KB integrals for methanol and ethanol mole fractions of 0.1 and 0.2. The force field combination qualitatively captures the concentration dependence of the alcohol-alcohol and water-water KB integrals, but due to inadequacies in the representation of the microscopic structures in such systems (which cannot be parametrized in any systematic fashion), a priori quantitative description of alcohol-water KB integrals remains elusive.
Related Concept Videos
02:45Acid-Catalyzed Hydration of Alkenes
02:15Preparation of Alcohols via Addition Reactions
The acid-catalyzed addition of water to the double bond of alkenes is a large-scale industrial method used to synthesize low-molecular-weight alcohols. An acidic atmosphere is required to allow the hydrogen in the water molecule to act as an electrophile and attack the double bond in an alkene. The addition of a proton to the double bond creates a carbocation intermediate. The proton preferentially bonds to the less substituted end of the double bond to create a more stable carbocation...
02:34Regioselectivity and Stereochemistry of Acid-Catalyzed Hydration
02:32Physical Properties of Alcohols and Phenols
Alcohols possess a higher boiling point than aliphatic hydrocarbons of similar...
02:17Physical Properties of Ethers
An ether molecule has a net dipole moment due to the polarity of C–O bonds. Subsequently, boiling points of ethers are lower than those of alcohols of comparable molecular weight and slightly higher than those of hydrocarbons of comparable molecular weight (Table 1).
Ethers can act as hydrogen bond acceptors, making them more water-soluble than hydrocarbons, but since ethers cannot act as hydrogen bond donors, they are much less soluble in water than alcohols. Ethers are considered...
02:12Solvating Effects