1. Introduction

Molecular-sized spaces formed within self-assembled hollow nano-structures, such as capsules, micelles/vesicles, and porous crystals, have attracted considerable attention due to their specific spatial functions for molecular encapsulation, separation, transportation, and transformation. In order to enhance selectivity and efficiency of these spatial functions, it is of significant importance to precisely control the size, shape, and chemical and physical properties of the interior surfaces of the nano-space. In line with this concept, a novel strategy is required for the arrangement of multiple functional groups in an accurately-oriented way at desired positions of the interior surface. However, it has long been a challenge to arrange a variety of molecular recognition sites on the surface in a site-selective manner. To realize this, I envisioned that self-assembly of metallo-macrocyclic compounds would provide novel porous crystalline materials with well-defined molecular receptors arising from the macrocyclic cavities on the inner pore surfaces.

In this study, I have synthesized a family of porous crystalline materials, Metal–Macrocycle Frameworks (MMFs), composed of one, two, or four stereoisomers of trinuclear macrocyclic Pd(II) complexes. These MMFs possess nano-sized pores surrounded by a variety of molecular binding pockets on the interior surfaces. The chemical and physical properties of the MMF surface can be adjusted by site-selective, reversible surface modification simply by soaking in a solvent containing organic/inorganic guest molecules. Notably, not only the size and shape of the pore but also the binding modes of guest molecules can be tuned by solvent-induced pseudopolymorphism of the MMFs. Furthermore, asymmetric crystallization of the MMFs was induced by optically-active sugar-derived lactones, generating chirality of the pore and the binding pockets of the MMFs.

2. Synthesis of Metal–Macrocycle Framework 1

A porous Metal–Macrocycle Framework 1 (MMF-1) with five kinds of enantiomeric-paired binding pockets was constructed from a structurally flexible tris-bidentate macrocyclic ligand L and PdCl2(CH3CN)2. Complexation of ligand L and 3 equiv. of PdCl2(CH3CN)2 in CH3CN produces yellow single-crystals in 41% yield which consist of an equal amount of four stereoisomers of neutral trinuclear macrocyclic Pd(II) complexes, Pd3LCl6 (Figure 1a). In the two conformational isomers (Syn and Anti), all the three or two Pd(II) centers, respectively, are located on the same side of the macrocyclic ligand (Figures 1b,c). For each isomer, two helical structures (P and M) are induced by intramolecular, circularly-oriented three C-H---π interactions (Figure 1d). Moreover, each trinuclear Pd(II) macrocyclic complex has a pair of guest binding pockets on their top and bottom faces, head- and tail-Pockets, respectively. In the crystal formed in CH3CN, the four isomers are regularly arranged mainly through N-H---Cl hydrogen bonding and Pd-Pd interactions to construct a rectangular nano-channel structure with the size of 1.4 × 1.9 nm2 (Figure 1e). This nano-channel can provide five enantiomerically-paired guest binding pockets on the pore surface.

3. Site-selective guest adsorption to the MMF-1 surface

Adsorption behaviors of small aromatic molecules to the MMF-1 surface were examined for the site-selective surface modification in a noncovalent manner. X-ray diffraction of a single-crystal, which was obtained as the result of the crystal-to-crystal transformation by the soaking of a single crystalline MMF-1 in a 1:1 (v/v) mixed solvent of CH3CN and benzene at 30 °C for one day, revealed that benzene molecules are included within two sets of binding pockets, (P/M)-Anti-head and (P/M)-Syn-tail Pockets, mainly through C-H---π interactions and van der Waals interactions (82% and 66% occupancies, respectively) (Figure 2a). Residual benzene molecules in the free pore space are highly disordered. Furthermore, other simple aromatic hydrocarbons, such as naphthalene and azulene, show different binding modes from that of benzene, indicating that the adsorption behaviors on the surface depend on the size and/or shape of guest molecules (Figure 2b).

To further assess the shape- and orientation-selectivities in the guest adsorption, three dibromobenzene isomers were selected as guests. Single-crystal X-ray analyses revealed that adsorption of dibromobenzene isomers is highly shape-selective on the MMF-1 surface (Figures 2c-e). O-isomer is captured in the (P/M)-Syn-tail and (P/M)-Ellipsoidal Pockets (51% and 53%, respectively). On the other hand, m-isomer is trapped in the (P/M)-Syn-tail and (P/M)-Anti-head Pockets (52% and 89%, respectively), and p-isomer is included only in the (P/M)-Ellipsoidal Pockets (68%). It should be noted that every dibromobenzene isomer is oriented without fluctuation as confirmed by electron densities of heavy Br atoms. Subsequently, a solution containing a mixture of m- and p-dibromobenzenes in CH3CN was used for binary guest arrangement. The crystal structure of MMF-1 including m- and p-isomers shows that two guests are sorted in different binding pockets (Figure 2f). The binding selectivity of the dibromobenzene mixture is completely consistent with those of both individual isomers.

Furthermore, highly diastereoselective guest adsorption was achieved when using optically-active, disubstituted aromatic molecules, (1R)- or (1S)-1-(3-chlorophenyl)ethanol (Figures 2g,h). Single-crystal X-ray diffraction of a single crystal, which was obtained by the soaking of the MMF-1 in a 1:2 (v/v) mixture of CH3CN and (1R)-isomer at 30 °C for one day, revealed that the guest molecules are encapsulated in one of the enantiomerically-paired binding pockets. As is obvious, the (1S)-isomer is encapsulated into each mirror-image binding pocket. In the electron density map, there is no electron density assignable to the guest molecule in the other enantiomerically-paired binding pockets. This strongly suggests that the resulting diastereoselectivity is substantially high.

4. Direct X-ray observation of a guest exchange process on the MMF-1 surface

In order to study adsorption kinetics of guest molecules on the MMF-1 surface, the time-course X-ray analysis was conducted. Four successive single-crystal X-ray measurements allowed to visualize a guest exchange process at the molecular binding pockets. To make the guest exchange more slowly, the experiment was carried out at –180 °C, and the incubation for the guest exchange was conducted at –40 °C (Figures 3a,b). The crystal structures of the MMF-1 crystal briefly-immersed into a 1:2 (v/v) mixed solvent of CH3CN and (1R)-1-(3-chlorophenyl)ethanol at 23 °C for 5 min are shown in Figures 3c-f. Comparative study of the four structures indicated a slow guest exchange process in the (P)-Syn-tail Pocket. Moreover, an intermediate guest adsorption was clearly detected as indicated by arrows. These atomic level observations would provide a new insight into the kinetics of guest adsorption behaviors on the inner crystal surface.

5. Three-dimensionally interconnected pores: MMF-2

The trinuclear macrocyclic PdII complex, Pd3LCl6, exhibits solvent-induced pseudopolymorphisms. One of them is MMF-2, which has a different size and shape of pore with different guest binding pockets on the surface from MMF-1. Complexation of ligand L and 3 equiv. of PdCl2(CH3CN)2 in a 1:9 (v/v) mixed solvent of DMSO and CH2Cl2 generates yellow-orange single crystals of rac-MMF-2 composed of only (P/M)-Syn isomers (Figure 4a). The single-crystal X-ray diffraction revealed that rac-MMF-2 crystallizes in a chiral cubic space group, I213, with a Flack parameter 0.48(5), indicating that rac-MMF-2 exists as a racemic mixed crystal. Namely, a unit cell of the rac-MMF-2 crystal consists of one kind of stereoisomers of Pd3LCl6, either a (P)- or an (M)-Syn isomer, but the rac-MMF-2 as a whole contains an equal amount of both (P)- and (M)-Syn isomers. In rac-MMF-2, (P/M)-Syn isomers interact with each other through N-H---Cl hydrogen bonds (average N-Cl distance, 3.3 A) and Pd-Pd interactions (Pd-Pd distance, 3.17 A) to form three-dimensionally connected pores. In addition, rac-MMF-2 has cylindrical nano-spaces with a diameter of 10 A and a length of 7 A surrounded by two types of the molecular binding pockets, Syn-head and -tail Pockets (Figure 4b).

Moreover, rac-MMF-2 can capture small organic molecules such as benzene and cyclohexane. Single-crystal X-ray analysis of a crystal, which was obtained after the soaking of crystalline MMF-2 in a 1:1 (v/v) mixed solvent of benzene and CH2Cl2 revealed that benzene molecules are adsorbed to both Syn-head and -tail Pockets mainly through C-H---Cl hydrogen bonding and C-H---π interactions (Figure 4c). For uptake experiments with cyclohexane, only a Syn-head Pocket captures cyclohexane but with low occupancy of 17%. So in competition experiments, a selective uptake behavior of benzene over cyclohexane was observed for the rac-MMF-2. The crystals of rac-MMF-2 were soaked into a CH2Cl2 solution of benzene and cyclohexane (1.0 M each) for one day at 30 °C, and then digested in DMSO-d6/DCl-D2O. The 1H NMR spectrum of the resulting mixture indicated that molar ratio of benzene and cyclohexane trapped in the MMF-2 pores is 90:10, namely the selectivity of benzene uptake over cyclohexane is 9. Thus, the crystal structures and 1HNMR spectroscopy suggest that MMF-2 exhibits a high capability of molecular separation through the nano-space surrounded by the molecular binding pockets.

6. Asymmetric crystallization of MMF-2 with optically-active lactones

Asymmetric crystallization of MMF-2 was achieved by chirality induction using optically-active sugar-derived lactones (Figure 5). Crystallization of Pd3LCl6 in a 1:9 (v/v) mixed solvent of DMSO and CH2Cl2 in the presence of 30 equiv. of D-glucono-1,5-lactone or 70 equiv. of D-glucurono-6,3-lactone produced homochiral MMF-2 crystals, P-MMF-2 or M-MMF-2, respectively. The single-crystal structures of P- and M-MMF-2 show that their unit cell structures are completely the same as that of rac-MMF-2 and no chiral lactones as the asymmetric induction reagents were therefore included in the crystals. Importantly, the Flack parameters of P- and M-MMF-2 are 0.07(9) and 0.06(7), respectively, indicating high asymmetric induction. Thus, the optically-active lactones have influence not on the crystal structures, but on the asymmetric induction of the MMF-2 crystals. The resulting chiral spaces could be applied for catalytic asymmetric reactions.

7. Other pseudopolymorphisms of MMF; MMF-3 and MMF-4

The trinuclear Pd(II) complexes show further solvent-induced pseudopolymorphisms to form two other types, MMF-3 and MMF-4 from a 1:9 (v/v) mixed solvent of DMSO and CHCl3 (Figure 6a). These two different porous MMF crystals composed of (P/M)-Syn isomers are simultaneously formed as concomitant polymorphs from a 1:9 (v/v) mixed DMSO-CHCl3 solution containing ligand L and 3 equiv. of PdCl2(CH3CN)2. The crystal habit and packing structure of MMF-3 are similar to those of rac-MMF-2. However, MMF-3 crystallizes in an achiral cubic space group, I43d, and contains both (P)- and (M)-Syn isomers in a unit cell. For MMF-4 whose unit cell also consists of both (P)- and (M)-Syn isomers, the packing structure is completely different from those of rac-MMF-2 and MMF-3 (Figure 6b). In MMF-4, (P)- and (M)-Syn isomers alternately are aligned in a head-to-tail manner along the c axis (Figure 6c). Furthermore, these columns of the (P/M)-Syn isomers make a hexagonal array in the packing structure to form a one-dimensional hexagonal nano-channel structure with a diameter of 1.2 nm.

8. Conclusion

To develop functional supramolecular spaces, I have constructed a family of Metal–Macrocycle Frameworks from trinuclear macrocylic Pd(II) complexes as the building blocks. The resulting self-assembled crystalline compounds have a variety of molecular binding pockets on their inner pore surfaces. Using these binding pockets, site-selective, reversible surface modification has been achieved with small aromatic organic molecules. Furthermore, the size and shape of the MMF pores and the types and chirality of the binding pockets on the surfaces can be controlled by solvent-induced pseudopolymorphisms and asymmetric crystallization in the presence of optically-active lactones. Such supramolecular, multi-functional spaces formed in MMF would show space-specific functions, such as molecular separation, highly efficient asymmetric catalytic reactions, and polymer formation.

Figure 1. (a) Complexation of ligand L and 3 equiv. of PdCl2(CH3CN)2. ORTEP drawings of (b) (P)-Syn and (c) (M)-Anti isomers at 50% probability level. (d) Helical structures of (P/M)-Syn isomers. Pd, yellow; Cl, green; N, blue; C, black. (e) A unit pore structure of MMF-1 possessing five different enantiomerically-paired binding pockets. 1: (P/M)-Anti-head Pockets, 2: (P/M)-Syn-tail Pockets, 3: (P/M)-Anti-tail Pockets, 4: (P/M)-Ellipsoidal Pockets, 5: (P/M)-Tubular Pockets. Carbon atoms for (P)-Syn, (M)-Syn, (P)-Anti, and (M)-Anti are shown in blue, aqua, red, and orange, respectively.

Figure 2. Unit pore structures of MMF-1 including (a) benzene, (b) naphthalene, (c) o-, (d) m-, (e) p-dibromobenzene, (f) a mixture of m- and p-dibromobenzenes, (g) (1R)-, and (h) (1S)-1-(3-chlorophenyl)ethanol. Stick model: MMF-1, space-filling model: guest molecules.

Figure 3. (a) Schematic illustration of the time-course X-ray diffraction of (1R)-1-(3-chlorophenyl)ethanol on a goniometer of the X-ray apparatus. (b) Detailed time table. XRD: single-crystal X-ray diffraction. Unit pore structures of the (c) 1st, (d) 2nd, (e) 3rd, and (f) 4th measurements. The carbon atoms of the intermediate guest molecule is shown in green and indicated by arrows.

Figure 5. Asymmetric crystallization of MMF-2 using optically-active sugar-derived lactones, D-glucono-1,5-lactone and D-glucurono-6,3-lactone.

Figure 6. (a) Synthesis of MMF-3 and MMF-4 as concomitant polymorphs. (b) A hexagonal packing structure of MMF-4. (c) Head-to-tail columnar packing along the c axis of MMF-4. Carbon atoms of (P)-Syn and (M)-Syn isomers are represented by blue and aqua, respectively.

自己集合性構造体が有する分子サイズのナノ空間は、分子包接・分離・輸送・変換等の機能を示すことから近年盛んに研究が行われている。これら空間機能の活性や選択性を制御・向上させる一つの手段として、多種の分子レセプターに囲まれたナノ空間の構築が挙げられる。分子レセプターにおける非共有結合を介したゲスト分子包接を利用することで、位置・配向選択的な異種官能基修飾に伴うナノ空間のサイズ・形状・化学的性質の精密制御が可能となる。本研究では、多種の分子レセプターに囲まれたナノ空間の構築手法として、大環状配位子と金属イオンとの錯体形成により得られる大環状金属錯体の複数の異性体の共結晶化を提案した。実際、一種類の比較的柔軟な大環状配位子LとPd(II)イオンを各種溶媒下混合することで、細孔壁面上に多種の分子レセプターを有する合計四種類の金属マクロサイクル集積体(Metal–Macrocycle Framework: MMF)の合成を達成した。さらにMMFが有する分子レセプターを活用することで、細孔壁面上における位置選択的ゲスト分子配列等の機能開発にも成功した。

本論文は全7章からなり、第1章では、本研究の目的、背景が記述されている。

第2章では、細孔壁面に五種類の鏡像体対分子包接ポケットを有する金属マクロサイクル集積体MMF-1の合成と分子包接ポケットを利用した位置選択的分子吸着について述べられている。大環状配位子LとPdCl2(CH3CN)2との錯体形成をアセトニトリル中にて行ったところ、大環状三核Pd(II)錯体の四種類の配座・鏡像異性体からなるMMF-1が黄色単結晶として得られた。単結晶X線構造解析から、MMF-1結晶内にサイズが1.4 × 1.9 nm2の一次元チャネル細孔が存在していることが明らかとされた。また、その細孔表面には大環状三核Pd(II)錯体のキャビティーおよび錯体間の空隙に由来する五種類の分子包接ポケットが鏡像体対として配列していた。この分子包接ポケットにおける分子認識により、ベンゼンなどの有機小分子が細孔表面において位置選択的に吸着することが明らかとされた。

第3章では、MMF-1細孔表面での分子吸着過程のその場X線観察について述べられている。単結晶X線装置の低温窒素気流の温度を制御することにより、細孔表面上の分子吸着を制御した。(1R)-1-(3-chlorophenyl)ethanolをゲスト分子として含むアセトニトリル溶液に短時間浸漬したMMF-1の単結晶X線回折により、(P)-Syn-tailポケットにおけるアセトニトリルからゲストへの分子交換挙動が原子レベルで観測された。

第4章では、三次元細孔を有する金属マクロサイクル集積体MMF-2の合成およびMMF-2細孔へのシクロヘキサン、1,4-シクロヘキサジエンに対するベンゼンの選択的包接について述べられている。大環状配位子Lと3当量のPdCl2(CH3CN)2との錯体形成を1:9 (v/v) DMSO-CH2Cl2混合溶媒中にて行うことで、rac-MMF-2が黄色単結晶として得られた。単結晶X線回折から、rac-MMF-2が大環状三核Pd(II)錯体の(P/M)-Syn体から構築されるラセミ混晶であることが確認された。またMMF-2はベンゼンなどの有機小分子を包接可能であることが単結晶X線回折や溶液NMR測定から確かめられた。さらに細孔表面に存在するポケットを利用することで、シクロヘキサン、1,4-シクロヘキサジエンに対するベンゼンの選択的包接が達成された。

第5章では、MMF-2の不斉結晶化およびそのメカニズムについて述べられている。大環状配位子LおよびPdCl2(CH3CN)2を含む結晶化溶液に、D-glucono-1,5-lactoneおよびD-glucurono-6,3-lactoneを加えることで不斉結晶化が進行し、それぞれP-MMF-2、M-MMF-2を得ることに成功している。用いたラクトンの構造を比較することで、エステルのα炭素のキラリティーが結晶のキラリティーに影響していることが示唆された。さらにrac-MMF-2を種結晶とする結晶成長実験により、キラル誘起が結晶成長段階で進行していることが確かめられている。

第6章では、MMF-3およびMMF-4の合成および大環状三核Pd(II)錯体が示す結晶擬多形のメカニズムについて述べられている。大環状配位子Lと3当量のPdCl2(CH3CN)2との錯体形成を1:9 (v/v) DMSO-CHCl3混合溶媒中にて行うことで、MMF-3およびMMF-4が同床多形として得られた。MMF-3、MMF-4ともに(P/M)-Syn体からなるラセミ結晶であることが単結晶X線回折により確かめられた。MMF-3の結晶構造はMMF-2と類似しており、MMF-2と同様に三次元細孔を有していることが明らかにされている。またMMF-4は(P/M)-Syn体がハニカム状に配列したパッキング構造を示し、直径1.2 nmの一次元チャネル細孔を有していた。また各種溶媒下における溶液NMR測定から、溶液中の異性体比が結晶擬多形の一因であることが示唆された。

第7章では、本研究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、細孔表面に多種の分子レセプターを有する多孔性結晶MMFの簡便な合成手法を確立し、レセプターの分子包接能を活かした位置選択的分子吸着等の機能開発に成功した。本研究成果は自己集合性ナノ空間の新たな構築法・修飾法のための有用な方法論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。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。