Effects of Spiro-Cyclohexane Substitution of Nitroxyl Biradicals on Dynamic Nuclear Polarization

Abstract

Spiro-substituted nitroxyl biradicals are widely used as reagents for dynamic nuclear polarization (DNP), which is especially important for biopolymer research. The main criterion for their applicability as polarizing agents is the value of the spin–spin exchange interaction parameter (J), which can vary considerably when different couplers are employed that link the radical moieties. This paper describes a study on biradicals, with a ferrocene-1,1′-diyl-substituted 1,3-diazetidine-2,4-diimine coupler, that have never been used before as DNP agents. We observed a substantial difference in the temperature dependence between Electron Paramagnetic Resonance (EPR) spectra of biradicals carrying either methyl or spirocyclohexane substituents and explain the difference using Density Functional Theory (DFT) calculation results. It was shown that the replacement of methyl groups by spirocycles near the N-O group leads to an increase in the contribution of conformers having J ≈ 0. The DNP gain observed for the biradicals with methyl substituents is three times higher than that for the spiro-substituted nitroxyl biradicals and is inversely proportional to the contribution of biradicals manifesting the negligible exchange interaction. The effects of nucleophiles and substituents in the nitroxide biradicals on the ring-opening reaction of 1,3-diazetidine and the influence of the ring opening on the exchange interaction were also investigated. It was found that in contrast to the methyl-substituted nitroxide biradical (where we observed the ring-opening reaction upon the addition of amines), the ring opening does not occur in the spiro-substituted biradical owing to a steric barrier created by the bulky cyclohexyl substituents.

An EPR Study on Highly Stable Nitroxyl-Nitroxyl Biradicals for Dynamic Nuclear Polarization Applications at High Magnetic Fields

“…A probable reason is that biradical 3 almost completely consists of a structure with J ≈ 200 MHz, in contrast to biradical 4 , which corresponds to the distribution of conformations centered at J ≈ 0 MHz. As demonstrated earlier, the presence of conformers with J ≈ 0 leads to a decrease in DNP efficiency [ 38 ]. In the 13 C MAS spectra, we observed comparable enhancements for radicals 3 and 4 for direct polarization transfer.…”

“…To investigate the polarization transfer in 13 C MAS NMR, spectra of biradicals 3 and 4 in glycerol-d 8 /D 2 O/H 2 O (60:30:10 v / v / v ) matrix, measured with and without microwave irradiation with a build-up of 300 s, were recorded. To distinguish between direct and indirect polarization transfer, two sets of spectra were measured as described in the literature [ 38 ]. The results are shown in Figure 5 .…”