Towards Ni(II) complexes with spin switches for 19F MR-based pH sensing
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Our aim was to demonstrate the potential of exploiting simultaneous changes in coordination geometry and spin state in fluorinated Ni(II) complexes as an avenue for 19F magnetic-resonance (MR)-based pH sensing.
Materials and methods
Crystal structures were studied using an Agilent Technologies SuperNova Dual Source diffractometer. Solution magnetic moment was determined using Evan’s method. MR images were collected on a 7.0-T MR scanner equipped with a quadrature 19F volume coil.
NiL1 and NiL2 were synthesized; crystallographic and spectroscopic data supported NiL1 as being diamagnetic and NiL2 as being paramagnetic. In aqueous solution, ligand dissociation from Ni(II) center was observed for both complexes at around pH 6, precluding their use as reversible pH sensors. The two complexes have distinct 19F nuclear magnetic resonance (NMR) signals in terms of both chemical shift and relaxation times, and selective imaging of the two complexes was achieved with no signal interference using two 19F MRI pulse sequences.
The significant difference in the chemical shift and relaxation times between NiL1 and NiL2 allowed selective imaging of these species using 19F MRI. While NiL1 and NiL2 were not stable to acidic environments, this report lays the framework for development of improved ligand scaffolds that stably coordinate Ni(II) in acidic aqueous solution and act as agents for ratiometric pH mapping by 19F MRI.
KeywordsFluorine-19 magnetic resonance imaging Contrast media Coordination complexes Acidosis
This work was funded by a grant from the Welch Foundation (F1883) (EQ). We gratefully acknowledge Dr. Vincent Lynch for X-ray crystallography support, Dr. Sam Einstein and Dr. James Bankson for help with MR imaging, and Que group members for discussions.
DX study conception and design, acquisition of data, analysis and interpretation of data, drafting of manuscript, critical revision. LO acquisition of data. EQ study conception and design, analysis, and interpretation of data, drafting of manuscript, critical revision.
Compliance with ethical standards
Conflict of interest
No conflicts of interest or funding sources are declared.
This article does not contain any studies performed with animals or human subjects.
- 1.Tannock IF, Rotin D (1989) Acid pH in tumors and its potential for therapeutic exploitation. Cancer Res 49(16):4373–4384Google Scholar
- 12.Demoin DW, Wyatt LC, Edwards KJ, Abdel-Atti D, Sarparanta M, Pourat J, Longo VA, Carlin SD, Engelman DM, Andreev OA, Reshetnyak YK, Viola-Villegas N, Lewis JS (2016) PET imaging of extracellular pH in tumors with 64Cu- and 18F-labeled pHLIP peptides: a structure-activity optimization study. Bioconjug Chem 27(9):2014–2023CrossRefGoogle Scholar
- 22.Woods M, Kiefer GE, Bott S, Castillo-Muzquiz A, Eshelbrenner C, Michaudet L, McMillan K, Mudigunda SDK, Ogrin D, Tircsó G, Zhang S, Zhao P, Sherry AD (2004) Synthesis, relaxometric and photophysical properties of a new pH-responsive MRI contrast agent: the effect of other ligating groups on dissociation of a p-nitrophenolic pendant arm. J Am Chem Soc 126(30):9248–9256CrossRefGoogle Scholar
- 25.Lowe MP, Parker D, Reany O, Aime S, Botta M, Castellano G, Gianolio E, Pagliarin R (2001) pH-dependent modulation of relaxivity and luminescence in macrocyclic gadolinium and europium complexes based on reversible intramolecular sulfonamide ligation. J Am Chem Soc 123(31):7601–7609CrossRefGoogle Scholar