Spin‐Labeled Heparins as Polarizing Agents for Dynamic Nuclear Polarization

Abstract

A potentially biocompatible class of spin-labeled macromolecules, spin-labeled (SL) heparins, and their use as nuclear magnetic resonance (NMR) signal enhancers are introduced. The signal enhancement is achieved through Overhauser-type dynamic nuclear polarization (DNP). All presented SL-heparins show high (1)H DNP enhancement factors up to E=-110, which validates that effectively more than one hyperfine line can be saturated even for spin-labeled polarizing agents. The parameters for the Overhauser-type DNP are determined and discussed. A striking result is that for spin-labeled heparins, the off-resonant electron paramagnetic resonance (EPR) hyperfine lines contribute a non-negligible part to the total saturation, even in the absence of Heisenberg spin exchange (HSE) and electron spin-nuclear spin relaxation (T(1ne)). As a result, we conclude that one can optimize the use of, for example, biomacromolecules for DNP, for which only small sample amounts are available, by using heterogeneously distributed radicals attached to the molecule.

Fractional Spin‐Labeling of Polymers for Enhancing NMR Sensitivity by Solvent‐Free Dynamic Nuclear Polarization

“…[8] If spin labels can accelerate the return of nuclear spins to their thermal equilibrium, they should also be able to enhance the nuclear spin polarization by DNP in the solid state, in analogy to liquid-state Overhauser effects on spin-labeled molecules [9] and to radicals embedded in glassy frozen solutions. Spin labels allow one to obtain long-range distance constraints, [10] particularly in large proteins.…”

Advanced magnetic resonance strategies for the elucidation of nanostructured soft matter

“…Therefore, the spin-labeled heparins exhibit almost the same coupling factor as free TEMPOL. 107 The electron spin-electron spin relaxation time T 2e on the other hand is decreased due to residual dipolar couplings and reduced mobility, resulting in broad EPR lines as shown in Fig. 12.…”

“…We have demonstrated how spin-labeling of macromolecules can lead to significantly higher DNP enhancements than free TEMPOL in the low-concentration regime. 107 This notably includes the absence of Heisenberg spin exchange and electron nuclear-spin relaxation (T 1ne ), mixing the EPR hyperfine states due to collision of the radicals and relaxation of a coupled nuclear spin, respectively. Such behavior is of interest for the investigation of biomolecules at physiological temperatures where only small sample amounts can be provided and where high radical concentration leads to NMR-line broadening and fast nuclear T 1 relaxation.…”

Characterization and optimization of the visualization performance of continuous flow overhauser DNP hyperpolarized water MRI: Inversion recovery approach

“…Furthermore, by combining TEMPOL moieties with other biomolecules, highly specific biosensors can be created. The first application of heparin‐(poly)nitroxide conjugates used as targeted MRI contrast media was reported recently , not long after the first experiments of its use for out‐of‐bore DNP were reported .…”