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

Abstract

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.

Inter- vs. Intramolecular Hydrogen Bond Patterns and Proton Dynamics in Nitrophthalic Acid Associates

“…Though dimers D3(I) – D3(VII) are the most stable forms, the formation of oligomers (structure G , Figure 5 ) and complexes of other types ( D and E dimers, Figure 5 ) is also possible. This fact is also supported by the crystallographic and spectroscopic studies [ 71 , 72 , 73 , 74 ].…”

Crystalline Peroxosolvates: Nature of the Coformer, Hydrogen-Bonded Networks and Clusters, Intermolecular Interactions

“…Simultaneous calculation of various properties of an organic crystal (energy of intermolecular interactions, enthalpy of sublimation, low-frequency IR and Raman spectra, etc.) requires the use of periodic DFT methods [123,124]. There are a number of methods and programs for performing this type of calculation [125,126].…”

Interplay of π-stacking and inter-stacking interactions in two-component crystals of neutral closed-shell aromatic compounds: periodic DFT study

“…This is a common approximation for the calculating of molecular crystals. 25,[47][48][49][50] Further details of periodic DFT computations are given in ESI. † A common approach to E latt estimation for two-component crystals is based on the total electronic energies of the crystal (E bulk ) and isolated molecules of its components (E i ) calculated per asymmetric unit: 50…”