Design Principles for the Development of Gd(III) Polarizing Agents for Magic Angle Spinning Dynamic Nuclear Polarization

Abstract

Nuclear magnetic resonance suffers from an intrinsically low sensitivity, which can be overcome by dynamic nuclear polarization (DNP). Gd(III) complexes are attractive exogenous polarizing agents for magic angle spinning (MAS) DNP due to their high chemical stability in contrast to nitroxide-based radicals. However, even the state-of-the-art Gd(III) complexes have so far provided relatively low DNP signal enhancements of ca. 36 in comparison to standard DNP biradicals, which show enhancements of over 200. Here, we report a series of new Gd(III) complexes for DNP and show that the observed DNP enhancements of the new and existing Gd(III) complexes are inversely proportional to the square of the zero-field splitting (ZFS) parameter D , which is in turn determined by the ligand-type and the local coordination environment. The experimental DNP enhancements at 9.4 T and the ZFS parameters measured with pulsed electron paramagnetic resonance (EPR) spectroscopy agree with the above model, paving the way for the development of more efficient Gd(III) polarizing agents.

Off-the-Shelf Gd(NO3)3 as an Efficient High-Spin Metal Ion Polarizing Agent for Magic Angle Spinning Dynamic Nuclear Polarization

“…It was concluded that signal enhancements from gadolinium PAs are inversely proportional to D 2 , and so a lower value of D leads to larger NMR signal enhancements, as powerfully demonstrated from the synthetic design of the structural complex [Gd­(tpcatcn)] . The value of D measured and the enhancement factors ϵ obtained in this work compare favorably with those of Gd­(tpcatcn), [Gd­(dota)­(H 2 O)] − , and GdCl 3 , from the previous literature , and the empirical reciprocal quadratic relationship . The value of D for the ZFS obtained from the EPR spectrum of GdCl 3 ·6H 2 O is marginally smaller (by a factor of ∼1.14) than the D reported in this work for the ZFS of Gd­(NO 3 ) 3 ·6H 2 O.…”

“…Recently, several gadolinium-based PAs have been developed for MAS DNP NMR experiments with a specific set of design principles in mind. 44 It was concluded that signal enhancements from gadolinium PAs are inversely proportional to D 2 , and so a lower value of D leads to larger NMR signal enhancements, as powerfully demonstrated from the synthetic design of the structural complex [Gd(tpcatcn)]. 43 The value of D measured and the enhancement factors ϵ obtained in this work compare favorably with those of Gd(tpcatcn), [Gd(dota)(H 2 O)] − , and GdCl 3 , from the previous literature 41 , 43 and the empirical reciprocal quadratic relationship.…”

“…Recently, several gadolinium-based PAs have been developed for MAS DNP NMR experiments with a specific set of design principles in mind . It was concluded that signal enhancements from gadolinium PAs are inversely proportional to D 2 , and so a lower value of D leads to larger NMR signal enhancements, as powerfully demonstrated from the synthetic design of the structural complex [Gd­(tpcatcn)] .…”

“…More recently, inspired by paramagnetic transition metal and lanthanide complexes used for in vivo magnetic resonance imaging (MRI) applications, 38 , 39 high-spin metal ions have shown potential 40 − 44 as alternatives to tailored nitroxide-based biradical PAs for specific applications, 1 H DNP, or the direct DNP of lower gamma nuclear spins. Gd 3+ is of particular interest, as it offers large 1 H NMR signal enhancements ϵ of ∼19 for [Gd(dota)(H 2 O)] − and ∼37 for [Gd(tpcatcn)] complexes at 9.4 T. 43 High-spin metal ions also allow for endogenous hyperpolarization where intrinsic ions are contained in the samples as dopants (in inorganic solids) such as Mn 2+ -doped Li 4 Ti 5 O 12 45 or (in oxide glasses) such as Gd 3+ -doped lithium silicate, lithium borate, and zinc phosphate 46 for bulk signal enhancements, in Gd 3+ -doped CeO 2 nanocomposite thin films on SrTiO 3 for detailed study of material interfaces, 47 and in spin-labels as chelator tags.…”

“…More recently, inspired by paramagnetic transition metal and lanthanide complexes used for in vivo magnetic resonance imaging (MRI) applications, , high-spin metal ions have shown potential − as alternatives to tailored nitroxide-based biradical PAs for specific applications, 1 H DNP, or the direct DNP of lower gamma nuclear spins. Gd 3+ is of particular interest, as it offers large 1 H NMR signal enhancements ϵ of ∼19 for [Gd­(dota)­(H 2 O)] − and ∼37 for [Gd­(tpcatcn)] complexes at 9.4 T .…”