Radical damage in lipids investigated with the fragment molecular orbital method

Highlights: • Analytic Hessian for large open-shell systems is developed. • IR and Raman spectra can be computed for multiple radical systems. • The fragment molecular orbital method is validated for lipids. • The energetics of hydrogen abstraction reactions in a typical lipid are studied. To quantify the thermodynamics for hydrogen abstraction lipids, the fragment molecular orbital method (FMO) is used to calculate structures and energies of the reactants and products. The analytic second derivative is developed for the open-shell Hartree–Fock formulation of FMO and used to calculate zero point energy corrections. The accuracy of FMO is evaluated for a lipid model and the errors in reaction energies are found not to exceed 0.5 kcal/mol. The reaction energies determined for multiple sites in two lipids are used to discuss likely sites and pathways of radical initiation in membranes.