Cell membrane as a model for the design of semi¯uorinated ion-selective nanostructured supramolecular systems Virgil Percec p and Tushar K. Bera Department of Chemistry, Roy and Diana Vagelos Laboratories, University of Pennsylvania, Philadelphia, PA 19104-6323, USA Received 7 November 2001; accepted 14 December 2001 Abstract ÐThe synthesis and polymerization of two AB 3 tapered, self-assembling methacrylate monomers 12 and 13) based on a ®rst generation semi¯uorinated alkyl-substituted monodendron i.e. minidendron) are described. These monomers contain either a benzo-15- crown-5 derivative, which is incorporated via the esteri®cation of 4 0 -hydroxymethyl-1,4,7,10,13-pentaoxabenzocyclopentadecane or a podant group, which is incorporated via the monoesteri®cation of tetraethylene glycol at its focal point, and both bear polymerizable groups on their periphery. The corresponding polymers 14 ± 16) self-assemble and subsequently self-organize into supramolecular networks, which form a 2-D hexagonal columnar lattice via the ¯uorophobic effect. These networks consist of a continuous phase, which is based on the semi¯uorinated, paraf®nic barrier layer and which is perforated in a hexagonal array by ion-selective or ion-active channels constructed from the benzo crown-ether and tetraethylene glycol respectively. The replacement of alkyl groups from the periphery of the tapered mono- dendrons with semi¯uorinated ones induces the self-assembly and, subsequently, the self-organization into supramolecular networks. These networks form 2-D hexagonal columnar lattices with thermal stability in some cases of up to 1108C. The design of such functional supramolecular systems was inspired by the bilayer ¯uid mosaic structure of the cell membrane. The lipid bilayer of the cell membrane, which in its ordered state acts as a barrier to the passage of polar molecules, was replaced with the semi¯uorinated paraf®nic barrier, while the protein-based ionic channels were replaced with benzo-15-crown-5 and tetraethylene glycol based channels. The resulting supramolecular material has the mechanical integrity required for both ion-active and ion-selective nanostructured supramolecular systems. q 2002 Elsevier Science Ltd. All rights reserved. 1. Introduction The ¯uid mosaic model of the cell membrane 1,2 consists of a self-assembled lipid bilayer containing protein-based active elements that are co-assembled in the bilayer structure. In its ordered state, the lipid bilayer is an excellent barrier to polar molecules and, as a consequence, has the capability to partition discrete metabolic aqueous compartments. The impermeability of the lipid bilayer to polar or charged molecules allows the solute concentration on each of its sides to differ dramatically. The second function of the lipid bilayer is to accommodate proteins with various tertiary structures that are able to provide and control the transfer of energy and materials and also to act as catalysts. Simultaneously, the cell membrane has the ability to respond to changing external conditions that may demand that certain molecules and ion-pairs pass through the lipid bilayer Fig. 1). The proteins that penetrate the bilayer structure are bound to the membrane mostly by hydrophobic interactions. In its disordered state, i.e. above the physio- logical temperature, the lipid bilayer loses its barrier and transport properties and therefore the cell membrane loses its fundamental functions. A similar synthetic supramolecular system capable of being externally regulated could have immense technological implications for areas such as selective membranes, ionic, protonic and electronic conductors, enzyme-like catalysis, energy transfer and conversion, particularly if all these applications could be exhibited by one self-assembled unit. A synthetic system must not copy the cell membrane concept, but use its principles as a model to create a system that is adaptable to the current technological methods. Therefore, the lipid bilayer barrier may be replaced with an alternative barrier material that has the required combi- nation of order and ¯uidity, at least during certain stages of its self-assembly and self-organization. Simultaneously, the membrane proteins may be replaced with currently avail- able ion-selective or ion-active elements such as crown- ethers or polypodants. The latter should be equipped with the ability to spontaneously self-assemble into channels, which are incorporated in the barrier part of the material. By analogy with a protein-based ionic channel, this material should be able to ¯ux energy and materials between various compartments. New synthetic mechanisms to externally regulate the on and off states of the channel should be discovered and/or designed. Therefore, bio-inspired design and synthesis are not necessarily expected to duplicate Tetrahedron 58 2002) 4031±4040 Pergamon TETRAHEDRON 0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved. PII: S0040-402002)00266-1 Keywords: hexagonal columnar; dendritic monomer; semi¯uorinated alkyl group; cell membrane; polymerization; nanostructured supramolecular network. p Corresponding author. Tel.: 11-215-573-5527; fax: 11-215-573-7888; e-mail: percec@sas.upenn.edu