Acyl Homoserine Lactone Analog Modulators of the Rhll Quorum Sensing Signal Synthase.

Virulence in the Gram-negative pathogen relies in part on the efficient functioning of two LuxI/R dependent quorum sensing (QS) cascades, namely, the LasI/R and RhlI/R systems that generate and respond to (3-oxo)-dodecanoyl-l-homoserine lactone and butyryl-l-homoserine lactone, respectively. The two acyl homoserine lactone (AHL) synthases, LasI and RhlI, use 3-oxododecanoyl-ACP and butyryl-ACP, respectively, as the acyl-substrates to generate the corresponding autoinducer signals for the bacterium. Although AHL synthases represent excellent targets for developing QS modulators in , and in other related bacteria, the identification of potent and signal synthase specific inhibitors has represented a significant technical challenge.

Effects of Solvent Stabilization on Pharmaceutical Crystallization: Investigating Conformational Polymorphism of Probucol Using Combined Solid-State Density Functional Theory, Molecular Dynamics, and Terahertz Spectroscopy.

Solid-state density functional theory (DFT), molecular dynamics (MD), and terahertz (THz) spectroscopy were used to study the formation of enantiotropically related conformational Form I and Form II polymorphs of the pharmaceutical compound, probucol. DFT calculations were performed on the crystal systems to compare relative lattice energies and the solvent stabilization of the metastable Form II structure. The thermodynamics of solvent inclusion in the Form II·MeOH crystal system were determined from MD simulations, as was the favored conformation of molecular probucol in methanol and ethanol solutions.