Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• when introduced to the human body, and not degrade or dissolve straight away. Poly(N-isopropylacrylamide) (PNIPAM) is a well-known example of a thermo-responsive polymer, which exhibits a phase transition close to body temperature and has been used in cryogels to infer temperature responsive behaviour

An amphiphilic pseudo[1]catenane: neutral guest-induced clouding point change

• Tomoki Ogoshi,
• Tomohiro Akutsu and
• Tada-aki Yamagishi

Beilstein J. Org. Chem. 2018, 14, 1937–1943, doi:10.3762/bjoc.14.167

• ; Introduction Thermo-responsive molecules exhibiting a lower critical solution temperature (LCST) are very important for applications such as controlled drug release [1], molecular separation [2], and tissue culture substrates [3]. Poly(N-isopropylacrylamide) (pNIPAAm) is a widely used thermo-responsive polymer

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• nanosystems suitable for many applications [113][114][115]. Catalysis in nanogels: Nanogels have intrinsic properties that make them well suited for green chemistry [116][117]. Water-compatible gels are usually based on poly(N-isopropylacrylamide) (PNIPAM), poly(N-vinylcaprolactam) (PVCL) or other water

• et al. described a nanogel composed of poly(N-isopropylacrylamide) brushes grafted on Pd-NPs (Pd@PNIPAM) to carry out coupling reactions in water under mild conditions [120]. They showed highly efficient coupling of several hydrophobic aryl halides with phenylboronic acid, which in all cases resulted

• for facile tuning of their properties such as size [13][74], membrane permeability [75] and stability [76]. Various copolymers have been reported for polymersome formation such as poly(ethylene glycol)-b-polystyrene (PEG-b-PS) [14][77], polystyrene-b-polyisocyanopeptide (PS-b-PIAT)[21][22] and poly(N

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• co-workers produced a nanogel injectable in humans to detect cancer cells. The nanogel was composed by sucrose acetate isobutyltyrate (SAIB) and poly(N-isopropylacrylamide) (PNIPAM)-coated AuNPs, compatible with SAIB matrix. The nanogel had good opacity for 2D X-ray visualization and was tested in

Supramolecular polymer assembly in aqueous solution arising from cyclodextrin host–guest complexation

• Jie Wang,
• Zhiqiang Qiu,
• Yiming Wang,
• Li Li,
• Xuhong Guo,
• Duc-Truc Pham,
• Stephen F. Lincoln and
• Robert K. Prud’homme

Beilstein J. Org. Chem. 2016, 12, 50–72, doi:10.3762/bjoc.12.7

• substituted poly(acrylamide) (pAAm) and poly(N-isopropylacrylamide) (pNiPAAM) hydrogels shown in Figure 24 [111]. Thus, a cube of (pNiPAAM) where the mol % ratio of β-CD to adamantyl to ferrocenyl substituents is 6:3:3 may be cut into halves and upon pressing the halves together self-healing occurs through

Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs

• Lisa F. Becker,
• Dennis H. Schwarz and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 2920–2927, doi:10.3762/bjoc.10.310

• amphiphiles, such as methyl cellulose [47], poly(N-isopropylacrylamide) (pNiPAAm) [48], and also for methylated CDs [49], and CDs completely modified with oligoethylene glycol units [50]. While the LCST transition of the statistical derivative 2b1 was within a rather broad temperature range (30–40 °C), the

Loose-fit polypseudorotaxanes constructed from γ-CDs and PHEMA-PPG-PEG-PPG-PHEMA

• Tao Kong,
• Lin Ye,
• Ai-ying Zhang and
• Zeng-guo Feng

Beilstein J. Org. Chem. 2014, 10, 2461–2469, doi:10.3762/bjoc.10.257

• cavity of γ-CDs to form stable and unconventionally conformational PPRs. γ-CDs can accommodate the bulkier poly(N-isopropylacrylamide) (PNIPAAm) blocks to give single-chain stranded, loose-fit PPRs or PRs [14][15][16]. To extend the scope of self-assembly of γ-CDs with polymers having bulkier cross

Influence of cyclodextrin on the UCST- and LCST-behavior of poly(2-methacrylamido-caprolactam)-co-(N,N-dimethylacrylamide)

• Alexander Burkhart and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 1951–1958, doi:10.3762/bjoc.10.203

• tissue engineering [1][2][3]. Especially polymers having a lower critical solution temperature (LCST) in water, like poly(N-isopropylacrylamide) or modified poly(N-vinylpyrrolidone) are extensively described in literature [4][5]. Below the critical temperature (TC) these polymers are soluble and they

• influenced significantly by supramolecular interactions with cyclodextrin [9]. Accordingly, we described in 2003 for the first time, that the LCST of a poly(N-adamantylacrylamide-co-N’-isopropylacrylamide) is influenced by CD [10]. Furthermore, the interaction of poly(pseudo-betaines) with CD leads to an

End-group-functionalized poly(N,N-diethylacrylamide) via free-radical chain transfer polymerization: Influence of sulfur oxidation and cyclodextrin on self-organization and cloud points in water

• Sebastian Reinelt,
• Daniel Steinke and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 680–691, doi:10.3762/bjoc.10.61

• during the phase transition is initiated at the chain ends, where the mobility is highest [36]. For poly(N-isopropylacrylamide) (PNIPAM) previous studies demonstrated a broadened phase transition for polydisperse and low molecular weight samples [18][32][43]. Although the polymers (8a–d, 9a–d

Oligomeric epoxide–amine adducts based on 2-amino-N-isopropylacetamide and α-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties

• Julian Fischer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2803–2811, doi:10.3762/bjoc.9.315

• solubility, whereas these bondings are increasingly disrupted on heating [3]. These LCST-type polymers are of interest for the development of e.g. hydrogels and drug delivery systems [2][4]. One of the most prominent LCST polymers is poly(N-isopropylacrylamide) (PNIPAM), which exhibits a LCST of about 32 °C

• for the formation of corresponding oligomers [16]. Inspired by the molecular structure of N-isopropylacrylamide, we synthesized a primary amine 2-amino-N-isopropylacetamide (5) that is based on the amino acid glycine (Scheme 1). This was achieved in a three-step reaction through protection of the

Polymeric redox-responsive delivery systems bearing ammonium salts cross-linked via disulfides

• Christian Dollendorf,
• Martin Hetzer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 1652–1662, doi:10.3762/bjoc.9.189

• this regard, poly(N-isopropylacrylamide) (PNIPAM) and poly(N,N-dimethylamino)ethyl methacrylate (PDMAEMA) based hydrogels are the most extensively studied representatives. Due to the protonation of covalently attached tertiary amine groups, PDMAEMA exhibits pH-responsive behavior and is used in gene

Cyclodextrin-induced host–guest effects of classically prepared poly(NIPAM) bearing azo-dye end groups

• Gero Maatz,
• Arkadius Maciollek and
• Helmut Ritter

Beilstein J. Org. Chem. 2012, 8, 1929–1935, doi:10.3762/bjoc.8.224

• topology, attract considerable interest for a wide range of optical, medical or reagent-immobilization applications [16]. Results and Discussion Here, we describe the free-radical polymerization of N-isopropylacrylamide (NIPAM, 1) in the presence of a chain–transfer agent and its end-group

• formation of a thermo- and pH-responsive polymer bearing an azo dye at the end group. In a first step, a chain-transfer polymerization (CTP) of N-isopropylacrylamide (1) was carried out in the presence of 3-mercaptopropionic acid (2) and with 4,4’-azobis(4-cyanovaleric acid) as initiator, to achieve a high

• autocorrelation function of the sample by a general purpose method, i.e., the non-negative least squares algorithm, included in the DTS software. Synthesis of 3. N-Isopropylacrylamide (1, 2 g, 0.02 mol) was dissolved in 10 mL of ethanol and flushed with argon for 15 min. To this solution, 3-mercaptopropionic acid

Influence of cyclodextrin on the solubility of a classically prepared 2-vinylcyclopropane macromonomer in aqueous solution

• Helmut Ritter,
• Jia Cheng and
• Monir Tabatabai

Beilstein J. Org. Chem. 2012, 8, 1528–1535, doi:10.3762/bjoc.8.173

• vinylcyclopropane end group and a poly(N-isopropylacrylamide) (poly(NiPAAm)) chain was obtained from amidation of 1-ethoxycarbonyl-2-vinylcyclopropane-1-carboxylic acid (4) with an amino-terminated poly(NiPAAm) 3 as an example. This macromonomer 5 showed an LCST effect after complexation of the vinyl end group with

• with a Viscotek GPCmax VE2001 using DMF as the eluent at 60 °C (flow rate: 1 mL/min). The ozonolysis was carried out on an ozone generator by Fischer Technology. In this ozone generator 45–50 liters of oxygen per hour was provided. Synthesis of amino-terminated poly(N-isopropylacrylamide) 3 A) In water

Chiral recognition of ephedrine: Hydrophilic polymers bearing β-cyclodextrin moieties as chiral sensitive host molecules

• Sabrina Gingter and
• Helmut Ritter

Beilstein J. Org. Chem. 2011, 7, 1516–1519, doi:10.3762/bjoc.7.177

• aromaticity and is pharmaceutically relevant (Scheme 1). Recently we described the monomer synthesis of mono-(6-azido-6-desoxy)-β-cyclodextrin with propargylmethacrylate and the copolymerization with N-isopropylacrylamide (NIPAAM) [20]. The properties of the polymer 1 were characterized further by use of size

Chiral recognition of macromolecules with cyclodextrins: pH- and thermosensitive copolymers from N-isopropylacrylamide and N-acryloyl-D/L-phenylalanine and their inclusion complexes with cyclodextrins

• Sabrina Gingter,
• Ella Bezdushna and
• Helmut Ritter

Beilstein J. Org. Chem. 2011, 7, 204–209, doi:10.3762/bjoc.7.27

• recognition of polymer attached tryptophan with CD [16]. In this paper we now wish to report the chiral recognition of polymeric attached phenylalanine (Phe) with randomly-methylated-β-CD (RAMEB-CD) and native β-CD. Results and Discussion Copolymers 3D and 3L comprising N-isopropylacrylamide (NIPAAm), N

• chloride (97%) and N-isopropylacrylamide (NIPAAm, 97%) were obtained from Aldrich, Germany, and used as received. Azobisisobutyronitrile (AIBN) (96%) and N,N-dimethylformamide (DMF) were purchased from Fluka, Germany. Dimethylsulfoxide-d6 (99.9 atom % D) and deuterium oxide D2O were obtained from Deutero

• %, N 7%, H 6.5%, 2L C 64.2%, N 5.7%, H 6%. Synthesis of poly(NIPAAm-co-D- or L-phenylalaninacrylamide) 3D, 3L 6.2 g (54 mmol) of N-isopropylacrylamide (NIPAAm) were dissolved in 5 mL of dimethylformamide. In each of two 100 mL flasks was placed 0.3 g (1.4 mmol) 2D/2L dissolved in 3 mL of DMF. Then 68

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

• inverse minemulsion [23]. The non-reacted vinyl groups, detected by NMR spectroscopy, could be subsequently further crosslinked. The syntheses of temperature-responsive microgels in inverse miniemulsion have also been reported [24]. N-isopropylacrylamide and methacrylic acid were polymerized in the

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

• molecular weight distributions. The best reaction conditions, optimized by kinetic studies, were bulk polymerization at 110 °C. Using P2VP as a macroinitiator, the synthesis of new soluble linear block copolymers of P2VP and poly(N-isopropylacrylamide) (PNIPAAm) (P2VP-block-PNIPAAm) was possible. The

• 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

• systems [4], as well as chemo-mechanical actuators [5], e.g., in valves where their characteristics have been studied extensively by a large range of methods [6][7]. One of the most intensively studied polymers in this field is poly(N-isopropylacrylamide) (PNIPAAm), which exhibits a sharp phase transition

Calix[4]arene-click-cyclodextrin and supramolecular structures with watersoluble NIPAAM-copolymers bearing adamantyl units: “Rings on ring on chain”

• Bernd Garska,
• Monir Tabatabai and
• Helmut Ritter

Beilstein J. Org. Chem. 2010, 6, 784–788, doi:10.3762/bjoc.6.83

• pump vacuum. N-Isopropylacrylamide (NIPAAM) 97%, sodium azide (99.5%) and azobisisobutyronitrile (98%) were purchased from Aldrich Chemicals (Germany) and used as received. Copper-(II)-sulfate pentahydrate (99%) was obtained from Carl Roth GmbH & CO., and sodium L(+)-ascorbate (99%) obtained from

RAFT polymers for protein recognition

• Alan F. Tominey,
• Julia Liese,
• Sun Wei,
• Klaus Kowski,
• Thomas Schrader and
• Arno Kraft

Beilstein J. Org. Chem. 2010, 6, No. 66, doi:10.3762/bjoc.6.66

• 5, 45117 Essen, Germany 10.3762/bjoc.6.66 Abstract A new family of linear polymers with pronounced affinity for arginine- and lysine-rich proteins has been created. To this end, N-isopropylacrylamide (NIPAM) was copolymerized in water with a binding monomer and a hydrophobic comonomer using a

Free radical homopolymerization of a vinylferrocene/cyclodextrin complex in water

• Helmut Ritter,
• Beate E. Mondrzik,
• Matthias Rehahn and
• Markus Gallei

Beilstein J. Org. Chem. 2010, 6, No. 60, doi:10.3762/bjoc.6.60

• MALDI-TOF which indicated a mass of 6172.7 [M+Na]+. Very recently a paper was published, reporting the expected LCST properties of the copolymer consisting of N-allylferrocenecarboxamide and N-isopropylacrylamide (poly(NiPAAM/FCN)) [26]. However, in this instance the copolymer was prepared by a

• classical synthesis in an organic solvent. Thus, we were encouraged to prepare a similar copolymer by free radical polymerization in water starting from cyclodextrin complexed vinylferrocene 1 and the water-soluble co-monomer N-isopropylacrylamide 5, the latter in a 20 fold molar excess. The copolymer

• obtained (PVFc-co-P(NiPAAM)) 7 was water-soluble, since the cyclodextrin is not covalently attached to the ferrocene moiety (Scheme 2). The strong complexation was shown by correlations between methyl-β-CD 2 and polyvinylferrocene-co-poly(N-isopropylacrylamide) 7 at 4.16 ppm (cp) + 3.54 ppm (2) and at 4.17