Abstract
We report a cobalt-based paramagnetic chemical exchange saturation transfer (PARACEST) magnetic resonance (MR) probe that is able to selectively bind and quantitate the concentration of Ca2+ ions under physiological conditions. The parent LCo complex features CEST-active carboxamide groups and an uncoordinated crown ether moiety in close proximity to a high-spin pseudo-octahedral CoII center. Addition of Na+, Mg2+, K+, and Ca2+ leads to binding of these metal ions within the crown ether. Single-crystal X-ray diffraction and solid-state magnetic measurements reveal the presence of a cation-specific coordination environment and magnetic anisotropy of CoII, with axial zero-field splitting parameters for the Na+- A nd Ca2+-bound complexes differing by over 90%. Owing to these differences, solution-based measurements under physiological conditions indicate reversible binding of Na+ and Ca2+ to give well-separated CEST peaks at 69 and 80 ppm for [LCoNa]+ and [LCoCa]2+, respectively. Dissociation constants for different cation-bound complexes of LCo, as determined by 1H NMR spectroscopy, demonstrate high selectivity toward Ca2+. This finding, in conjunction with the large excess of Na+ in physiological environments, minimizes interference from related cations, such as Mg2+ and K+. Finally, variable-[Ca2+] CEST spectra establish the ratio between the CEST peak intensities for the Ca2+- A nd Na+-bound probes (CEST80 ppm/CEST69 ppm) as a measure of [Ca2+], providing the first example of a ratiometric quantitation of Ca2+ concentration using PARACEST. Taken together, these results demonstrate the ability of transition metal PARACEST probes to afford a concentration-independent measure of [Ca2+] and provide a new approach for designing MR probes for cation sensing. ©
Original language | English (US) |
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Pages (from-to) | 7163-7172 |
Number of pages | 10 |
Journal | Journal of the American Chemical Society |
Volume | 141 |
Issue number | 17 |
DOIs | |
State | Published - May 1 2019 |
Funding
This research was funded by the Air Force Research Laboratory under agreement no. FA8659-15-2-5518 and Northwestern University.
ASJC Scopus subject areas
- Catalysis
- General Chemistry
- Biochemistry
- Colloid and Surface Chemistry
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CCDC 1912440: Experimental Crystal Structure Determination
Du, K. (Creator), Thorarinsdottir, A. E. (Creator) & Harris, T. D. (Creator), Cambridge Crystallographic Data Centre, 2019
DOI: 10.5517/ccdc.csd.cc2261mz, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc2261mz&sid=DataCite
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CCDC 1912437: Experimental Crystal Structure Determination
Du, K. (Creator), Thorarinsdottir, A. E. (Creator) & Harris, T. D. (Creator), Cambridge Crystallographic Data Centre, 2019
DOI: 10.5517/ccdc.csd.cc2261jw, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc2261jw&sid=DataCite
Dataset
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CCDC 1912436: Experimental Crystal Structure Determination
Du, K. (Creator), Thorarinsdottir, A. E. (Creator) & Harris, T. D. (Creator), Cambridge Crystallographic Data Centre, 2019
DOI: 10.5517/ccdc.csd.cc2261hv, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc2261hv&sid=DataCite
Dataset