X-ray crystallography is a method for determining the three-dimensional arrangement of atoms in matter. The term X-ray crystallography refers to studies of substances, especially solids, in crystal form. However, the basic method used in X-ray crystallography can be applied to a broad range of materials that are not in crystal form. X-ray crystallography plays a vital role in such fields as chemistry, materials science, mineralogy, molecular biology, pharmacology, and polymer science. It can provide the accurate knowledge of molecular structures needed for the design of new drugs. X-ray crystallography can also be helpful in designing new materials, predicting the properties of new materials, and understanding how materials function.

This program applies the techniques of X-ray crystallography to determine the fundamental structures of crystalline and non-crystalline materials so as to facilitate the discovery and development of novel materials. These novel materials may have a wide variety of properties of interest to the Navy. Success can lead to new drugs, antibiotics, vaccines, new propellant formulations, new electronic or optical sensors, and materials with unanticipated properties. Two examples from recent studies in this area are given below.

Antimicrobial Agents

Antimicrobial resistance represents a global threat to healthcare and new approaches are needed to target organisms that are resistant to antibiotics. Production of b-lactamase is the most common mechanism by which bacteria become resistant to b-lactam antibiotics. In collaboration with researchers at American University a novel class of b-lactam pro-drugs has been synthesized. It is hypothesized that these compounds react with b-lactamases to release the corresponding thiols upon opening the b-lactam ring. These compounds have shown weak intrinsic activity against Mycobacterium tuberculosis wild type strain (Mtb) and beta-lactamase producing Moraxella catarrhalis clinical isolates.

Energetic Materials

In a study on polymorphs of picryl bromide three types of intermolecular interactions were identified: C-H· · ·O hydrogen bonds, N-O· · · Br dipole-induced interactions, and finally, N-O· · ·pi interactions. The C-H· · ·O hydrogen bonds and N-O· · · Br dipole-induced interactions organize the molecules into sheets (Figure 1) while the N-O· · ·pi interactions hold these sheets together (Figure 2). An analysis of the N-O· · ·pi interactions revealed more than 300 structures in the CSD in which a nitro oxygen is within 3.2 Å of an aromatic ring centroid.

This suggests that there is a general tendency for molecules involving nitro groups to use such an interaction to assemble and stabilize themselves in the solid state. While many groups are studying the forces that stabilize 3-D assemblies, no other research group has previously identified the N-O· · ·pi interaction as an important stabilizing force in the solid state.