Appraisal of the Fragments‐In‐Fragments Method for the Energetics of Individual Hydrogen Bonds in Molecular Crystals

Abstract

We report a direct application of the molecular tailoring approach‐based (MTA‐based) method to calculate the individual hydrogen bond (HB) energy in molecular crystal. For this purpose, molecular crystals of nitromalonamide (NMA) and salicylic acid (SA) were taken as test cases. Notably, doing a correlated computation using a large molecular crystal structure is difficult. Among 15 density functional theory functionals, the B3LYP provides accurate estimates of HB energies closed to the CCSD(T) ones using the 6–311 + G(d,p) basis set for all atoms. The direct application of the MTA‐based method to these crystal structures is although straightforward. For instance, the calculated energy suggests that three intramolecular HBs in NMA crystal are of stronger strength (7.3–17.0 kcal/mol) than the intermolecular ones (2.7–4.0 kcal/mol). On the other hand, intermolecular HB in SA crystal is moderately stronger (9.9 kcal/mol) than intramolecular one (8.1 kcal/mol). However, these energy calculations by the MTA‐based method are very expensive. For instance, the time needed to evaluate the energy of all seven HBs in NMA crystal (having molecules within maximum of 15 unit cells) is 122,681 min (~2.7 months). In view of this, we assessed our recently proposed linear‐scaling Fragments‐in‐Fragments (Frags‐in‐Frags) method for estimating the single‐point energies of parent molecular crystal and fragments of the MTA‐based method. It has been found that the estimated HB energies by the Frags‐in‐Frags method are in excellent linear agreement with their MTA‐based counterparts (R2 = 0.9993). Furthermore, root mean square deviation is 0.12 kcal/mol. Mean and maximum absolute errors are 0.10 and 0.5 kcal/mol, respectively, and the standard deviation is 0.14 kcal/mol. Importantly, the Frags‐in‐Frags method is computationally efficient; it needs only 18,289 min (~12.7 days) for the estimation of energy of all HBs in NMA crystal and 3499 min (~2.4 days) for all HBs in SA crystal.