Quantitative Analysis the Weak Non-Covalent Interactions of the Polymorphs of Donepezil

Donepezil has polymorphism. Different crystalline forms can exhibit different physicochemical properties and biological activities. Exploration of intermolecular interactions is essential to reveal the formation mechanism and differences in properties of polymorphs. This study explores the weak non covalent intermolecular interactions of donepezil polymorphs through fully ab initio quantum mechanical methods, semi empirical methods, and Hirshfeld surface analysis. The results show that the Hirshfeld surface analysis method can clearly and intuitively reveal the intermolecular interactions. Theoretical calculations using the atom-atom Coulomb-London-Pauli (AA-CLP) method were also performed to understand the interaction energies toward the total lattice energy. The value of the lattice energy was in accordance with the melting points of the donepezil polymorphs and brought to light the nature of thermal stability. In the specific energy distribution, the contribution of the dispersion force is the most prominent. Further interaction energy analysis found that within a distance of 3.8 angstrom from the center of the donepezil molecule, different crystalline forms of donepezil molecules have different interaction energies with surrounding molecules. The different interaction energies between polymorphs may lead to polymorphs with different physical-chemical properties.

Automated summary

This study explores the weak non-covalent intermolecular interactions of donepezil polymorphs using various computational methods. The results show that analysis using the Hirshfeld surface method provides clear insights into these interactions. Theoretical calculations also reveal different interaction energies between different crystalline forms of donepezil, which may contribute to the differences in their physical-chemical properties.