Hydrophilic Reduction-Resistant Spin Labels of Pyrrolidine and Pyrroline Series from 3,4-Bis-hydroxymethyl-2,2,5,5-tetraethylpyrrolidine-1-oxyl
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis of the Hydrophilic Nitroxides
2.2. EPR Studies of the New Nitroxides
2.3. Lipophilicity
2.4. Reduction Rates in Ascorbate-Containing Systems
2.5. Decay in the Rat Liver Homogenates
3. Materials and Methods
3.1. General Information
3.2. Synthesis
3.2.1. A Reaction of Hydroxymethyl Nitroxides 1 and 8 with Methanesulfonyl Chloride
3.2.2. Reaction of Mesylates with Sodium Azide (General Method)
3.2.3. The Eschweiler–Clarke Methylation of Nitroxides 10 and 13a,b (General Method)
3.2.4. General Procedure for Quaternization of Dimethylamino Group
3.2.5. Reaction of Nitroxide 12a with Dimethyl Acetylenedicarboxylate (DMAD)
3.2.6. General Procedure of the Synthesis of Amines 13a,b and 14a,b with PPh3
3.2.7. General Procedure of the Synthesis of Maleimides 7 and 15a,b
3.3. EPR Measurements and Kinetics
3.4. Animals
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Nitroxide | aN, mT ±0.005 | aH, mT ±0.005 | Hp-p, mT ±0.005 | g-Factor ±0.00002 | Kp | kred × 104, M−1 s−1 |
---|---|---|---|---|---|---|
1 | 1.57 | 0.22; 0.22 | 0.125 | 2.00563 [27] | 41 ± 2 | 3.3 ± 0.8 [26] |
5 | 1.52 | 0.22; 0.24 | 0.27 | 2.00562 | ||
6 | 1.51 | 0.22; 0.23 | 0.26 | 2.00562 | ||
7 | 1.52 | 0.24; 0.26 | 0.28 | 2.00562 | 84 ± 2 | |
8 | 1.52 | 0.24; 0.25 | 0.27 | 2.00562 | 6.0 ± 2.0 | |
9 | 1.51 | 0.23; 0.27 | 0.28 | 2.00562 | 3.0 ± 1.0 | |
10 | 1.50 | 0.23; 0.25 | 0.27 | 2.00562 | 3.0 ± 1.0 | |
11a | 1.49 | 0.23; 0.27 | 0.26 | 2.00563 | 52 ± 5 | 4.0 ± 1.0 |
11b | 1.51 | 0.21 | 2.00562 | 15 ± 1 | 15 ± 4.0 | |
13a | 1.49 | 0.22; 0.28 | 0.26 | 2.00563 | 350 ± 35 | 6.3 ± 0.9 |
pH = 1.5 * | 1.51 | |||||
pH = 13 * | 1.53 | |||||
13b | 1.51 | 0.18 | 2.00562 | 45 ± 2 | 7.6 ± 0.3 | |
pH = 1.5 * | 1.53 | |||||
pH = 13 * | 1.55 | |||||
14a | 1.51 | 0.20; 0.28 | 0.26 | 2.00562 | 6.4 ± 1.0 | |
pH = 7.4 * | 1.52 | 0.23; 0.23 | ||||
pH = 1.5 * | 1.46 | 0.31; 0.31 | ||||
pH = 13 * | 1.54 | 0.25; 0.25 | ||||
14b | 1.52 | 0.19 | 2.00563 | 7 ± 0.3 | 8 ± 1.0 | |
pH = 7.4 * | 1.53 | |||||
pH = 1.5 * | 1.49 | |||||
pH = 13 * | 1.55 | |||||
15a | 1.48 | 0.26; 0.31 | 2.00562 | |||
15b | 1.51 | 0.23 | 2.00563 | |||
16a | 1.47 | 0.23; 0.36 | 0.29 | 2.00562 | 0 | |
16b | 1.48 | 0.25 | 2.00562 | |||
17a | 1.48 | 0.22; 0.27 | 0.26 | 2.00561 | 0 | 3.0 ± 1.0 |
17b | 1.49 | 0.23 | 2.00562 | 0 | 16 ± 3.0 | |
20 | 1.50 | 0.24; 0.31 | 0.28 | 2.00561 | 0 | 5.9 ± 1.2 |
21 | 1.55 | 0.19 | 0.26 | 2.00563 | 270 | 12.5 ± 0.3 [22] |
22 | 1.54 | 0.16 | 2.00563 | 37 ± 2 | 3.4 ± 0.1 | |
23 | 1.53 | 0.24; 0.29 | 0.27 | 2.00562 |
No. | 1, g/mmol | MsCl, g/eq. | DIPEA, g/eq. | CHCl3, mL | Conversion of 1, % | Yield | |
---|---|---|---|---|---|---|---|
3, % | 4, % | ||||||
1 | 2/7.75 | 1.4/1.58 | 1.4/1.4 | 50 | 85 | 12 | 68 |
2 | 4/15.5 | 3/1.68 | 3/1.5 | 50 | >95 | 35 | 55 |
3 | 4/15.5 | 5/2.8 | 4.8/2.2 | 50 | 100 | >95 | 0 |
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Usatov, M.S.; Dobrynin, S.A.; Polienko, Y.F.; Morozov, D.A.; Glazachev, Y.I.; An’kov, S.V.; Tolstikova, T.G.; Gatilov, Y.V.; Bagryanskaya, I.Y.; Raizvikh, A.E.; et al. Hydrophilic Reduction-Resistant Spin Labels of Pyrrolidine and Pyrroline Series from 3,4-Bis-hydroxymethyl-2,2,5,5-tetraethylpyrrolidine-1-oxyl. Int. J. Mol. Sci. 2024, 25, 1550. https://doi.org/10.3390/ijms25031550
Usatov MS, Dobrynin SA, Polienko YF, Morozov DA, Glazachev YI, An’kov SV, Tolstikova TG, Gatilov YV, Bagryanskaya IY, Raizvikh AE, et al. Hydrophilic Reduction-Resistant Spin Labels of Pyrrolidine and Pyrroline Series from 3,4-Bis-hydroxymethyl-2,2,5,5-tetraethylpyrrolidine-1-oxyl. International Journal of Molecular Sciences. 2024; 25(3):1550. https://doi.org/10.3390/ijms25031550
Chicago/Turabian StyleUsatov, Mikhail S., Sergey A. Dobrynin, Yuliya F. Polienko, Denis A. Morozov, Yurii I. Glazachev, Sergey V. An’kov, Tatiana G. Tolstikova, Yuri V. Gatilov, Irina Yu. Bagryanskaya, Arthur E. Raizvikh, and et al. 2024. "Hydrophilic Reduction-Resistant Spin Labels of Pyrrolidine and Pyrroline Series from 3,4-Bis-hydroxymethyl-2,2,5,5-tetraethylpyrrolidine-1-oxyl" International Journal of Molecular Sciences 25, no. 3: 1550. https://doi.org/10.3390/ijms25031550