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Modulation of the Prototropic Exchange Rate in pH‐Responsive Yb‐HPDO3A Derivatives as ParaCEST Agents
Author(s) -
Dastrù Walter,
Menchise Valeria,
Ferrauto Giuseppe,
Fabretto Serena,
Carrera Carla,
Terreno Enzo,
Aime Silvio,
Castelli Daniela Delli
Publication year - 2018
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201800283
Subject(s) - chemistry , proton , derivative (finance) , paramagnetism , inorganic chemistry , medicinal chemistry , physics , quantum mechanics , financial economics , economics
The aim of this work was to design new pH‐sensitive paramagnetic chemical exchange saturation transfer (paraCEST) agents with a more acidic pH readout window with respect to the Yb complex of the 10‐(2‐hydroxypropyl)‐1,4,7,10‐ tetraazacyclododecane‐1,4,7‐triacetic acid (HPDO3A). In particular, three HPDO3A derivatives have been synthesized by substituting the methyl group on the 2‐hydroxypropyl arm with the electron withdrawing substituents –CF 3 , –CH 2 NH 2 and –CH 2 OH. The Yb complexes have been characterized in terms of i) number and relative abundance of isomers present and, ii) pH sensitivity range in CEST applications. The influence of the introduced substituents on the –OH proton acidity and k ex has been investigated and the new agents have been compared with the parent Yb‐HPDO3A. All complexes showed an increased acidity and an enhanced exchange rate of the –OH proton. As a consequence, the pH‐CEST sensitivity has been shifted to more acidic values. Eventually, the –CH 2 OH bearing derivative has been tested to assess the intra‐endosomal pH which is too acidic to be determined with Yb‐HPDO3A.