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

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

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

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

Nitroxide biradicals are efficient polarizing agents in dynamic nuclear polarization (DNP) solid-state nuclear magnetic resonance. Many recently reported radicals possess substantial DNP efficiency in organic solvents but have poor solubility in water media which is unfavorable for biological applications. In this paper, we report DNP efficiency at a high magnetic field for two water-soluble biradicals resistant to reducing media. Water solubility was achieved by obtaining the radicals in the form of quaternary ammonium salts. Parameters of hyperfine interaction and exchange interaction were quantified by EPR spectroscopy, and their influence on the DNP effect was determined. The resistance of the biradicals to strongly reducing media was characterized. High stability was achieved using tetraethyl substituents and pyrrolidine moieties

Thermal Properties and Ionic Conductivity of Tetra-n-Butylammonium Perchlorate

The thermal parameters of the phase transitions and transport properties of tetra-n-butylammonium (TBA) perchlorate (n-C4H9)4NClO4 (TBAClO4) were investigated. TBAClO4 has a polymorphous transition at 330 K and melts at 487 K. The structure of the high-temperature (HT) phase belongs to cubic symmetry and is similar to the HT phases of TBABF4 and TBAI salts. The conductivity parameters of the low-temperature and HT phases of TBAClO4 were determined from the Arrhenius plots. The thermodynamic parameters and transport properties of TBAClO4 were compared with those of other TBA salts having isostructural HT phases. The polymorphous phase transition entropy was found to correlate with the conductivity of HT phases of TBA salts; TBAClO4 has the lowest conductivity compared to TBABF4 and TBAI salts

Fluorinated Organic Paramagnetic Building Blocks for Cross-Coupling Reactions

New stable polyfluorinated nitroxide radicals for use in cross-coupling reactions, namely, N-tert-butyl-N-oxyamino-2,3,5,6-tetrafluoro-4-iodobenzene and N-tert-butyl-N-oxyamino-2,3,5,6-tetrafluoro-4-ethynylbenzene, were prepared from perfluoroiodobenzene. The reaction of the polyfluoro derivative with tert-butylamine under autoclaving conditions leading to the formation of N-tert-butyl-2,3,5,6-tetrafluoro-4-iodoaniline proved to be the key stage of the whole process. The fluorinated tert-butyl iodophenyl nitroxide was found to form in a solid state via N–O···I halogen bonds, a one-dimensional assembly of the radicals. The acceptor role of the nitroxide group in the halogen bonding changes to a donor role when the nitroxide reacts with Cu(hfac)2. In the last case, zero-dimensional assembly prevails, giving a three-spin complex with axial coordinated nitroxide groups and, as a consequence, causing ferromagnetic intramolecular exchange interactions between Cu(II) and radical spins

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

Nitroxide biradicals are efficient polarizing agents in dynamic nuclear polarization (DNP) solid-state nuclear magnetic resonance. Many recently reported radicals possess substantial DNP efficiency in organic solvents but have poor solubility in water media which is unfavorable for biological applications. In this paper, we report DNP efficiency at a high magnetic field for two water-soluble biradicals resistant to reducing media. Water solubility was achieved by obtaining the radicals in the form of quaternary ammonium salts. Parameters of hyperfine interaction and exchange interaction were quantified by EPR spectroscopy, and their influence on the DNP effect was determined. The resistance of the biradicals to strongly reducing media was characterized. High stability was achieved using tetraethyl substituents and pyrrolidine moieties

2-Butyl-2-tert-butyl-5,5-diethylpyrrolidine-1-oxyls: Synthesis and Properties

Nitroxides are broadly used as molecular probes and labels in biophysics, structural biology, and biomedical research. Resistance of a nitroxide group bearing an unpaired electron to chemical reduction with low-molecular-weight antioxidants and enzymatic systems is of critical importance for these applications. The redox properties of nitroxides are known to depend on the ring size (for cyclic nitroxides) and electronic and steric effects of the substituents. Here, two highly strained nitroxides, 5-(tert-butyl)-5-butyl-2,2-diethyl-3-hydroxypyrrolidin-1-oxyl (4) and 2-(tert-butyl)-2-butyl-5,5-diethyl-3,4-bis(hydroxymethyl)pyrrolidin-1-oxyl (5), were prepared via a reaction of the corresponding 2-tert-butyl-1-pyrroline 1-oxides with butyllithium. Thermal stability and kinetics of reduction of the new nitroxides by ascorbic acid were studied. Nitroxide 5 showed the highest resistance to reduction

The Reactions of 6-(Hydroxymethyl)-2,2-dimethyl-1-azaspiro[4.4]nonanes with Methanesulfonyl Chloride or PPh3-CBr4

Activation of a hydroxyl group towards nucleophilic substitution via reaction with methanesulfonyl chloride or PPh3-CBr4 system is a commonly used pathway to various functional derivatives. The reactions of (5R(S),6R(S))-1-X-6-(hydroxymethyl)-2,2-dimethyl- 1-azaspiro[4.4]nonanes 1a–d (X = O·; H; OBn, OBz) with MsCl/NR3 or PPh3-CBr4 were studied. Depending on substituent X, the reaction afforded hexahydro-1H,6H-cyclopenta[c]pyrrolo[1,2-b]isoxazole (2) (for X = O), a mixture of 2 and octahydrocyclopenta[c]azepines (4–6) (for X = OBn, OBz), or perhydro-cyclopenta[2,3]azeto[1,2-a]pyrrol (3) (for X = H) derivatives. Alkylation of the latter with MeI with subsequent Hofmann elimination afforded 2,3,3-trimethyl-1,2,3,4,5,7,8,8a-octahydrocyclopenta[c]azepine with 56% yield