Supramolecular Catalysis DOI: 10.1002/ange.201102834 Artificial Molecular Clamp: A Novel Device for Synthetic Polymerases** Yoshinori Takashima, Motofumi Osaki, Yoshihiro Ishimaru, Hiroyasu Yamaguchi, and Akira Harada* Renewable materials have attracted much attention from the viewpoints of environmental protection and efficient utiliza- tion of natural resources. Certain polyesters, polyamides, and polylactides, which are synthesized by either biological methods or chemical processes using a metal catalyst, have been extensively investigated as biodegradable and renew- able polymers. However, biological methods are inefficient, and chemical processes involve harmful metals and organic solvents. Thus, more efficient and environmentally benign processes are necessary. In our studies, we hypothesized that innovative syntheses are best developed using chemical processes that take advantages of biological systems. Herein, we successfully obtained synthetic polymerases including an artificial molecular clamp to yield high-molec- ular-weight polymers without solvents or co-catalysts. This system is reminiscent of highly efficient DNA polymerases including a sliding clamp where the ring-shaped protein assembly of DNA polymerases plays an important role in the replication of polynucleotides. [1–7] Although the clamp does not have an active site, polymerization does not proceed well without the clamp. Similarly, cyclodextrins (CDs) are ring- shaped host molecules, which include various guests to form supramolecular complexes such as rotaxanes. [8–11] An early example of supramolecular catalysis [12–14] is the hydrolysis of activated phenyl esters using CDs. These catalysts have also been utilized as enzyme models. [15–20] Moreover, modern supramolecular catalysts using host– guest interactions have achieved highly efficient and selective reactions, including hydrolysis reactions, [19, 20] C ÀH bond activation, [23–25] epoxidation of olefins, [26–28] Diels–Alder reac- tions, [29–31] and 1,3-dipolar cycloadditions. [32, 33] The bases of supramolecular catalysts are selective molecular recognition and substrate activation. One limitation of these catalysts is product inhibition because of their complex design, but introduction of an artificial molecular clamp into supramolec- ular catalysts can resolve the problems. Herein, we show that cyclodextrins play an important role as an artificial molecular clamp in polymerization reactions. We selected b-CD as a supramolecular polymerization catalyst because it does not require a highly reactive catalytic center (metal complexes, cationic or anionic groups). CDs can include and activate lactones, yielding an oligomer tethered to a single CD at the end of the polymer chain. [34, 35] However, the produced oligo(lactone)s bearing a b-CD unit did not initiate the polymerization reaction. We hypothesized that an artificial molecular CD clamp attached to the active site of the b-CD plays an important role in the polymerization by holding the polymer chain and consequently securing the active site. First, we studied the polymerization activity of the a,b- TPA-dimer linked with terephthalamide between the a- and b-CDs for d-valerolactone (d-VL; Scheme 1). Polymeri- zations of d-VL initiated by CD dimers were carried out by stirring and heating a bulk mixture of the CD dimers and d- VL ([d-VL]/[CD unit] = 50) at 100 8C. Table 1 summarizes the polymerization of d-VL by CDs. Although intact a-CD did not initiate polymerization of d-VL (Entry 1), intact b-CD and a mixture of a- and b-CD resulted in low polymerization activities for d-VL under the same conditions (Entries 2 and 3). In contrast, the a,b-TPA-dimer displayed a significantly higher polymerization activity to give poly(d-VL) with M n = 11 000 (Entry 5). Because of the absence of the active b-CD site, the a,a-TPA-dimer showed a much lower polymerization activity (Entry 4). Thus, the molecular a-CD clamp connected to the active b-CD site through a covalent bond is important for the polymerization. Scheme 1. Polymerization of d-VL initiated by the a,b-TPA-dimer linked with terephthalamide between the a-CD (gray-blue) and b-CD (yellow). [*] Dr. Y. Takashima, Dr. M. Osaki, Dr. H. Yamaguchi, Prof. Dr. A. Harada Department of Macromolecular Science Graduate School of Science, Osaka University Toyonaka, Osaka, 560-0043 (Japan) E-mail: harada@chem.sci.osaka-u.ac.jp Prof. Dr. Y. Ishimaru Department of Functional Materials Science School of Engineering, Saitama University (Japan) Prof. Dr. A. Harada Core Research for Evolutional Science and Technology (CREST) Japan Science and Technology Agency (JST) Sanban-cho Building, 4F, 5 Sanban-cho, Chiyoda-ku Tokyo 102-0075 (Japan) [**] This research was supported by the CREST project, Japan Science and Technology Agency. The authors thank Seiji Adachi (Osaka University) for his helpful advice on the measurement of 2D NOESY spectra. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201102834. Zuschriften 7666  2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. 2011, 123, 7666 –7670