Nitroxides In Solution Research Articles

Competition between n → π* interactions and H-bonding: a way to stabilize aminoxyl anions and to improve electron transfer kinetics

A new approach to stabilization of the reduced state of nitroxides in solution is suggested. Thermodynamic stabilization of the strongly basic aminoxyl anions toward protonation and hydrogen bond formation with the solvent was achieved by intramolecular n → π* interactions. A new stable nitroxide radical bearing ortho-acyl group was synthesized to demonstrate this effect by means of cyclic voltammetry.

Redox‐Amphoteric 4,4’‐Dicyclopropyldiphenylnitroxyl Radical: Unexpectedly High Stability

AbstractAtom‐economy cyclopropyl group turned out to be the substituent of choice for stabilization of diphenylnitroxyl radical in solution (τ1/2=1280 h, i. e., ca. 2 months, in benzene). Though the benzylic H‐atom commonly provokes fast decomposition of nitroxides in solution and the cyclopropyl moiety is prone to the ring opening in substrates with significant spin density at the α‐position, both processes are not implemented in 4,4’‐dicyclopropyldiphenylnitroxide. Instead, the stereoelectronic properties of the cyclopropyl group lead to significant stabilization of the oxidized and reduced states of the nitroxide, making it redox‐amphoteric and suitable for practical application.

First determination of the spin relaxation properties of a nitronyl nitroxide in solution by electron spin echoes at X-band: A comparison with Tempone

We studied by electron spin echo pulse methods the spin relaxation properties of a phenyl nitronyl nitroxide radical (2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide, PTIO) at X-band in fluid toluene solution in a wide temperature range, and in a water/glycerol 1:1 mixture near room temperature. The relaxation properties of PTIO have been compared with that of Tempone, as a widely used nitroxide. By a new procedure, based on experimental results on the temperature dependences of the relaxation times T1 and T2, and on the approximation of an isotropic Brownian rotational diffusion, we separated non-secular, spin rotational and residual terms from the transverse relaxation rate to isolate secular and pseudosecular contributions. By comparing the results for the two radicals we found the differences in the magnetic properties that give rise to slower transverse (T2) and longitudinal (T1) electron spin relaxation for PTIO in the whole temperature range explored in this work.

Assessing the accuracy of a QM/MM//MD combined protocol to compute spectromagnetic properties of polyfunctional nitroxides in solution

In the field of spin trapping chemistry, we proposed a promising new theoretical QM/MM//MD combined protocol to assist the development of new nitrone-based spin traps (Houriez et al. in J Phys Chem B 114:11793–11803, 2010). In the present study, we test its accuracy and its transferability by investigating the spectromagnetic properties in water of DMPO–OH, the nitroxide spin adduct of the 5,5-dimethyl-1-pyrroline-N-oxide nitrone (DMPO) with the OH· radical. Thanks to our theoretical method, we obtain quantitative estimates of the DMPO–OH hyperfine coupling constants (hcc’s) in very good agreement with experiment. Moreover, our study reveals that the DMPO–OH hcc values are related to the main features of an equilibrium between two major conformations of the nitroxide five-membered ring. Together with our earlier results, the present study clearly establishes the reliability of our theoretical protocol to investigate in condensed phase the behavior of flexible and large nitroxides. Particularly, note that with our method, it is possible to point out clearly fundamental differences in spectromagnetic properties even for two molecules very similar in geometrical structure.

A novel variable field system for field-cycled dynamic nuclear polarization spectroscopy

Dynamic nuclear polarization (DNP) is an NMR-based technique which enables detection and spectral characterization of endogenous and exogenous paramagnetic substances measured via transfer of polarization from the saturated unpaired electron spin system to the NMR active nuclei. A variable field system capable of performing DNP spectroscopy with NMR detection at any magnetic field in the range 0–0.38 T is described. The system is built around a clinical open-MRI system. To obtain EPR spectra via DNP, partial cancellation of the detection field B 0 NMR is required to alter the evolution field B 0 EPR at which the EPR excitation is achieved. The addition of resistive actively shielded field cancellation coils in the gap of the primary magnet provides this field offset in the range of 0–100 mT. A description of the primary magnet, cancellation coils, power supplies, interfacing hardware, RF electronics and console are included. Performance of the instrument has been evaluated by acquiring DNP spectra of phantoms with aqueous nitroxide solutions (TEMPOL) at three NMR detection fields of 97 G, 200 G and 587 G corresponding to 413 kHz, 851.6 kHz and 2.5 MHz respectively and fixed EPR evolution field of 100 G corresponding to an irradiation frequency of 282.3 MHz. This variable-field DNP system offers great flexibility for the performance of DNP spectroscopy with independent optimum choice of EPR excitation and NMR detection fields.

Further Insights into the Environmental Effects on the Computed Hyperfine Coupling Constants of Nitroxides in Aqueous Solution

We investigated the main two factors influencing the mean hyperfine coupling constants of small nitroxide radicals in aqueous solution, i.e., the out-of-plane displacement of their nitrogen atom and the environmental effects (solvent effects), by means of the approach we previously developed and fine-tuned to study the solvation of the dimethyl nitroxide radical. Our methodology efficiently combines classical molecular dynamics based on a polarizable force field at the nanosecond scale and quantum mechanics/molecular mechanics (QM/MM) computations to account for the bulk instantaneous electrostatic environmental effect. Our method has been applied to five small nitroxides, namely methyl nitroxide, ethyl nitroxide, dimethyl nitroxide, di-tert-butyl nitroxide, and PROXYL. The theoretical nitrogen hyperfine coupling constant values for the five nitroxides in solution are in good agreement with experiment (difference of 0.3 G on average). Our approach showed that the solvent shift in nitroxide hyperfine coupling constants is almost constant whatever the nitroxide, and, particularly, whatever the nitroxide NO moiety's accessibility to the solvent. This result contrasts with earlier results derived from 10 ps scale trajectories based on Car-Parrinello molecular dynamics approach. However, we show that if we consider on average these latter results, they are in agreement with our conclusion. We also present an attempt to identify the origin of this result by analyzing the solvent contributions in terms of effects of the nitroxide first hydration shell and of the bulk, and by investigating the relation between these two contributions and the solvent structure at the vicinity of the NO moiety.

Regio‐ and Stereoselectivity in the Decatungstate Photocatalyzed Alkylation of Alkenes by Alkylcyclohexanes

Tetrabutylammonium decatungstate (WO) photocatalyzes radical alkylation reactions starting directly from alkanes. When using tert-butylcyclohexane and methylcyclohexane as the radical precursors, the addition to electrophilic alkenes (beta,beta-dialkylmethylenemalononitriles, acrylonitrile, methyl acrylate, methyl vinyl ketone) is regioselective and exclusively gives 3- and 4-substituted cyclohexyl adducts, with no significant functionalization of the other positions. Furthermore, when a beta,beta-disubstituted alkene is used, the reaction is stereoselective (cis stereochemistry for the 1,3-cyclohexane derivatives and trans for the 1,4 isomers). Some of the reactions have also been carried out by using benzophenone as the photocatalyst, giving the same product distribution. However, the decatungstate anion is a superior catalyst from a preparative point of view, because it is efficient at low concentrations (0.002 m, 2 mol %) and allows for a simple work up. From a mechanistic point of view, the role of both the alkyl radicals and the radical adducts has been assessed by trapping experiments in the presence of suitable additives (alpha-phenyl-N-tert-butylnitrone, PBN, and 2-methyl-2-nitrosopropane, MNP) and by EPR spectroscopic detection of the resulting nitroxides in solution. Furthermore, trapping by the nitroxide TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidine N-oxide) gives O-(tert-butylcyclohexyl)hydroxylamines, again as only the 3- and the 4-substituted isomers. We conclude that the observed regioselective activation originates from the initial hydrogen abstraction step (the statistically corrected ratio for positions 3 and 4 ranges from 1.1 to 1.35 for all of the trapping products). The selectivity is mainly due to steric hinderence.

TH-D-304A-01: Development of Multi-Parametric Molecular Imager by Integrating Overhauser-Enhanced MRI (OMRI) with Prepolarized MRI (PMRI)

Purpose: To develop a multi‐parametric molecular imager to assess tumor hypoxia and redox status by integrating Overhauser‐enhanced MRI (OMRI) with prepolarized MRI (PMRI). Method and Materials: PMRI system acquires anatomic MR images comparable to conventional MRI. With a moderate hardware augmentation of the PMRI, we implemented field‐cycled OMRI and obtained electron paramagnetic resonance(EPR)images of nitroxide spin probes. Phantoms were made of 2‐cc tubes filled with pure water, <5‐mM solutions of 3‐carbamoyl‐PROXYL. A custom MRI console was used to insert 25‐W EPR radiofrequency (RF) pulses that enhanced NMR signal of the coupled water protons. A saddle coil (3.5 cm diameter, 2.5 cm length) tuned to 186 MHz was used as the EPR irradiator. To elicit the Overhauser effect, each NMR RF pulse (2.23 MHz) was preceded by the EPR RF pulse during a low field‐cycled interval. Free induction decay (FID) was observed at the EPR B0 swept from 4.2 mT to 9.5 mT. For OMRI, the low‐field cycle was fixed at 4.8 mT to exploit the low‐frequency hyperfine peak of the nitroxide. Generic gradient‐echo 0.05‐T MR images were obtained with either prepolarization or Overhauser enhancement. Results: FID acquisition of a 2.5‐mM nitroxide phantom identified three hyperfine lines of 14 N at 4.8, 6.2 and 8.1 mT. Each peak represented an enhancement factor of 13 with 300‐ms EPR RF pulse. Increasing enhancements were observed with longer durations of EPR irradiation, which indicated 0.71‐s T1 of the phantom. We observed similar intensities of water and <5‐mM nitroxide solutions from 0.15‐T PMRI. The OMRI showed characteristic EPR intensities and clearly separated the 2.5‐mM and 5‐mM nitroxide phantoms from the water phantom. Conclusion: The integrated OMRI‐PMRI system demonstrated sensitivity to both EPR and NMR. The imager can potentially acquire physiological information in small animals accurately co‐registered with high‐quality anatomic NMRimages.

Characterization of a conformationally sensitive TOAC spin-labeled substance P

To probe the binding of a peptide agonist to a G-protein coupled receptor in native membranes, the spin-labeled amino acid analogue 4-amino-4-carboxy-2,2,6,6-tetramethylpiperidino-1-oxyl (TOAC) was substituted at either position 4 or 9 within the substance P peptide (RPKPQQFFGLM-NH2), a potent agonist of the neurokinin-1 receptor. The affinity of the 4-TOAC analog is comparable to the native peptide while the affinity of the 9-TOAC derivative is ∼250-fold lower. Both peptides activate receptor signaling, though the potency of the 9-TOAC peptide is substantially lower. The utility of these modified ligands for reporting conformational dynamics during the neurokinin-1 receptor activation was explored using EPR spectroscopy, which can determine the real-time dynamics of the TOAC nitroxides in solution. While the binding of both the 4-TOAC substance P and 9-TOAC substance P peptides to isolated cell membranes containing the neurokinin-1 receptor is detected, a bound signal for the 9-TOAC peptide is only obtained under conditions that maintain the receptor in its high-affinity binding state. In contrast, 4-TOAC substance P binding is observed by solution EPR under both low- and high-affinity receptor states, with evidence of a more strongly immobilized peptide in the presence of GDP. In addition, to better understand the conformational consequences of TOAC substitution into substance P as it relates to receptor binding and activation, atomistic models for both the 4- and 9-TOAC versions of the peptide were constructed, and the molecular dynamics calculated via simulated annealing to explore the influence of the TOAC substitutions on backbone structure.

Synthesis and Evaluation of Sterically Hindered 1,1-Diadamantyl Nitroxide as a Low-Temperature Mediator for the Stable Free Radical Polymerization Process

An efficient procedure for the oxidation of 1,1-diadamantylamine with m-chloroperbenzoic acid (m-CPBA) to the corresponding sterically hindered nitroxide in high yield (72%) is reported. The corresponding styrene-based alkoxyamine was synthesized by an atom transfer radical addition (ATRA) reaction. Because of the bulkiness of the adamantyl substituents, the cleavage of the C−ON bond of the alkoxyamine occurred readily at temperatures below 100 °C. However, in spite of the low bond dissociation temperature of the alkoxyamine, the (co)polymerizations of styrene and n-butyl acrylate proceeded poorly. The results in this paper support the argument that the most important determinant in a nitroxide-mediated polymerization of styrene and acrylate is the ability to control the excess concentration of nitroxide in solution either by an inherent instability of the nitroxide or by the use of additives that destroy the excess nitroxide. Thus, for the 1,1-diadamantyl nitroxide case, and maybe more generally, while a lower C−O bond dissociation energy of an alkoxyamine moiety at the end of the chain may allow lower polymerization temperatures and faster reactions rates, it does not enable polymerizations to proceed to high conversions if the excess nitroxide is not controlled in some manner.

Acyclic β-Phosphonylated Nitroxides: A New Series of Counter-Radicals for “Living”/Controlled Free Radical Polymerization

Oxidation of α-(N-alkylamino) phosphonic acid esters, carrying one or two alkyl groups as substituents on their α-carbon, by m-chloroperbenzoic acid afforded the corresponding stable β-phosphonylated nitroxides. The nitroxides derived from α-mono-tert-butyl α-alkylaminophosphonic acid esters are stable compounds despite the presence of a hydrogen atom on the α-carbon bound to the nitroxyl group. The ESR study of these nitroxides in solution showed that this β-hydrogen atom lies in the nodal plane to the nitroxyl function. These β-phosphonylated nitroxides were found to efficiently control the free radical polymerization reaction of styrene, with a much faster rate of propagation than that observed in TEMPO-mediated systems.

The Influence of Chemical Surroundings on the Properties of α-Nitronyl Nitroxide Radicals in Solution. Its Relation with the Magnetic Properties in Solid State

α-Nitronyl nitroxide radicals have been widely used for obtaining molecular magnetic materials. We report two characteristics of this radicals that are important in order to interpret their bulk magnetic properties in the solid state. On one hand, we describe the modification of the spin density distribution in the radical molecule caused by different chemical surroundings and by different substituents using the Linear Solvation Energy Relationship multiparametric approximation. On the other hand, we report the self-assembly of some hydroxylated α-nitronyl nitroxides in solution. The supramolecular aggregates, formed in solution, are found to be very similar than those present in the crystal structures. This fact allows to establish clear magneto-structural correlations that facilitate the interpretation of solid state magnetic properties.

Proton-electron double resonance: Spectroscopy and imaging in very low magnetic fields

Proton-electron double resonance, also named dynamic nuclear polarization (DNP) is characterized by an enhancement of the proton NMR signal when the electron resonance of a free radical coupled to water protons is saturated. In very low magnetic fields, new EPR transitions are allowed. The complete theory of DNP in nitroxide solutions is recalled, in order to interpret the experimental spectra. Proton-electron double resonance images (PEDRI) were obtained with 7 out of the 10 EPR transitions allowed in low fields. Field cycled PEDRI were obtained in magnetic fields as low as 0.6 G. The optimum field strength for PEDRI is discussed according to the theoretical and experimental results of DNP obtained with nitroxide solutions.

ESR study of rotational motions of spin‐labeled long‐chain nitroxides in solution

Information on the rotational motion of various types of spin-labelled long-chain nitroxides was obtained from the anisotropic ESR signals. By varying the position of the nitroxide moiety along the chain, the intrinsic flexibility of molecular chain was examined. The rotational correlation times (τc) of spin-labelled long-chain nitroxides were about 10−10 s. The activation parameters for rotational motion were estimated from the temperature and pressure dependences of τc. It was found that the activation entropy observed for methyl 16-doxyl stearate is obviously large compared with those for methyl 5- and methyl 12-doxyl stearates. The results suggest an increase in the molecular motions at the end of the hydrocarbon chain. The viscosity dependence of τc is discussed in terms of the difference in the strength between solute-solvent and solvent-solvent interactions.

ESR study of rotational motions of spin-labeled long-chain nitroxides in solution

ESR study of rotational motions of spin-labeled long-chain nitroxides in solution

ESR study of rotational motions of spin‐labeled long‐chain nitroxides in solution

ESR study of rotational motions of spin‐labeled long‐chain nitroxides in solution

Accuracy of Oxygen Measurements in T2 (Line Width) EPR Oximetry

EPR oximetry is used for in vivo and in vitro measurements of oxygen in biological systems, including experimental animals. The accuracy of oxygen measurements in T2 (line width) EPR oximetry is significantly improved if least-squares simulation is used to extract the line width parameters. The oxygen effect on the EPR spectra of nitroxide solutions and aqueous suspensions of fusinite can be described as an additional homogeneous broadening that modifies the EPR spectrum of the oxygen-free probe. This allows one to use a one-parameter line width model in most cases. The simulations were carried out with the use of a fast-convolution algorithm followed by Levenberg-Marquardt optimization. The validity of error estimates provided by this method was tested on sets of experimental spectra taken under common conditions. It is shown that the accuracy of oxygen measurements in line width (T2) oximetry is determined not only by the probe sensitivity (rate of line width change versus oxygen concentration), but also by the signal-to-noise ratio, inhomogeneous contribution to the line shape (e.g., unresolved proton superhyperfine structure), and the spectral window. The accuracy of oxygen measurements is compared for aqueous solutions of two nitroxide radicals with different superhyperfine structure and for aqueous suspensions of fusinite.

Determination of electrostatic potentials at biological interfaces using electron-electron double resonance

A new general method for the determination of electrostatic potentials at biological surfaces is presented. The approach is based on measurement of the collision frequency of a charged nitroxide in solution with a nitroxide fixed to the surface at the point of interest. The collision frequency is determined with 14N:15N double label electron-electron double resonance (ELDOR). As a test, the method is shown to give values for phospholipid bilayer surface potentials consistent with the Gouy-Chapman theory, a simple model shown by many independent tests to accurately describe charged, planar surfaces. In addition, the method is applied to determine the electrostatic potential near the surface of DNA. The results indicate that the potential is significantly smaller than that predicted from Poisson-Boltzmann analysis, but is in qualitative agreement with that predicted by Manning's theory of counter ion condensation. The method is readily extended to measurement of surface potentials of proteins.

Electron spin echo decays of nitroxide solutions adsorbed on zeolites

The echo decays of D 2O solutions of a positively charged nitroxide radical adsorbed on X- and Y-zeolites are analyzed both for two-pulse and three-pulse sequences. A best-fit simulation procedure is used to obtain data concerning the concentration of adsorbed spins and their reorientational times. The results obtained show noticeable differences depending on the kind of zeolite; limits on the adsorption capacity are also found, that are not linearly dependent on the concentration of the initial solutions. The time-behavior of the spins appears to be determined by the rotation of methyl groups of the radical.

Adsorption of nitroxide solutions on X zeolite. 3. Electron spin resonance and electron spin echo modulation study of deuteriated methanol solutions

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAdsorption of nitroxide solutions on X zeolite. 3. Electron spin resonance and electron spin echo modulation study of deuteriated methanol solutionsM. Romanelli, M. F. Ottaviani, G. Martini, and L. KevanCite this: J. Phys. Chem. 1989, 93, 1, 317–322Publication Date (Print):January 1, 1989Publication History Published online1 May 2002Published inissue 1 January 1989https://doi.org/10.1021/j100338a063RIGHTS & PERMISSIONSArticle Views34Altmetric-Citations15LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (662 KB) Get e-Alerts