Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• successful nitroxide-mediated polymerization (NMP). In 1993, Georges et al. used benzoyl peroxide (BPO) as the initiator and 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) as the control agent. It was called a bicomponent initiating system containing both stable free nitroxide and a conventional thermal

• weight and polymerization rate precisely. In order to solve these problems, Hawker et al. [32][33][34] proposed the concept of the unimolecular initiation system. In this system, an alkoxyamine compound is used instead of the original nitroxide radical/initiator combination. These unimolecular initiators

• can decompose to produce a stoichiometric pair of the primary initiating radical and a nitroxide radical, thus combining the roles of a conventional initiator and a control agent. The mechanism is shown in Scheme 4 [35]. Due to the steric effect of TEMPO, the dissociation rate constant, kd, of the

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• in studying the HIV-inactivating lectin cyanovirin-N protein as a model system (S52CCV-N). Single fluorine atoms were introduced at the 4-, 5-, 6- or 7-positions of Trp49 and the 4-position of Phe4, Phe54, and Phe80 (Figure 8). Simultaneously, the paramagnetic nitroxide spin label was chemically

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• molar masses and narrow molecular weight distributions. These techniques allow linear increase of molar mass by time and monomer conversion and low dispersity (principally between 1.2 to 1.5). The most common methods of controlled radical polymerization are namely the nitroxide-mediated radical

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• a sterically shielded polycyclic nitroxide. The EPR spectra and spin relaxation behavior of the nitroxide were studied in solution. The spin relaxation seems well suited for the use as a biological spin label and are comparable with those of cyclic nitroxides with two spirocyclic moieties adjacent

• to the N–O· group. Keywords: domino reactions; EPR; nitroxide; spin relaxation; Introduction Domino reactions have attracted much attention as an approach for the synthesis of complex molecules in a few steps [1]. The utility of multicomponent reactions involving amines, activated olefins and

• nitroxide [4]. Here we report the unexpected formation of a highly strained polycyclic amine from cyclopentanone, dimethyl fumarate and ammonium acetate. This multistep reaction obviously includes the 1,3-dipolar cycloaddition of dimethyl fumarate with cyclic azomethine ylide formed in situ from

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• ; sterically shielded nitroxide; Introduction Sterically shielded nitroxides are currently attracting much attention due to their high resistance to bioreduction [1][2]. It has been demonstrated that 2,2,5,5-tetraethylpyrrolidine nitroxides have the highest stability, sometimes exceeding that of trityl

• effect may be useful for structural studies by means of PELDOR or DQC [5]. We recently reported the synthesis of sterically shielded pyrrolidine nitroxide 1 via a stereospecific consecutive assembly of two spiro-(2-hydroxymethyl)cyclopentane moieties. These procedures included the addition of pent-4

• -enylmagnesium bromide to the corresponding nitrone, oxidation to alkenylnitrone, intramolecular 1,3-dipolar cycloaddition, and isoxazolidine ring opening. Nitroxide 1 showed both an unexpectedly low reduction rate [6] and long relaxation times t1 and tm at room temperature [4]. Unexpectedly high resistance of

Photochemical generation of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical from caged nitroxides by near-infrared two-photon irradiation and its cytocidal effect on lung cancer cells

• Ayato Yamada,
• Manabu Abe,
• Yoshinobu Nishimura,
• Shoji Ishizaka,
• Masashi Namba,
• Taku Nakashima,
• Kiyofumi Shimoji and
• Noboru Hattori

Beilstein J. Org. Chem. 2019, 15, 863–873, doi:10.3762/bjoc.15.84

• , Japan Department of Molecular and Internal Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima 734-8551, Japan 10.3762/bjoc.15.84 Abstract Novel caged nitroxides (nitroxide donors) with near-infrared two-photon (TP) responsive

• counterparts (65.8% vs 85.5%). Keywords: caged compound; nitroxide; photolysis; radical; theranostics; two-photon; Introduction Nitroxides (aminoxyl radicals) possess a delocalized unpaired electron and exhibit negligible dimerization reactivity, making them persistent open-shell species [1][2][3][4]. In

• sciences. These applications include spin-labels [5][6][7], fluorophore-nitroxide probes [8], contrast agents in magnetic resonance imaging (MRI) [9], polarization transfer agents for nuclear magnetic resonance (NMR) [10][11][12][13], and radical batteries [14][15]. Furthermore, the efficient synthesis of

Olefin metathesis in multiblock copolymer synthesis

• Maria L. Gringolts,
• Yulia I. Denisova,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2019, 15, 218–235, doi:10.3762/bjoc.15.21

• preparing telechelics uses a symmetrical difunctional olefin compound as a chain-transfer agent (CTA). This was applied for the synthesis of styrene (S)–isoprene (I)–butadiene (B) multiblock copolymers by combining ROMP with nitroxide-mediated polymerization (NMP) [56]. A perfectly regioregular α,ω

Phosphoramidite building blocks with protected nitroxides for the synthesis of spin-labeled DNA and RNA

• Timo Weinrich,
• Eva A. Jaumann,
• Ute M. Scheffer,
• Thomas F. Prisner and
• Michael W. Göbel

Beilstein J. Org. Chem. 2018, 14, 1563–1569, doi:10.3762/bjoc.14.133

• could be incorporated by unmodified standard procedures into four different self-complementary DNA and two RNA oligonucleotides. After photochemical removal of the protective group, elimination of formic aldehyde and spontaneous air oxidation, the nitroxide radicals were regenerated in high yield. The

• oligonucleotides by phosphoramidite building blocks [27][28][29][30][31][32][33][34][35][36][37][38][39][40]. However, some degradation of the spin labels inevitably will occur. Nitroxide labeled DNA strands of the general structures 2 and 4 have been prepared by this way [30][34][37]. In recent years, we have

• deprotection and enzymatic ligation. Amidite 6 has been applied to synthesize a full-length TAR RNA labeled with two nitroxide precursors. In the last step, the 2-nitrobenzyloxymethyl groups were removed by irradiation at 365 nm. After elimination of formic aldehyde induced by gentle heating, the resulting

Block copolymers from ionic liquids for the preparation of thin carbonaceous shells

• Sadaf Hanif,
• Bernd Oschmann,
• Dmitri Spetter,
• Muhammad Nawaz Tahir,
• Wolfgang Tremel and
• Rudolf Zentel

Beilstein J. Org. Chem. 2017, 13, 1693–1701, doi:10.3762/bjoc.13.163

• about controlled/living radical polymerization, like nitroxide-mediated polymerization (NMP), atom transfer radical polymerization (ATRP) and reversible addition–fragmentation chain transfer polymerization (RAFT) [2]. In general, by controlled radical polymerization techniques it is possible to prepare

Recent advances in metathesis-derived polymers containing transition metals in the side chain

• Ileana Dragutan,
• Valerian Dragutan,
• Bogdan C. Simionescu,
• Albert Demonceau and
• Helmut Fischer

Beilstein J. Org. Chem. 2015, 11, 2747–2762, doi:10.3762/bjoc.11.296

• synthesis of these targets presently accessible through controlled and living polymerization techniques including controlled radical polymerizations (CRP) such as atom transfer radical polymerization (ATRP), nitroxide-mediated polymerization (NMP) and reversible addition–fragmentation chain transfer (RAFT

Reactions of nitroxides 15. Cinnamates bearing a nitroxyl moiety synthesized using a Mizoroki–Heck cross-coupling reaction

• Jerzy Zakrzewski and
• Bogumiła Huras

Beilstein J. Org. Chem. 2015, 11, 1155–1162, doi:10.3762/bjoc.11.130

• the Mizoroki–Heck cross-coupling reaction. Despite the observation that an unpaired electron in nitroxides does not participate in organic reactions has been well known since the beginning of the nitroxide progress in 60's [33] the reactions of nitroxides involving an unpaired electron are also

TEMPO-derived spin labels linked to the nucleobases adenine and cytosine for probing local structural perturbations in DNA by EPR spectroscopy

• Dnyaneshwar B. Gophane and
• Snorri Th. Sigurdsson

Beilstein J. Org. Chem. 2015, 11, 219–227, doi:10.3762/bjoc.11.24

• paired with A, G, C or T in a DNA duplex. UA and UC had similar mobility order for the different base pairs, with the lowest mobility when paired with C and the highest when paired with T. Keywords: aminoxyl radical; ESR spectroscopy; nitroxide; nucleic acids; site-directed spin labeling (SDSL); spin

• UC-containing oligonucleotides The phosphoramidites of TA (5), UA (10) and UC (14) were used to incorporate the spin-labeled nucleosides into DNA oligonucleotides using solid-phase synthesis [77]. The low stability of the nitroxide functional group in the TEMPO moiety towards acids lead to almost ca

• . 50% reduction of the nitroxide during oligonucleotide synthesis, which utilized dichloroacetic acid for the removal of the trityl groups. However, in spite of low yields, the spin-labeled oligonucleotides were readily separated from those containing the reduced spin label by denaturing polyacrylamide

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• the sensitivity of the nitroxide group of TOAC [129]. Koglin et al. used the photo-cleavable protecting group Nvoc for selective 3H-labeling of full length NPY. Here, lysine residues as well as the free N-terminus of resin-bound peptide, which should not be radio-labeled, were protected with Nvoc

A new building block for DNA network formation by self-assembly and polymerase chain reaction

• Holger Bußkamp,
• Sascha Keller,
• Marta Robotta,
• Malte Drescher and
• Andreas Marx

Beilstein J. Org. Chem. 2014, 10, 1037–1046, doi:10.3762/bjoc.10.104

• properties of biological macromolecules, e.g., DNA [48][49][50][51][52][53]. Since the systems studied in the current investigation are diamagnetic, nitroxide labels had to be inserted enzymatically [54][55]. EPR spectra of nitroxide labels are sensitive to dynamics on the picosecond to microsecond

• timescales and these dynamics are greatly altered upon attachment to a macromolecule. The nitroxide labels report not only the dynamics of the macromolecules as a whole, but additionally, they undergo rotations around the chemical bonds of the linker, and furthermore, the site of attachment can undergo

• approximated by a simple motional model to provide information on the properties of the macromolecule [56]. Since DNA polymerases are known to tolerate several dNTP modifications [57][58], we next investigated whether dTTP can be partially replaced by the nitroxide labeled dT*TP to generate DNA networks

Stability of SG1 nitroxide towards unprotected sugar and lithium salts: a preamble to cellulose modification by nitroxide-mediated graft polymerization

• Guillaume Moreira,
• Laurence Charles,
• Mohamed Major,
• Florence Vacandio,
• Yohann Guillaneuf,
• Catherine Lefay and
• Didier Gigmes

Beilstein J. Org. Chem. 2013, 9, 1589–1600, doi:10.3762/bjoc.9.181

• of applications of cellulose, a glucose-based polysaccharide, is limited by its inherently poor mechanical properties. The grafting of synthetic polymer chains by, for example, a “grafting from” process may provide the means to broaden the range of applications. The nitroxide-mediated polymerization

• of crucial importance to perform the graft modification of polysaccharide by NMP. The aim of this work is to offer a model study of the stability of the SG1 nitroxide in organic media in the presence of unprotected glucose or cellobiose (used as a model of cellulose) and in the presence of lithium

• salts (LiBr or LiCl) in DMF or DMA. Contrary to TEMPO, SG1 proved to be stable in the presence of unprotected sugar, even with an excess of 100 molar equivalents of glucose. On the other hand, lithium salts in DMF or DMA clearly degrade SG1 nitroxide as proven by electron-spin resonance measurements

Structures of the reaction products of the AZADO radical with TCNQF₄ or thiourea

• Hideto Suzuki,
• Yuta Kawahara,
• Hiroki Akutsu,
• Jun-ichi Yamada and
• Shin’ichi Nakatsuji

Beilstein J. Org. Chem. 2013, 9, 1487–1491, doi:10.3762/bjoc.9.169

• compound; nitroxide radical; TCNQF4; thiourea; Introduction TEMPO radical (2,2,6,6-tetramethylpiperidinyl-N-oxyl) (1) is a typical nitroxide radical and is persistent because of the steric hindrance of the four neighboring methyl groups of the NO moiety protecting it from attack by various reagents

• including oxygen [1]. Sometimes, however, the merit turns out to be a drawback by limiting its properties and reactivity. For example, 1 is inefficient in the oxidation of sterically hindered secondary alcohols. The AZADO radical (2) [2] is an intriguing nitroxide radical with adamantane-like structure and

• acceptor. Moreover, we tried to prepare a supramolecule from 2 with thiourea (4), as structurally similar 1-bromoadamantane was reported to form an intriguing inclusion compound with thiouea [9]. There are some reported examples of inclusion compounds derived from TEMPO and related nitroxide radicals with

Reactions of nitroxides XIII: Synthesis of the Morita–Baylis–Hillman adducts bearing a nitroxyl moiety using 4-acryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl as a starting compound, and DABCO and quinuclidine as catalysts

• Jerzy Zakrzewski

Beilstein J. Org. Chem. 2012, 8, 1515–1522, doi:10.3762/bjoc.8.171

• nitroxide moiety on the MBH reaction is unknown. Herein we present the MBH reaction with a nitroxyl radical, 4-acryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl, used as a starting material as an olefin activated with EWG. Acrylates are considered as rather unreactive in the MBH reaction [44]. It was shown

• with increasing chain length of the alcohol moiety in an acrylate [20][45]. The alcohol moiety in 4-acryloyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl is undoubtly sterically hindered, so the expected reaction times will be long; however, this nitroxide has been chosen based on the availability of such

Miniemulsion polymerization as a versatile tool for the synthesis of functionalized polymers

• Daniel Crespy and
• Katharina Landfester

Beilstein J. Org. Chem. 2010, 6, 1132–1148, doi:10.3762/bjoc.6.130

• ), degenerative iodine transfer [48], and nitroxide mediated polymerization (NMP). ATRP in miniemulsions was recently described in several reviews [52][53]. The kinetics of RAFT polymerization in miniemulsion has been discussed by Tobita [54] and thus no detailed description is required here. Surfactant monomer

Novel multi-responsive P2VP-block-PNIPAAm block copolymers via nitroxide-mediated radical polymerization

• Cathrin Corten,
• Katja Kretschmer and
• Dirk Kuckling

Beilstein J. Org. Chem. 2010, 6, 756–765, doi:10.3762/bjoc.6.89

• block copolymers are able to form so called schizophrenic micelles in aqueous solution. Here, such polymers are prepared via nitroxide-mediated radical polymerization (NMRP). In a first step nitroxide-terminated poly(2-vinylpyridine) (P2VP) was prepared with different molecular weights and narrow

• nitroxide terminated polymers were characterized by nuclear magnetic resonance (NMR) spectroscopy, size exclusion chromatography (SEC) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Thermal properties were investigated by the differential scanning

• delivery systems. Keywords: block copolymers; N-isopropylacrylamide; nitroxide-mediated radical polymerization; stimuli-responsive polymers; 2-vinylpyridine; Introduction Functional polymers have attracted much attention because of their technological and scientific importance. Polymers, which respond