Characterization of Pharmaceutical Polymorphs

The three-dimensional arrangement of drug molecules in the solid state is of critical importance to physical properties such as solubility and bioavailability. Drugs often exhibit multiple stable polymorphs (crystalline packing motifs) that are interconvertible through mechanisms such as temperature changes, choice of crystallization solvent, and even ambient humidity. These various pharmaceutical polymorphs each exhibit unique identifying crystal lattice vibrations that occur in the THz region of the electromagnetic spectrum. Terahertz spectroscopy provides a rapid non-destructive method for the real-time monitoring of pharmaceutical polymorph content in bulk APIs (active pharmaceutical ingredients) for manufacturing line quality assurance and also in final formulated products to ensure long-term stability.

Selected publications:

King, Matthew D.; Buchanan, William D.; Korter, Timothy M..   Identification and Quantification of Polymorphism in the Pharmaceutical Compound Diclofenac Acid by Terahertz Spectroscopy and Solid-State Density Functional Theory. Analytical Chemistry (Washington, DC, United States)  (2011),  83(10),  3786-3792.

King, Matthew D.; Buchanan, William D.; Korter, Timothy M..   Understanding the terahertz spectra of crystalline pharmaceuticals: Terahertz spectroscopy and solid-state density functional theory study of (S)-(+)-ibuprofen and (RS)-ibuprofen. Journal of Pharmaceutical Sciences  (2011),  100(3),  1116-1129.

Non-Invasive Explosives Detection and Identification

The detection and identification of concealed explosive threats is one of the greatest challenges facing the defense and security communities. There is a clear need for a technology that is able to address this problem in an accurate and safe manner. Terahertz radiation has attracted much attention as a potential solution. Terahertz radiation is able to pass through many common materials such as paper, plastic, and fabric much like X-rays, but unlike X-rays, THz radiation is non-ionizing and is safe to use in the direct screening of people. Also unlike X-ray methods, THz radiation is able to provide unambiguous chemical identification of concealed explosives through the interaction of the THz radiation with the unique crystalline lattice vibrations of these materials. The chemical specificity and non-invasive nature of THz spectroscopy enables the rapid discrimination of innocuous and hazardous materials (for example, two white powders such as sucrose vs. TNT) while minimizing the occurrence of false positives.

Selected publications:

Wilkinson, John; Konek, Christopher T.; Moran, Jesse S.; Witko, Ewelina M.; Korter, Timothy M..  Terahertz absorption spectrum of triacetone triperoxide (TATP).Chemical Physics Letters  (2009),  478(4-6),  172-174. DOI: 10.1016/j.cplett.2009.07.079

Allis, Damian G.; Zeitler, J. Axel; Taday, Philip F.; Korter, Timothy M..  Theoretical analysis of the solid-state terahertz spectrum of the high explosive RDX.Chemical Physics Letters  (2008),  463(1-3),  84-89. DOI: 10.1016/j.cplett.2008.08.014

Understanding Weak Intermolecular Forces in Molecular Crystals

The bulk macroscopic properties (such as melting point and solubility) of solid-state materials are governed by weak intermolecular forces that originate from atomic-scale interactions. These forces range greatly in strength and specificity from the biologically critical hydrogen bond to the ubiquitous London dispersion force. Terahertz spectroscopy is able to directly probe intermolecular forces through the low-frequency vibrations exhibited by molecular crystals. Combining terahertz spectroscopy with solid-state density functional theory calculations (including corrections for weak London forces) enables a detailed understanding of intermolecular forces to be obtained in a variety of solids such as pharmaceutical polymorphs and crystalline solvates.

Selected publications:

King, Matthew D.; Ouellette, Wayne; Korter, Timothy M..   Noncovalent Interactions in Paired DNA Nucleobases Investigated by Terahertz Spectroscopy and Solid-State Density Functional Theory. Journal of Physical Chemistry A  ACS ASAP.

King, Matthew D.; Buchanan, William D.; Korter, Timothy M..   Investigating the Anharmonicity of Lattice Vibrations in Water-Containing Molecular Crystals through the Terahertz Spectroscopy of L-Serine Monohydrate. Journal of Physical Chemistry A  (2010),  114(35),  9570-9578.