Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design

RE--OPTIMIZATION OF AN ELECTRON--WATER PSEUDOPOTENTIAL

Author Institution: Department of Chemistry, the Ohio State University, Columbus, OH 43210In order to assess the role of self-consistent polarization in simulated properties of electron--water clusters and the experimental extrapolation of VEBE (Vertical Electron Binding Energies) to their bulk counterparts we have previously parameterized an electron--water pseudopotential similar to that most commonly used. This potential was shown to perform very well in reproducing VEBE's of a large database of clusters as well as reproducing relative isomer energies of small clusters as compared to MP2 predictions. However, when applied to study the dynamics of large systems (greater than 20 water molecules) this potential yielded a diffusely bound, interpenetrating, unstructured picture of the hydrated electron, inconsistent with chemical intuition and experimental results predicting a well defined solvation cavity. We re--evaluate assumptions that went into our previous parameterization, in particular the repulsive potential that arises when casting the true many--electron problem into an effective one--electron problem. Cluster and bulk binding energies as well as electronic absorption spectra will be investigated

IMPORTANCE OF SELF-CONSISTEN POLARIZATION IN ELECTRON WATER PSEUDO-POTENTIAL

Author Institution: Department of Chemistry, the Ohio State University, Columbus; OH 43201The hydrated electron has been a species of interest in chemical physics for many decades and single electron pseudo-potentials have allowed calculation of large system properties of this species. Due to stabilization of unfavorable neutral water geometries on the anion potential energy surface polarization is known to play an important role in determining the energetics of such systems. Pseudo-potentials applied to large systems have largely ignored this fact. We construct a new electron-water pseudo-potential which treats polarization in a self-consistent manner. Using a grid based representation of the electron and classical nuclei we investigate the effect of the inclusion of self consistent polarization on structural and energetic distributions

Large Computational Survey of Intrinsic Reactivity of Aromatic Carbon Atoms with Respect to a Model Aldehyde Oxidase

Aldehyde oxidase (AOX) and other related molybdenum-containing enzymes are known to oxidize the C–H bonds of aromatic rings. This process contributes to the metabolism of pharmaceutical compounds and, therefore, is of vital importance to drug pharmacokinetics. The present work describes an automated computational workflow and its use for the prediction of intrinsic reactivity of small aromatic molecules toward a minimal model of the active site of AOX. The workflow is based on quantum chemical transition state searches for the underlying single-step oxidation reaction, where the automated protocol includes identification of unique aromatic C–H bonds, creation of three-dimensional reactant and product complex geometries via a templating approach, search for a transition state, and validation of reaction end points. Conformational search on the reactants, products, and the transition states is performed. The automated procedure has been validated on previously reported transition state barriers and was used to evaluate the intrinsic reactivity of nearly three hundred heterocycles commonly found in approved drug molecules. The intrinsic reactivity of more than 1000 individual aromatic carbon sites is reported. Stereochemical and conformational aspects of the oxidation reaction, which have not been discussed in previous studies, are shown to play important roles in accurate modeling of the oxidation reaction. Observations on structural trends that determine the reactivity are provided and rationalized

Large Computational Survey of Intrinsic Reactivity of Aromatic Carbon Atoms with Respect to a Model Aldehyde Oxidase

Aldehyde oxidase (AOX) and other related molybdenum-containing enzymes are known to oxidize the C–H bonds of aromatic rings. This process contributes to the metabolism of pharmaceutical compounds and, therefore, is of vital importance to drug pharmacokinetics. The present work describes an automated computational workflow and its use for the prediction of intrinsic reactivity of small aromatic molecules toward a minimal model of the active site of AOX. The workflow is based on quantum chemical transition state searches for the underlying single-step oxidation reaction, where the automated protocol includes identification of unique aromatic C–H bonds, creation of three-dimensional reactant and product complex geometries via a templating approach, search for a transition state, and validation of reaction end points. Conformational search on the reactants, products, and the transition states is performed. The automated procedure has been validated on previously reported transition state barriers and was used to evaluate the intrinsic reactivity of nearly three hundred heterocycles commonly found in approved drug molecules. The intrinsic reactivity of more than 1000 individual aromatic carbon sites is reported. Stereochemical and conformational aspects of the oxidation reaction, which have not been discussed in previous studies, are shown to play important roles in accurate modeling of the oxidation reaction. Observations on structural trends that determine the reactivity are provided and rationalized

Large Computational Survey of Intrinsic Reactivity of Aromatic Carbon Atoms with Respect to a Model Aldehyde Oxidase

Aldehyde oxidase (AOX) and other related molybdenum-containing enzymes are known to oxidize the C–H bonds of aromatic rings. This process contributes to the metabolism of pharmaceutical compounds and, therefore, is of vital importance to drug pharmacokinetics. The present work describes an automated computational workflow and its use for the prediction of intrinsic reactivity of small aromatic molecules toward a minimal model of the active site of AOX. The workflow is based on quantum chemical transition state searches for the underlying single-step oxidation reaction, where the automated protocol includes identification of unique aromatic C–H bonds, creation of three-dimensional reactant and product complex geometries via a templating approach, search for a transition state, and validation of reaction end points. Conformational search on the reactants, products, and the transition states is performed. The automated procedure has been validated on previously reported transition state barriers and was used to evaluate the intrinsic reactivity of nearly three hundred heterocycles commonly found in approved drug molecules. The intrinsic reactivity of more than 1000 individual aromatic carbon sites is reported. Stereochemical and conformational aspects of the oxidation reaction, which have not been discussed in previous studies, are shown to play important roles in accurate modeling of the oxidation reaction. Observations on structural trends that determine the reactivity are provided and rationalized

Large Computational Survey of Intrinsic Reactivity of Aromatic Carbon Atoms with Respect to a Model Aldehyde Oxidase

Aldehyde oxidase (AOX) and other related molybdenum-containing enzymes are known to oxidize the C–H bonds of aromatic rings. This process contributes to the metabolism of pharmaceutical compounds and, therefore, is of vital importance to drug pharmacokinetics. The present work describes an automated computational workflow and its use for the prediction of intrinsic reactivity of small aromatic molecules toward a minimal model of the active site of AOX. The workflow is based on quantum chemical transition state searches for the underlying single-step oxidation reaction, where the automated protocol includes identification of unique aromatic C–H bonds, creation of three-dimensional reactant and product complex geometries via a templating approach, search for a transition state, and validation of reaction end points. Conformational search on the reactants, products, and the transition states is performed. The automated procedure has been validated on previously reported transition state barriers and was used to evaluate the intrinsic reactivity of nearly three hundred heterocycles commonly found in approved drug molecules. The intrinsic reactivity of more than 1000 individual aromatic carbon sites is reported. Stereochemical and conformational aspects of the oxidation reaction, which have not been discussed in previous studies, are shown to play important roles in accurate modeling of the oxidation reaction. Observations on structural trends that determine the reactivity are provided and rationalized

Large Computational Survey of Intrinsic Reactivity of Aromatic Carbon Atoms with Respect to a Model Aldehyde Oxidase

Aldehyde oxidase (AOX) and other related molybdenum-containing enzymes are known to oxidize the C–H bonds of aromatic rings. This process contributes to the metabolism of pharmaceutical compounds and, therefore, is of vital importance to drug pharmacokinetics. The present work describes an automated computational workflow and its use for the prediction of intrinsic reactivity of small aromatic molecules toward a minimal model of the active site of AOX. The workflow is based on quantum chemical transition state searches for the underlying single-step oxidation reaction, where the automated protocol includes identification of unique aromatic C–H bonds, creation of three-dimensional reactant and product complex geometries via a templating approach, search for a transition state, and validation of reaction end points. Conformational search on the reactants, products, and the transition states is performed. The automated procedure has been validated on previously reported transition state barriers and was used to evaluate the intrinsic reactivity of nearly three hundred heterocycles commonly found in approved drug molecules. The intrinsic reactivity of more than 1000 individual aromatic carbon sites is reported. Stereochemical and conformational aspects of the oxidation reaction, which have not been discussed in previous studies, are shown to play important roles in accurate modeling of the oxidation reaction. Observations on structural trends that determine the reactivity are provided and rationalized