Advances in theory and algorithms for electronic structure calculations must be incorporated into program packages to enable them to become routinely used by the broader chemical community. This work reviews advances made over the past five years or so that constitute the major improvements contained in a new release of the Q-Chem quantum chemistry package, together with illustrative timings and applications. Specific developments discussed include fast methods for density functional theory calculations, linear scaling evaluation of energies, NMR chemical shifts and electric properties, fast auxiliary basis function methods for correlated energies and gradients, equation-of-motion coupled cluster methods for ground and excited states, geminal wavefunctions, embedding methods and techniques for exploring potential energy surfaces.

The reaction pathways and kinetics of steam methane reforming (SMR) over Ni(111) are investigated using plane wave density functional theory. The thermochemical data are used to develop a microkinetic model of SMR that allows for the investigation of reforming pathways and the most abundant reaction intermediates on the catalyst surface at industrially relevant temperatures and pressures. Pairing the kinetic model with a statistical thermodynamic treatment, surface behavior under a wide range of temperatures, pressures, and initial concentrations can be examined. We present our results at T = 800 °C and P = 10 bar with an initial H2O/CH4 ratio of 2.5:1. Sensitivity analysis is used to provide information about rate-limiting steps in the reaction network. The reaction intermediate CH* is found to be the most important carbon-containing intermediate. CH4(g) adsorption as well as the reactions CH* + O* → CHO* and CH* + OH* → CHOH* are found to be the most sensitive reactions in the mechanism. Consistent accounting for entropic effects was found to be important in obtaining reasonable surface coverages of reaction intermediates, which can influence the determination of active reforming pathways on the catalyst surface.

A fast, fragment-based hybrid many-body interaction model is used to optimize the structures of five small-molecule organic crystals (with fixed experimental lattice parameters) and predict their lattice energies with accuracies of ∼2-4 kJ/mol compared to experiment. This model treats individual molecules in the central unit cell and their short-range two-body interactions quantum mechanically, while long-range electrostatics and many-body induction are treated with a classical polarizable force field. For the hydrogen bonded ice, formamide, and acetamide crystals, MP2 calculations extrapolated to the complete-basisset limit provide good accuracy. However, MP2 exhibits difficulties for crystals such as benzene and imidazole, where π-stacking dispersion interactions are important, and post-MP2 corrections determined from small-basis-set CCSD(T) calculations are required to achieve chemical accuracy. Using these techniques, accurate crystal lattice energy predictions for small-molecule organic crystals are feasible with currently available computing power.

We combine quantum and classical mechanics in a fragment-based many-body interaction model to predict organic molecular crystal lattice energies. Individual molecules in the central unit cell and their short-range pairwise interactions are modeled quantum mechanically, while long-range pairwise and many-body interactions are approximated classically. The classical contributions are evaluated using an accurate ab initio force field that is constructed on-the-fly from quantum mechanical calculations on the individual molecules in the unit cell. The force field parameters include ab initio distributed multipole moments, distributed polarizabilities, and isotropic two- and three-body atomic dispersion coefficients. This QM/MM fragment model reproduces full periodic MP2 lattice energies to within a couple kJ/mol at substantially reduced cost. When high-level electronic structure methods are coupled with the ab initio force field, molecular crystal lattice energies are predicted to within 2 kJ/mol of their experimental values for six of the seven crystals examined here. Finally, Axilrod-Teller-Muto three-body dispersion energy plays a nontrivial role in several of the molecular crystals studied here.

Many-body intermolecular interaction expansions provide a promising avenue for the efficient quantum mechanical treatment of molecular clusters and condensed-phase systems, but the computationally expensive three-body and higher terms are often nontrivial. When polar molecules are involved, these many-body terms are typically dominated by electrostatic induction effects, which can be approximated relatively easily. We demonstrate an accurate and inexpensive hybrid quantum/classical model in which one- and two-body interactions are computed quantum mechanically, while the many-body induction effects are approximated with a simple classical polarizable force field. Whereas typical hybrid quantum/classical models partition a system spatially into distinct quantum and classical regions, the model demonstrated here partitions based on the order in the many-body interaction series. This enables a spatially homogeneous treatment of the entire system, which could prove advantageous in studying a wide range of condensed-phase molecular systems.

Crystal structure prediction driven by density functional theory has become an increasingly useful tool for the pharmaceutical industry and others interested in understanding and controlling organic molecular crystal packing. However, delocalization error in widely used density functionals leads to problematic conformational energies that can cause incorrect predictions of polymorph stabilities. In five examples ranging from small molecules to the polymorphically challenging pharmaceuticals axitinib and galunisertib, the present work demonstrates how inexpensively correcting the intramolecular conformational energies with higher-level electronic structure methods leads to polymorph stability predictions that agree far better with experiment. This approach also provides a valuable diagnostic for when skepticism about predicted polymorph stabilities is warranted.

Significant advances in fragment-based electronic structure methods have created a real alternative to force-field and density functional techniques in condensed-phase problems such as molecular crystals. This perspective article highlights some of the important challenges in modeling molecular crystals and discusses techniques for addressing them. First, we survey recent developments in fragment-based methods for molecular crystals. Second, we use examples from our own recent research on a fragment-based QM/MM method, the hybrid many-body interaction (HMBI) model, to analyze the physical requirements for a practical and effective molecular crystal model chemistry. We demonstrate that it is possible to predict molecular crystal lattice energies to within a couple kJ mol(-1) and lattice parameters to within a few percent in small-molecule crystals. Fragment methods provide a systematically improvable approach to making predictions in the condensed phase, which is critical to making robust predictions regarding the subtle energy differences found in molecular crystals.

Widely used crystal structure prediction models based on density functional theory can perform poorly for conformational polymorphs, but a new model corrects those polymorph stability rankings.