DOI: 10.1002/chem.201002193 Self-Assembly of Chiral trans-Cyclobutane-Containing b-Dipeptides into Ordered Aggregates Esther Gorrea, [a] Pau Nolis, [b] Elisabeth Torres, [a] Eric Da Silva, [a] David B. Amabilino, [c] VicenÅ Branchadell,* [a] and Rosa M. OrtuÇo* [a] Dedicated to the memory of Professor Rafael Suau Introduction The study of non-covalent interactions (e.g., hydrogen bonds) that could be responsible for the hierarchical self-as- sembly of molecules into fibrils, which in turn could interact with one another to form gels, is of fundamental importance in the rational design and preparation of materials suitable for different applications. [1] For instance, gel-phase nanoma- terials are useful in biomedicine, [2] asymmetric catalysis [3] and also as organic conducting materials. [4] Gels are current- ly used in cosmetics, food or pharmaceuticals. Low-molecu- lar-weight gelator compounds (LMWGs) are especially at- tractive because they consist of small molecules that contain hydrogen-bonding functional groups and/or apolar chains, which can induce order or piling through solvophobic van der Waals interactions. Structural studies are indispensable for knowledge and tuning of their properties, such as gel sta- bility, the scope of gelated solvents and morphology of the gels. Therefore, the systematic study of structural parame- ters and the relationship with the gel properties is a field of growing interest. [5] Different kinds of LMWGs have been described, includ- ing linear or branched molecules. Among the latter, C 3 -sym- metric organogelators have been described. [6] Peptide-based gelators are prominent because they provide amide groups that favour supramolecular interactions, such as those in proteins. In fact, the biomimetic self-assembly of some func- tional fibrous nanomaterials has been inspired by natural proteins. [7] We are interested in the use of the cyclobutane structural unit as a molecular construction element in peptides and ureas [8] to induce well-defined molecular conformations for these compounds in the solution state, as well as to form regular fibrillar networks for related materials. According to this research program, we have synthesised a variety of Abstract: Two chiral synthetic b-dipep- tides have been constructed, one with two trans-cyclobutane residues and the other with one trans and one cis frag- ment, 1 and 2, respectively, and investi- gated to get insight into the non-cova- lent interactions responsible for their self-assembly to form ordered aggre- gates, as well into parameters such as their morphology and size. Experimen- tal evidence of the formation of these assemblies was provided by spectrosco- py, microscopy and X-ray diffraction experiments that suggest the formation of nanoscale helical aggregates. This process involves a conformational change in the molecules of each dipep- tide with respect to the preferred con- formation of the isolated molecules in solution. A high-resolution NMR spec- troscopy study allowed the determina- tion of the dynamics of the gelation process in [D 8 ]toluene and the sol–gel transition temperature, which was around 270 K in this solvent at a con- centration of 15 mm. NMR spectrosco- py experiments also provided some in- formation about conformational changes involved in the sol–gel transi- tion and also suggested a different gel packing for each dipeptide. These ob- servations have been nicely explained by computational studies. The self-as- sembly of the molecules has been mod- elled and suggested a head-to-head molecular arrangement for 1 and a head-to-tail arrangement for 2 to give helical structures corresponding to hy- drogen-bonded single chains. These chains interact with one another in an antiparallel way to afford bundles, the significant geometry parameters of which fit well to the main peaks ob- served in wide-angle X-ray diffraction spectra of the aggregates in the solid state. Keywords: chirality · peptides · mo- lecular modeling · organogels · self- assembly [a] E. Gorrea, Dr. E. Torres, Dr. E. DaSilva, Prof. V. Branchadell, Prof. R. M. OrtuÇo Departament de Química, Universitat Autònoma de Barcelona 08193 Bellaterra (Spain) Fax: (+ 34) 935811265 E-mail: vicenc.branchadell@uab.es rosa.ortuno@uab.es [b] Dr. P. Nolis Servei de Ressonància Magntica Nuclear Universitat Autònoma de Barcelona, 08193 Bellaterra (Spain) [c] Prof. D. B. Amabilino Institut de Cincia de Materials de Barcelona (CSIC) Campus UAB, 08193 Bellaterra (Spain) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201002193.  2011 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim Chem. Eur. J. 2011, 17, 4588 – 4597 4588