An assessment of pure, hybrid, meta, and hybrid‐meta GGA density functional theory methods for open‐shell systems: The case of the nonheme iron enzyme 8R–LOX

The performance of a range density functional theory functionals combined in a quantum mechanical (QM)/molecular mechanical (MM) approach was investigated in their ability to reliably provide geometries, electronic distributions, and relative energies of a multicentered open‐shell mechanistic intermediate in the mechanism 8R–Lipoxygenase. With the use of large QM/MM active site chemical models, the smallest average differences in geometries between the catalytically relevant quartet and sextet complexes were obtained with the B3LYP * functional. Moreover, in the case of the relative energies between 4 II and 6 II , the use of the B3LYP * functional provided a difference of 0.0 kcal mol –1 . However, B3LYP ± and B3LYP also predicted differences in energies of less than 1 kcal mol –1 . In the case of describing the electronic distribution (i.e., spin density), the B3LYP * , B3LYP, or M06‐L functionals appeared to be the most suitable. Overall, the results obtained suggest that for systems with multiple centers having unpaired electrons, the B3LYP * appears most well rounded to provide reliable geometries, electronic structures, and relative energies. © 2012 Wiley Periodicals, Inc.