Theoretical and Computational Chemistry

Computer-based and theoretical approaches to chemical problems can provide atomistic understanding of complex processes at the molecular level. Examples ranging from rates of ligand-binding reactions in proteins to structural and energetic investigations of diastereomers relevant to organo-catalysis are discussed in the following. They highlight the range of application of theoretical and computational methods to current questions in chemical research

Computational Vibrational Spectroscopy

Vibrational spectroscopy is a powerful technique to characterize the near-equilibrium dynamics of molecules in the gas and the condensed phase. This contribution summarizes efforts from computer-based methods to gain insight into the relationship between structure and spectroscopic response. Methods for this purpose include physics-based and machine-learned energy functions, and methods that separate sampling conformational space and determining the data for spectral analysis such as map-based techniques

Higher order multipole moments for molecular dynamics simulations

In conventional force fields, the electrostatic potential is represented by atom-centred point charges. This choice is in principle arbitrary, but technically convenient. Point charges can be understood as the first term of multipole expansions, which converge with an increasing number of terms towards the accurate representation of the molecular potential given by the electron density distribution. The use of multipole expansions can therefore improve the force field accuracy. Technically, the implementation of atomic multipoles is more involved than the use of point charges. Important points to consider are the orientation of the multipole moments during the trajectory, conformational dependence of the atomic moments and stability of the simulations which are discussed her

Energy Redistribution following CO2 Formation on Cold Amorphous Solid Water

The formation of molecules in and on amorphous solid water (ASW) as it occurs in interstellar space releases appreciable amounts of energy that need to be dissipated to the environment. Here, energy transfer between CO2 formed within and on the surface of amorphous solid water (ASW) and the surrounding water is studied. Following CO(1Σ+) + O(1D) recombination the average translational and internal energy of the water molecules increases on the ∼10 ps time scale by 15–25% depending on whether the reaction takes place on the surface or in an internal cavity of ASW. Due to tight coupling between CO2 and the surrounding water molecules the internal energy exhibits a peak at early times which is present for recombination on the surface but absent for the process inside ASW. Energy transfer to the water molecules is characterized by a rapid ∼10 ps and a considerably slower ∼1 ns component. Within 50 ps a mostly uniform temperature increase of the ASW across the entire surface is found. The results suggest that energy transfer between a molecule formed on and within ASW is efficient and helps to stabilize the reaction products generated

Numerical Accuracy Matters: Applications of Machine Learned Potential Energy Surfaces

The role of numerical accuracy in training and evaluating neural network-based potential energy surfaces is examined for different experimental observables. For observables that require third- and fourth-order derivatives of the total energy with respect to Cartesian coordinates single-precision arithmetics as is typically used in ML-based approaches is insufficient and leads to roughness of the underlying PES as is explicitly demonstrated. Increasing the numerical accuracy to double-precision yields a smooth PES with higher-order derivatives that are numerically stable and yield meaningful anharmonic frequencies and tunneling splitting as is demonstrated for H$_2$CO and malonaldehyde. For molecular dynamics simulations, which only require first-order derivatives, single-precision arithmetics appears to be sufficient, though

Molecular Determinants for Rate Acceleration in the Claisen Rearrangement Reaction

The Claisen rearrangement is a carbon-carbon bond-forming, pericyclic reaction of fundamental importance due to its relevance in synthetic and mechanistic investigations of organic and biological chemistry. Despite continued efforts, the molecular origins of the rate acceleration in going from the aqueous phase into the protein is still incompletely understood. In the present work, the rearrangement reactions for allyl-vinyl-ether (AVE), its dicarboxylated variant (AVE-(CO2)2), and the biologically relevant substrate chorismate are investigated in the gas phase, water, and in chorismate mutase. Only the rearrangement of chorismate in the enzyme shows a negative differential barrier when compared to the reaction in water, which leads to the experimentally observed catalytic effect for the enzyme. The molecular origin of this effect is the positioning of AVE-(CO2)2 and chorismate in the protein active site compared to AVE. Furthermore, in going from AVE-(CO2)2 to chorismate, entropic effects due to rigidification and ring formation are operative, which lead to changes in the rate. On the basis of "More O'Ferrall-Jencks" diagrams, it is confirmed that C-O bond breaking precedes C-C bond formation in all cases. This effect becomes more pronounced in going from the gas phase to the protein

Energy Redistribution following CO2 Formation on Cold Amorphous Solid Water

The formation of molecules in and on amorphous solid water (ASW) as it occurs in interstellar space releases appreciable amounts of energy that need to be dissipated to the environment. Here, energy transfer between CO2 formed within and on the surface of amorphous solid water (ASW) and the surrounding water is studied. Following CO(1Σ+) + O(1D) recombination the average translational and internal energy of the water molecules increases on the ∼10 ps time scale by 15–25% depending on whether the reaction takes place on the surface or in an internal cavity of ASW. Due to tight coupling between CO2 and the surrounding water molecules the internal energy exhibits a peak at early times which is present for recombination on the surface but absent for the process inside ASW. Energy transfer to the water molecules is characterized by a rapid ∼10 ps and a considerably slower ∼1 ns component. Within 50 ps a mostly uniform temperature increase of the ASW across the entire surface is found. The results suggest that energy transfer between a molecule formed on and within ASW is efficient and helps to stabilize the reaction products generated

Thermal and Vibrationally Activated Decomposition of the syn-CH3_3CHOO Criegee Intermediate

The full reaction pathway between the syn-CH$_3$CHOO Criegee Intermediate via vinyl hydroxyperoxide to OH+CH$_2$COH is followed for vibrationally excited and thermally prepared reactants. The rates from vibrational excitation are consistent with those found from experiments and tunneling is not required for reactivity at all initial conditions probed. For vibrationally excited reactant, VHP accumulates and becomes a bottleneck for the reaction. The two preparations - relevant for laboratory studies and conditions in the atmosphere - lead to a difference of close to one order of magnitude in OH production (~ 5 % vs. 35 %) on the 1 ns time scale which is an important determinant for the chemical evolution of the atmosphere.Comment: 40 pages , 16 figure

Transfer-Learned Potential Energy Surfaces: Towards Microsecond-Scale Molecular Dynamics Simulations in the Gas Phase at CCSD(T) Quality

The rise of machine learning has greatly influenced the field of computational chemistry, and that of atomistic molecular dynamics simulations in particular. One of its most exciting prospects is the development of accurate, full-dimensional potential energy surfaces (PESs) for molecules and clusters, which, however, often require thousands to tens of thousands of ab initio data points restricting the community to medium sized molecules and/or lower levels of theory (e.g. DFT). Transfer learning, which improves a global PES from a lower to a higher level of theory, offers a data efficient alternative requiring only a fraction of the high level data (on the order of 100 are found to be sufficient for malonaldehyde). The present work demonstrates that even with Hartree-Fock theory and a double-zeta basis set as the lower level model, transfer learning yields CCSD(T)-level quality for H-transfer barrier energies, harmonic frequencies and H-transfer tunneling splittings. Most importantly, finite-temperature molecular dynamics simulations on the sub-microsecond time scale in the gas phase are possible and the infrared spectra determined from the transfer learned PESs are in good agreement with experiment. It is concluded that routine, long-time atomistic simulations on PESs fulfilling CCSD(T)-standards become possible

Ligand and interfacial dynamics in a homodimeric hemoglobin

The structural dynamics of dimeric hemoglobin (HbI) from Scapharca inaequivalvis in different ligand-binding states is studied from atomistic simulations on the μs time scale. The intermediates are between the fully ligand-bound (R) and ligand-free (T) states. Tertiary structural changes, such as rotation of the side chain of Phe97, breaking of the Lys96-heme salt bridge, and the Fe-Fe separation, are characterized and the water dynamics along the R-T transition is analyzed. All these properties for the intermediates are bracketed by those determined experimentally for the fully ligand-bound and ligand-free proteins, respectively. The dynamics of the two monomers is asymmetric on the 100 ns timescale. Several spontaneous rotations of the Phe97 side chain are observed which suggest a typical time scale of 50-100 ns for this process. Ligand migration pathways include regions between the B/G and C/G helices and, if observed, take place in the 100 ns time scale