Calculation of relative free energy differences for the covalent hydration of organic compounds: A combined quantum mechanical and free energy perturbation study

✍ Scribed by Mark D. Erion; M. Rami Reddy

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 838 KB
• Volume: 16
• Category: Article
• ISSN: 0192-8651
• DOI: 10.1002/jcc.540161208

✦ Synopsis

The relative free energy difference (AAGhyd) for the reversible addition of water to two unsaturated molecules is accurately computed using a combination of ab initio quantum mechanical calculations and free energy perturbation methods. Initial attempts to calculate the absolute hydration free energy difference (AGhyd for formaldehyde and trichloroacetaldehyde gave values that differed substantially from experimental results even after inclusion of electron correlation energy contributions using third-order (MP3) and fourth-order (MP4) Mdler-Plesset perturbation theory and QCISNT) correlation methods at the 6-31G** basis set level. Inaccuracies in AG,,, were attributed to errors in the calculation of both AG,,, and AAG,,,. Gas phase quantum mechanical free energies (AGgas) varied significantly (2-3 kcal/mol) depending on the level of theory. Errors in A AGsol were attributed to slow convergence of the calculations using the thermodynamic cycle perturbation (TCP) method with explicit solvent. These errors were minimized or canceled, however, when relative hydration free energy differences (AAGhyd) were calculated using a combination of ab initio quantum mechanical calculations and free energy perturbation methods. Calculated values for a variety of aldehydes and ketones were consistent with experimental data.