Mechanochemical reaction kinetics and mechanisms

This project studies the chemical kinetics of mechanochemical reactions in a ball mill while the reactions are occurring, toward proposing reaction mechanisms, and testing the validity of the stress-enhanced thermal activation model (in ball mill reactions). The determination of activation energies is also sought.

In situ mechanochemical monitoring measurements are done using Raman spectroscopy, while ex situ measurements are done (for some reactions) by stopping them and analyzing the products by laboratory X-ray powder diffraction (quantitative phase analysis), sometimes combined with in situ Raman spectroscopy. Three mechanochemical reactions are under study, a Diels Alder cycloaddition, the synthesis of a metal-organic framework (MOF), and an organic cocrystallization.

Synthesis and study of relevant solid-state properties of pharmaceutical cocrystals, drug-drug cocrystals and salts

Pharmaceutical cocrystals are new drug delivery forms with improved properties (e.g., increased solubility, chemical stability, etc), composed of a pharmaceutically active ingredient (API) and another molecule (a cocrystal former). Drug-drug cocrystals or salts are made of two APIs. These materials can be synthesized by mechanochemistry and other methods and their crystal structures obtained from synchrotron X-ray powder diffraction, single crystal diffraction, or microED data. We use additional solid-state techniques to study relevant properties (e.g., thermogravimetry, differential scanning calorimetry, FT-IR and Raman spectroscopies, optical microscopy, NMR, etc.). The drug-drug combinations under study are designed using crystal engineering principles.

Different polymorphs (crystal structures) can be synthesized by milling the reactants with small volumes of different organic solvents, a mechanochemical synthetic method called liquid assisted grinding (LAG). 

Mechanochemical synthesis of binary and ternary organic cocrystals with potential ferroelectric properties, crystal growth, and solid-state properties characterization

Students synthesize by mechanochemistry binary and ternary hydrogen-bonded organic cocrystals. X-ray powder diffraction is used for the identification of crystalline products and leftover reactants. Once new materials are identified, single crystals (for crystal structure determination) are grown, or crystal structures are solved by synchrotron X-ray powder diffraction, or microED. A Bruker D8 QUEST ECO X-ray single crystal diffractometer is used for crystal structure analysis. The solid-state properties of the new materials are studied by various techniques, such as FT-IR and Raman spectroscopies, optical microscopy, thermogravimetry, differential scanning calorimetry, SEM, EDS, or others. Crystallographic phase transitions at low temperatures can be investigated by single crystal X-ray diffraction, and FT-IR spectroscopy as a function of temperature.

Development of the software WinPSSP

PSSP and WinPSSP are computer programs applying direct-space methods for the crystal structure determination of organic materials from X-ray powder diffraction. We plan to elaborate and test modifications in the search algorithm of PSSP (in C/C++ programming language), to improve its structure solution search performance. We plan to elaborate instructional materials for newcomers to powder diffraction using use free-distribution software.