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Title: Co II Complexes as Liposomal CEST Agents
Abstract

Three paramagnetic CoIImacrocyclic 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 by1H NMR spectroscopy. X‐ray crystallographic studies show one isomer with 1,8‐pendants incis‐configuration and a second isomer with 1,4‐pendants intrans‐configuration. The [Co(L2)]2+complex has 1,8‐pendants in acis‐configuration. Remarkably, the paramagnetic‐induced shift of water1H NMR resonances in the presence of the [Co(L1)]2+complex is as large as that observed for one of the most effective LnIIIwater proton shift agents. Incorporation of [Co(L1)]2+into the liposome aqueous core, followed by dialysis against a solution of 300 mOsm L−1produces 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 CoIIlipoCEST agents.

 
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NSF-PAR ID:
10154579
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Angewandte Chemie
Volume:
132
Issue:
29
ISSN:
0044-8249
Page Range / eLocation ID:
p. 12191-12195
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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  1. Abstract

    Three paramagnetic CoIImacrocyclic 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 by1H NMR spectroscopy. X‐ray crystallographic studies show one isomer with 1,8‐pendants incis‐configuration and a second isomer with 1,4‐pendants intrans‐configuration. The [Co(L2)]2+complex has 1,8‐pendants in acis‐configuration. Remarkably, the paramagnetic‐induced shift of water1H NMR resonances in the presence of the [Co(L1)]2+complex is as large as that observed for one of the most effective LnIIIwater proton shift agents. Incorporation of [Co(L1)]2+into the liposome aqueous core, followed by dialysis against a solution of 300 mOsm L−1produces 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 CoIIlipoCEST agents.

     
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