Combined X-ray Crystallographic, IR/Raman Spectroscopic, and Periodic DFT Investigations of New Multicomponent Crystalline Forms of Anthelmintic Drugs: A Case Study of Carbendazim Maleate.

Synthesis of multicomponent solid forms is an important method of modifying and fine-tuning the most critical physicochemical properties of drug compounds. The design of new multicomponent pharmaceutical materials requires reliable information about the supramolecular arrangement of molecules and detailed description of the intermolecular interactions in the crystal structure. It implies the use of a combination of different experimental and theoretical investigation methods. Organic salts present new challenges for those who develop theoretical approaches describing the structure, spectral properties, and lattice energy Elatt. These crystals consist of closed-shell organic ions interacting through relatively strong hydrogen bonds, which leads to Elatt > 200 kJ/mol. Some technical problems that a user of periodic (solid-state) density functional theory (DFT) programs encounters when calculating the properties of these crystals still remain unsolved, for example, the influence of cell parameter optimization on the Elatt value, wave numbers, relative intensity of Raman-active vibrations in the low-frequency region, etc. In this work, various properties of a new two-component carbendazim maleate crystal were experimentally investigated, and the applicability of different DFT functionals and empirical Grimme corrections to the description of the obtained structural and spectroscopic properties was tested. Based on this, practical recommendations were developed for further theoretical studies of multicomponent organic pharmaceutical crystals.