This thesis describes metal arrangement abilities and aggregation behaviors of rigid macrocycles with two inward phenanthroline coordination sites directed toward the construction of novel supramolecular architectures containing multiple metal ions. The thesis is composed of four chapters as summarized below.

[Chapter 1: General Introduction]

Constrained nanoscopic spaces surrounded by multiple functional sites have specific chemical environments to provide a platform for molecular recognition and transformation. Macrocyclic compounds can be appropriately designed so as to have a variety of functional groups directing inward for their cooperative characteristics within the inner spaces. Furthermore, when these macrocycles are stacked in a face-to-face manner, they would form a laminate structure with a multifunctional channel (Figure 1).

In this work, novel rigid macrocycles have been constructed which possess two chemically-equivalent metal binding sites within their cavity. These macrocyclic ligands form various dinuclear metal complexes (Figure 1 left). Since metal ions have specific chemical and physical properties with regard to geometrical and dynamic coordination behaviors, oxidation-reduction, magnetism, and conductivity, such endohedral metallo-macrocycles would provide functional inner spaces based on the kind of metals and how they stay inside. Furthermore, self-assembly of these macrocycles is expected to lead to the metal-assembled, higher-order structures. For example, layer-by-layer accumulation of metallo-macrocycles would result in the formation of polymetallo-nano-tubes (Figure 1 right), which may exhibit metal clustered-centered functions in the micron-scale range.

[Chapter 2: Homo and Heterodinuclear Metal Arrangements within a Bisphenanthroline Macrocycle]

A macrocyclic ligand 1 (Figure 2a left), which possesses a rigid aromatic cyclic skeleton and two inward phenanthroline coordination sites, was newly designed and synthesized aiming at well-defined metal arrangement within the cavity, and its metal complexation behaviors were examined.

Firstly, the addition of Zn(CF3CO2)2 (2.0 eq) to 1 in CDCl3/CD3CN = 10/1 resulted in the formation of a dinuclear Zn(II) complex. In 1H NMR titration study, a complex with C2v symmetry was firstly observed, followed by a complex with D2h symmetry. The signals of protons around phenanthroline coordination sites showed down-field shift, which indicates metal coordination of phenanthroline (Figure 2b-2). Thus, it is suggested that a D2h dinuclear Zn(II) complex, in which two Zn(II) ions are bound to the phenanthroline coordination sites, is formed via a C2v mononuclear Zn(II) complex. This dinuclear Zn(II)-macrocycle formation was also supported by electrospray ionization-time-of-flight (ESI-TOF) MS (m/z 1619.4 as [Zn21(CF3CO2)4 + Na]+) and the single-crystal X-ray analysis (Figure 2c). In the crystal structure, it turned out that two Zn(II) ions are bound by the phenanthroline site and two CF3CO2 - ions to result in a tetrahedral coordination geometry.

Next, Cu(I) ions, in stead of Zn(II) ions, which also prefer a tetrahedral coordination geometry, were examined for macrocycle 1. Upon the addition of Cu(CH3CN)4BF4 (2.3 eq) to 1 in CDCl3/CD3CN = 10/1, the 1H NMR signals of phenanthroline protons showed down-field shift (Figure 2b-3). The formation of dinuclear Cu(I)-macrocycle was also confirmed by ESI-TOF MS (m/z 1268.4 as [Cu21BF4(CH3CN)]+).

Based on these results, heterodinuclear complexation was then examined. The addition of both Zn(CF3CO2)2 (1.0 eq) and Cu(CH3CN)4BF4 (1.0 eq) to 1 in CDCl3/CD3CN = 10/1 resulted in the formation of a heterodinuclear Zn(II)-Cu(I)-complex in which each metal ion binds to one of the two chemically-equivalent phenanthroline sites. Its 1H NMR spectrum showed a lower symmetrical pattern compared with those of homodinuclear Zn(II)- and Cu(I)-macrocycles, that is, two sets of signals for phenanthroline protons were observed (Figure 2b-4). ESI-TOF MS measurement also supported the formation of this heterodinuclear Zn(II)-Cu(I)-macrocycle (m/z = 1408.1 as [CuZn1(CF3CO2)2(CH3CN)]+). This heterodinuclear Zn(II)-Cu(I) complex was formed with high efficiency (> 90%). Evaluation of binding constants of stepwise metal complexation well explained this high selectivity of the heterodinuclear complex formation due to the relatively low stability of the homodinuclear Cu(I) complex. Thus, a homodinuclear Zn(II)-macrocycle, a homodinuclear Cu(I)-macrocycle, and a heterodinuclear Zn(II)-Cu(I)-macrocycle were efficiently formed using macrocycle 1 with two chemically-equivalent metal binding sites within the molecule (Figure 2a).

[Chapter 3: Aggregation Behaviors of Bisphenanthroline Macrocycles]

With a view to the aggregation of macrocycles, macrocycle 2, which has the same cyclic skeleton as 1 and six long alkyl side chains (Figure 3a left), was synthesized. In general, compounds with a rigid aromatic core and long alkyl chains tend to stack in a low polar solvent due to their different affinities to the solvent. Thus, macrocycle 2 with these peripheral side chains was expected to form aggregates in a solvent-dependent manner.

In fact, macrocycle 2 was found to stack in low polar solvents such as cyclohexane to form fibrous structures. The 1H NMR spectrum of 2 in cyclohexane-d12 was extremely broadened whereas that of 2 in CDCl3 showed sharp signals. This suggests that self-aggregates are formed in the low polar cyclohexane (Figure 3b). Furthermore, atomic force microscope (AFM) measurements of mica surfaces, on which a cyclohexane solution of 2 was dropped and dried, gave fibrous images with up to micrometer-scale length and a height of about 6 nm corresponding to the diameter of 2 (Figure 3a right). This suggests the face-to-face self-stacking of 2.

For the purpose of construction of supramolecular structures with multiple metal ions, aggregation behaviors of mixtures containing 2 and metal ions were examined. For example, aggregation of the complex composed of 2 and ZnCl2 in a mixture of CHCl3-cyclohexane was suggested by 1H NMR signal broadening. AFM measurements on the mica surface eventually revealed that the aggregation is due to the formation of particle-like structures.

Meanwhile, fibrous structures with up to micrometer-scale length were observed by AFM and transmission electron microscope (TEM) measurements of a CHCl3 solution containing 2 and FeCl3 (Figure 4a). To estimate the association structure, a model study was performed using FeCl3 and a ligand 2,9-diphenyl-1,10-phenanthroline (17), a partial structure of macrocycle 2. As the result, no Fe(III)-coordinating complexes of 17 were formed but a salt containing protonated 17 and FeCl4 - was obtained (for the X-ray structure, see Figure 4b). This may be a result of the self-disproportionation followed by deprotonation of some Fe(III) species aquated by contaminated water, leading to the protonation of phenanthroline moieties. Thus, it is most likely that the formation of fibrous structures are not due to aggregation of endohedral Fe(III)-macrocycles but to a salt formation from protonated 2 and FeCl4 - leading to a laminated structure (Figure 4c).

[Chapter 4: Conclusions and Perspectives]

For the purpose of constructing endohedral metallo-macrocycles and their supramolecular aggregates, I have synthesized novel macrocyclic ligands which have two chemically-equivalent, inward phenanthroline parts as metal binding sites. As the result, homo- and heterodinuclear endohedral metallo-macrocycles were efficiently and selectively constructed. Furthermore, the metal-free macrocycle was found to stack in a low polar solvent. Meanwhile, the reaction of the macrocyclic ligand and FeCl3 provided fibrous structures, as shown in AFM and TEM measurements, which is considered from the model study to be a salt type laminate. Thus, this study demonstrates the ability of bisphenanthroline macrocycles to construct discrete and polymeric structures containing multiple metal ions from nanometer- to micrometer-scale. These supramolecular architectures would provide a clue to multi-point molecular recognition or electron conduction based on the multiple metal centers.

Figure 1. Schematic illustration of aggregation of metallo-macrocycles.

Figure 2. Dinuclear metal arrangement within the macrocycle 1; (a) Scheme of metal complexation; (b) 1H NMR spectra of 1 and its complexes (500 MHz, CDCl3/CD3CN = 10/1, 293 K) 1) [1] = 0.30 mM, 2) [1] = 0.13 mM,[Zn(CF3CO2)2] = 0.26 mM, 3) [1] = 0.13 mM, [Cu(CH3CN)4BF4] = 0.29 mM, 4) [1] = [Zn(CF3CO2)2] = [Cu(CH3CN)4BF4] = 0.24 mM; (c) X-ray structure of the dinuclear Zn(II)-macrocycle, Zn21(CF3CO2)4 (hydrogen atoms, side chains, solvent molecules are omitted for clarity.).

Figure 3. Aggregation behaviors of macrocycle 2 in cyclohexane; (a) chemical structure of 2 and an AFM image of a mica surface on which cyclohexane solution of 2 was dropped and dried; (b) the comparison of 1H NMR spectra of 2 in CDCl3 and cyclohexane-d12 (500 MHz, 293 K, [2] = 0.05 mM).

Figure 4. Aggregate formation from macrocycle 2 and FeCl3; (a) chemical structure of 2 and an AFM image of a mica surface on which a CHCl3 solution containing 2 and FeCl3 (4.0 eq) was dropped and dried, and a TEM image (black bar: 100 nm) of support membrane on which a CHCl3 solution containing 2 and FeCl3 (4.0 eq) was dropped and dried; (b) X-ray structure of a salt formed from the protonated model ligand 17 and FeCl4 -, [H・17][FeCl4] (hydrogen atoms are omitted for clarity.); (c) a plausible laminate structure consisting of the salt formed from protonated 2 and FeCl4 -.

マクロサイクルは、外界とは異なる化学的環境の内部空間を提供する環状分子であり、その主骨格への化学修飾や内孔の空間に基づき、ゲスト分子の認識や反応性制御などの内部機能を発現する。さらに、これらの機能性マクロサイクルがさまざまな様式で自己集合することにより、サブミクロンからマイクロメートルオーダーに至る空間機能を有する高次構造体を構築する。これらのマクロサイクルおよびその集合体における内部空間の機能は、環の内孔に配列する機能性部位の種類と配置により制御される。このような内向型機能性部位として、環内に金属イオンを配置すれば、酸化還元や配位特性など金属イオンの特徴的な物性とマクロサイクルの立体的な効果が協同的に作用し、新たな内部機能を実現しうる。本研究では、内側に複数の金属配位部位を有する大環状配位子を用いることにより、金属イオンとマクロサイクルからなる機能性超分子構造体を構築することを目的とした。まず、内側に二カ所のフェナントロリン金属配位部位を有する大環状配位子と金属イオンとの反応により、環内に二核の同種ないし異種金属イオンを配列した金属内包マクロサイクルを構築した。また、長鎖アルキル側鎖を付与した大環状配位子を用いることにより、マクロサイクルおよびその錯体の超分子集合体を構築することに成功した。

本論文は全4章からなり、第1章では天然および人工のマクロサイクルとその集合体の機能に基づき、本研究の背景と目的が詳述されている。

第2章では、ビスフェナントロリン骨格を有する大環状配位子の内孔における、同種および異種金属イオンの二核精密配列について報告している。まず、金属イオンを配列させるマクロサイクルとして内側に二カ所のフェナントロリン部位を有する剛直な大環状配位子を設計、合成した。この配位子と金属イオンを反応させることにより、環の内孔にZn(II)イオンあるいはCu(I)イオンを配列したホモ二核金属内包マクロサイクルを構築した。錯体形成の挙動は、1H NMRスペクトルおよび紫外可視吸収スペクトルにより追跡し、それぞれ錯体形成の安定度定数を見積もった。また、ホモ二核Zn(II)マクロサイクルの構造は、X線結晶構造解析により確認され、フェナントロリン部位に結合したZn(II)イオンにはさらに二つのトリフルオロ酢酸アニオンが結合し、正四面体型四配位の配位構造をとることが明らかとなった。さらに、同種だけではなく異種の金属イオンを環内配列にも成功した。この大環状配位子にZn(II)イオンとCu(I)イオンを等量添加したところ、環内の二カ所のフェナントロリン部位にZn(II)イオンとCu(I)イオンが一つずつ結合したヘテロ二核Zn(II)-Cu(I)マクロサイクルが、90%以上の高効率で生成した。溶液内平衡の解析により、この高いヘテロ選択性がホモ二核Cu(I)マクロサイクルの相対的に低い安定性に由来することが明らかになった。

第3章では、長鎖アルキル鎖を有する大環状配位子およびその錯体の会合挙動を論じている。溶媒極性に応答した会合挙動の制御を指向し、6本の長鎖アルキル側鎖を付与したビスフェナントロリン大環状配位を新たに設計・合成した。この配位子は、シクロヘキサンなどの低極性溶媒中において積層会合し、長さ数マイクロメートルの繊維状構造を構築することが、1H NMRスペクトル、紫外可視吸収スペクトル、およびAFMによる形状観察から明らかとなった。さらに、本配位子は金属イオンと反応することにより、サブミクロンからマイクロメートルオーダーに及ぶ超分子会合体を構築することを明らかにした。本配位子と塩化亜鉛から形成されるホモ二核Zn(II)マクロサイクルは、低極性溶媒中において粒状の会合体を生成した。一方、本配位子は塩化鉄(III)と反応することにより、長さ数マイクロメートルの繊維状会合体を構築した。大環状配位子の部分構造を有する配位子を用いたモデル実験から、この繊維状会合体はプロトン化された配位子とFeCl4-の塩状積層体であることが推定された。また、このような塩状積層体は、本配位子と酸との反応からもその生成が示唆された。

第4章では、本論文の総括と、今後の展望が述べられている。

以上のように、本博士論文では、内側に二カ所の金属配位部位を有する大環状配位子を用いることにより、ナノサイズの金属内包マクロサイクル、およびマクロサイクルの自己集合体の構築を行った。本研究成果は、超分子会合によるナノからマイクロメートルに至る分子構造の定量的な構築に有用な方針を与えるものであり、理学の発展に大いに貢献するものである。よって、博士(理学)取得を目的とする学術研究として十分な意義を有する。なお、本論文における各章の研究は、他の複数の研究者との共同研究によるものであるが、論文提出者が主体となって実験、解析および考察を行ったものであり、論文提出者の寄与が十分であると判断する。

したがって、博士(理学)の学位を受けるのに十分な資格を有するものと認める。