Semiempirical orthogonalization-corrected methods (OM1, OM2, and OM3) go beyond the standard MNDO model by explicitly including additional interactions into the Fock matrix in an approximate manner (Pauli repulsion, penetration effects, and core–valence interactions), which yields systematic improvements both for ground-state and excited-state properties. In this Article, we describe the underlying theoretical formalism of the OMx methods and their implementation in full detail, and we report all relevant OMx parameters for hydrogen, carbon, nitrogen, oxygen, and fluorine. For a standard set of mostly organic molecules commonly used in semiempirical method development, the OMx results are found to be superior to those from standard MNDO-type methods. Parametrized Grimme-type dispersion corrections can be added to OM2 and OM3 energies to provide a realistic treatment of noncovalent interaction energies, as demonstrated for the complexes in the S22 and S66×8 test sets.

The geometries of pure-carbon fullerenes synthesized thus far follow exclusively the isolated-pentagon rule (IPR), which states that the pentagons in the most stable fullerenes are isolated from each other by hexagons. [1,2] Due to enhanced steric strain (steric effect) and resonance destabilization pertaining to the pentalene-type 8p-electron system (electronic effect), pure-carbon non-IPR fullerenes with abutted pentagons are always unstable and synthetically unattainable.[3] However, it appears that non-IPR fullerenes can be stabilized by either endohedral inclusion of electron-donating metal atoms/clusters [4,5] or exohedral derivatization, [6] as exemplified by such non-IPR fullerene derivatives as the endofullerenes Sc 2 @C 66 , [4b] La 2 @C 72 , [4c] and Sc 3 N@C 68 [5] as well as the exohedral derivative C 50 Cl 10 .[6] On the other hand, many metal-carbide endofullerenes, for example, Sc 2 C 2 @C 84 , [7] Ti 2 C 2 @C 78 , [8] Y 2 C 2 @C 82 , [9] and Sc 3 C 2 @C 80 , [10] have been synthesized and characterized exclusively with IPR-satisfying fullerene cages. Herein we report the isolation and characterization of Sc 2 C 2 @C 68 , which is, to the best of our knowledge, the first metal-carbide endofullerene having a non-IPR cage.

Dihydrofolate reductase (DHFR) catalyzes the reduction of 7,8-dihydrofolate by nicotinamide adenine dinucleotide phosphate hydride (NADPH) to form 5,6,7,8-tetrahydrofolate and oxidized nicotinamide. DHFR is a small, flexible, monomeric protein with no metals or SS bonds and serves as one of the enzymes commonly used to examine basic aspects in enzymology. In the current work, we present extensive benchmark calculations for several model reactions in the gas phase that are relevant to the DHFR catalyzed hydride transfer. To this end, we employ G4MP2 and CBS-QB3 ab initio calculations as well as numerous density functional theory methods. Using these results, we develop two specific reaction parameter (SRP) Hamiltonians based on the semiempirical AM1 method. The first generation SRP Hamiltonian does not account for dispersion, while the second generation SRP accounts for dispersion implicitly via the AM1 core-repulsion functions. These SRP semiempirical Hamiltonians are subsequently used in hybrid quantum mechanics/molecular mechanics simulations of the DHFR catalyzed reaction. Finally, kinetic isotope effects are computed using a mass-perturbation-based path-integral approach.

The semiempirical orthogonalization-corrected OMx methods (OM1, OM2, and OM3) go beyond the standard MNDO model by including additional interactions in the electronic structure calculation. When augmented with empirical dispersion corrections, the resulting OMx-Dn approaches offer a fast and robust treatment of noncovalent interactions. Here we evaluate the performance of the OMx and OMx-Dn methods for a variety of ground-state properties using a large and diverse collection of benchmark sets from the literature, with a total of 13035 original and derived reference data. Extensive comparisons are made with the results from established semiempirical methods (MNDO, AM1, PM3, PM6, and PM7) that also use the NDDO (neglect of diatomic differential overlap) integral approximation. Statistical evaluations show that the OMx and OMx-Dn methods outperform the other methods for most of the benchmark sets.