Grid: A Python library for molecular integration, interpolation, differentiation, and more.

Grid is a free and open-source Python library for constructing numerical grids to integrate, interpolate, and differentiate functions (e.g., molecular properties), with a strong emphasis on facilitating these operations in computational chemistry and conceptual density functional theory. Although designed, maintained, and released as a stand-alone Python library, Grid was originally developed for molecular integration, interpolation, and solving the Poisson equation in the HORTON and ChemTools packages. Grid is designed to be easy to use, extend, and maintain; this is why we use Python and adopt many principles of modern software development, including comprehensive documentation, extensive testing, continuous integration/delivery protocols, and package management. We leverage popular scientific packages, such as NumPy and SciPy, to ensure high efficiency and optimized performance in grid development. This article is the official release note of the Grid library showcasing its unique functionality and scope.

Can we predict ambident regioselectivity using the chemical hardness?

The hard/soft acid/base (HSAB) principle is a cornerstone in our understanding of chemical reactivity preferences. Motivated by the success of the original ("global") version of this rule, a "local" counterpart was readily proposed to account for regioselectivity preferences, in particular, in ambident reactions. However, ample experimental evidence indicates that the local HSAB principle often fails to provide meaningful predictions. Here we examine the assumptions behind the standard proof of the local HSAB rule, showing that it is based on a flawed premise. By solving this issue, we show that it is critical to consider not only the charge transferred between the different reacting centers but also the charge reorganization within the non-reacting parts of the molecule. We propose different reorganization models and derive the corresponding regioselectivity rules for each.

1,3 Dipolar Cycloaddition of Münchnones: Factors behind the Regioselectivity.

The 1,3 dipolar cycloaddition reactions of münchnones and alkenes provide an expedite synthetic way to substituted pyrroles, an exceedingly important structural motif in the pharmaceutical and material science fields of research. The factors governing their regioselectivity rationalization are not well understood. Using several approaches, we investigate a set of 14 reactions (featuring two münchnones, 12 different alkenes, and two alkynes). The Natural Bond Theory and the Non-Covalent Interaction Index analyses of the noncovalent interaction energies fail to predict the experimental major regioisomer. Employing global cDFT descriptors or local ones such as the Fukui function and dual descriptor yields similarly inaccurate predictions. Only the local softness pairing, within Pearson's Hard and Soft Acids and Bases principle, constitutes a reliable predictor for the major reaction product. By taking into account an estimator for the steric effects, the correct regioisomer is predicted. Steric effects play a major role in driving the regioselectivity, as was corroborated by energy decomposition analysis of the transition states.

Role of Augmented Basis Sets and Quest for ab Initio Performance/Cost Alternative to Kohn-Sham Density Functional Theory.

Following a previous work, we have assessed the feasibility of MP2/CBS(d, t) as an alternative to state-of-the-art density functionals. The effect of using augmented basis sets is here tested on the 76 barrier heights and 10 isomerization reactions previously utilized. Moreover, calculations for 20 sets of the GMTKN24 database for thermochemistry, kinetics, and noncovalent interactions have been performed. For the density functional theory calculations, M06-2X and B3LYP-D3 functionals are utilized as two representative functionals, while MP2 and CCSD(T) methods are employed as the ab initio counterparts. The results show that MP2 calculations perform similarly to the ones obtained with M06-2X insofar as accuracy and computational cost are concerned. For all methods, the use of augmented basis sets yields enhanced results for anionic systems when compared with the ones from non-augmented bases. Otherwise, the basis-set change effect is found to be minimal. It is therefore concluded that the use of large basis sets is unjustified when facing the increase in computational cost.

How Biochemical Environments Fine-Tune a Redox Process: From Theoretical Models to Practical Applications.

In this study, we give a new physical insight into how enzymatic environments influence a redox process. This is particularly important in a biochemical context, in which oxidoreductase enzymes and low-molecular-weight cofactors create a microenvironment, fine-tuning their specific redox potential. We present a new theoretical model, quantitatively backed up by quantum chemically calculated data obtained for key biological sulfur-based model reactions involved in preserving the cellular redox homeostasis during oxidative stress. We show that environmental effects can be quantitatively predicted from the thermodynamic cycle linking ΔΔ G(OX/RED)ref-ligand values to the differential interaction energy ΔΔ Gint of the reduced and oxidized species with the environment. Our obtained data can be linked to hydrogen-bond patterns found in protein active sites. The thermodynamic model is further understood in the framework of molecular orbital theory. The key insight of this work is that the intrinsic properties of neither a redox couple nor the interacting environment (e.g., ligand) are enough by themselves to uniquely predict reduction potentials. Instead, system-environment interactions need to be considered. This study is of general interest as redox processes are pivotal to empower, protect, or damage organisms. Our presented thermodynamic model allows a pragmatically evaluation on the expected influence of a particular environment on a redox process, necessary to fully understand how redox processes take place in living organisms.

Assessing How Correlated Molecular Orbital Calculations Can Perform versus Kohn-Sham DFT: Barrier Heights/Isomerizations.

To assess the title issue, 38 hydrogen transfer barrier heights and 38 non-hydrogen transfer barrier heights/isomerizations extracted from extensive databases have been considered, in addition to 4 2 p-isomerization reactions and 6 others for large organic molecules. All Kohn-Sham DFT calculations have employed the popular M06-2X functional, whereas the correlated molecular orbital (MO)-based ones are from single-reference MP2 and CCSD(T) methods. They have all utilized the same basis sets, with raw MO energies subsequently extrapolated to the complete basis set limit without additional cost. MP2 calculations are found to be as cost-effective as DFT ones and often slightly more, while showing a satisfactory accuracy when compared with the reference data. Although the focus is on barrier heights, the results may bear broader implications, in that one may see successes and difficulties of DFT when compared with traditional MO theories for the same data.

Theoretical Study on the Mechanism of the Thermal Retro-Cycloaddition of Isoxazolinofullerenes.

The retro-cycloaddition thermal reaction of isoxazolino[4,5:1,2][60]fullerenes to pristine fullerene seems to be guided by the electronic nature of the substituted nitrile oxide 1,3-dipole in the isoxazoline ring. Trapping experiments proved that the reaction mechanism occurs by thermal removal of the nitrile oxide 1,3-dipole in a process that is favored in the presence of a big excess of a highly efficient dipolarophile such as maleic anhydride. Theoretical gas phase calculations carried out at the B3LYP/6-31G(d) and M06-2X/6-31G(d) levels of theory underpin the experimental findings and predict that compound 1c, bearing the p-(CH3)2N-Ph substituent on the isoxazoline ring and with a remarkable experimental conversion efficiency in just 12 h, showed the lowest activation energy. Solvent calculations have predicted the same behavior in gas phase. Different approaches such as electrostatic natural population analysis and Houk's distortion/interaction model have been applied to understand how the electronic nature of these substituents affects the retro-cycloaddition reaction process. Analysis of the values of the condensed Fukui functions and dual descriptor shed light on the mechanism of the retro-cycloaddition reaction.

Electronegativity and redox reactions.

Using the maximum hardness principle, we show that the oxidation potential of a molecule increases as its electronegativity increases and also increases as its electronegativity in its oxidized state increases. This insight can be used to construct a linear free energy relation for the oxidation potential, which we train on a set of 31 organic redox couples and test on a set of 10 different redox reactions. Better results are obtained when the electronegativity of the oxidized/reduced reagents are adjusted to account for the reagents' interaction with their chemical environment.