(C5H6N)Pb2X5 (X = Cl, Br): Hybrid Lead Halides Based on Seven-Coordinate Pb(II).

Hybrid lead halides are a diverse family of compounds, of interest for their optoelectronic properties, that vary in the dimensionality and connectivity of their inorganic substructures. The great majority of these compounds are based on lead-centered octahedra, with few examples featuring inorganic architectures containing higher coordination numbers. Here, we report the synthesis and characterization of a pyridinium lead bromide phase that is based on seven-coordinate Pb(II) centers. Through edge- and face-sharing, the polyhedra form a corrugated, two-dimensional inorganic substructure. Electronic structure calculations were used to examine the band structure and the role of the stereoactive lone pair in the inherently asymmetric, seven-coordinate Pb(II) geometry. For reference, we have visualized the role of the lone pair in the binary halide PbBr2, which also has a seven-coordinate inner ligand sphere. A comparison of the new structure with the limited number of existing hybrid lead halides with similar inorganic architectures highlights the templating role of the organic cation for these compounds. We also contribute characterization and discussion of isomorphic pyridinium lead chloride, which had been deposited in the Cambridge Structural Database but never, to our knowledge, addressed in the literature. The compounds were synthesized using solution conditions and structures determined with single-crystal X-ray diffraction. The materials were also characterized via powder X-ray diffraction, combustion elemental analysis, and diffuse reflectance UV-vis spectroscopy. While the structures reported here are centrosymmetric, the seven-coordinate, capped trigonal prismatic geometry that we have identified is a source of local asymmetry that could be used as a component in designing globally noncentrosymmetric structures.

Development of succinimide-based inhibitors for the mitochondrial rhomboid protease PARL.

While the biochemistry of rhomboid proteases has been extensively studied since their discovery two decades ago, efforts to define the physiological roles of these enzymes are ongoing and would benefit from chemical probes that can be used to manipulate the functions of these proteins in their native settings. Here, we describe the use of activity-based protein profiling (ABPP) technology to conduct a targeted screen for small-molecule inhibitors of the mitochondrial rhomboid protease PARL, which plays a critical role in regulating mitophagy and cell death. We synthesized a series of succinimide-containing sulfonyl esters and sulfonamides and discovered that these compounds serve as inhibitors of PARL with the most potent sulfonamides having submicromolar affinity for the enzyme. A counterscreen against the bacterial rhomboid protease GlpG demonstrates that several of these compounds display selectivity for PARL over GlpG by as much as two orders of magnitude. Both the sulfonyl ester and sulfonamide scaffolds exhibit reversible binding and are able to engage PARL in mammalian cells. Collectively, our findings provide encouraging precedent for the development of PARL-selective inhibitors and establish N-[(arylsulfonyl)oxy]succinimides and N-arylsulfonylsuccinimides as new molecular scaffolds for inhibiting members of the rhomboid protease family.