Nickel(II) Complexes as Paramagnetic Shift and paraCEST Agents

Abstract

Five Ni II macrocyclic complexes are studied as water proton shift agents and as paraCEST agents (paraCEST = paramagnetic chemical exchange saturation transfer) for MRI applications. The five macrocycles have amide and/or alcohol pendent groups with either tetraaza-or triazamacrocycles including 1,1′,1′′-(1,4,7-triazonane-1,4,7-triyl)tris(propan-2-ol) (L1), 1,1′,1′′,1′′′-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra)tetrakis(propan-2-ol) (L2), 1,1′,1′′, 1′′′-(1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetrayl)tetrakis(propan-2-ol) (L3), 2,2′,2′′-(1,4,7triazonane-1,4,7-triyl)triacetamide (L4), or 2,2′-(7-benzyl-1,4,7triazonane-1,4-diyl) diacetamide (L5). Solution magnetic moments are consistent with paramagnetic Ni II complexes. The complexes are characterized by pH-potentiometric titrations to

CoII Complexes as Liposomal CEST Agents

“…The minor form of [Co(L1)] 2+ is most likely the 1,4‐isomer in trans ‐III form, based on comparison of proton shifts to that of the [Co(L4)] 2+ isomers . The z ‐spectra of the two complexes also support this analysis by showing weak CEST peaks characteristic of OH exchangeable protons bound to Co II . [Co(L2)] 2+ shows a single CEST peak at 33 ppm versus bulk water, consistent with a single isomer.…”

“…[Co(L1)] 2+ produces two CEST peaks consistent with the two isomers, one at 33 and one at 58 ppm. The pH dependence of the CEST effect increases with pH up to pH 7.2 with exchange rate constants ranging from 800 to 3900 s −1 , characteristic of ligand donor groups that have exchanging OH protons . The low intensity of CEST peaks suggests that these complexes would not be useful as paraCEST agents.…”

“…High‐spin Co II and Fe II macrocyclic complexes are alternatives to Ln III complexes for the production of highly paramagnetically shifted water protons . Interestingly, while paramagnetic complexes with inner‐sphere water ligands produce strongly shifted water protons, so do complexes that interact with water through second‐sphere interactions . Here we report three new Co II complexes that produce highly shifted water proton resonances.…”

Metal-based redox-responsive MRI contrast agents

“…Finally, a comparative study including five Ni II macrocyclic complexes in water was undertaken using triaza (TACN) derivatives with three (100) or two(105) amino and three OH (101) groups; it also includes two CYCLEN and CYCLAM tetraaza complexes with four OH pendants (109 and 111). These complexes were characterized by X-ray diffraction, 1 H NMR, CEST and 17 O NMR relaxometry 154. These macrocycles have five (105), six (100, 101) or eight (109, 111) donor groups for coordinating the Ni II ion.…”

“…No redox response studies have been reported so far for any of the described Ni II systems, perhaps because they are difficult to oxidize, as shown by the redox potential of aquated Ni II (E o = +2.290 mV vs NHE). Despite the large hyperfine shifts observed, further studies are needed to take such compounds to in vivo evaluation 154.…”