Introduction

Detection of ions is attracting great interest not only in the field of chemistry, but also in biology,pharmacology, and environmentology. Among many methods for detection of ions, the application of fluorescentchemosensors has advantages in terms of sensitivity, cost, response time, and local observation. Although a lot ofstudies about cation- or anion-sensing have been reported, there are few examples of ditopic ion-pair sensing,which can recognize cations and anions at the same time, probably due to difficulty in synthesizing complicatedreceptors and overcoming energetic disadvantage by charge separation. Colorimetric ion-pair receptors can also beapplied to molecular logic gates, elucidation of the biological functions, or salt extraction.

Since fluoride ion is closely relating to environmental problems and diseases such as caries or osteoporosis,fluoride ion sensing has been intensely studied using triarylboranes, which have strong affinity for F-. On theother hand, cation sensors especially for transition metal ions often contain hetero aromatics, e.g., pyridine, azoles,and thiophene, which recognize metal ions by forming complexes.Considering these properties, boranes bearing hetero aromaticscan be used as chemosensors for ion-pairs. During my Ph.D. work,I have achieved the synthesis of boranes shown in Figure 1, whichhave the recognition abilities toward F- and metal ions.

Synthesis, Structures, and Optical Properties of Boranes Bearing Two Thiophenes or Thiophene Derivatives

To avoid oxidation and hydrolysis, ordinary triarylboranes require steric protection groups. However, these groups seem to decrease the binding constant with F- (e. g. Mes3B: KF = 3.3 × 105 M-1 in THF). Introduction ofsmaller aryl groups, such as thienyl groups instead of bulky ones reduces steric repulsion in the generatedfluoroborates, and thus enhancement of the binding constant is expected. Furthermore, high affinity of sulfur atomfor soft metal ions such as Hg2+ or Cd2+ seems to realize the selective recognition of soft metal ions bytriarylboranes bearing thienyl groups. Moreover, a lot of boranes with extended π-conjugation systems often showintense fluorescence. Taking advantages of these merits, dithienylboranes were synthesized aiming at selectivefluorescent chemosensors for soft metal-fluoride ion-pair.

Dithienylborane 1 was synthesized by the reaction of 2-lithiothiophene with MesB(OMe)2 in Et2O (Scheme 1).Benzothiophene derivative 2 (Figure 1) was also synthesized by a similar method. They were stable against airand moisture both in the solid state and in solution, but benzodithiophene derivative 3' bearing a Mes group on theboron atom was slightly unstable and hydrolyzed during purification. Therefore, introduction of a bulkier Tipgroup, instead of the Mes group, was necessary in order to isolate stablecompound 3. X-ray crystallographic analyses of 1 and 2 revealed thatthe central boron plane and two thiophene rings are almost coplanar,which means that π-conjugation is extended to the whole molecularframework. All compounds 1, 2, and 3 exhibitedlongest absorption bands at 328, 362, and 423 nm inCH2Cl2. In addition, 3 showed fluorescence at 472nm (Φ = 0.097) in CH2Cl2, indicating the potentialability for a fluorescent chemosensor.

Ion Sensing Abilities of Boranes Bearing Two Thiophenes or Thiophene Derivatives

To clarify the sensingability for fluoride ion,absorbance changes of 1, 2,and 3 upon addition ofn-Bu4NF (TBAF) wereobserved. The longestabsorption bands of eachcompound disappeared byaddition of TBAF, andnew bands arose with the isosbestic points, respectively (Figure 3). The titration experiment revealed theirassociation constants are much larger than that of Mes3B (2.3 × 106 M-1 for 1, 6.2 × 107 M-1 for 2, and 1.3 × 107M-1 for 3 in CH2Cl2). In addition, the color change of 3, from yellow to colorless, was observed, and it can beuseful for colorimetric sensing of F- by the naked eye. Furthermore, the blue fluorescence of 3 was quenchedupon addition of TBAF, which realizes the use as a fluorescent chemosensor.

On the other hand, metal ion sensing abilities of 1, 2, and 3 were also investigated by the similar method. Among all the investigated metal ions (Ag+, Au+, Cd2+, Cu+, Hg2+, Zn2+), only Hg2+ caused spectral changes of 1,2, and 3. Upon addition of Hg2+, blue shift of the absorption band and quenching the fluorescent emission wereobserved (Figure 4). The spectral changes of 11B NMR of 1 indicated the decomposition of 1 giving boronicacid(s) by addition of Hg2+

Synthesis, Structures, and Optical Properties of Pyridylquinolines Bearing an Arylethynyl Group

Although bipyridyl derivatives have highcomplexation ability for various metal ions,cation sensors with bipyridyl-based receptorshave been reported much less than those withcrown ether- or clixarene-based receptors. It isprobably due to the lack of metal ion selectivityof bipyridyls, which can form complexes with avariety of d- and f-block elements. However,sensors with bipyridyl units have advantagessuch as high sensitivity, unnecessity of chromophore, and facility of the synthesis. In order to employ theseadvantages of bipyridyls, a borane bearing a pyridylquinoline moiety, which is a derivative of bipyridyl, wasdesigned as an ion-pair sensor. Since an ethynyl group works as an effective ligand for soft metal ions, it isexpected that selectivity for the soft metal ion should increase. Furthermore, proximity of both ion receptors willenable the ion-pair recognition due to the stabilization of zwitter ionic complex by intramolecular electrostaticinteraction (Scheme 2).

Ortho-boryl substituted compound 4a was prepared by Sonogashira reaction of 5b with reported terminalalkyne 7 in good yield (Scheme 3). Pyridylquinolines 4b-e were synthesized by a similar method in order toelucidate the effect of functional groups and their substituted position on the optical properties. 4b, 4d, and 4eshowed intense fluorescence in visible region, while 4a and 4c exhibited very weak fluorescence at roomtemperature. The optical properties of 4 were largely changed by the functional group (Table 1). The solventeffects on the emission wavelength and the fluorescence quantum yield of 4e were observed, because of its polar excited state.

Ion-Pair Sensing Abilities of Pyridylquinolines Bearing a Boryl Group

Ion and ion-pair recognition abilities of 4a were investigated.Although complexation of 4a with Ag+, Cd2+, Cu2+, Fe2+, Hg2+,Ni2+, and Zn2+ proceeded, remarkable increase of photoluminescenceintensity was not observed. Addition of halide ionalso hardly affected the photoluminescent property of 4a.However, addition of both Cd2+ and F- caused the observation ofbright green phosphorescence at room temperature. Next, in orderto reveal the selectivity, various metal ions and halide ions wereadded one-by-one, and luminescence spectra were measured. Thebright green phosphorescence was observed only in the case ofCd2+-F- ion-pair, meaning achievement of highly selective ion-pair sensing. These results also mean thepossibility to apply 4a as an AND logic gate. Moreover, recognition ability for Cd2+ was enhanced in the presenceof F-, which means the positive allosteric effect by F-. Then, the effect of an ethynyl group on complexation withsoft metal ions was investigated. The improvement of recognition ability of 4b for a soft metal ion suchas Cd2+ and Ag+ compared to pyridylquinoline 8 was confirmed by UV-vis spectra titration. In addition,4a recognized CN- and exhibited blue fluorescence, which was not observed in the case of halide ion.Summarizing these phenomena, compound 4a can be used both as a cadmium-fluoride recognitionsensor and as a cyanide ion selective anion sensor.

Conclusion

Two classes of ion-pair recognition molecules bearing a tricoordinate borane site and hetero aromatics weresynthesized and their abilities to recognize metal ions and fluoride ion were investigated. Dithienylboranesshowed high recognition ability for fluoride ion, and selective sensing of mercury ion. Benzodithiophenederivative 3 showed absorption and fluorescence in visible region, and hence it has potential ability as afluorescent chemosensor. It was also revealed that cadmium and fluoride ion pair can be detected selectively byappearance of photoluminescence of 4a. This compound exhibited blue fluorescence only by addition of cyanideion, meaning the availability of 4a as a selective cyanide ion sensor.

Figure 1. Molecular designs of ion-pair sensors.

Scheme 1. Synthetic scheme of dithienyloborane 1.

Figure 2. Structures of benzothiophene and benzodithiophwnw derivatives.

Figure 3. Changes in UV-vis absorption of 1 (20uM) in CH3CN upon addition of TBAF.

Figure 4. Changes in UV-vis absorption of 1 (21uM) in CH3CN upon addition of Hg(ClO4)2.

Scheme 2. The mechanism of ion-pair recognition.

Scheme 3. Synthetic schemes of pyridylquinolines bearing an arylethynyl group.

Table1. Optical properties of 4a-e

Figure 5. Changes of photoluminescence spectra of 4a (20μmM) in CH3CN upon addition of TBAF and/or Cd(CIO4)2.

本論文は6章からなり、第1章では序論、第2章では二つのチオフェンもしくはチオフェン誘導体を有するボランの合成、構造、および光学特性、第3章では二つのチオフェンもしくはチオフェン誘導体を有するボランによるイオンセンシング、第4章ではアリールエチニル基を有するピリジルキノリンの合成、構造、および光学特性、第5章ではボリル基を有するピリジルキノリンによるイオン対センシング、そして第6章では結論および今後の展望について述べている。

第1章では、有機化合物を用いたイオンセンシングの原理を代表的な例とともに示し、その応用について述べている。また、カチオンレセプターとして複素芳香環を、アニオンレセプターとして三配位ホウ素を挙げ、その利点と欠点を例とともに示している。これらの考察を踏まえた上で、カチオンとアニオンを同時に検出するイオン対センサーの設計について述べている。イオン対センサーは生体イメージングや無機塩の選択的抽出、分子ロジックゲートなど幅広い応用が期待さている化合物群であることを示す一方で、イオン対センサーの研究例が非常に少ない理由を述べ、その克服への道筋を考案している。協同的イオン対認識の利用によるエネルギー的損失の軽減だけでなく、レセプターと発色団の機能を同一ユニットに組み込むことで合成を容易にするという戦略は非常に斬新だと言える。

第2章では、ホウ素上に二つのチオフェンもしくはチオフェン誘導体を有するボランの合成と、それらの構造、光学特性について述べている。これらが既知化合物からわずか一段階で容易に合成でき、かつ既存の三配位ホウ素化合物に比べ立体保護基が少ないにも関わらず、酸素、水に対して高い安定性を示したことは新たな発見であると言える。また、立体保護基が少ないため分子が高い平面性を有していることもその結晶構造から明らかにしている。さらに、π共役系を拡張することで可視光領域に吸収、発光を示すようになることも見出している。

第3章では、前章で合成した化合物を用いたイオンセンシングについて述べている。紫外可視吸収スペクトルや蛍光スペクトルの変化から、種々の金属イオンの中で水銀イオンのみを選択的に検出できることを明らかにしている。さらに、フッ化物イオンに対して非常に高い会合定数を有することも見出している。これはホウ素周りが立体的に混雑しておらずフルオロボラートの安定性が向上しているためであることを結晶構造から考察しており、より求核性が低くかさも大きいメタノールとさえ錯形成することを見出している。

第4章では、種々のアリールエチニル基を有するピリジルキノリンの合成と、それらの構造、光学特性について述べている。まず合成において、オルトアミノベンズアルデヒドの簡便な合成法と薗頭反応を利用することで、工程数の短縮と収率の向上を達成している。また、目的化合物の結晶構造から、カチオンレセプターがカドミウムや銀イオンに適したサイズであることを示している。目的化合物の紫外可視吸収スペクトルおよび蛍光スペクトルはともに置換基の種類や置換位置によって大きく変化しており、その理由を理論計算による考察とともに述べている。さらに、アミノ基を有する化合物はソルバトクロミズムを示すことを見出している。

第5章では、前章で合成した化合物のうち、ボリル基を有する化合物を用いたイオンセンシングおよびイオン対センシングについて述べている。エチニル基のオルト位にボリル基を導入した化合物はほとんど蛍光、りん光を示さず、種々の金属イオンもしくはハロゲン化物イオンの添加による発光効率の向上もほとんど見られなかったが、カドミウムイオンとフッ化物イオンを同時に添加した場合に非常に強い緑色のりん光を発することを見出している。すなわち、カドミウムイオンおよびフッ化物イオンの選択的イオン対センシングを達成している。また、この化合物の異性体を用いた同様の検討を行い、結果を比較することで分子設計の妥当性を証明している。さらに、シアン化物イオンを添加することで青色の蛍光を示すことも見出しており、シアン化物イオン選択的センサーとして用いることも可能であると述べている。

以上の研究成果は、小分子による選択的イオン対センシングを初めて達成しただけでなく、イオン対センサーの分子設計における指針を示したという意味で非常に意義深いものであるといえる。これらの知見はイオンセンシングの分野の発展に大きく寄与し、イオン対が関与する様々な現象の解明に大きな貢献をするものと評価される。

なお、本論文は川島隆幸・小林潤司との共同研究であるが、論文提出者が主体となって実験および解析を行ったものであり、論文提出者の寄与が充分であると判断する。

したがって、博士(理学)の学位を授与できるものと認める。