Co(II) Macrocyclic Complexes with Amide-Glycinate Pendants as ParaCEST and Liposomal CEST Agents.

Autor: Raymond JJ; Department of Chemistry, University at Buffalo, the State University of New York, Amherst, NY 14260., Chowdhury MSI; Department of Chemistry, University at Buffalo, the State University of New York, Amherst, NY 14260., Crawley MR; Department of Chemistry, University at Buffalo, the State University of New York, Amherst, NY 14260., Morrow JR; Department of Chemistry, University at Buffalo, the State University of New York, Amherst, NY 14260.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2024 Aug 22; Vol. 30 (47), pp. e202401638. Date of Electronic Publication: 2024 Jul 31.
DOI: 10.1002/chem.202401638
Abstrakt: Macrocyclic Co(II) complexes with appended amide-glycinate groups were prepared to develop paramagnetic Co(II) chemical exchange saturation transfer (CEST) agents of reduced overall charge. Complexes with reduced charge and lowered osmolarity are important for their loading into liposomes and to provide complexes that are highly water soluble and well tolerated in animals. Co(L1) has two non-coordinating benzyl groups and two amide-glycinate pendants, whereas Co(L2) has two unsubstituted amide pendants and two amide-glycinate pendants on cyclam (1,4,8,11-tetraazacyclododecane). The 1 H NMR spectrum of Co(L1) is consistent with a single cis-pendant isomer with both amide protons in the trans-configuration, as supported by an X-ray crystal structure. Co(L2) has a mixture of different isomers in solution, including the trans-1,4 and 1,8 pendant isomers. The Z-spectrum of Co(L1) shows one highly-shifted CEST peak, whereas Co(L2) exhibits six CEST peaks. Encapsulation of 40 mM Co(L1) in a liposome with osmotically-induced shrinking at 300 mOsm/L produces a liposomal CEST agent with saturation frequency offset of 3 ppm. Addition of the amphiphilic 1,4,7-triazacyclononane-based complex Co(L5) to the liposomal bilayer at 18 mM with Co(L1) encapsulated in the liposome at 50 mM changes the sign and increases the magnitude of the saturation frequency offset to -7.5 ppm at 300 mOsm/L.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
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