Molecular Imprinting Inside Dendrimers Steven C. Zimmerman,* Ilya Zharov, Michael S. Wendland, Neal A. Rakow, and Kenneth S. Suslick* Contribution from the Department of Chemistry and Beckman Institute for AdVanced Science and Technology, UniVersity of Illinois at Urbana-Champaign, Urbana, Illinois 61801 Received April 21, 2003; E-mail: sczimmer@uiuc.edu Abstract: Synthetic hosts capable of binding porphyrins have been produced by a mixed-covalent- noncovalent imprinting process wherein a single binding site is created within cross-linked dendrimers. Two synthetic hosts were prepared, using as templates 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin and 5,10,15,20-tetrakis(3,5-dihydroxyphenyl)porphyrin. These two templates were esterified with, respectively, fourth- and third-generation Fre ´ chet-type dendrons containing homoallyl end-groups. The resulting tetra- and octadendron macromolecules underwent the ring-closing metathesis reaction using Grubbs’ Type I catalyst, RuCl 2(P(C6H5)3)2(CHCH2C6H5), to give extensive interdendron cross-linking. Hydrolytic removal of the porphyrin cores afforded imprinted hosts whose ability to bind porphyrins with various peripheral substituents was investigated by UV-visible spectrophotometric titrations and size exclusion chromatog- raphy. The results indicate a high yield of imprinted sites that show high selectivity for binding of porphyrins capable of making at least four hydrogen bonds, but only a moderate degree of shape selectivity. Introduction Host-guest chemistry has emerged as a central paradigm within organic chemistry. 1 The design and synthesis of diverse host molecules that selectively and tightly complex many different classes of guest molecules have been notably success- ful. As effective as this approach has been, especially for small molecule hosts, the requirement to prepare hosts bond by bond through multistep synthetic routes has limited their widespread application. Furthermore, each new target guest typically requires an entirely new host design and development program. Two strategies that have the potential to significantly extend the host-guest approach involve molding an organic receptor around the guest “template”. The first, using molecularly imprinted polymers (MIP), was initially described in Wulff’s seminal 1972 report, 2 in which a matrix was polymerized around the template molecules, followed by removal of the template; this leaves host cavities that, ideally, retain a shape and functional group complementarity to the guest-template. This early synthesis of a MIP is referred to as the covalent approach because the template is reversibly linked to the matrix by covalent bonds. 3 A noncovalent approach, in which one or more monomers complex the template, was pioneered by Mosbach and co-workers and is now the most commonly used method of MIP synthesis. 4 Subsequently, mixed covalent-noncovalent methods were developed 5 as well as numerous related ap- proaches. 6,7 Indeed, molecularly imprinted polymers (MIPs) have been among the most extensively studied host-guest systems. MIPs have several drawbacks, however, including incomplete template removal and slow mass transfer; 6,7-9 their practical application is also severely limited by the heterogeneity of the binding sites for which a broad range of affinities are observed. 6,10 A second strategy for rapid host construction has emerged more recently. It uses a dynamic combinatorial library (DCL) of hosts, in which one or more members are bound to and stabilized by the guest molecule. 11-13 The molding process in the DCL approach is different in two ways. First, the molding uses reversible reactions so that ineffective hosts may be sacrificed in favor of superior ones. The DCL approach is further distinguished in that the molded receptors each contain a single binding site so that individual receptors or classes of receptors can be separated, characterized, and studied in solution. We recently described a “monomolecular imprinting” ap- proach, which contains elements of both the DCL and the mixed-covalent-noncovalent imprinting approaches and pro- (1) ComprehensiVe Supramolecular Chemistry; Lehn, J.-M., Series Ed.; Elsevier Science Ltd.: New York, 1996; Vols. 1-2. Lehn, J.-M. Angew. Chem., Int. Ed. Engl. 1988, 27, 89-112. Cram, D. J. Angew. Chem., Int. Ed. Engl. 1988, 27, 1009-1020. (2) Wulff, G.; Sarhan, A. Angew. Chem., Int. Ed. 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Nature 1993, 361, 645-647. (11) Cousins, G. R. L.; Poulsen, S.-A.; Sanders, J. K. M. Curr. Opin. Chem. Biol. 2000, 270, 270-279. (12) Lehn, J.-M.; Eliseev, A. V. Science 2001, 291, 2331-2332. (13) Klekota, B.; Miller, B. L. Trends Biotechnol. 1999, 17, 205-209. Published on Web 10/10/2003 13504 9 J. AM. CHEM. SOC. 2003, 125, 13504-13518 10.1021/ja0357240 CCC: $25.00 © 2003 American Chemical Society