JP3905244B2 - Nucleotide responsive hydrogel - Google Patents
Nucleotide responsive hydrogel Download PDFInfo
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- JP3905244B2 JP3905244B2 JP11759199A JP11759199A JP3905244B2 JP 3905244 B2 JP3905244 B2 JP 3905244B2 JP 11759199 A JP11759199 A JP 11759199A JP 11759199 A JP11759199 A JP 11759199A JP 3905244 B2 JP3905244 B2 JP 3905244B2
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- C—CHEMISTRY; METALLURGY
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- C08F230/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal
- C08F230/04—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal containing a metal
- C08F230/06—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal containing a metal containing boron
Description
【０００１】
【発明の属する技術分野】
本発明は、ＡＭＰやＡＴＰのようなヌクレオチド類に応答して膨潤したり収縮する新規な機能性ゲルに関する。
【０００２】
【従来の技術とその課題】
近年、各種の外部刺激に応答して、膨潤・収縮現象を示す機能性ゲル（インテリジェントゲル）に関する研究が行われている。このようなゲルは、ドラッグデリバリーシステム（ＤＤＳ：薬物送達システム）、ケミカルアクチュエーター（例えば、人工筋肉）、物質分離など多岐の分野にわたる応用の可能性を有している。
【０００３】
これまでに知られている機能性ゲルは、専ら、温度、電場、ｐＨ等を外部刺激とするものであり、特定の物質に直接応答して膨潤・収縮するものは少ない。特に生体内に存在する物質、例えばＡＭＰ（アデノシン一リン酸：アデニル酸）やＡＴＰ（アデノシン三リン酸）のようなヌクレオチド類に応答するゲルが得られれば、上記のごとき分野において一層の応用展開が期待されが、そのようなゲルは殆ど見当たらない。
本発明の目的は、ヌクレオチド類に応答することのできる新しいタイプの機能性ゲルを提供することにある。
【０００４】
【課題を解決するための手段】
本発明者は、ボロン酸ユニットとカチオンユニットを有する架橋高分子から成るヒドロゲルを合成し、これが特定の構造を持つヌクレオチド類に対して選択的に膨潤・収縮挙動を示すことを見出し上記の目的を達成したものである。
【０００５】
すなわち、本発明は、ビニル基を有するボロン酸モノマーとビニル基を有するカチオンモノマーとを架橋剤の存在下に共重合して得られるヒドロゲルから成ることを特徴とするヌクレオチド応答性ヒドロゲルを提供する。
【０００６】
本発明のヌクレオチド応答性ヒドロゲルの好ましい具体例に従えば、ボロン酸モノマーはフェニルボロン酸から選ばれ、カチオンモノマーのカチオンは第４級アンモニウムイオンであり、且つ、架橋剤がアクリレート系化合物から選ばれる。さらに、本発明のヌクレオチド応答性ヒドロゲルの特に好ましい具体例においては、ボロン酸モノマーは、アクリルアミドフェニルボロン酸、ビニルフェニルボロン酸およびアクリロイロキシフェニルボロン酸から成る群より選ばれ、カチオンモノマーは、（アクリロアミドプロピル）トリメチルアンモニウムクロライド、アクリロイロキシエチルトリメチルアンモニウムクロライドおよびビニルベンジルトリメチルアンモニウムクロライドから選ばれ、且つ、架橋剤は、メチレンビスアクリロアミド、エチレングリコールジアクリレート、ジエチレングリコールジメタクリレートおよびトリメチロールプロパントリアクリレートから成る群より選ばれる。
【０００７】
【発明の実施の形態】
図１は、本発明のゲルの合成および作用を模式的に示すものである。すなわち、ビニル基を有するボロン酸モノマー（図１中のＡ）とビニル基を有するカチオンモノマー（Ｂ）とを架橋剤（Ｃ）の存在下に共重合させることにより、ボロン酸ユニット（Ｂ（ＯＨ）２）およびカチオンユニットを有する架橋高分子から成るゲル（Ｄ）が得られる。ここでＡＴＰのようなヌクレオチド類が存在すると、高分子中のボロン酸基とヌクレオチド中の糖部分のジオール（シス−ジオール基）とがエステル結合するとともに、高分子中のカチオンがヌクレオチド類のアニオン部位と結合し（図１の（Ｅ）参照）、高分子中のボロン酸とカチオンの比率、およびヌクレオチド類の電荷のバランスに応じて高分子ゲルの荷電状態が変化し、これに従ってゲルの膨潤または収縮が起こることになる。
【０００８】
このように、本発明のゲルが応答するヌクレオチド類とは、有機塩基と糖がグリコシド結合した化合物であって、糖部分にシス−ジオール基を有するとともに、イオン（アニオン）性部位を含む化合物を指称する。すなわち、後記の実施例からも明らかなように、本発明のゲルはＡＭＰやＡＴＰのようなヌクレオチドが存在すると膨潤したり収縮し、さらには、グアニル酸、シチジル酸、ウリジル酸、イノシン酸のようなヌクレオチドまたはその類縁化合物に応答する。しかしながら、Ａｄ（アデノシン）のようなシス−ジオール基を有するがアニオン部位を含まないものには応答せず、さらに、ＤＡＭＰ（デオキシアデノシン一リン酸）のようなアニオン部位（リン酸イオン）を含むがシス−ジオール基を有しないものにも応答しない。
【０００９】
本発明のゲルを形成するためのビニル基を有するボロン酸モノマーは、特に限定されるものではないが、安定であり合成が容易であるということから、フェニルボロン酸系化合物が好ましい。特に好適なフェニルボロン酸の例は、図２に示すようなアクリルアミドフェニルボロン酸〔化１〕、ビニルフェニルボロン酸〔化２〕、およびアクリロイロキシフェニルボロン酸〔化３〕である。
【００１０】
また、本発明のゲルを調製するのに用いられるビニル基を有するカチオンモノマーも特に限定されるものではないが、安定なカチオンを与える点から第４級アンモニウムイオンを含む化合物が好ましい。特に好適なカチオンモノマーの例は、図３に示すように、（アクリロアミドプロピル）トリメチルアンモニウムクロライド〔化４〕、アクリロイロキシエチルトリメチルアンモニウムクロライド〔化５〕およびビニルベンジルトリメチルアンモニウムクロライド〔化６〕である。
【００１１】
本発明のゲルは、以上のようなビニル基を有するボロン酸モノマーとビニル基を有するカチオンモノマーとを架橋剤の存在下に共重合することによって得られる。架橋剤は、フェニルボロン酸モノマーとカチオンモノマーとの共重合ポリマー鎖間を架橋して三次元化することによりゲルを形成させるものであり、少なくとも２個のビニル基を有する化合物から選ばれる。架橋剤として好ましいのは反応性が高いことからアクレート系化合物であり、特に好適な架橋剤の例は図４に示すようにメチレンビスアクリルアミド〔化７〕、エチレングリコールジアクリレート〔化８〕、ジエチレングリコールジメタクリレート〔化９〕およびトリメチロールプロパントリアクリレート〔化１０〕である。
【００１２】
ゲルを形成するための共重合反応は、一般に、モノマー原料（ボロン酸モノマーおよびカチオンモノマー）に対し、０．５〜２モル％程度の架橋剤および重合開始剤を添加し、水または水／メタノール混合溶媒のような溶媒中で室温〜７０℃の温度下で２０〜３０時間行い、重合が徐々に進行してゲルが形成されるようにする。重合開始剤は、特に限定されるものではなく、熱または光により分解し遊離基またはイオンを生成して重合を開始させ得る化合物として知られているものから選択して用いることができる。好適な重合開始剤の例は図４に〔化１１〕として示す化合物である。
【００１３】
本発明のヒドロゲルは、ゲルを構成する共重合体におけるボロン酸ユニットとカチオンユニットの組成比を変えることにより電荷（正の電荷）を変化させ、これによりヌクレオチド類に対する応答特性を制御することができるという特徴を有する。かくして、本発明のゲルは、特定のヌクレオチド類に応答して膨潤または収縮することができ、さらに、その膨潤・収縮の程度を制御することも容易であるので、この性質を利用して、例えば、ヌクレオチド類の存否の環境下に応じて薬剤の放出を制御するＤＤＳ（ドラッグデリバリーシステム）、ヌクレオチド類の分離システム、あるいはケミカルアクチュエーターなどに応用される可能性を有している。
【００１４】
【実施例】
以下に本発明のゲルの特徴をさらに明らかにするため実施例を示すが、本発明はこの実施例によって限定されるものではない。
実施例１：高分子ゲルの合成
ボロン酸モノマーとして３−アクリルアミドフェニルボロン酸（図２の〔化１〕）、カチオンモノマーとして（３−アクリルアミドプロピル）トリメチルアンモニウムクロライド（Aldrich社製）（図３の〔化４〕）、架橋剤としてメチレンビスアクリルアミド（和光純薬製）（図４の〔化７〕）をそれぞれ用いた。３−アクリルアミドフェニルボロン酸は、３−アミノフェニルボロン酸１５５ｍｇと塩化アクリロイル１８０ｍｇを炭酸水素ナトリウム１６８ｍｇの存在下、水１０ｃｍ３およびテトラヒドロフラン５ｃｍ３からなる混合溶媒中０℃で１時間反応させ、水から再結晶により精製することにより合成した。
【００１５】
ボロン酸モノマーとカチオンモノマー（合わせて４００μｍｏｌ：実施例２で示すように仕込み比を変化させた）および架橋剤４μｍｏｌを水２００ｍｍ３とメタノール１００ｍｍ３から成る混合溶媒に溶解し、重合開始剤（図４の〔化１１〕）５μｍｏｌを添加後、５０℃で２４時間反応させた。得られたゲルを多量の水中に１日以上浸して、未反応のモノマー等の不純物を除去した後、真空乾燥機で乾燥した。元素分析（炭素および窒素）により、合成したゲル中のカチオンユニットとボロン酸ユニットの組成比が、モノマーの仕込み比にほぼ対応することを確認した。
【００１６】
実施例２：ゲルの膨潤試験
実施例１に示すように、カチオンモノマーとボロン酸モノマーの仕込み比（モル比）の異なる５種類のゲルを合成した。種々の濃度のヌクレオチド類（ＡＭＰ、ＡＴＰ等、図５参照）を含む水溶液（ｐＨは５０ｍＭ Ｎａ２ＣＯ３＋５０ｍＭ ＮａＨＣＯ３により１０．２に設定した）に乾燥ゲルを投入し、２４時間放置後の膨潤度を測定した。その結果を図６〜図１０に示す。
【００１７】
カチオン：ボロン酸＝１：１のゲルは、ヌクレオチド類を含まない水溶液中で、比較的収縮した状態にある。これは、ゲル中のカチオン単位の正電荷とボロン酸単位の負電荷がバランスし、電気的に中性のゲルになっているためであると理解される。これにＡＭＰやＡＴＰを添加すると、ボロン酸基とシス−ジオール部位との相互作用によりヌクレオチド類がゲルに結合し、ゲルが負電荷を帯びるため膨潤が起こる（図６参照）。
【００１８】
カチオン：ボロン酸＝２：１のゲルは、当初膨潤状態にあるが、ＡＭＰやＡＴＰを加えると収縮する。さらに、高濃度のヌクレオチド類の存在下ではゲルは再び膨潤する。これは、ヌクレオチド類の濃度の増加とともにゲルの荷電状態が正→中性→負と変化するためであると理解される（図７参照）。
【００１９】
カチオン：ボロン酸＝３：１のゲルは、ＡＭＰとＡＴＰに対する応答挙動に大きな違いは見られなかった（図８参照）。しかし、ボロン酸の含有量を更に減らす（例えば、カチオン：ボロン酸＝９：１）と、ＡＭＰ中では収縮が起こらず、ＡＴＰ中でのみ収縮するという挙動が見られた。また、ボロン酸含有量の低いゲルでは、高濃度のヌクレオチド類中でも再膨潤は起こらなかった。これは、すべてのボロン酸基がヌクレオチド類と結合しても、電荷の逆転が起こらないためであると理解される（図１０参照）。
【００２０】
カチオン：ボロン酸＝５：１のゲルのＤＡＭＰおよびＡｄに対する応答を調べたが、これらの溶液中では膨潤状態に変化は見られなかった（図９参照）。このことから、ゲルの膨潤・収縮にはリン酸基およびシス−ジオール部位の存在が不可欠であることが示された。
【００２１】
以上のように、カチオンモノマーとボロン酸モノマーおよび架橋剤から合成される本発明の高分子ヒドロゲルは、溶液中のヌクレオチド類の濃度に応答して膨潤・収縮変化を示すこと、そして、その応答特性はゲル中のカチオンユニットとボロン酸ユニットの組成比を変化させることにより、コントロール可能であることが明らかになった。
【図面の簡単な説明】
【図１】本発明のゲルの合成および作用を模式的に示すものである。
【図２】本発明のゲルを合成するのに用いられるボロン酸モノマーの好適な例の化学構造式を示す。
【図３】本発明のゲルを合成するのに用いられるカチオンモノマーの好適な例の化学構造式を示す。
【図４】本発明のゲルを合成するのに用いられる架橋剤および重合開始剤の好適な例の化学構造式を示す。
【図５】本発明の実施例で用いたヌクレオチド類の化学構造式を示す。
【図６】本発明に従うゲルの１例であり、カチオン：ボロン酸の比が１：１のゲルの膨潤・収縮挙動を示すグラフである。
【図７】本発明に従うゲルの１例であり、カチオン：ボロン酸の比が２：１のゲルの膨潤・収縮挙動を示すグラフである。
【図８】本発明に従うゲルの１例であり、カチオン：ボロン酸の比が３：１のゲルの膨潤・収縮挙動を示すグラフである。
【図９】本発明に従うゲルの１例であり、カチオン：ボロン酸の比が５：１のゲルの膨潤・収縮挙動を示すグラフである。
【図１０】本発明に従うゲルの１例であり、カチオン：ボロン酸の比が９：１のゲルの膨潤・収縮挙動を示すグラフである。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a novel functional gel that swells and contracts in response to nucleotides such as AMP and ATP.
[0002]
[Prior art and its problems]
In recent years, research has been conducted on functional gels (intelligent gels) that exhibit swelling and shrinkage in response to various external stimuli. Such gels have potential applications in a wide variety of fields, such as drug delivery systems (DDS: drug delivery systems), chemical actuators (eg, artificial muscles), and material separation.
[0003]
The functional gels known so far exclusively use temperature, electric field, pH, and the like as external stimuli, and few swell and shrink in direct response to specific substances. If a gel that responds to nucleotides such as AMP (adenosine monophosphate: adenylic acid) and ATP (adenosine triphosphate) is obtained, it will be further applied in the above fields. Is expected, but few such gels are found.
It is an object of the present invention to provide a new type of functional gel that can respond to nucleotides.
[0004]
[Means for Solving the Problems]
The present inventor has synthesized a hydrogel comprising a crosslinked polymer having a boronic acid unit and a cation unit, and found that this selectively exhibits swelling / contraction behavior with respect to nucleotides having a specific structure. Achieved.
[0005]
That is, the present invention provides a nucleotide-responsive hydrogel comprising a hydrogel obtained by copolymerizing a boronic acid monomer having a vinyl group and a cationic monomer having a vinyl group in the presence of a crosslinking agent.
[0006]
According to a preferred embodiment of the nucleotide-responsive hydrogel of the present invention, the boronic acid monomer is selected from phenylboronic acid, the cation of the cationic monomer is a quaternary ammonium ion, and the crosslinking agent is selected from an acrylate compound. . Further, in a particularly preferred embodiment of the nucleotide-responsive hydrogel of the present invention, the boronic acid monomer is selected from the group consisting of acrylamidophenylboronic acid, vinylphenylboronic acid and acryloyloxyphenylboronic acid, and the cationic monomer is ( Acrylamidopropyl) trimethylammonium chloride, acryloyloxyethyltrimethylammonium chloride and vinylbenzyltrimethylammonium chloride and the cross-linking agent is methylenebisacryloamide, ethylene glycol diacrylate, diethylene glycol dimethacrylate and trimethylolpropane Selected from the group consisting of triacrylates.
[0007]
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 schematically shows the synthesis and action of the gel of the present invention. That is, a boronic acid unit (B (OH) is obtained by copolymerizing a boronic acid monomer having a vinyl group (A in FIG. 1) and a cationic monomer having a vinyl group (B) in the presence of a crosslinking agent (C). 2 ) and a crosslinked polymer having a cationic unit (D). When nucleotides such as ATP are present, the boronic acid group in the polymer and the diol (cis-diol group) of the sugar moiety in the nucleotide are ester-bonded, and the cation in the polymer is an anion of the nucleotide. The charge state of the polymer gel changes according to the balance between the boronic acid and cation ratio in the polymer and the charge balance of the nucleotides, and the gel swells accordingly. Or contraction will occur.
[0008]
Thus, nucleotides to which the gel of the present invention responds are compounds in which an organic base and a sugar are glycoside-bonded, and a compound having a cis-diol group in the sugar moiety and an ionic (anionic) site. Refer to it. That is, as will be apparent from the examples described later, the gel of the present invention swells and shrinks in the presence of nucleotides such as AMP and ATP, and further, such as guanylic acid, cytidylic acid, uridylic acid, and inosinic acid. It responds to new nucleotides or related compounds. However, it does not respond to those having a cis-diol group such as Ad (adenosine) but not including an anion site, and further includes an anion site (phosphate ion) such as DAMP (deoxyadenosine monophosphate). Also does not respond to those without a cis-diol group.
[0009]
The boronic acid monomer having a vinyl group for forming the gel of the present invention is not particularly limited, but a phenylboronic acid compound is preferable because it is stable and easy to synthesize. Examples of particularly preferred phenylboronic acids are acrylamide phenylboronic acid [Chemical Formula 1], vinylphenylboronic acid [Chemical Formula 2], and acryloyloxyphenylboronic acid [Chemical Formula 3] as shown in FIG.
[0010]
Further, the cationic monomer having a vinyl group used for preparing the gel of the present invention is not particularly limited, but a compound containing a quaternary ammonium ion is preferable from the viewpoint of giving a stable cation. Examples of particularly suitable cationic monomers include (acrylamidopropyl) trimethylammonium chloride [Chemical Formula 4], acryloyloxyethyltrimethylammonium chloride [Chemical Formula 5] and vinylbenzyltrimethylammonium chloride [Chemical Formula 6] as shown in FIG. ].
[0011]
The gel of the present invention can be obtained by copolymerizing the above boronic acid monomer having a vinyl group and a cationic monomer having a vinyl group in the presence of a crosslinking agent. The cross-linking agent is one that forms a gel by cross-linking three-dimensionally between the copolymer polymer chains of a phenylboronic acid monomer and a cationic monomer, and is selected from compounds having at least two vinyl groups. Preferred as the cross-linking agent is an acrylate compound because of its high reactivity. Examples of particularly suitable cross-linking agents are methylene bisacrylamide [7], ethylene glycol diacrylate [8], diethylene glycol as shown in FIG. Dimethacrylate [Chemical Formula 9] and trimethylolpropane triacrylate [Chemical Formula 10].
[0012]
The copolymerization reaction for forming a gel is generally performed by adding about 0.5 to 2 mol% of a crosslinking agent and a polymerization initiator to monomer raw materials (boronic acid monomer and cationic monomer), and water or water / methanol. The reaction is performed in a solvent such as a mixed solvent at a temperature of room temperature to 70 ° C. for 20 to 30 hours so that the polymerization proceeds gradually to form a gel. The polymerization initiator is not particularly limited, and can be selected from those known as compounds that can be decomposed by heat or light to generate free radicals or ions to initiate polymerization. An example of a suitable polymerization initiator is a compound shown as [Chemical Formula 11] in FIG.
[0013]
The hydrogel of the present invention can change the charge (positive charge) by changing the composition ratio of the boronic acid unit and the cation unit in the copolymer constituting the gel, thereby controlling the response characteristics to nucleotides. It has the characteristics. Thus, the gel of the present invention can swell or shrink in response to specific nucleotides, and furthermore, it is easy to control the degree of swelling / shrinkage. It has the potential to be applied to a DDS (drug delivery system) that controls the release of a drug according to the presence or absence of nucleotides, a nucleotide separation system, or a chemical actuator.
[0014]
【Example】
Examples are given below to further clarify the characteristics of the gel of the present invention, but the present invention is not limited to these examples.
Example 1: Synthesis of polymer gel 3-acrylamidophenylboronic acid ([Chemical Formula 1] in FIG. 2) as a boronic acid monomer and (3-acrylamidopropyl) trimethylammonium chloride (Aldrich) as a cationic monomer ([Chemical Formula 4] in FIG. 3) and methylenebisacrylamide (manufactured by Wako Pure Chemical Industries, Ltd.) ([Chemical Formula 7] in FIG. 4) were used as the crosslinking agent. 3-acrylamide phenylboronic acid, 3-amino phenyl boronic acid 155mg and the presence of the acryloyl chloride 180 mg 168 mg sodium bicarbonate, with
[0015]
Boronic acid monomer and a cationic monomer: a and crosslinking agent 4Myumol (combined 400μmol is not a changed charge ratio as shown in Example 2) was dissolved in a mixed solvent consisting of water 200 mm 3 and methanol 100 mm 3, the polymerization initiator (Figure 4 [Chemical 11]) After adding 5 μmol, the mixture was reacted at 50 ° C. for 24 hours. The obtained gel was immersed in a large amount of water for 1 day or longer to remove impurities such as unreacted monomers and then dried with a vacuum dryer. By elemental analysis (carbon and nitrogen), it was confirmed that the composition ratio of the cation unit and the boronic acid unit in the synthesized gel substantially corresponded to the monomer charge ratio.
[0016]
Example 2: Gel swelling test As shown in Example 1, five types of gels having different charging ratios (molar ratios) of a cationic monomer and a boronic acid monomer were synthesized. The dried gel was put into an aqueous solution (pH was set at 10.2 with 50 mM Na 2 CO 3 +50 mM NaHCO 3 ) containing various concentrations of nucleotides (AMP, ATP, etc., see FIG. 5), and left for 24 hours. The degree of swelling was measured. The results are shown in FIGS.
[0017]
The gel of cation: boronic acid = 1: 1 is in a relatively contracted state in an aqueous solution containing no nucleotides. It is understood that this is because the positive charge of the cation unit in the gel and the negative charge of the boronic acid unit are balanced to form an electrically neutral gel. When AMP or ATP is added thereto, nucleotides bind to the gel due to the interaction between the boronic acid group and the cis-diol site, and the gel is negatively charged, so that swelling occurs (see FIG. 6).
[0018]
The gel of cation: boronic acid = 2: 1 is initially in a swollen state, but shrinks when AMP or ATP is added. Furthermore, the gel swells again in the presence of high concentrations of nucleotides. This is understood to be because the charge state of the gel changes from positive to neutral to negative as the concentration of nucleotides increases (see FIG. 7).
[0019]
The cation: boronic acid = 3: 1 gel showed no significant difference in response behavior to AMP and ATP (see FIG. 8). However, when the boronic acid content was further reduced (for example, cation: boronic acid = 9: 1), there was a behavior in which contraction did not occur in AMP and contracted only in ATP. Further, in the gel having a low boronic acid content, re-swelling did not occur even in a high concentration of nucleotides. It is understood that this is because even when all boronic acid groups are bonded to nucleotides, charge reversal does not occur (see FIG. 10).
[0020]
The response of the gel of cation: boronic acid = 5: 1 to DAMP and Ad was examined, but no change was observed in the swollen state in these solutions (see FIG. 9). This indicates that the presence of phosphate groups and cis-diol sites is indispensable for gel swelling and shrinkage.
[0021]
As described above, the polymer hydrogel of the present invention synthesized from a cation monomer, a boronic acid monomer and a crosslinking agent exhibits swelling / shrinkage changes in response to the concentration of nucleotides in the solution, and its response characteristics. It was revealed that can be controlled by changing the composition ratio of cation units and boronic acid units in the gel.
[Brief description of the drawings]
FIG. 1 schematically shows the synthesis and action of a gel of the present invention.
FIG. 2 shows the chemical structure of a preferred example of a boronic acid monomer used to synthesize the gel of the present invention.
FIG. 3 shows the chemical structure of a preferred example of a cationic monomer used to synthesize the gel of the present invention.
FIG. 4 shows a chemical structural formula of a suitable example of a crosslinking agent and a polymerization initiator used to synthesize the gel of the present invention.
FIG. 5 shows a chemical structural formula of nucleotides used in Examples of the present invention.
FIG. 6 is a graph showing the swelling / shrinking behavior of a gel according to the present invention, which has a cation: boronic acid ratio of 1: 1.
FIG. 7 is a graph showing the swelling / contraction behavior of a gel according to the present invention, which is a gel having a cation: boronic acid ratio of 2: 1.
FIG. 8 is a graph showing the swelling / shrinking behavior of a gel according to the present invention, which is a gel having a cation: boronic acid ratio of 3: 1.
FIG. 9 is a graph showing the swelling / shrinking behavior of a gel according to the present invention, which is a gel having a cation: boronic acid ratio of 5: 1.
FIG. 10 is a graph showing the swelling / contraction behavior of a gel according to the present invention, which is a gel having a cation: boronic acid ratio of 9: 1.
Claims (3)
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| JP11759199A JP3905244B2 (en) | 1999-04-26 | 1999-04-26 | Nucleotide responsive hydrogel |
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| CN103252218A (en) * | 2013-04-26 | 2013-08-21 | 浙江工业大学 | Hybrid overall crystal gel medium and preparation method thereof |
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| JP4938252B2 (en) * | 2005-05-27 | 2012-05-23 | 一般財団法人川村理化学研究所 | Sugar chain recognition sensor using borate group-containing (meth) acrylate polymer |
| JP4694922B2 (en) * | 2005-09-07 | 2011-06-08 | 財団法人川村理化学研究所 | Borate group-containing hydrogel and method for producing the same |
| JP5040176B2 (en) * | 2006-05-30 | 2012-10-03 | 富士ゼロックス株式会社 | Microchannel device |
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