Hybrid Models for Combined Quantum Mechanical and Molecular Mechanical Approaches

A hierarchy of three models for combined quantum mechanical (QM) and molecular mechanical (MM) approaches is presented. They simplify the QM description of large molecules by reducing it to the electronically important fragment which interacts with the molecular mechanically treated remainder of the molecule. In the simplest model A, the QM fragments are only mechanically embedded in their MM environment. The more refined models B and C include a quantum mechanical treatment of electrostatic interactions between the fragments and a semiclassical description of polarization. The implementation of models A-C for MNDO type wavefunctions and the MM3 force field is outlined. Selected applications in organic chemistry are discussed, addressing the ability of the proposed models to reproduce substituent effects (MM) on chemical structure and reactivity (QM). These applications include protonations, deprotonations, hydride transfer reactions, nucleophilic additions, and nucleophilic ring cleavage reactions

First-principles calculations of the structural, electronic, vibrational and magnetic properties of C_{60} and C_{48}N_{12}: a comparative study

In this work, we perform first-principles calculations of the structural, electronic, vibrational and magnetic properties of a novel ${\rm C}_{48}{\rm N}_{12}$ azafullerene. Full geometrical optimization shows that ${\rm C}_{48}{\rm N}_{12}$ is characterized by several distinguishing features: only one nitrogen atom per pentagon, two nitrogen atoms preferentially sitting in one hexagon, ${\rm S}_{6}$ symmetry, 6 unique nitrogen-carbon and 9 unique carbon-carbon bond lengths. The highest occupied molecular orbital of ${\rm C}_{48}{\rm N}_{12}$ is a doubly degenerate level of $a_{g}$ symmetry and its lowest unoccupied molecular orbital is a nondegenerate level of $a_{u}$ symmetry. Vibrational frequency analysis predicts that ${\rm C}_{48}{\rm N}_{12}$ has in total 116 vibrational modes: 58 infrared-active and 58 Raman-active modes. ${\rm C}_{48}{\rm N}_{12}$ is also characterized by 8 $^{13}{\rm C}$ and 2 $^{15}{\rm N}$ NMR spectral signals. Compared to ${\rm C}_{60}$, ${\rm C}_{48}{\rm N}_{12}$ shows an enhanced third-order optical nonlinearities which implies potential applications in optical limiting and photonics.Comment: a long version of our manuscript submitted to J.Chem.Phy

Anomalous Thermal Stability of Metastable C_20 Fullerene

The results of computer simulation of the dynamics of fullerene C_20 at different temperatures are presented. It is shown that, although it is metastable, this isomer is very stable with respect to the transition to a lower energy configuration and retains its chemical structure under heating to very high temperatures, T ~ 3000 K. Its decay activation energy is found to be E_a ~ 7 eV. Possible decay channels are studied, and the height of the minimum potential barrier to decay is determined to be U = 5.0 eV. The results obtained make it possible to understand the reasons for the anomalous stability of fullerene C_20 under normal conditions.Comment: Slightly corrected version of the paper submitted to Phys. Solid Stat

Raman scattering in C_{60} and C_{48}N_{12} aza-fullerene: First-principles study

We carry out large scale {\sl ab initio} calculations of Raman scattering activities and Raman-active frequencies (RAFs) in ${\rm C}_{48}{\rm N}_{12}$ aza-fullerene. The results are compared with those of ${\rm C}_{60}$. Twenty-nine non-degenerate polarized and 29 doubly-degenerate unpolarized RAFs are predicted for ${\rm C}_{48}{\rm N}_{12}$. The RAF of the strongest Raman signal in the low- and high-frequency regions and the lowest and highest RAFs for ${\rm C}_{48}{\rm N}_{12}$ are almost the same as those of ${\rm C}_{60}$. The study of ${\rm C}_{60}$ reveals the importance of electron correlations and the choice of basis sets in the {\sl ab initio} calculations. Our best calculated results for ${\rm C}_{60}$ with the B3LYP hybrid density functional theory are in excellent agreement with experiment and demonstrate the desirable efficiency and accuracy of this theory for obtaining quantitative information on the vibrational properties of these molecules.Comment: submitted to Phys.Rev.

Molecular dynamics simulation of biomolecular systems

The group for computer-aided chemistry at the ETH Zurich focuses its research on the development of methodology to simulate the behavior of biomolecular systems and the use of simulation techniques to analyze and understand biomolecular processes at the atomic level. Here, the current research directions are briefly reviewed and illustrated with a few examples

Coupling and uncoupling mechanisms in the methoxythreonine mutant of cytochrome P450cam: a quantum mechanical/molecular mechanical study

The Thr252 residue plays a vital role in the catalytic cycle of cytochrome P450cam during the formation of the active species (Compound I) from its precursor (Compound 0). We investigate the effect of replacing Thr252 by methoxythreonine (MeO-Thr) on this protonation reaction (coupling) and on the competing formation of the ferric resting state and H2O2 (uncoupling) by combined quantum mechanical/molecular mechanical (QM/MM) methods. For each reaction, two possible mechanisms are studied, and for each of these the residues Asp251 and Glu366 are considered as proton sources. The computed QM/MM barriers indicate that uncoupling is unfavorable in the case of the Thr252MeO-Thr mutant, whereas there are two energetically feasible proton transfer pathways for coupling. The corresponding rate-limiting barriers for the formation of Compound I are higher in the mutant than in the wild-type enzyme. These findings are consistent with the experimental observations that the Thr252MeO-Thr mutant forms the alcohol product exclusively (via Compound I), but at lower reaction rates compared with the wild-type enzyme