Hydrophilic Reduction-Resistant Spin Labels of Pyrrolidine and Pyrroline Series from 3,4-Bis-hydroxymethyl-2,2,5,5-tetraethylpyrrolidine-1-oxyl

Hydrophilic Reduction-Resistant Spin Labels of Pyrrolidine and Pyrroline Series from 3,4-Bis-hydroxymethyl-2,2,5,5-tetraethylpyrrolidine-1-oxyl Full article

Journal

International Journal of Molecular Sciences
ISSN: 1661-6596

Output data

Year: 2024, Volume: 25, Number: 3, Article number : 1550, Pages count : 20 DOI: 10.3390/ijms25031550

Tags

reduction-resistant nitroxide; spin label; spin probe; EPR; hyperfine coupling

Authors

Usatov Mikhail S. ^1,2 , Dobrynin Sergey A. ¹ , Polienko Yuliya F. ¹ , Morozov Denis A. ¹ , Glazachev Yurii I. ³ , An’kov Sergey V. ¹ , Tolstikova Tatiana G. ¹ , Gatilov Yuri V. ¹ , Bagryanskaya Irina Yu. ¹ , Raizvikh Arthur E. ^1,4 , Bagryanskaya Elena G. ¹ , Kirilyuk Igor A. ¹

Affiliations

1	N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS, Lavrentiev Ave. 9, Novosibirsk 630090, Russia
2	Department of Natural Sciences, Novosibirsk State University, Pirogova Str. 1, Novosibirsk 630090, Russia
3	Voevodsky Institute of Chemical Kinetics and Combustion SB RAS, Institutskaya 3, Novosibirsk 630090, Russia
4	Department of Physics, Novosibirsk State University, Pirogova Str. 1, Novosibirsk 630090, Russia

Funding (1)

Российский Научный Фонд

23-13-00178

Abstract Highly resistant to reduction nitroxides open new opportunities for structural studies of biological macromolecules in their native environment inside living cells and for functional imaging of pH and thiols, enzymatic activity and redox status in living animals. 3,4-Disubstituted nitroxides of 2,2,5,5-tetraethylpyrrolidine and pyrroline series with a functional group for binding to biomolecules and a polar moiety for higher solubility in water and for more rigid attachment via additional coordination to polar sites were designed and synthesized. The EPR spectra, lipophilicities, kinetics of the reduction in ascorbate-containing systems and the decay rates in liver homogenates were measured. The EPR spectra of all 3,4-disubstituted pyrrolidine nitroxides showed additional large splitting on methylene hydrogens of the ethyl groups, while the spectra of similar pyrroline nitroxides were represented with a simple triplet with narrow lines and hyperfine structure of the nitrogen manifolds resolved in oxygen-free conditions. Both pyrrolidine and pyrroline nitroxides demonstrated low rates of reduction with ascorbate, pyrrolidines being a bit more stable than similar pyrrolines. The decay of positively charged nitroxides in the rat liver homogenate was faster than that of neutral and negatively charged radicals, with lipophilicity, rate of reduction with ascorbate and the ring type playing minor role. The EPR spectra of N,N-dimethyl-3,4-bis-(aminomethyl)-2,2,5,5-tetraethylpyrrolidine-1-oxyl showed dependence on pH with pKa = 3, ΔaN = 0.055 mT and ΔaH = 0.075 mT.

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. , Bagryanskaya E.G. , Kirilyuk I.A.
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. V.25. N3. 1550 :1-20. DOI: 10.3390/ijms25031550 WOS Scopus

Submitted:	Nov 28, 2023
Accepted:	Dec 24, 2023
Published online:	Jan 26, 2024
Published print:	Feb 1, 2024

Web of science	WOS:001160339200001
Scopus	2-s2.0-85184677319
OpenAlex	W4391262973