Nickel(ii) complexes of N-CH₂CF₃ cyclam derivatives as contrast agents for ¹⁹F magnetic resonance imaging

Abstract

Kinetically inert Ni(ii) complexes of N(1),N(8)-bis(2,2,2-trifluoroethyl)cyclams with hydrogen atoms or phosphonic acid groups in the N(4),N(11)-positions show significant (19)F NMR relaxation rate enhancement useful for 19-fluorine MRI imaging.

Fluorinated Paramagnetic Complexes: Sensitive and Responsive Probes for Magnetic Resonance Spectroscopy and Imaging

“…As in Parker's study, the paramagnetic metal ions decrease the T 1 of the 19 F nuclei by up to two orders of magnitude with the greatest decrease observed with those metal ions having the highest μ eff , namely Tb III , Dy III , Ho III , and Fe II . Paramagnetic Ni II cyclam complexes featuring trans -trifluoroethyl groups were also recently reported by Blahut et al ( 2016 , 2017 ). The trans- [Ni(te2f2p)] 2− ( 13 , Figure 1 ) with phosphate ligands has a 19 F–Ni distance of ~ 5 Å which facilitates a nearly 180-fold reduction in T 1 vs. the free ligand (Table 2 ).…”

“… Chemical structures of non-responsive paramagnetic 19 F probes ( 1 , Kim et al, 1997 ; 2 , Cakic et al, 2016 ; 3 , Placidi et al, 2013 ; 4 , Chalmers et al, 2010 ; 5–6 , Chalmers et al, 2011a ; 7 , Chalmers et al, 2011a , b ; 8–9 , Davies et al, 2015 ; 10 , Jiang et al, 2011 ; 11 , Chalmers et al, 2010 ; 12 , Srivastava et al, 2017a , b ; 13 , Blahut et al, 2016 , 2017 ). …”

Nickel(II) Complexes as Paramagnetic Shift and paraCEST Agents

“…These pendents have exchangeable NH protons that are used for CEST imaging . There are also recent reports on the development of Ni II complexes as paramagnetic relaxation agents for 19 F MRI . In these reports the Ni II complexes promote the relaxation of the 19 F nuclei on ligands to enhance the contrast.…”

“…However, in many coordination geometries, Ni II complexes have relatively broadened proton resonances that signal a lengthening of the electronic relaxation times to produce higher relaxivity and broadened proton resonances , . These Ni II complexes are used for applications that require higher T 1 relaxivities for 1 H or other nuclei such as 19 F but are not optimal for development as paraCEST agents.…”

1,8-bis(2-hydroxy-3,5-di-tert-butylbenzyl)-4,11-dibenzyl-1,4,8,11-tetraazacyclotetradecane

“…Subsequently, complexes of these ligands have potential to be utilised for medical imaging and therapy, such as anti-HIV drugs [1][2][3][4], magnetic resonance imaging (MRI) contrast agents [5] and positron emission tomography (PET) theranostic compounds [6][7][8][9]. The strong affinity that these ligands have for important metal ions, such as copper(II), has seen them becoming increasingly used in the formation of sensors for either environmental analysis or cellular studies [10][11][12].…”