Supramolecular Chemistry DOI:10.1002/ange.200701272 A Chemical-Responsive Supramolecular Hydrogel from Modified Cyclodextrins** Wei Deng, Hiroyasu Yamaguchi, Yoshinori Takashima, and Akira Harada* The design and preparation of molecular hydrogels has attracted increasing attention because of their intrinsic scientific interest and technological applications. Elegant hydrogels were reported to lead to new polymeric systems with remarkable properties. [1] Supramolecular gels, in partic- ular, which are held together by noncovalent bonds and showing responses to external stimuli, have the potential to act as biodegradable materials in drug-delivery systems and chemical sensors. [2] Supramolecular gels form from the self- assembly of subunits and lead to the formation of a three- dimensional network of intertwined, elongated fibrils that immobilize the solvent molecules on the macroscopic scale. It is well known that cyclodextrins (CDs) incorporate various guest compounds into their cavities through hydrophobic interactions to form inclusion complexes in aqueous media. We have reported many kinds of supramolecular polymers from modified CDs. [3] Furthermore, CD units can congregate together through hydrogen-bonding interactions, as a conse- quence of the abundant number of OH groups on the CD ring. Many research groups have reported that the mixture of CDs with polymers resulted in the formation of supramolec- ular gels. [4] Biodegradable gels without a polymeric backbone seem more advantageous and more applicable to biological applications and environmental protection. To our knowl- edge, there is no report about gel formation from modified CDs in aqueous solutions in the absence of polymers. [5] Herein, we report for the formation of a supramolecular gel from aqueous solutions of modified CDs. Previously, we reported the formation of a supramolecular oligomer from 6-aminocinnamoyl-b-CD derivative 1 (Scheme 1). [6] Compound 1 forms crystals from a super- saturated solution. The X-ray structure shows that 1 forms intermolecular complexes in a tail-to-tail fashion and so the dimer stacks tightly through the formation of intermolecular hydrogen bonds to form a head-to-head channel-type struc- ture. [7] Therefore, much attention has been paid to the modification of 1 to avoid formation of the dimer. [3b,6c] In the current study, a trinitrophenyl group was directly linked to 1 to give [N-(2,4,6-trinitrophenyl)-6-amino-trans- cinnamoyl]-b-CD (2 ; Scheme 1). The 2D ROESY NMR spectrum (Figure 1) shows the rotational NOE (ROE) interactions between the inner protons of the CD and both protons of 2,4,6-trinitrophenyl (TNB) as well as the cinnamic protons, thus indicating that these units are included in the CD cavities, and that the trinitrophenyl group, a traditional stopper for a-CDs, acts as a good guest for b-CD. The observed C(1)H protons are widely dispersed in the range from d = 4.8 to 5.5 ppm, which is due to the reduction of the sevenfold symmetry of the modified CD after inclusion of the substituent at the 6-position of the b-CD in the other CD cavity. [8] Protons a and b in the cinnamoyl moiety show strong Scheme 1. Compounds 1–5 andthesynthesisof 2. [*] Dr.W.Deng,Dr.H.Yamaguchi,Dr.Y.Takashima,Prof.Dr.A.Harada DepartmentofMacromolecularScience GraduateSchoolofScience OsakaUniversity Toyonaka,Osaka560-0043(Japan) Fax:(+ 81)6-6850-5445 E-mail:harada@chem.sci.osaka-u.ac.jp Homepage:http://www.chem.sci.osaka-u.ac.jp/lab/harada/eng/ lab-01e.htm [**] ThisworkwaspartiallysupportedbyGrantin-Aidno.S14103015for ScientificResearch,andhasbeenconductedwithfinancialsupport fromthe21stCenturyCOE(CenterofExcellence)programofthe MinistryofEducation,Culture,Sports,Science,andTechnology, Japan. SupportinginformationforthisarticleisavailableontheWWW underhttp://www.angewandte.orgorfromtheauthor. Zuschriften 5236 # 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. 2007, 119, 5236–5239