Control of Rapid Phase Transition Induced by Supramolecular Complexation of -Cyclodextrin-Conjugated Poly(ǫ-lysine) with a Specific Guest Hak Soo Choi, Tooru Ooya, Shintaro Sasaki, and Nobuhiko Yui* School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Tatsunokuchi, Ishikawa 923-1292, Japan Received February 27, 2003; Revised Manuscript Received April 16, 2003 ABSTRACT: -Cyclodextrin-conjugated poly(ǫ-lysine) (-CDPL) was synthesized and used as a polymeric host for inclusion complexation with 3-trimethylsilylpropionic acid (TPA). The specific host-guest interaction was analyzed by electrospray ionization mass and X-ray diffraction spectroscopies. In this system, TPA included into the hydrophobic cyclodextrin cavity acted as a physical cross-linker by cooperative hydrophobic and ionic interactions, which gave an important role in viscosity or transmittance changes near physiological conditions. The pronounced effect of pH on the change of viscosity was supported by rheological data. On the other hand, reversible phase transitions of the supramolecular assembling system occurred very rapidly in response to minute changes of temperature, which was verified by UV-vis measurements. The delicate control of critical aggregation temperature was accomplished by changing the degree of substitution as well as varying molar feed ratio or solution concentrations across their upper critical solution temperature. This rapid and elaborate supramolecular assembling system is promising as smart materials and can find a broad range of applications. Introduction Cyclodextrins (CDs), composed of six, seven, or eight D-glucopyranose units, possess truncated cone-shaped hydrophobic cavities, at the narrow side are the primary and at the wide side the secondary hydroxyl groups. No hydroxyl groups are inside the cavity, so that this region of the molecule is hydrophobic and can include various hydrophobic guest molecules, such as organic, inorganic, and biological molecules to form stable host-guest inclusion complexes. 1 The inclusion complexation of these host-guest systems occurs through various in- teractions, such as hydrogen bonding, van der Waals, electrostatic, or hydrophobic interactions. Although the magnitude of bond energy is not so large compared to a covalent bond, physical interaction plays a key role in many chemical and biological systems. In this sense, CDs have been extensively studied as supramolecular receptors. 2 Recently, to improve the molecular binding abilities of the native CDs, a great deal of effort has been concentrated on the design and synthesis of novel CD derivatives. A wide variety of native and chemically modified CDs have been employed in the studies of their molecular recognition behaviors with various guest molecules. 3,4 On the basis of these studies, we recently designed a new biocompatible and biodegradable poly- meric host by chemical conjugation of CDs into poly(ǫ- lysine) main-chain (CDPL), which was used to construct unique supramolecular-structured assembly with 3-tri- methylsilylpropionic acid (TPA). 5,6 Structurally, TPA has two specific characteristic parts, hydrophobic and ionic groups at both ends, which play a dominant role in inducing dual complexation phenomena: host-guest interaction and cooperative ionic interaction with su- pramolecular cationic CDPL. In the -CDPL/TPA sys- tem, the induction time of supramolecular aggregates observed by a stopped flow spectrophotometer was found to be very short (within 100 ms), which resulted from the inclusion complexation between the polymeric hosts and specific guest molecules. At the same time, they are likely to associate each other because of the cooperative intermolecular interactions between the inclusion com- plexes. On the basis of this dual complex interactions, this supramolecular assembly showed rapid responses with a small change of pH or temperature (Figure 1). 6 In this study, we focused on investigating the specific interactions affecting the supramolecular assembly system and controlling the critical aggregation point with small changes of temperature in aqueous media. The degree of substitution (DS) of CDs per PL monomer unit, molar feed ratio, and solution concentrations were changed to evaluate how the critical aggregation tem- perature in the -CDPL/TPA system could be affected. Furthermore, the effect of pH on the viscosity change in the mixture solution of -CDPL and specific anionic guest molecules was investigated by rheological mea- surements. The obtained results suggest that changing the compositions and solution concentrations of -CDPL systems could modulate the critical response rapidly and reversibly with a small change of pH or temperature. Results and Discussion Preparation of Inclusion Complexes. The syn- thetic results of -CDPL are presented in Table 1. DS and molecular weight of copolymers were determined by the peak integration in 1 H NMR spectra. In our previous report, 6 the inclusion complexation of -CDPL with TPA was confirmed by 2D-NMR spec- troscopy. However, the stoichiometry was not checked. To investigate the stoichiometry of R- or -CD with TPA, electrospray ionization (ESI) spectroscopy coupled on external source Fourier transform ion cyclotron reso- nance mass spectrometry (FTMS) was used. As shown * To whom correspondence should be addressed: Tel +81-761- 51-1640; FAX +81-761-51-1645; e-mail yui@jaist.ac.jp. 5342 Macromolecules 2003, 36, 5342-5347 10.1021/ma034259o CCC: $25.00 © 2003 American Chemical Society Published on Web 06/20/2003