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Novel Biradicals for Direct Excitation Highfield Dynamic Nuclear Polarization Sarah Bothe, Jens Nowag, Vytautas Klimavi#ius, Markus M. Hoffmann, Tatiana I. Troitskaya, Evgenii V. Amosov, Victor M. Tormyshev, Igor Kirilyuk, Andrey Taratayko, Andrey A. Kuzhelev, Dmitriy Parkhomenko, Elena G. Bagryanskaya, Torsten Gutmann, and Gerd Buntkowsky J. Phys. Chem. C, Just Accepted Manuscript • DOI: 10.1021/acs.jpcc.8b02570 • Publication Date (Web): 04 May 2018 Downloaded from http://pubs.acs.org on May 5, 2018

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The Journal of Physical Chemistry

Novel Biradicals for Direct Excitation Highfield Dynamic Nuclear Polarization Sarah Bothe,a Jens Nowag,a Vytautas Klimavičius,a Markus Hoffmann,b Tatiana I. Troitskaya,c Evgenii V. Amosov,c Victor M. Tormyshev, c,d Igor Kirilyuk, c,d Andrey Taratayko, c,d Andrey Kuzhelev, c,d Dmitriy Parkhomenko,c Elena Bagryanskaya,c,d* Torsten Gutmann,a*Gerd Buntkowskya*

a

TU Darmstadt; Eduard-Zintl-Institute for Inorganic and Physical Chemistry, Alarich-Weiss-Straße 8, 64287 Darmstadt, Germany

b

Department of Chemistry and Biochemistry, The College at Brockport, State University of New York, Brockport, NY, 14420, USA

c

N.N.Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Pr. Lavrentieva 9, Novosibirsk, 630090 Russian Federation d

Novosibirsk State University, Pirogova 2, Novosibirsk, 630090 Russian Federation

Abstract The synthesis of novel trityl-nitroxyl bi-radicals and their performance as polarization agents in DNP enhanced solid-state MAS NMR spectroscopy is presented. Signal enhancements in 1H, 1H→13C CP MAS and

13

C MAS experiments obtained with these radicals dissolved in 1,1,2,2-tetrachloroethane

(TCE) solution are compared with the enhancements obtained from TCE solutions of binitroxyl radicals. The signal enhancements are correlated with the distance between the radical centers of the biradicals, as determined by theoretical structure calculations. Some of the biradical TCE solutions display direct channel resonances in

13

C MAS experiments as well as indirect channel resonances

induced via the proton spin reservoir. Differential Scanning Calorimetry reveals that only these solutions do not form any solid crystalline phases upon rapid cooling, suggesting that molecular motions needed for polarization transfer from radicals to

13

C via the proton spin reservoir remain

active at the experimental low temperatures of nominal 120 K. DNP magnetic field sweep enhancement profiles for selected new bi-radicals are presented as well. These indicate that the DNP transfer is dominated by the cross-effect mechanism.

Introduction Since the establishment of high field dynamic nuclear polarization by the pioneering works of the Griffin group,1-3 many efforts have been made to investigate the mechanism of polarization transfer experimentally and theoretically (see recent reviews and references therein

4-7

), and to optimize the

sample preparation for experiments in the solid-state. 8-11 However, there is still a need for innovations, especially in the field of

13

C direct polarization experiments ACS Paragon Plus Environment

12-13

for which recently different

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polarization transfer pathways were proposed, namely a direct and an indirect one via the proton reservoir.

14-15

In the following the indirect one is called “DNP-CR” since it is induced by cross-

relaxation (CR). The development of novel polarization sources has been one research area for optimizing signal enhancements in solid-state DNP. Classical stable organic radicals 16-19 or metal-ion based systems of Gd3+ or Mn2+

20-22

may serve as polarization agent. The most common polarization source are stable

organic radicals dissolved in an aqueous or organic solvent matrix. Initially, simple mono-nitroxyl radicals such as the 2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO)23 served as polarization source. Significantly larger DNP enhancements have been obtained with more recent nitroxyl biradical systems containing different side-chain substituents (see for example refs. 24-30) with the currently most efficient radicals being TEKPol

31

and AMUPol.

32

Another important group of radical systems,

already introduced in the early days of high-field DNP, are BDPA type radicals. of radicals the Overhauser Effect was obtained in the solid state,

35

1-2, 33-34

For this type

which opened up the possibility of

ultra-high field DNP. Finally, trityl-type radicals have been synthesized and used in dynamic nuclear polarization research.

36-37

As prominent example OX063

source in DNP of quadrupolar nuclei.

39-40

superoxide radical anions,

has been used as efficient polarization

Moreover, trityl radicals have been utilized in various

applications such as to measure the extracellular 44

38

41

and intracellular

42-43

oxygen level, to detect

or as spin labels for room temperature interatomic distance measurements

in biomolecules.45-46 Compared to nitroxyl radicals, trityl radical derivatives are mostly inert to biological reductants such as glutathione and ascorbate. This restricts the application of trityl radical derivatives as redox probes.

44, 47

The combination of nitroxyl and trityl functional groups in one

biradical changes the electronic properties of the system, and thus enables the specific application of these biradicals as redox probes in biological systems.

48-50

Furthermore, trityl-nitroxyl radicals have

also been successfully applied as controllers in the nitroxide-mediated polymerization (NMP) of styrene.

51

Given these advantages, trityl-nitroxyl biradicals have recently been explored as

polarization source for ultra-high field DNP. 19, 52 These cited studies were motivated by the hypothesis that the combination of trityl and nitroxy moieties should yield a highly efficient polarization source. The goal of the present study is to further promote the promising effort of developing effective polarization sources by establishing structure-DNP performance relationships. Towards this goal, we will present in this report a series of novel nitroxyl – trityl biradicals 1-4 (Scheme 1) and compare their DNP performance with that of binitroxyl radicals 5-9 (Scheme 2) to investigate their potential in heteronuclear direct polarization experiments. In this context, their ability to generate DNP-CR resonances is studied as a function of their chemical structure. The rest of the paper is organized as follows. After this brief introduction, the experimental details on synthesis and DNP characterization of the novel radicals is described. In the results and discussion section, the enhancements obtained for the different novel radicals in 1,1,2,2-tetrachloroethane (TCE) are discussed in terms of their structure and resulting phase behavior upon rapid cooling. Finally, the 1H, 13C direct channel and 13C DNP-CR

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enhancement profiles for four different radicals, namely the three nitroxyl-trityl biradicals 1-3 and the dinitroxyl radical 6 are shown and discussed.

Scheme 1. Chemical structures of the nitroxyl-trityl radicals 1-4.

Scheme 2. Chemical structures of the nitroxyl biradicals 5-8 and TEKPol (9).

Experimental General: 1H and

13

C solution NMR spectroscopic data were obtained on a Bruker AV-400

1

spectrometer ( H NMR: 400.13 MHz,

13

C NMR: 100.62 MHz) employing solutions in CDCl3.

Chemical shifts (δ scale) are given in ppm with reference to residual signals of [1H] chloroform (1H NMR: 7.26, 13C NMR: 77.16). IR spectra were recorded using a Bruker Tensor 27, and a Bruker Vector 22 FTIR spectrometer, respectively, and samples were prepared as KBr pellets. Wavenumber values are given in cm–1.



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Electrospray ionization high resolution mass spectra (ESI-HRMS) were recorded using a hybrid quadrupole/time-of-flight Bruker micrOTOF-Q spectrometer using methanol as solvent. Spectra were scanned in the m/z range of 100-3000 in positive and negative ionization modes. Nitrogen was used as a drying gas at 220 °C, and at a flow rate of 4 L min−1. The nebulizer pressure was set to 1.0 bar. The capillary voltage was set to -4.0 kV. The samples were introduced into the ESI source at FIA mode (Flow Injection Analysis, 2–3 µL at a flow rate of the solvent of 0.1 mL min−1). FIA was performed using a LC pump-autosampler system from Agilent 1200 HPLC. The high-resolution mass spectra (HRMS, electron impact, 70 eV) were registered on a Finnigan MAT-8200 spectrometer (direct inlet, temperature of vaporizer 200-270 °C). Melting points were determined with a Boetius micro-heating plate BHMK 05 (Rapido, Dresden) and were not corrected. CW EPR experiments for radicals 1-4 were performed at the X-band using the commercial spectrometer Bruker EMX. Experimental CW EPR settings at room temperature were as follows: sweep width, 7 mT; microwave power, 0.015 mW; modulation frequency, 100 kHz; modulation amplitude, 0.05 mT; time constant, 81.92 ms; sweep time, 83.89 s; number of points, 1024; number of scans, 4. EPR measurements were done for chloroform solutions of the radicals (concentration 0.3-0.5 mM). CW EPR experiments for radicals 5-8 were performed at the X-band using a commercial ADANI SpinScan X spectrometer. Measurements were done on toluene solutions containing 0.1 mM of the biradicals. In order to prevent the line broadening caused by oxygen, the samples were deoxygenated employing between 3 and 10 repeated “freeze-pump-thaw” cycles. Experimental CW EPR settings at room temperature were as follows: sweep width, 12 mT; microwave power, 0.2 mW; modulation frequency, 100 kHz; modulation amplitude, 0.05 mT; time constant, 117.197 ms; sweep time, 120 s; number of points, 1024; number of scans 1. The simulation of the obtained CW EPR spectra was performed using the Easyspin tool. 53 Preparative column chromatography was performed using 60–200 µm silica gel purchased from Acros. Chemicals were purchased from Sigma Aldrich and Acros and were used without further purification, unless otherwise stated. 1,1,2,2-tetrachloroethane (TCE) (purity >98%) was used as obtained from Sigma Aldrich.

Syntheses of the Radicals Tert-butyl bromoacetate was prepared according to the reported method by Pospisil et al. carboxyl-2,2,6,6-tetramethylbenzo[1,2-d;4,5-d’]bis[1,3]dithiole-4-yl)methanol according to the literature protocol.

55-56

A known literature method

57

(10)

was

54

Tris(8-

obtained

was applied for the synthesis of

bis(8-methoxycarbonyl-2,2,6,6-tetramethylbenzo[1,2-d;4,5-d’]bis[1,3]dithiole-4-yl)mono(8-carboxyl2,2,6,6-tetramethylbenzo[1,2-d;4,5-d’]bis[1,3]dithiole-4-yl)methyl (11). Bromoacetyl derivatives of TEMPO 12 and 13 have been obtained by a modified literature procedure

56

(details of the syntheses

are given in Supporting Information). The synthesis of nitroxyl-trityl radicals 1-4 and nitroxyl-nitroxyl


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biradicals 5, 6, 7, 8 were performed according to schemes 3 and 4 correspondingly. Details of the syntheses are given in the Supporting Information.

Scheme 3. Synthesis of nitroxyl-trityl radicals 1-4.



Page 6 of 21

Scheme 4. Synthesis of nitroxyl biradicals 5, 6, 7, 8.

DNP sample Preparation The radical sample solutions with concentrations of nominally 15 mM were prepared by weighing the radicals at room temperature and dissolving in TCE by vortex mixing. A list containing all initial weights is given in Table S1 in the supporting information. Samples for DNP measurements were prepared by taking ca 30 µl of the sample solution into a 3.2 mm sapphire MAS rotor that was sealed then with a silicone plug to prevent solution leakage from the rotors, and capped with a ZrO2 driving cap. DNP-Enhanced Solid-State NMR Experiments All solid-state DNP experiments were carried out on a Bruker Avance III 400 MHz NMR spectrometer equipped with an AscendTM 400 sweep-able DNP magnet, and a 3.2 mm low temperature H/X/Y triple resonance probe. This DNP spectrometer works with a 9.4 T Bruker gyrotron system generating microwaves at a frequency of 263 GHz. All 1H MAS, 1H→13C CP MAS, 13C MAS NMR spectra with and without microwave (MW) irradiation were acquired with a MAS frequency of 8 kHz at resonance frequencies of 400.02 MHz and 100.59 MHz, respectively. The sample temperature was nominally 107 K without microwave irradiation and 117 K with microwave irradiation and was stabilized by a Bruker BioSpin low temperature MAS cooling system. The 1H MAS experiments were performed with a background suppression pulse sequence

58

where

after an initial 90° excitation pulse of 2.58 µs two 180° refocusing pulses with a 0.1 µs spacing were applied. 8 scans were performed with a repetition delay of 4 s. 1H→13C CP MAS NMR experiments


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were performed with 16 scans using a 100-50% ramp on 1H with a repetition delay of 3 s and a contact time of 2 ms. SPINAL-64 59 was employed to decouple dipolar interactions with protons. In addition, the 1H saturation recovery experiments were performed for radicals 1-4 by collecting 12 increments with 4 scans and variable delays which varied from 0.01 s to 240 s. The obtained T1 values were then used to measure 1H MAS and 1H→13C CP MAS spectra by setting the repetition delay equal to 3·T1, which corresponds to 95 % of the maximum reachable intensity for infinite repetition delays. To suppress the build-up of 1H-magnetization during the 13C hyperpolarization, the standard 13C MAS saturation recovery experiment was modified. In order not to damage the probe by the prolonged decoupling during the 13C signal build-up, a sequence of rotor synchronized 180° pulses on the proton channel was executed as described in a previous work.14, 60 For these experiments, twenty 2.2 µs pulses with a spacing of 5 ms were initially used to saturate the 13C magnetization. Afterwards, during the build-up of the 13C, rotor synchronized 180° pulses were applied on the 1H channel every 500 ms. The pulse length for the proton pulses was set to 5.15 µs and the final 13C detection pulse was set to 3.7 µs. During data acquisition SPINAL-64 decoupling59 was applied and 24 scans were performed with a build-up time of 10 s to obtain the data points for the DNP enhancement profiles, while 64-256 scans were performed to get a better S/N ratio for the determination of the enhancement factors. The same modified saturation recovery experiment was employed with the same parameter set for the standard

13

C MAS except that the pulse power for the rotor synchronized 180° pulses on the proton

channel was set to zero. Again, these13C MAS spectra were obtained with a build-up time of 10s. The

13

C build-up times and T1 times, which are needed for obtaining fully relaxed spectra, were

determined for trityl-nitroxyl radicals 1-4 in TCE solution (ESI Table S2). The respective spectral data were obtained by employing the above-mentioned recovery pulse sequence with and without microwave irradiation (MWon and MWoff). Build-up spectra were acquired for a total of 14 variable delay increments ranging from 0.5 to 3000 s. From these experiments the separation of the already described before.

14

13

While the standard

C direct and 13

13

C DNP-CR resonances is feasible as

C MAS experiment measures both, the direct and

DNP-CR resonances, in the case of suppression of the 1H magnetization by rotor synchronous 180° pulses the DNP-CR channel is suppressed. Calculating the difference spectrum between the standard 13

C MAS and the 13C MAS with suppressed DNP-CR channel yields a spectrum where only the DNP-

CR resonances are visible. The measured

13

C spectra were fitted with a Lorentzian function and the DNP enhancements were

calculated as the ratio of peak heights from the respective spectra with MW irradiation and the corresponding spectra without MW irradiation. The DNP enhancement profiles were obtained in the field range from around 9.35 T to 9.40 T by repeating spectral data acquisition and processing at varied magnetic fields. The DNP enhancements were then plotted as a function of the magnetic field strength to get the desired DNP enhancement profiles. To evaluate the DNP enhancement factors ε, the



Page 8 of 21

signal peak intensities IMWon obtained in the 1H MAS and 1H→13C CP MAS spectra with MW irradiation were divided by the corresponding signal peak intensities IMWoff obtained without MW irradiation. The fitted signals from the spectra with MW irradiation were employed for the calculation of enhancements of

13

depolarization effects

61-64

C MAS direct and DNP-CR channel resonances. Influences such as were not taken into account in this calculation. Errors for the enhancement

of C direct polarization were estimated according to eq. 1 by multiplying the enhancement ε by the 13

cumulative noise to signal ratio of the MW on and MW off spectra.

 noise MWon noise MWoff  ∆ε = ε ⋅  +  I MWoff   I MWon

(1)

In eq. 1, noise MWon and noise MWoff are the maximum level of noise in the MW on and MW off spectrum, and I MWon and I MWoff are the absolute intensities of the signals in the MW on and MW off spectrum. Note that the deviations for the enhancement profiles are higher, as the signal to noise ratio for the spectra measured for the enhancement profile is lower due to the smaller number of scans.

Differential Scanning Calorimetry (DSC) DSC thermograms were measured with a DSC Polyma® calorimeter from Netzsch using alumina crucibles. Each sample was cooled with liquid nitrogen and analyzed in the range of 25 °C to -170 °C with a heating and cooling rate of 40 °C min−1. For each sample four cycles of cooling and heating were performed.

Results and Discussions Signal enhancements In Fig. 1, the set of spectra is shown that was recorded at 9.396 T for a 15 mM solution of 2 in TCE. The obtained peaks at 5.5 ppm in the 1H spectrum, and at 77 ppm in the 1H→13C CP MAS and 13C MAS spectra refer to the isotropic signals of the solvent TCE. Beside these peaks a signal occurred at about 4.6 ppm in the 13C spectra that is attributed to the silicon plug. All other signals are spinning side bands originating from the TCE. To determine the signal enhancement for 1H MAS and 1H→13C CP MAS, the spectra measured with and without microwave irradiation were compared as shown for 2 in Fig. 1a,b. For the

13

C direct

polarization experiments, the DNP-CR and direct channel resonances were extracted by fitting with Lorentzian functions, as illustrated for 2 in Fig. 1c-e.


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The enhancements for the radicals (1-9) (IµWon/IµWoff ) at 9.395 T for 1H MAS, 1H→13C CP MAS and 13

C direct and DNP-CR channel resonances are listed in Table 1. Since for the radicals 1-3 and 6

enhancement profiles were measured, their maximum enhancement for 1H MAS, 1H→13C CP MAS, 13

C direct and DNP-CR channel could be also obtained. For all radicals, the 1H and the 1H→13C CP

enhancement show the same magnitude within the experimental error margin. This is in accordance with the theory, as the polarization should be evenly spread throughout the proton spin reservoir by 1

H-1H spin diffusion, that in the case of a pure radical TCE solution should be uniform. This proton

spin polarization is then detected as enhanced proton signal, but as the proton spin reservoir is actively transferred to the 13C in the 1H→13C CP MAS experiment the same enhancement should be obtained also in the

13

C CP MAS spectrum.

1

1

65

The maximum enhancement is achieved for radical 3 in TCE

13

solution for H and H→ C CP MAS spectra with an enhancement of around 50, which is in good agreement with the signal enhancement obtained for similar trityl-nitroxyl radicals in earlier works. 19, 52

Fig. 1. Full set of the recorded spectra at 9.396 T and 8 kHz spinning for 15 mM of 2 in TCE with and without microwave irradiation. a) 1H MAS spectra recorded with background suppression, b) 1H→13C CP MAS spectra, c) 13C MAS spectrum 13

1

13

obtained with the modified C MAS pulse sequence employing 180° pulses on the H channel during build-up of the C magnetization, resulting in only the direct channel resonances in the spectrum. The solid red line is the Lorentzian 13

13

function fit. d) C MAS spectrum obtained with the standard C MAS pulse sequence showing both, direct and DNP-CR channel resonances. The solid red line shows the convolution of direct and DNP-CR channel resonances. The dashed red lines are the fits determined from spectra c) and e) adding up to the solid line. e) Difference spectrum between c) and d) representing only the DNP-CR channel resonances. The solid red line is the fit curve with a Lorentzian function.



Page 10 of 21

Table 1: Enhancement factors ε obtained for 1H MAS, 1H→13C CP MAS, 13C MAS direct and DNP-CR channel, measured at 8 kHz at a magnetic field of 9.395 T. a Values were obtained at the optimum field for 13C.

Radical

¹H MAS

1

H→ ¹³C CP MAS

¹³C MAS direct

¹³C DNP-CR

channel 9.395 T

9.395 T

9.395 T

channel a

optimum

9.395 T

1

2.8±0.1

2.7±0.1

5±1

6±2

0

2

40.0±0.1

43.2±1.8

14±3

38±6

24±7

3

49.8±0.1

52.2±2.1

6±2

37±12

16±9

4

14.3±0.1

13.7±0.7

1±0.3

5

11.2±0.2

10.7±0.6

7±2

6

14.9±0.1

15.0±0.5

13±4

7

24.5±0.1

24.2±1.2

18±2

0

8

7.5±0.1

7.3±0.5

3±1

0

9

78.6±0.1

82.0±2.1

29±11

0

7±2 0 17±4

0

The average distances between the radical centers in the biradicals were calculated by MD simulations. Details on these calculations are given in the ESI. The distance dependencies of the enhancements obtained in the 1H→13C CP MAS and for the direct and DNP-CR channel resonances in the

13

C MAS are displayed in Fig. 2. Fig. 2a reveals a distance at ca. 14 Å for the maximal

enhancement in 1H→13C CP NMR, which is in good agreement with literature values, where maximum enhancements are found at distances of 11.2 to 11.9 Å that were calculated by density functional theory (DFT) or determined by X-ray diffraction (XRD).

16-17

The maximal enhancement

13

for the direct channel C resonance is also found in the range of 14 Å. However, the dependency of the signal enhancement from the distance between the radical centers does only follow a trend. There are several possible reasons for deviations, as the distance between two radical centers is just one parameter responsible for high signal enhancements. Others are the orientation of the g-tensors between both radical centers, radical,

69-70

16-17, 24, 66-68

electron relaxation times of the

and the derived ones such as the electron saturation factor T1e·T2e and dubbed the

relaxation factor T1e·T2e·T1n 16 .


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Fig. 2. Dependency of the signal enhancement on the distance between the two radical centers in the biradicals 1

13

13

investigated for H→ C CP MAS (a), as well as for C MAS direct (b) and DNP-CR channel resonances (c). Distances with uncertainties were determined from MD simulation data.

DNP-CR channel enhancement Comparing the 13C DNP-CR channel enhancements for the different radicals, it is clearly visible that 2, 3, 4 induce signal enhancements while all others induce no significant enhancements. This observation let us to the assumption that the DNP-CR pathway is influenced by the nature of the radical. As some of us have shown in a previous paper,

60

unusual dynamics may induce DNP-CR

channel resonances. In the original paper, where always the same radical was employed, these dynamics were primarily caused by dynamics of the solvent matrix respectively of solute molecules in these solvents. In the present study, it seems that also the structure and rigidity of the radical has a strong influence on this phenomenon. While radicals 2, 3, 4 show a relatively high flexibility in their structure all other radicals are more rigid. This is seen from molecular dynamics simulations, from which the standard deviation of the intramolecular distance distribution (Fig. 2 and Figure S9) for these radicals is calculated as 2-3 times higher compared to the more rigid ones. This is a clear indication for the statement that these radicals possess higher mobility. To confirm this experimentally, EPR measurements at 9.4 T and 117 K would be required that are beyond the scope of the present work. ACS Paragon Plus Environment


In principle, the obtained DNP-CR channel resonances may be induced due to different reasons. (i) A different transfer mechanism occurs. (ii) The radical structure influences the local dynamics in the TCE solvent. When comparing the enhancement profiles for 1H, 1H→13C CP and 13C DNP-CR signals for radicals 2 and 3 (ESI Figure S3), it is visible that all profiles are identical in their shapes. Furthermore, the 13C MAS spectrum measured with MW on of radical 3 in TCE-d2 (ESI Figure S4a) clearly shows the absence of DNP-CR resonances. These observations lead to the assumption that the DNP-CR channel polarization transfer is related to a mechanism that occurs via the 1H spin reservoir, as proposed in our previous work. 71 Thus, a different transfer mechanism can be excluded. To shed more light on the influence of the radical structure on the solvent dynamics, the freezing and the melting behavior of the radical containing TCE solutions was investigated by differential scanning calorimetry (DSC). These measurements were conducted at a cooling /heating rate of 40 K/min. These fast rates correspond to the cooling of the sample in the DNP spectrometer that takes less than 5 min to equilibrate the sample at around 110 K. The DSC curves obtained for the cooling process are displayed in Fig. 3a. For pure TCE as well as for all radical solutions except for 6 and 7, a glass transition is visible in the DSC cooling curve, which is indicated by a step-like feature instead of an enthalpic peak. 72 As TCE has a crystallization point at ca. 230 K but no crystallization peak is visible in the DSC curves, it seems that the cooling rate of 40 K/min is too fast for the solutions to respond, and a shock-cooled liquid is formed. The DSC curves obtained for the reverse heating process are displayed in Fig. 3b. For pure TCE and radical solutions of 1, 5, 8 and 9, the freezing processes continue to progress during the heating of the samples. The quenched-in amorphous structure becomes sufficiently mobile above the glass transition (cold crystallization), and reorganization of the molecule towards a thermodynamic more stable state takes place. This process is visible in the DSC curves as an exothermic crystallization peak in the range between 170 K and 180 K. Furthermore, the melting of TCE becomes visible at ca. 235 K as an endothermic melting peak. In contrary, the DSC curves for 2-4 show only a glass transition, and an endothermic peak attributed to a melting process is not obtained. This means that the solutions of these three radicals do not freeze into a crystalline state. The DSC thermograms for 6 and 7 suggest a different phase transition behavior. In the cooling curve a crystallization peak at around 178 K is visible. This clearly shows that next to the glass transition also crystallization occurs in these systems upon cooling. In the heating curves, an endothermic peak appeared at 235 K that is attributed to the melting of the TCE in analogy with the radical solutions of 1, 5, 8 and 9 as well as the pure TCE. Comparing the obtained DSC data with the

13

C MAS data obtained with MW on, a correlation is

visible. Radicals (2-4), which show a DNP-CR channel resonance in the NMR spectra, are in a glassy state and exhibit only a glass transition. In contrast, radicals (1, 5-9) exhibit in addition to the glass


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transition also both crystallization and melting peaks, showing a coexistence of glassy and crystalline domains. Since radicals 1, 5-9 contain rigid structures, it is highly plausible that they act as efficient seed crystals, which yield crystallization of the solvent in the environment of the radicals and restrict local motions. In contrary, radicals 2-4, which contain flexible structures, seem to restrict local crystallization of the solvent leading to motions that are probably the origin for the DNP-CR channel resonances.

Fig. 3. DSC cooling curves (a) and heating curves (b) measured at 40 K/min of the novel radicals 1-8 in TCE, as well as of pure TCE. Details of the DSC curves for 1, 3 and 6 are given in ESI Figure S5.

Field dependency of signal enhancement To get deeper insights into the mechanism that occurs for the different radicals, the 1H, 1H→13C CP MAS and 13C MAS direct and DNP-CR channel enhancement profiles were analyzed for the radicals 3 and 2 (Fig. 4 and ESI Figure S1), that show the DNP-CR pathway and for 6 and 1 (Fig. 5 and ESI Figure S2), that show no DNP-CR pathway. The enhancement profiles for 1H and 1H→13C CP for all four biradicals show the same progress within the experimental error. The shape of 1H, 1H→13C CP and

13

C direct channel enhancements obtained for 6 possess a broad profile as it is typical for

binitroxides. The shape of the DNP-CR channel sweep profile for 3 and 2 follows the shape of the inverted 1H enhancement profile, while the magnitude of the DNP-CR enhancement is about one third for 3 and about one half for 2, respectively, compared to the 1H enhancement (see ESI Figure S3). The 1H, 1H→13C CP and 13C DNP-CR enhancement profiles for 3 (Fig. 4) and 2 (ESI Figure S1) and likewise 1H and 1H→13C CP for 1 (ESI Figure S2) in TCE possess an asymmetric shape with a narrow region of positive enhancement with a maximum at ca. 9.396 T and a broad shallow region with negative enhancement. Similar asymmetric enhancement profiles were obtained by Hu et al. mixture of TEMPO and trityl at a ratio of 50/50, as well as by Mathies et al.

19

73

for a

and Mentink-Vigier et

al.52 for trityl-nitroxyl mixed radicals who analyzed 1H enhancements. Analysis of the data obtained at 200, 600 and 800 MHz showed that the asymmetric shape of the enhancement profiles of tritylnitroxyl biradicals decrease at higher magnetic fields. It was then concluded that the enhancement predominantly arises from intermolecular nitroxide–nitroxide CE at lower fields, while at higher fields ACS Paragon Plus Environment


Page 14 of 21

the influence of intramolecular trityl-nitroxide CE rises and induces a large positive enhancement. Moreover, it was shown in ref.

19

that the electronic spin-spin exchange interaction (

1

2)

between trityl and nitroxide moieties can be comparable to the electronic dipolar interaction (

1z 2z

1

2)).

Therefore, it contributes to the state mixing required for the CE for trityl-nitroxyl

biradicals. In contrary, for binitroxide radicals,

1

2

is smaller than

1z 2z

1

2)

and thus

plays no role. In the case of trityl-nitroxyl biradicals, the simplified CE matching condition (

) is no longer valid. This causes a shift in the optimal DNP condition , where

is the off-diagonal term introduced by

non-secular terms S1xS2x and S1yS2y. In our study, the analysis of the ratio between the maximum and minimum enhancement yield a value 3.5 for 1H and 1H→13C CP at 400 MHz, which is in good agreement with previously obtained values by Mathies et al. (2.5 at 211 MHz, 6 at 600 MHz and 8 at 800 MHz). 19 Such a value and the asymmetric profile with a shoulder part show that at 400 MHz both intermolecular nitroxide–nitroxide CE and intramolecular trityl–nitroxide CE take place.

Fig. 4. DNP enhancement profiles obtained for a 15 mM solution of the niroxyl-trityl radical 3 in TCE. a) Enhancement 1

1

13

13

profiles for H MAS and H→ C CP MAS. b) Enhancement profiles for C MAS direct and DNP-CR channel resonances.

Fig. 5. DNP enhancement profiles obtained for a 15 mM solution of the dinitroxyl radical 6 in TCE. a) Enhancement 1

1

13

13

profiles for H MAS and H→ C CP MAS. b) Enhancement profiles for C MAS direct and DNP-CR channel resonances.


Page 15 of 21 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Conclusion A series of eight novel trityl-nitroxyl and binitroxyl radicals was investigated by signal enhanced solid-state 1H, 1H→13C CP MAS and 13C MAS experiments. The maximum enhancements of ca. 50 were obtained for radicals 2 and 3 that contain an average distance between the radical centers of approximately 14 Å according to calculations. Depending on the structure of the radicals, DNP-CR and/or direct channel resonances are obtained in signal enhanced

13

C MAS spectra. While the rigid

radicals 1, 4-8 show no DNP-CR channel resonances, for the flexible radicals 2-4 DNP-CR channel resonances are clearly visible. The combination of solid-state NMR data and DSC measurements revealed that this phenomenon refers to local motions of the solvent molecules, which are influenced by the structure of the radicals. Finally, the DNP enhancement profiles were analyzed in details showing that the cross effect is the dominating polarization transfer mechanism for the investigated radical systems.

Associated Content

*Supporting Information: Details of synthesis of radicals and intermediate compounds, additional enhancement profiles and DNP NMR spectra, details of DSC curves, CW EPR spectra and simulated EPR parameters, details of MD simulations and obtained distance distributions

Author Information Corresponding Authors: Elena Bagryanskaya E-mail: [email protected] Tel.: +73833308850 ORCHID: 0000-0003-0057-383X

Torsten Gutmann E-mail: [email protected] Tel.: + 49 6151 16-21122 Fax: + 49 6151 16-21119 ORCHID: 0000-0001-6214-2272

Gerd Buntkowsky E-mail: [email protected] Tel.: + 49 6151 16-21116 Fax: + 49 6151 16-21119 ORCHID: 0000-0003-1304-9762 ACS Paragon Plus Environment


Notes The authors declare no competing financial interest.

ACKNLOWLEDGEMENTS: Financial support by the Deutsche Forschungsgemeinschaft (DFG) under grants Bu 911/20-1 (DNP spectrometer) and Bu 911/24-1, including a Mercator fellowship for Prof. Markus Hoffmann, is gratefully acknowledged. The synthesis of compounds and their EPR study was financially

supported by the Ministry of Education and Science of the Russian Federation (state contract no. 2017-220-06-7355).

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