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CD-Ru phosphine-catalyzed metathesis polymerization

Recently, supramolecular catalysts for organic reactions in aqueous systems have been in demand. In this study, we synthesized supramolecular catalysts with a substrate recognition moiety and a catalyst activation moiety and attempted polymerization reactions in water. Ruthenium complexes with dicyclohexylphosphine ligands based on cyclodextrins (CDs) were synthesized as substrate recognition sites , and their activity for ring-opening metathesis polymerization in aqueous systems was investigated.
As shown in the figure below, βcompounds with a phosphine bonded to CD and Ru coordination were synthesized for ring-opening metathesis polymerization (ROMP) of norbornene derivatives. Polymerization was carried out at [monomer]/[catalyst] = 100, and the polymerization reaction proceeded, yielding polymers. Compared to the reaction in organic solvents, polymerization using PCy2-Ru-βCD as a catalyst resulted in higher polymer yields and molecular weights. The polymerization reaction did not proceed under the same conditions when the complexes of RuCl3-3H2O and RuCl3-3H2O with tris(3-sulfonatephenyl)phosphine hydrate, sodium salt (TPPTS), which are typical ROMP catalysts, were compared. The polymerization reaction did not proceed under the same conditions. The polymerization reaction was inhibited by the addition of competitive guests (alcohols, adamantane, etc.) that interact more strongly than the monomer, indicating that the CD moiety of PCy2-Ru-βCD acts effectively against the polymerization reaction. The CD moiety of PCy2-Ru-βCD was found to be effective against the polymerization reaction.

Takashima, Y.; Uramatsu, K.; Jomori, D.; Harima, A; Otsubo, M; Yamaguchi, H.; Harada, A
Ring-Opening Metathesis Polymerization by a Ru Phosphine Derivative of Cyclodextrin in Water
ACS Macro Lett. 2013, 2, 384-387. (DOI: 10.1021/mz4001942)

Development of Supramolecular Energy Conversion System

Energy transfer system using cyclodextrin-oligothiophene rotaxane

In recent years, conjugated molecules have attracted a great deal of attention due to their luminescence and electrical properties, and many studies have been conducted. However, precise control of the higher-order structure is essential to fully demonstrate their properties. In order to control the structure of π-conjugated molecules using a supramolecular scientific approach, we have investigated the structural control by combining CD and conjugated molecules. In this study, we investigated supramolecular formation and energy transfer in a mixture system of rotaxane and guest molecules using the terminal βCD moiety of rotaxane.
2T-[2]rotaxane and 3T-[2]rotaxane with a βCD moiety capable of encapsulating guest molecules at the end were used as hosts, and oligothiophene derivatives Disodium salt of 2,2':5',2'':5'',2''': 5''',2'''':5'''',2'''''-sexithiophene-3'',4'''-dicarboxylic acid (6TCA2Na2) was synthesized. (see figure below)

6TCA2Na2 does not emit strong luminescence by itself, but when 6TCA2Na2 is mixed with rotaxane, it emits strong luminescence, stronger than when 6TCA2Na2 alone is excited directly (λex = 424 nm). This is thought to be due to energy transfer with rotaxane as the donor and 6TCA2Na2 as the acceptor. Furthermore, the energy transfer efficiency was calculated from the degree of decrease in emission at the rotaxane site, and was found to be more than 90% efficient. On the other hand, when an excess amount of competing guests was added, the emission from 6TCA2Na2 decreased in the fluorescence spectrum of the mixed system. This may be due to the inhibition of complex formation between rotaxane and 6TCA2Na2. When these solutions were applied to a quartz plate and allowed to dry, the difference in luminescence intensity was more clearly observed: 6TCA2Na2 alone is self-quenched and does not emit light at all, while the mixture of rotaxane and 6TCA2Na2 shows brilliant fluorescence emission and efficient energy transfer in the solid state. (see figure below)

Sakamoto, K.; Takashima, Y.; Hamada, N.; Ichida, H.; Yamaguchi, H.; Yamamoto, H.; Harada, A.
Selective Photoinduced Energy Transfer from a Thiophene Rotaxane to Acceptor
Org. Lett. 2011, 13, 672-675.

Luminescence Control of Perylenediimide-modified Cyclodextrin Compounds for Sensing Films

In recent years, dialkyl-substituted perylenediimide compounds have shown promise as optoelectronic materials such as organic field effect transistors (OFETs) and fluorescent sensors. On the other hand, perylene diimide compounds (PDIs) are soluble in some organic solvents but insoluble in many organic solvents, and their solubility in water and polar solvents is very low. We have synthesized efficient luminescent films utilizing the luminescent properties of PDIs and the molecular recognition ability of cyclodextrins (CDs) and investigated their luminescent properties.

When various PDI-CD dimers were mixed and dried with an aqueous solution of polyvinyl alcohol (PVA), films showing specific luminescence properties depending on the CD pore size were obtained, with PDIC7-3?CD2 showing particularly strong luminescence properties. (see figure below).

It is important to make these films from aqueous solutions; luminescent films cannot be obtained from organic solvents, which is thought to be related to the molecular recognition ability and tumbling of CDs. In the future, these luminescent films may be applied as films for detecting chemical substances.

Takashima, Y.; Fukui, Y.; Otsubo, M.; Hamada, N.; Yamaguchi, H.; Yamamoto, H.; Harada, A.
Emission Properties of Cyclodextrin Dimers Linked with Perylenediimide - Effect of Cyclodextrin Tumbling
Polymer Journal 2012, 44, 278-285.

Polymerization of lactone by CD dimer

When CD dimer was synthesized and used as a catalyst, CD dimer was more active than CD monomer and produced a high molecular weight polymer. However, when polymerization was attempted using the product (polymer) obtained with the CD dimer as a catalyst by adding more monomer, it was found that further polymerization proceeded. This was found to be because one of the CD dimers acted as an active site for polymerization, and the other played a role in drawing out the generated polymer. By using the CD dimer, polyesters with molecular weights in the tens of thousands were obtained (see figure below). (see figure below)

Takashima, Y.; Osaki, M.;Ishimaru, M.; Yamaguchi, H.; Harada, A.
Artificial Molecular Clamp: A Novel Device for Synthetic Polymerases
>Angew. Chem.,Int. Ed. 2011, 50, 7524-7528.

Observation of the shuttling of ring molecules through the rotational motion of the glucopyranose unit of the terminal CD

Rotaxane was synthesized by using a compound with an alkyl chain modified with CD as the axle molecule. In conventional rotaxanes, the shuttling of the rotor molecule is controlled by the interaction between the axis molecule and the rotor molecule, but in this system, the CD of the axis molecule is not only bulky as a stopper but also has a function to take in the axis molecule, and we observed changes in the shuttling of the rotor molecule.
The results showed that in [2]rotaxane, the rotor encapsulated alkyl chains in methanol and DMSO-d6. In water, on the other hand, the rotor encapsulated the stilbene moiety and some units of the CD of the stopper somersaulted (tumbling) and encapsulated the alkyl chain. The conventional method of controlling the shuttling was to control the shuttling by the interaction between the axis molecule and the rotor. In this system, we succeeded in controlling the shuttling of rotaxane by using a CD in the rotor, which is not only bulky as a stopper but also has the function of reeling in the axial molecule. (see figure below)

Yamauchi, K.; Miyawaki, A.; Takashima, Y.; Yamaguchi, H.; Harada, A.
A Molecular Reel: Shuttling of a Rotor by Tumbling of a Macrocycle
J. Org. Chem. 2010, 75, 1040-1046.

Observation of [1]rotaxane dimer through rotational movement of glucopyranose unit of CD dimer

With the development of supramolecular chemistry, various host compounds have appeared in the world. Calix[n]arene is a representative host compound along with CD, and its units are known to somersault (tumbling or flipping). On the other hand, unmodified CDs are thought not to somersault due to the formation of hydrogen bonds between glucopyranoses. We have studied in detail the structure of αCD dimers with a flexible alkyl chain modified in the immediate vicinity of the CD.
The results suggest that the alkyl chains are not drawn into the CD cavity to form inclusion complexes, but are pseudo[1]rotaxane dimers realized by somersaulting of the glucopyranose unit. Kinetic analysis revealed that the somersault velocity is 6.58e10-4 s-1 (288 K) and Go = -8.1 kJ/mol-1 (288 K). The conformational change from the unbound αCD dimer to the bound pseudo[1]rotaxane dimer requires a high activation free energy (288K = 88.0 kJ/mol-1). This is thought to be the energy required to break the hydrogen bond between the hydroxyl groups of αCD and somersault the glucopyranose unit. (see figure below).

Yamauchi, K.; Miyawaki, A.; Takashima, Y.; Yamaguchi, H.; Harada, A.
Switching from altro-α-Cyclodextrin Dimer to pseudo[1]Rotaxane Dimer through Tumbling
Org. Lett. 2010, 12, 1284-1286.

Social Self-Sorting Supramolecular Complexes

We investigated the formation behavior of supramolecular complexes by introducing cinnamic acid into the secondary or tertiary position of the secondary hydroxyl group of α-CD through an ester bond, thinking that the structure of supramolecular complexes formed may differ depending on the substitution position of the secondary hydroxyl group of CD.
As a result, not only the rearrangement reaction of cinnamic acid ester modified at the 2- or 3-position was observed, but also the supramolecular complexes formed in the single state and the mixed state showed different behaviors.

Tomimasu, N.; Kanaya, A.; Takashima,Y.; Yamaguchi, H.; Harada, A.
Social Self-Sorting: Alternating Supramolecular Oligomer Consisting of Isomers
J. Am. Chem. Soc. 2009, 131 (34), 12339-12343.

Controlling Supramolecular Polymer Arrangement in Response to Optical Stimulation

Acyl group rearrangement reactions in monosaccharides are widely known, but there have been no detailed reports on the rearrangement reactions of cyclodextrins (CDs), which are cyclic oligosaccharides with α-D-glucose as a component unit. In this study, stilbenes, which have high association constants with αCD, were introduced as acyl groups into their secondary hydroxyl groups, and it was found that each compound produced by the acyl group rearrangement reaction formed a different supramolecular complex. Furthermore, in the present study, we observed that the rearrangement rate differs depending on the isomer of stilbene, and that this rate is affected by the supramolecular structure.
It was shown that the rearrangement reaction of acyl groups is suppressed by the formation of supramolecular complexes. Therefore, to investigate the structure of the supramolecular complexes formed, we performed 2D ROESY NMR measurements and found that even in mixed solutions of 2-StiO-αCD and 3-StiO-αCDthe same isomers (2- S tiO-αCD and 3-StiO-αCD ) in mixed solutions of 2-StiO-αCD and 3-StiO-αCD (see figure below). (see figure below).

Kanaya, A.; Takashima, Y.; Harada A.
Double Threaded Dimer and Supramolecular Oligomer Formed by Stilbene Modified Cyclodextrin? Effect of Acyl Migration and Photo Stimuli
J. Org. Chem. 2011, 76, 492-499.

External Stimulus-Responsive Supramolecular Structures

A double-threaded dimer bearing a long substituent part and a large stopper group has been prepared and showed the conformational change with increased solvent polarity.

Tsukagoshi, S.; Miyawaki, A.; Takashima, Y.; Yamaguchi, H.; Harada, A.
Contraction of Supramolecular Double-Threaded Dimer Formed by alpha-Cyclodextrin with a Long Alkyl Chain
Org. Lett. 2007, 9 (6), 1053-1055.

We prepared a stilbene bis(β-CD) dimer and controlled its trans-cis conformation by photoirradiation in aqueous solution. With a ditopic adamantyl guest molecule, in trans conformation, it formed dimer or small supramolecular assemblies (oligomers), whereas in cis conformation, supramolecular linear polymer with high molecular weight were observed. The control of the structure of the supramolecular polymers by an external stimulus may open the way to various applications.

Kuad, P.; Miyawaki, A.; Takashima, Y.; Yamaguchi, H.; Harada, A.
External Stimulus-Responsive Supramolecular Structures Formed by a Stilbene Cyclodextrin Dimer
J. Am. Chem. Soc. 2007, 129 (42), 12630-12631.

We have succeeded in controlling formation of a double threaded dimer and that of non-threaded supramolecular self-assembly consisting of stilbene amide α-CD by photoirradiation as shown in Figure 4. First, we thought that 3-trans-Sti-α-CD would form a supramolecular polymer, and then 3-cis-Sti-α-CD would decompose it after photoirradiation. The facts are contrary to what we expected. Formations of these supramolecular complexes might be due to p-p stacking interactions between stilbene amide groups. These interactions are presumed to inhibit the formation of a supramolecular polymer. Instead, it created more interesting supramolecular system, in other words, "Switching between supramolecular dimer and non-threaded supramolecular self-assembly". The unit of α-CD and the cis-stilbene group play an important role to form supramolecular assembly as a hydrophilic and hydrophobic part, respectively. These interaction and environment promote the p-p stacking of the cis-stilbene group and affect cooperatively the formation of the supramolecular assembly.

Yamauchi, K.; Takashima, Y.; Hashidzume, A.; Yamaguchi, H.; Harada, A.
Switching between Supramolecular Dimer and Non-Threaded Supramolecular Self-Assembly of Stilbene Amide alpha-Cyclodextrin by Photoirradiation
J. Am. Chem. Soc. 2008, 130 (15), 5024-5025.

Preparation of pseudo-Polyrotaxanes Containing Poly(thiophene)s

p-Conjugated polymers have attracted much interest due to their high charge-mobility along individual polymer chains. Recently, p-conjugated polymers have been used in practical applications, including light-emitting diodes, thin-film field effect transistors, photovoltaic cells, and sensors. We have prepared and determined the crystal structure of cyclodextrins inclusion complexes with various thiophenes, and the polymerization of the corresponding inclusion complexes in a selective way to obtain polyrotaxanes.

Utlizing coupling reaction, DM-β-CD poly pseudo rotaxane with polythiophene as axis was obtained.

Takashima, Y.; Sakamoto, K.; Oizumi, Y.; Yamaguchi, H.; Kamitori, S.; Harada, A.
Complex Formation of Cyclodextrins with Various Thiophenes and Their Polymerization in Water: Preparation of pseudo-Polyrotaxanes Containing Poly(thiophene)s
J. Incl. Phenom. Macrocycl. Chem. 2006, 56 (1-2), 45-53.

Preparation and Properties of Rotaxanes Formed by Dimethyl-β-Cyclodextrin and Oligo(thiophene)s with β-Cyclodextrin Stoppers

A series of novel DM-β-CD-oligothiophene based rotaxanes have been prepared by the palladium catalyzed coupling reaction. [2] Rotaxanes and [3] rotaxanes which have various chain lengths and inclusion ratios of DM-β-CD were isolated from the crude products by using preparative reversed phase chromatography. Their photochemical properties have been investigated by UV-vis and fluorescence measurements. The inclusion ratio and the chain length of rotaxanes have been found to relate to the emission properties and the emission intensities of oligothiophene. In aqueous solutions, fluorescence quantum yields of rotaxanes were higher than those of dumbbell-shaped molecules. The increase in the fluorescence efficiency of rotaxane is caused by the suppression of intermolecular interactions, indicating the effect of insulated oligothiophene with DM-β-CD.

Sakamoto, K.; Takashima, Y.; Yamaguchi, H.; Harada, A.
Preparation and Properties of Rotaxanes Formed by Dimethyl-beta-cyclodextrin and Oligo(thiophene)s with beta-Cyclodextrin Stoppers
J. Org. Chem. 2007, 72 (2), 459-465

Supramolecular Catalyst Using Modified Cyclodextrin

Cyclodextrins (CDs) have been widely employed as substrate-recognition moieties in enzyme models. CDs accelerate the hydrolysis of activated esters, such as p-nitrophenyl acetate. However, the accelerated reactions have been limited to the degradation of the activated aryl esters in the presence of excess amounts of CDs. We found that CDs selectively form inclusion complexes with some lactones (the starting materials of the polyesters) to promote or suppress the hydrolysis of lactones.

Takashima, Y.; Kawaguchi, Y.; Nakagawa, S.; Harada, A.
Inclusion Complex Formation and Hydrolysis of Lactones by Cyclodextrins
Chem. Lett. 2003, 32, 1122-1123.

We speculated that if lactones are heated with CDs in bulk without water, they might form polymers because hydrolysis cannot occur. CDs were found to initiate ring-opening polymerizations of lactones selectively to give polyesters in high yields in bulk without water. This polymerization system requires neither a conventional metal catalyst, nor CDs with substituent groups. The products were found to be a polymer chain attached to the hydroxyl group of CD via an ester bond.

Takashima, Y.; Osaki, M.; Harada, A.
Cyclodextrin-Initiated Polymerization of Cyclic Esters in Bulk: Formation of Polyester-Tethered Cyclodextrins
J. Am. Chem. Soc. 2004, 126 (42), 13588-13589.

Osaki, M.; Takashima, Y.; Yamaguchi, H.; Harada, A.
Polymerization of Lactones Initiated by Cyclodextrins: Effects of Cyclodextrins on the Initiation and Propagation Reactions
Macromolecules 2007, 40 (9), 3154-3158.

Cinnamoyl CD has been found to initiate polymerization of lactone to give a polymer in high yield. The polymerization activity could be switched by the photoisomerization of the cinnamoyl group attached to the rim of CD. Specific monomer recognition and polymerization in the active site of the CD cavity is changed by the photoisomerization.

Osaki, M.; Takashima, Y.; Yamaguchi, H.; Harada, A.
Switching of Polymerization Activity of Cinnamoyl-alpha-Cyclodextrin
Org. Biomol. Chem. 2009, 7, 1646 - 1651.

In the polymerization, the propagating polymer chain was included by the CDs. The polymer chain was found to elongate in the solid state, whereas the polymer chain without threading CDs formed random coil conformation. CDs have two roles. One CD at the end of the polymer chain initiates the polymerization. Other CDs threaded onto the polymer chain are immune to the initiation directly, but have an essential role to fold the polymer chain in a proper way as an artificial chaperone.

Osaki, M.; Takashima, Y.; Yamaguchi, H.; Harada, A.
An Artificial Molecular Chaperone: Poly-pseudo-rotaxane with an Extensible Axle
J. Am. Chem. Soc. 2007, 129 (46), 14452-14457.

Harada, A.; Osaki, M.; Takashima, Y.; Yamaguchi, H.
Ring-Opening Polymerization of Cyclic Esters by Cyclodextrins
Acc. Chem. Res. 2008, 41 (9), 1143-1152.

CD-based nanosphere initiated the oligomerization of lactone on the surface of the nanosphere to give oligo(lactone)-tethered CD nanosphere in bulk. The addition of other CDs to the nanosphere led to the formation of poly-pseudo-rotaxane on the surface of the nanosphere. the poly-pseudo-rotaxane repropagated upon the addition of lactone. These behaviors are reminiscent of the function of a spherical virus, which forms an ordered spherical structure and releases RNA chains from the capsid surface.

Osaki, M.; Takashima, Y.; Yamaguchi, H.; Harada, A.
Nanospheres with Polymerization Ability Coated by Polyrotaxane
J. Org. Chem. 2009, 74 (5), 1858-1863.