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Co II Complexes as Liposomal CEST Agents
Author(s) -
Abozeid Samira M.,
Asik Didar,
Sokolow Gregory E.,
Lovell Jonathan F.,
Nazarenko Alexander Y.,
Morrow Janet R.
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202003479
Subject(s) - liposome , chemistry , radiochemistry , nanotechnology , materials science
Abstract Three paramagnetic Co II macrocyclic complexes containing 2‐hydroxypropyl pendant groups, 1,1′,1′′,1′′′‐(1,4,8,11‐tetraazacyclotetradecane‐1,4,8,11‐tetrayl)tetrakis‐ (propan‐2‐ol) ([Co(L1)] 2+ , 1,1′‐(4,11‐dibenzyl‐1,4,8,11‐tetraazacyclotetradecane‐1,8‐diyl)bis(propan‐2‐ol) ([Co(L2)] 2+ ), and 1,1′‐(4,11‐dibenzyl‐1,4,8,11‐tetraazacyclotetradecane‐1,8‐diyl)bis(octadecan‐2‐ol) ([Co(L3)] 2+ ) were synthesized to prepare transition metal liposomal chemical exchange saturation transfer (lipoCEST) agents. In solution, ([Co(L1)] 2+ ) forms two isomers as shown by 1 H NMR spectroscopy. X‐ray crystallographic studies show one isomer with 1,8‐pendants in cis ‐configuration and a second isomer with 1,4‐pendants in trans ‐configuration. The [Co(L2)] 2+ complex has 1,8‐pendants in a cis ‐configuration. Remarkably, the paramagnetic‐induced shift of water 1 H NMR resonances in the presence of the [Co(L1)] 2+ complex is as large as that observed for one of the most effective Ln III water proton shift agents. Incorporation of [Co(L1)] 2+ into the liposome aqueous core, followed by dialysis against a solution of 300 mOsm L −1 produces a CEST peak at 3.5 ppm. Incorporation of the amphiphilic [Co(L3)] 2+ complex into the liposome bilayer produces a more highly shifted CEST peak at −13 ppm. Taken together, these data demonstrate the feasibility of preparing Co II lipoCEST agents.