Cu single sites on BO2 as thyroid peroxidase mimicking for iodotyrosine coupling and pharmaceutical assess

Designing three-dimensional (3D) catalytic sites in single-atom catalysts (SACs) that mimic thyroid peroxidase (TPO) function for achieving iodotyrosine coupling, although highly desirable for the synthesis of thyroid hormones, poses a great challenge. Herein, we design and synthesize a class of SACs with 3D catalytic centers composed of Cu-N₅ as catalytic sites and BO₂ as binding sites (BO₂/CuN₅C) for mimicking TPO in activating H₂O₂ to facilitate tyrosine iodination and conjugation for producing thyroid hormones. We demonstrate that the as-prepared BO₂/CuN₅C not only provides binding sites for H₂O₂ through hydrogen bond interactions but also possesses catalytic sites to promote an alternative O–O heterolysis process. BO₂/CuN₅C with TPO-like catalytic centers can produce 3,3′,5-triiodothyronine and d-thyroxine with 2.4-fold and 11.1-fold improvements relative to those of CuN₅C. Besides, the assessment of 2-mercapto-1-methylimidazole and 6-propyl-2-thiouracil in vitro investigations of antithyroid drugs corresponds well with the European Thyroid Association guidelines and therefore can provide clinical medication guidance to prevent toxic reactions. Overall, this work unlocks an approach to precisely simulate the natural enzyme active site for amino acid coupling and pharmaceutical assessment.