In Silico Design of DNP Polarizing Agents: Can Current Dinitroxides Be Improved?

Abstract

Numerical calculations of enhancement factors offered by dynamic nuclear polarization in solids under magic angle spinning (DNP-MAS) were performed to determine the optimal EPR parameters for a dinitroxide polarizing agent. We found that the DNP performance of a biradical is more tolerant to the relative orientation of the two nitroxide moieties than previously thought. Generally, any condition in which the g tensor components of both radicals are perpendicular to one another is expected to have near-optimal DNP performance. Our results highlight the important role of the exchange coupling, which can lessen the sensitivity of DNP performance to the inter-radical distance, but also lead to lower enhancements when the number of atoms in the linker becomes less than three. Lastly, the calculations showed that the electron T value should be near 500 μs to yield optimal performance. Importantly, the newest polarizing agents already feature all of the qualities of the optimal polarizing agent, leaving little room for further improvement. Further research into DNP polarizing agents should then target non-nitroxide radicals, as well as improvements in sample formulations to advance high-temperature DNP and limit quenching and reactivity.

Continuous wave electron paramagnetic resonance of nitroxide biradicals in fluid solution

“…Dipolar interactions between the 2 nitroxides can be designed to match the nuclear Zeeman frequency. Studies of many dinitroxides demonstrate that the largest DNP enhancements are achieved with rigid linkages that orient the g yy tensors orthogonal to one another . Spiro linkages assisted in creating orthogonal arrangements of the g tensors.…”

“…Studies of many dinitroxides demonstrate that the largest DNP enhancements are achieved with rigid linkages that orient the g yy tensors orthogonal to one another. 8,[11][12][13][14][15][16][17][18] Spiro linkages assisted in creating orthogonal arrangements of the g tensors. DNP enhancement is increased by increasing the saturation factor that depends on the T 1 T 2 product.…”

Large-scale ab initio simulations of MAS DNP enhancements using a Monte Carlo optimization strategy

“…13,[20][21][22][23] A recent in silico study of the design of dinitroxide polarization agents has, however, concluded that there is little room remaining for improvement within this family of polarizing agents. 24 Nevertheless, other developments, such as the discovery of the Overhauser effect in insulating solids [25][26][27] and the synthesis of trityl-nitroxide biradicals, 28 promise to greatly improve DNP at ultra-high magnetic fields for which they are already outperforming dinitroxides. 27,28 A highly efficient in silico quantum-mechanical treatment would greatly help in better understanding the mechanisms of MAS DNP and guide further advancements of the technique, but carrying it out over the relevant time scales presents a large computational challenge.…”

“…As a result of this, all quantum mechanical MAS DNP simulations have, to date, been performed on small spin systems (most consisting only of a single nuclear spin with two electrons). 24,[29][30][31][32][33][34] Second, DNP is a very slow process, requiring several seconds to reach equilibrium, which nonetheless depends on a series of very rapid (<1 ns) processes due to the large sizes of the radical's interactions. The spin dynamics must then be calculated using gargantuan matrices for several seconds in nanosecond increments.…”

Many-body kinetics of dynamic nuclear polarization by the cross effect

“…This enables for the first time the investigation of the polarization dynamics of hundreds of interacting nuclei on an individual spin level. Our study paves the way towards a systematic analysis, utilization and optimization of realistic many-body CE DNP and may serve as a guidance for the design of optimal DNP regimes and tailor-made polarising agents (biradicals) [22][23][24][25][26][27][28]. Furthermore, we expect our insights to be applicable to the non-equilibrium dynamics of nitrogen-vacancies in diamond [29,30], which is becoming a popular platform for the implementation of quantum sensing and diagnostics.…”