TY - JOUR

T1 - Recyclable Palladium-Polysiloxane Catalyst with Ultra-Low Metal Leaching for Drug Synthesis

AU - Головенко, Екатерина Алексеевна

AU - Петрова, Полина Павловна

AU - Панькин, Дмитрий Васильевич

AU - Байков, Сергей Валентинович

AU - Кукушкин, Вадим Юрьевич

AU - Боярский, Вадим Павлович

AU - Исламова, Регина Маратовна

PY - 2025/11/19

Y1 - 2025/11/19

N2 - A carbon-supported palladium-containing polysiloxane macrocatalyst (Pd-PDMS) was developed for pharmaceutical-grade cross-coupling reactions. The catalyst demonstrates exceptional year-long stability at room temperature while maintaining full catalytic activity. Pd-PDMS efficiently promotes three pharmaceutically relevant reactions: Suzuki coupling (80% yield), copper-free Sonogashira coupling (90% yield at 55 °C), and Heck coupling (80% yield at 90 °C). The copper-free Sonogashira protocol eliminates toxic copper cocatalysts, phosphine ligands, and organic bases while operating under mild conditions. Most significantly, palladium contamination in products reaches ultra-low levels of 22 ppb (Sonogashira, Suzuki) and 167 ppb (Heck), representing a 60-450-fold improvement over European Medicines Agency requirements (10 ppm). The catalyst exhibits excellent recyclability without activity loss over multiple cycles, with simple washing protocols between uses. Scanning electron microscopy and X-ray photoelectron spectroscopy confirmed uniform Pd-PDMS coating on carbon fibers, while density functional theory calculations revealed specific coordination interactions between the palladium complex and carbon support at 3.26 Å distance. This convergence of pharmaceutical-grade metal contamination control, exceptional stability, and multi-reaction versatility establishes a significant advancement for sustainable cross-coupling catalysis in pharmaceutical applications.

AB - A carbon-supported palladium-containing polysiloxane macrocatalyst (Pd-PDMS) was developed for pharmaceutical-grade cross-coupling reactions. The catalyst demonstrates exceptional year-long stability at room temperature while maintaining full catalytic activity. Pd-PDMS efficiently promotes three pharmaceutically relevant reactions: Suzuki coupling (80% yield), copper-free Sonogashira coupling (90% yield at 55 °C), and Heck coupling (80% yield at 90 °C). The copper-free Sonogashira protocol eliminates toxic copper cocatalysts, phosphine ligands, and organic bases while operating under mild conditions. Most significantly, palladium contamination in products reaches ultra-low levels of 22 ppb (Sonogashira, Suzuki) and 167 ppb (Heck), representing a 60-450-fold improvement over European Medicines Agency requirements (10 ppm). The catalyst exhibits excellent recyclability without activity loss over multiple cycles, with simple washing protocols between uses. Scanning electron microscopy and X-ray photoelectron spectroscopy confirmed uniform Pd-PDMS coating on carbon fibers, while density functional theory calculations revealed specific coordination interactions between the palladium complex and carbon support at 3.26 Å distance. This convergence of pharmaceutical-grade metal contamination control, exceptional stability, and multi-reaction versatility establishes a significant advancement for sustainable cross-coupling catalysis in pharmaceutical applications.

UR - https://www.mdpi.com/2073-4360/17/22/3066

UR - https://www.mendeley.com/catalogue/829764b0-e665-3bef-8b4d-9093b7a41531/

U2 - 10.3390/polym17223066

DO - 10.3390/polym17223066

M3 - Article

C2 - 41304431

VL - 17

JO - Polymers

JF - Polymers

SN - 2073-4360

IS - 22

M1 - 3066

ER -