Synthesis and application of stable nitroxide free radicals fused with carbocycles and heterocycles

Balázs Bognár, Györgyi Úr, Cecília Sár, Olga H. Hankovszky, K. Hideg, T. Kalai

Research output: Contribution to journalArticle

Abstract

Stable nitroxide free radicals have traditionally been associated with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or its 4-substituted derivatives as relatively inexpensive and readily accessible compounds with limited possibilities for further chemical modification. Over the past two decades, there has been a resurgence of interest in stable free radicals with proper functionalization tuned for various applications. The objective of this review is to present recent results with synthetic methodologies to achieve stable nitroxide free radicals fused with aromatic carbocycles and heterocycles. There are two main approaches for accessing stable nitroxide free radicals fused with arenes, e.g., isoin-doline-like nitroxides: further functionalization and oxidation of phthalimide or inventive functionalization of pyrroline nitroxide key compounds. The latter also offers the con-structions of versatile heterocyclic scaffolds (furan, pyrrole, thiophene, 1,2-thiazole, selenophene, pyrazole, pyrimidine, pyridine, pyridazine, 1,5-benzothiazepine) that are fused with pyrroline or tetrahydropyridine nitroxide rings. The possible applications of these new stable nitroxide free radicals, such as covalent spin labels and noncovalent spin probes of proteins and nucleic acids, profluorescent probes, building blocks for construction of dual active drugs and electroactive materials, and substances for controlled free radical polymerization, are discussed.

Original languageEnglish
Pages (from-to)480-501
Number of pages22
JournalCurrent Organic Chemistry
Volume23
Issue number4
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Free Radicals
Nucleic Acid Probes
Spin Labels
Thiazoles
Thiophenes
Pyrroles
Chemical modification
Free radical polymerization
Scaffolds
Derivatives
Oxidation
Pharmaceutical Preparations
Proteins
pyrroline

Keywords

  • Antioxidants
  • C-C bond formation
  • Carbocycles
  • Heterocycles
  • Nitroxide free radicals
  • Pd-catalyzed cross-coupling
  • Spin-labels

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Synthesis and application of stable nitroxide free radicals fused with carbocycles and heterocycles. / Bognár, Balázs; Úr, Györgyi; Sár, Cecília; Hankovszky, Olga H.; Hideg, K.; Kalai, T.

In: Current Organic Chemistry, Vol. 23, No. 4, 01.01.2019, p. 480-501.

Research output: Contribution to journalArticle

Bognár, Balázs ; Úr, Györgyi ; Sár, Cecília ; Hankovszky, Olga H. ; Hideg, K. ; Kalai, T. / Synthesis and application of stable nitroxide free radicals fused with carbocycles and heterocycles. In: Current Organic Chemistry. 2019 ; Vol. 23, No. 4. pp. 480-501.
@article{1091ba4caa54486abc5531295d495101,
title = "Synthesis and application of stable nitroxide free radicals fused with carbocycles and heterocycles",
abstract = "Stable nitroxide free radicals have traditionally been associated with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or its 4-substituted derivatives as relatively inexpensive and readily accessible compounds with limited possibilities for further chemical modification. Over the past two decades, there has been a resurgence of interest in stable free radicals with proper functionalization tuned for various applications. The objective of this review is to present recent results with synthetic methodologies to achieve stable nitroxide free radicals fused with aromatic carbocycles and heterocycles. There are two main approaches for accessing stable nitroxide free radicals fused with arenes, e.g., isoin-doline-like nitroxides: further functionalization and oxidation of phthalimide or inventive functionalization of pyrroline nitroxide key compounds. The latter also offers the con-structions of versatile heterocyclic scaffolds (furan, pyrrole, thiophene, 1,2-thiazole, selenophene, pyrazole, pyrimidine, pyridine, pyridazine, 1,5-benzothiazepine) that are fused with pyrroline or tetrahydropyridine nitroxide rings. The possible applications of these new stable nitroxide free radicals, such as covalent spin labels and noncovalent spin probes of proteins and nucleic acids, profluorescent probes, building blocks for construction of dual active drugs and electroactive materials, and substances for controlled free radical polymerization, are discussed.",
keywords = "Antioxidants, C-C bond formation, Carbocycles, Heterocycles, Nitroxide free radicals, Pd-catalyzed cross-coupling, Spin-labels",
author = "Bal{\'a}zs Bogn{\'a}r and Gy{\"o}rgyi {\'U}r and Cec{\'i}lia S{\'a}r and Hankovszky, {Olga H.} and K. Hideg and T. Kalai",
year = "2019",
month = "1",
day = "1",
doi = "10.2174/1385272823666190318163321",
language = "English",
volume = "23",
pages = "480--501",
journal = "Current Organic Chemistry",
issn = "1385-2728",
publisher = "Bentham Science Publishers B.V.",
number = "4",

}

TY - JOUR

T1 - Synthesis and application of stable nitroxide free radicals fused with carbocycles and heterocycles

AU - Bognár, Balázs

AU - Úr, Györgyi

AU - Sár, Cecília

AU - Hankovszky, Olga H.

AU - Hideg, K.

AU - Kalai, T.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Stable nitroxide free radicals have traditionally been associated with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or its 4-substituted derivatives as relatively inexpensive and readily accessible compounds with limited possibilities for further chemical modification. Over the past two decades, there has been a resurgence of interest in stable free radicals with proper functionalization tuned for various applications. The objective of this review is to present recent results with synthetic methodologies to achieve stable nitroxide free radicals fused with aromatic carbocycles and heterocycles. There are two main approaches for accessing stable nitroxide free radicals fused with arenes, e.g., isoin-doline-like nitroxides: further functionalization and oxidation of phthalimide or inventive functionalization of pyrroline nitroxide key compounds. The latter also offers the con-structions of versatile heterocyclic scaffolds (furan, pyrrole, thiophene, 1,2-thiazole, selenophene, pyrazole, pyrimidine, pyridine, pyridazine, 1,5-benzothiazepine) that are fused with pyrroline or tetrahydropyridine nitroxide rings. The possible applications of these new stable nitroxide free radicals, such as covalent spin labels and noncovalent spin probes of proteins and nucleic acids, profluorescent probes, building blocks for construction of dual active drugs and electroactive materials, and substances for controlled free radical polymerization, are discussed.

AB - Stable nitroxide free radicals have traditionally been associated with 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or its 4-substituted derivatives as relatively inexpensive and readily accessible compounds with limited possibilities for further chemical modification. Over the past two decades, there has been a resurgence of interest in stable free radicals with proper functionalization tuned for various applications. The objective of this review is to present recent results with synthetic methodologies to achieve stable nitroxide free radicals fused with aromatic carbocycles and heterocycles. There are two main approaches for accessing stable nitroxide free radicals fused with arenes, e.g., isoin-doline-like nitroxides: further functionalization and oxidation of phthalimide or inventive functionalization of pyrroline nitroxide key compounds. The latter also offers the con-structions of versatile heterocyclic scaffolds (furan, pyrrole, thiophene, 1,2-thiazole, selenophene, pyrazole, pyrimidine, pyridine, pyridazine, 1,5-benzothiazepine) that are fused with pyrroline or tetrahydropyridine nitroxide rings. The possible applications of these new stable nitroxide free radicals, such as covalent spin labels and noncovalent spin probes of proteins and nucleic acids, profluorescent probes, building blocks for construction of dual active drugs and electroactive materials, and substances for controlled free radical polymerization, are discussed.

KW - Antioxidants

KW - C-C bond formation

KW - Carbocycles

KW - Heterocycles

KW - Nitroxide free radicals

KW - Pd-catalyzed cross-coupling

KW - Spin-labels

UR - http://www.scopus.com/inward/record.url?scp=85067522998&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067522998&partnerID=8YFLogxK

U2 - 10.2174/1385272823666190318163321

DO - 10.2174/1385272823666190318163321

M3 - Article

AN - SCOPUS:85067522998

VL - 23

SP - 480

EP - 501

JO - Current Organic Chemistry

JF - Current Organic Chemistry

SN - 1385-2728

IS - 4

ER -