RESUMO
Herein, we report the synthesis and characterization of a new class of hybrid Wells-Dawson polyoxometalate (POM) containing a diphosphoryl group (P2 O6 X) of the general formula [P2 W17 O57 (P2 O6 X)]6- (X=O, NH, or CR1 R2 ). Modifying the bridging unit X was found to impact the redox potentials of the POM. The ease with which a range of α-functionalized diphosphonic acids (X=CR1 R2 ) can be prepared provides possibilities to access diverse functionalized hybrid POMs. Compared to existing phosphonate hybrid Wells-Dawson POMs, diphosphoryl-substituted POMs offer a wider tunable redox window and enhanced hydrolytic stability. This study provides a basis for the rational design and synthesis of next-generation hybrid Wells-Dawson POMs.
RESUMO
Phosphoinositide-3-kinase δ (PI3Kδ) is a critical regulator of cell growth and transformation and has been explored as a therapeutic target for a range of diseases. Through the exploration of the thienopyrimidine scaffold, we have identified a ligand-efficient methylation that leads to remarkable selectivity for PI3Kδ over the closely related isoforms. Interrogation through the Free-Wilson analysis highlights the innate selectivity the thienopyrimidine scaffold has for PI3Kδ and provides a predictive model for the activity against the PI3K isoforms.