Cell Membrane as a Model for the Design of Ion-Active Nanostructured Supramolecular Systems Virgil Percec* and Tushar K. Bera Roy & Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323 Received August 27, 2001; Revised Manuscript Received October 8, 2001 The synthesis and polymerization of six AB 3 tapered self-assembling methacrylate monomers (5a, 5b, 5c, 5d, 17a, and 17b) based on first generation alkyl substituted benzyl ether monodendrons (i.e., minidendrons) containing oligooxyethylene units at their focal point and the polymerizable group on their periphery are described. The corresponding polymers (6a, 6b, 6c, 6d, 18a, and 18b) self-assemble and subsequently self- organize in supramolecular networks that form a 2-D hexagonal lattice. This network consists of a continuous phase based on a paraffin barrier material perforated in a hexagonal array by ion-active channels constructed from the oligooxyethylenic units protected by the aromatic groups of the taper. Complexation of the oligooxyethylene channels of 6a-d with LiCF 3 SO 3 salt enhances the thermal stability of their hexagonal columnar (φ h ) liquid crystalline phase. The enhancement of the thermal stability of the φ h phase of both monomers and polymers up to 86 °C is also achieved by shifting the placement of the polymerizable group from the 3 position to the 4 position of the 3,4,5-trisubstituted AB 3 benzoate monodendrons. The design of these macromolecules was inspired by the bilayer fluid mosaic structure of the cell membrane. The lipid bilayer of the cell membrane that acts in its ordered state as a barrier to the passage of polar molecules was replaced with the paraffinic barrier, while the protein-based ionic channels were replaced with oligooxy- ethylenic-based channels. The resulted supramolecular material has the mechanical integrity required for the design of ion-active nanostructured supramolecular systems. Introduction The fluid mosaic model of the cell membrane 1,2 consists of a lipid bilayer containing active elements constructed from proteins. In its ordered state, this lipid bilayer represents an excellent barrier to the passage of polar molecules and therefore has the ability 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 the transfer of energy and materials and also act as catalysts. Simultaneously, the cell membrane has the ability to respond to changing external conditions that demand that certain molecules and ions pass through the lipid bilayer (Figure 1). Although the cell membrane is fluid, the proteins that frequently penetrate its bilayer structure are bound to the membrane mostly by hydrophobic interactions. A similar synthetic supramolecular system capable to be externally regulated could have immense technological implications for areas such as selective membranes, ionic, protonic, and electronic conductors, enzymatic-like catalysis, energy transfer and conversion, particularly if all these functions could be incorporated into the same unit. A bioinspired synthetic system must not copy the cell membrane concept but use its principles as models to create a non- natural system that is adaptable to the current technological concepts. Therefore, the lipid bilayer barrier may be replaced with an alternative barrier material that has the required combination of order and fluidity at least during certain stages of its self-assembly and self-organization. Simulta- neously, the membrane proteins may be replaced with currently available ion-selective or ion-active elements such as crown ethers or polypodants that are equipped with the ability to spontaneously self-assemble into channels that are incorporated in the barrier part of the material. By analogy with a protein-based ionic channel, this material should be able to flux energy and materials among various compart- ments. New synthetic mechanisms to externally regulate the on and off states of the channel should be discovered and/or designed. Therefore, bioinspired design and synthesis are not always expected to duplicate concepts from Nature but also can be used to design new concepts that may be suitable for related or different applications. With the goal of creating ion-active self-regulated su- pramolecular systems, we have first pioneered the design and synthesis of conventional side-chain, 2 main-chain, 3 and macrocyclic 4 liquid crystalline polymers and oligomers containing crown ethers and polypodants. In all cases, calamitic mesogenic groups have been employed to induce in these systems 1-D or 2-D liquidlike nematic and smectic order complemented by ionic activity. Polymerization has been used as the most frequent tool to enable mechanical integrity and provide a broad range of thermal stability of the liquid ordered state. 5 Some of this research has been reviewed. 6 167 Biomacromolecules 2002, 3, 167-181 10.1021/bm010138p CCC: $22.00 © 2002 American Chemical Society Published on Web 12/04/2001