Density Functional Theory and Density Functional Tight Binding Studies of Thiamine Hydrochloride Hydrates.

Thiamine hydrochloride (THCL), also known as vitamin B1, is an active pharmaceutical ingredient (API), present on the list of essential medicines developed by the WHO, which proves its importance for public health. THCL is highly hygroscopic and can occur in the form of hydrates with varying degrees of hydration, depending on the air humidity. Although experimental characterization of the THCL hydrates has been described in the literature, the questions raised in previously published works suggest that additional research and in-depth analysis of THCL dehydration behavior are still needed. Therefore, the main aim of this study was to characterize, by means of quantum chemical calculations, the behavior of thiamine hydrates and explain the previously obtained results, including changes in the NMR spectra, at the molecular level. To achieve this goal, a series of DFT (CASTEP) and DFTB (DFTB+) calculations under periodic boundary conditions have been performed, including molecular dynamics simulations and GIPAW NMR calculations. The obtained results explain the differences in the relative stability of the studied forms and changes in the spectra observed for the samples of various degrees of hydration. This work highlights the application of periodic DFT calculations in the analysis of various solid forms of APIs.

Review of Applications of Density Functional Theory (DFT) Quantum Mechanical Calculations to Study the High-Pressure Polymorphs of Organic Crystalline Materials.

Since its inception, chemistry has been predominated by the use of temperature to generate or change materials, but applications of pressure of more than a few tens of atmospheres for such purposes have been rarely observed. However, pressure is a very effective thermodynamic variable that is increasingly used to generate new materials or alter the properties of existing ones. As computational approaches designed to simulate the solid state are normally tuned using structural data at ambient pressure, applying them to high-pressure issues is a highly challenging test of their validity from a computational standpoint. However, the use of quantum chemical calculations, typically at the level of density functional theory (DFT), has repeatedly been shown to be a great tool that can be used to both predict properties that can be later confirmed by experimenters and to explain, at the molecular level, the observations of high-pressure experiments. This article's main goal is to compile, analyze, and synthesize the findings of works addressing the use of DFT in the context of molecular crystals subjected to high-pressure conditions in order to give a general overview of the possibilities offered by these state-of-the-art calculations.

Can We Predict the Isosymmetric Phase Transition? Application of DFT Calculations to Study the Pressure Induced Transformation of Chlorothiazide.

Isosymmetric structural phase transition (IPT, type 0), in which there are no changes in the occupation of Wyckoff positions, the number of atoms in the unit cell, and the space group symmetry, is relatively uncommon. Chlorothiazide, a diuretic agent with a secondary function as an antihypertensive, has been proven to undergo pressure-induced IPT of Form I to Form II at 4.2 GPa. For that reason, it has been chosen as a model compound in this study to determine if IPT can be predicted in silico using periodic DFT calculations. The transformation of Form II into Form I, occurring under decompression, was observed in geometry optimization calculations. However, the reverse transition was not detected, although the calculated differences in the DFT energies and thermodynamic parameters indicated that Form II should be more stable at increased pressure. Finally, the IPT was successfully simulated using ab initio molecular dynamics calculations.