Martinelli Elisa, Spiller Marie, Weck Remo, Llompart Pierre, Minoletti Claire, Güssregen Stefan, Sib Anna, Derdau Volker
Sanofi Germany, Integrated Drug Discovery, Industriepark Höchst, G876, 65926, Frankfurt am Main, Germany.
Sanofi France, Integrated Drug Discovery, 1 impasse des Ateliers, 94 400, Vitry-sur-Seine, France.
Chemistry. 2024 Aug 27;30(48):e202402038. doi: 10.1002/chem.202402038. Epub 2024 Jul 30.
The synthesis of a water-soluble, phosphine-pegylated iridium(I) catalyst and its application in hydrogen isotope exchange (HIE) reactions in buffer is reported. The longer polyethylene glycol side chains on the phosphine increased the water solubility independently from the pH. HIE reactions of polar substrates in protic solvents were studied. DFT calculations gave further insights into the catalytic processes. The scope and limitation of the pegylated catalyst was studied in HIE reactions of several complex compounds in borax buffer at pH 9 and the best conditions were applied in a tritium experiment with the drug telmisartan.
报道了一种水溶性、膦-聚乙二醇化铱(I)催化剂的合成及其在缓冲液中氢同位素交换(HIE)反应中的应用。膦上较长的聚乙二醇侧链独立于pH值提高了水溶性。研究了质子溶剂中极性底物的HIE反应。密度泛函理论计算进一步深入了解了催化过程。在pH 9的硼砂缓冲液中研究了聚乙二醇化催化剂在几种复杂化合物的HIE反应中的适用范围和局限性，并将最佳条件应用于药物替米沙坦的氚实验。
