Microscopic and macroscopic anisotropy in supramolecular hydrogels of histidine-based surfactants Andreea Pasc a, * , Patrick Gizzi b , Nicolas Dupuy a , Stéphane Parant b , Jaafar Ghanbaja c , Christine Gérardin a a LERMAB, Nancy-University, BP 239, 54506 Vandoeuvre-lès-Nancy, France b SRSMC UMR 7565, Nancy-University, BP 239, 54506 Vandoeuvre-lès-Nancy, France c SCMEM, Nancy-University, BP 239, 54506 Vandoeuvre-lès-Nancy, France article info Article history: Received 29 May 2009 Revised 12 August 2009 Accepted 26 August 2009 Available online 1 September 2009 Keywords: Amino acid Surfactant Hydrogel Supramolecular Soft matter abstract The synthesis of novel histidine-based surfactants and their self-assembling properties into anisotropic microscopic and macroscopic spaces are reported. Below pH 8, surfactant molecules self-assemble into micelles whereas hydrogelation occurs above pH 8 even at very low concentrations (0.3%w/v). Structure, size, and morphology of the fiber-like lamellar aggregates were determined by SAXS and WAXS measure- ments, polarized optical microscopy, transmission and scanning electron microscopy, and linear and cir- cular dichroism. Ó 2009 Elsevier Ltd. All rights reserved. Soft materials known as hydrogels have gathered recently much attention, owing to their unique properties and versatile applications in many areas, from applied chemistry to biomedicine. In this respect, a major challenge is the development of biocompatible and/or biode- gradable low molecular weight hydrogelators with well-defined chemical structures and predictable properties, as compared to poly- mers. To this end, amphiphilic molecules, namely surfactants, appear as suitable candidates since they form well-characterized supramo- lecular structures. Appropriately grafted with amino acid moieties they are able to form stimuli sensitive hydrogels. The design of chiral low molecular weight gelators (LMWGs) with chirality transcribed to the supramolecular architectures is of particular interest due to the promising features and practical applications in the field of nanomaterials, tissue engineering, drug carriers, molecular recognition, or microfluidic devices. 1 Amino acid derivatives could provide such optical activity due to their intrinsic chirality. They have already been used success- fully as building blocks for hydrogels, based on weak, non-covalent interactions such as hydrogen bonding, p–p stacking and the hydrophobic effect: compounds based on phenylalanine, 2 valine, isoleucine, lysine, 3 cystine, 4 L-alanine, 5 have already been reported. Furthermore, some surfactants such as amphiphiles, 6 bola-amphi- philes, 7 and gemini amphiphiles, 8 can be used as gelators to form supramolecular hydrogels. In this work, our interests focus on supramolecular hydrogels of L-histidine amphiphilic pseudo-peptide which involves discrete chi- ral molecular components with a well-defined chemical structure. The presence of biocompatible and biodegradable moieties makes them suitable for biological applications. A triblock pseudo-peptidic amphiphile (alkyl-polyethylenoxide-aminoacid, C 14 H 29 -(EO) 3 -AA 3 ), designated as GlyGlyHisEO 3 C 14 , was synthesized and characterized. The morphology of supramolecular hydrogels induced by this LMWG GlyGlyHisEO 3 C 14 was investigated by using microscopy techniques. Both linear dichroism (LD) and circular dichroism (CD) were used to investigate the gel formation and the interactions between the gel and amino acids, suited for chiral discrimination within induced chi- ral spaces. The triblock (hydrophobic–hydrophilic–peptidic) gelator inves- tigated in this work was synthesized step-by-step, similarly to a pep- tide coupling. The reaction route is outlined in Scheme 1. In the first step, 2,2 0 -(ethylenedeoxy)bis(ethyleneamine) was monoprotected by tritylation. The monoprotection was easily realized by using a large excess of diamine which can be removed at the end of the reac- tion by a simple extraction with an aqueous phase. The alkyl group is then grafted by amidation of the tetradecanoic acid using the pep- tide coupling method. Similarly, the amino acids are successively introduced by using BOP coupling reagent. Then, the Boc protective group was removed with gaseous HCl in a mixture of Et 2 O and THF. The resulting products are obtained in good to excellent yields. 0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetlet.2009.08.093 * Corresponding author. E-mail address: andreea.pasc@lesoc.uhp-nancy.fr (A. Pasc). Tetrahedron Letters 50 (2009) 6183–6186 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet