Rapid prediction of conformationally-dependent DFT-level descriptors using graph neural networks for carboxylic acids and alkyl amines.

Data-driven reaction discovery and development is a growing field that relies on the use of molecular descriptors to capture key information about substrates, ligands, and targets. Broad adaptation of this strategy is hindered by the associated computational cost of descriptor calculation, especially when considering conformational flexibility. Descriptor libraries can be precomputed agnostic of application to reduce the computational burden of data-driven reaction development.

Computational Library Enables Pattern Recognition of Noncovalent Interactions and Application as a Modern Linear Free Energy Relationship.

A quantitative and predictive understanding of how attractive noncovalent interactions (NCIs) influence functional outcomes is a long-standing goal in mechanistic chemistry. In that context, better comprehension of how substituent effects influence NCI strengths, and the origin of those effects, is still needed. We sought to build a resource capable of elucidating fundamental origins of substituent effects in NCIs and diagnosing NCIs in chemical systems.

Development of a Deactivation-Resistant Dialkylbiarylphosphine Ligand for Pd-Catalyzed Arylation of Secondary Amines.

Despite the prevalence of N-heteroarenes in small-molecule pharmaceuticals, Pd-catalyzed C-N cross-coupling reactions of aryl halides and amines containing these rings remain challenging due to their ability to displace the supporting ligand via coordination to the metal center. To address this limitation, we report the development of a highly robust Pd catalyst supported by a new dialkylbiarylphosphine ligand, FPhos. The FPhos-supported catalyst effectively resists N-heteroarene-mediated catalyst deactivation to readily promote C-N coupling between a wide variety of Lewis-basic aryl halides and secondary amines, including densely functionalized pharmaceuticals.

Small-molecule properties define partitioning into biomolecular condensates.

Biomolecular condensates regulate cellular function by compartmentalizing molecules without a surrounding membrane. Condensate function arises from the specific exclusion or enrichment of molecules. Thus, understanding condensate composition is critical to characterizing condensate function.