Microfluidic Mixing of Polyamine with Acrolein Enables the Detection of the [4+4] Polymerization of Intermediary Unsaturated Imines: The Properties of a Cytotoxic 1,5-Diazacyclooctane Hydrogel

Ambara R. Pradipta; Ayumi Tsutsui; Akihiro Ogura; Shinya Hanashima; Yoshiki Yamaguchi; Almira Kurbangalieva; Katsunori Tanaka

doi:10.1055/s-0034-1378634

Synlett, Inhaltsverzeichnis

Synlett 2014; 25(17): 2442-2446
DOI: 10.1055/s-0034-1378634

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Microfluidic Mixing of Polyamine with Acrolein Enables the Detection of the [4+4] Polymerization of Intermediary Unsaturated Imines: The Properties of a Cytotoxic 1,5-Diazacyclooctane Hydrogel

Ambara R. Pradipta

^aBiofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan Fax: +81(48)4679379 eMail: kotzenori@riken.jp

,

Ayumi Tsutsui

^aBiofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan Fax: +81(48)4679379 eMail: kotzenori@riken.jp

,

Akihiro Ogura

^aBiofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan Fax: +81(48)4679379 eMail: kotzenori@riken.jp

,

Shinya Hanashima

^bStructural Glycobiology Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan

,

Yoshiki Yamaguchi

^bStructural Glycobiology Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, RIKEN Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan

,

Almira Kurbangalieva

^cBiofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russian Federation

,

Katsunori Tanaka*

^aBiofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan Fax: +81(48)4679379 eMail: kotzenori@riken.jp

^cBiofunctional Chemistry Laboratory, A. Butlerov Institute of Chemistry, Kazan Federal University, 18 Kremlyovskaya Street, Kazan 420008, Russian Federation

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Abstract

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Abstract

The [4+4] polymerization of an unsaturated imine, generated from the condensation of a polyamine and excess acrolein, was investigated. The polyamine was added by micropipet to acrolein, immediately yielding a mixture of the immiscible polymeric material. Microfluidic mixing was used to gradually form the soluble diazacyclooctane polymers. The polymerization reaction ultimately gave an insoluble cationic hydrogel that adhered strongly to anionic compounds on cell surfaces, including sialoglycan, and displayed a high cytotoxicity.

Key words

acrolein - N-alkyl unsaturated imine - cytotoxicity - 1,5-diazacyclooctane - hydrogel - microreactor - polyamine - [4+4] polymerization - sialoglycan

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Referenzen

Reference and Notes

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14 Comet X-01 micromixer: http://homepage3.nifty.com/techno-applications/ or E-mail: yukio-matsubara@nifty.com.
15 The [4+4] Polymerization of the Spermine/Polyamine-Derived Diimine under Microfluidic Conditions A solution of spermine (150 mg, 741 μmol) in PBS (2.0 mL) was injected, in advance, into the micromixer, a Comet X-01, using a syringe pump at a flow rate of 1.5 mL/min. A solution of acrolein (100 μL, 741 μmol) dissolved in PBS (2.0 mL) was then injected into the micromixer using another syringe pump at a same flow rate. The reaction was mixed at r.t. The reaction mixture was allowed to flow at r.t. for a few seconds through a Teflon tube reactor (Φ = 1.0 mm, l = 3.0 m) and was then introduced into a flask and left for 2 d at this temperature. A deuterated PBS buffer was used in the procedure described above to analyze the polymerization reaction over time using NMR methods. The PBS buffer was freeze-dried twice from D₂O prior to use.
16 When the reaction mixture was eluted from the microfluidic apparatus, a complex mixture of smaller polymerized diazacyclooctane fragments with molecular weights of 1,000–3,0000 were detected.
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19 Interactions between the 1,5-Diazacyclooctane Hydrogel and Sialoglycan 2 The 1,5-diazaoctane hydrogel 1aa (2.0 mg) was treated with an aqueous solution of sialoglycan 2 (10^–5 M), and the mixture was allowed to incubate for 3.5 h at r.t. The gel was washed with H₂O (3×) and further soaked in H₂O for 1 h. The resulting gel was analyzed by OLYMPUS fluorescence microscopy, IX71-23FL/DIC.