This journal is c The Royal Society of Chemistry 2012 Chem. Commun., 2012, 48, 12011–12013 12011 Cite this: Chem. Commun., 2012, 48, 12011–12013 Amino acid–bile acid based molecules: extremely narrow surfactant nanotubes formed by a phenylalanine-substituted cholic acidw Leana Travaglini, a Andrea D’Annibale, a Karin Schille´n, b Ulf Olsson, b Simona Sennato, c Nicolae V. Pavel a and Luciano Galantini* a Received 20th August 2012, Accepted 26th October 2012 DOI: 10.1039/c2cc36030f An amino acid-substituted bile acid forms tubular aggregates with inner and outer diameters of about 3 and 6 nm. The diameters are unusually small for surfactant self-assembled tubes. The results enhance the spectrum of applications of supramolecular tubules and open up possibilities for investigating a novel class of biological amphiphiles. Self-associating molecules that are biocompatible have attracted growing interest in the last few decades for their employment in the preparation of nanostructured biomaterials. Amino acid-based molecules, such as peptides, are among the most investigated, particularly due to their ability to self-organize into many supra- molecular structures that in some cases are sensitive to external stimuli. 1 Bile acids constitute a further class of self-assembling molecules of biological importance. 2 Depending on the external conditions and the bile acid type, they form systems of globular 3 or rod-like 4 aggregates as well as gel fibrils and tubules. 5 Moreover, derivatives are affordable by relatively small modifications of their molecular structure, which can provide other supramolecular organizations, e.g. lamellae and vesicles, 6 and additional self- association properties, such as extreme gelation efficiency, stimuli responsiveness and aggregate charge tunability. 7 With this back- ground, this work was inspired by the general idea of preparing new molecules by merging amino acid and bile acid moieties. To this purpose a bile acid derivative was synthesized by introducing an L-Phe residue on the rigid skeleton of the cholic acid (HC), to form the 3b-(2 0 -(S)-amino-3 0 -phenylpropanamido)- 7a,12a-dihydroxy-5b-cholan-24-oic acid (b-L-PheC) as reported in ESIw (Fig. 1). Unlike the amino acid-conjugated bile acids available in nature, this molecule presents a free amino group, while keeping its carboxylic function unmodified, and is therefore amphoteric. The molecule presents a complex amphiphilic structure and opens up possibilities for investigating a novel class of self-assembling compounds of biological origin that combine properties of both bile acid and amino acid based molecules. Preliminary solubility tests at different pH values were performed on the derivative in pure water, 60 mM sodium carbonate–bicarbonate buffer and hydrochloric acid aqueous solutions. b-L-PheC is insoluble in pure water (pH = 5.9) where it carries no neat charge. Conversely, homogeneous samples are obtained under basic (pH = 10.0) and acidic (pH = 1.1) conditions, where the molecule is negatively and positively charged, respectively. At pH = 10.0, the derivative self-assembles into small micelles. The change from basic to acidic conditions causes the movement of the charge from the carboxylic to the amino group, situated at the opposite side of the molecule. This results in a significant change of its self-assembly behavior. In fact, hydrogels are obtained for b-L-PheC at pH = 1.1, in the presence of added electrolyte (Fig. 2). The gels were observed for 18.0 and 36.0 mM b-L-PheC samples in the presence of 0.15 M NaCl at room temperature after 24 hours of the sample preparation. Cryogenic transmission electron microscopy (cryo-TEM) images show that elongated structures with a monodisperse cross section constitute the b-L-PheC gel (Fig. 2b and Fig. S1 in ESIw). The structures present an inhomogeneous contrast of the cross section that is typical of tubular morphologies (darker at the edges with respect to the middle). The tubes appear with a very long persistence length, which suggests that they are rigid and formed by an ordered or quasi-crystalline supramolecular packing of the monomers. Atomic force micro- scopy (AFM) performed on a dried sample (Fig. 2b) confirms the Fig. 1 Molecular structures of b-L-PheC and its precursor HC. a Department of Chemistry, ‘‘Sapienza’’ University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy. E-mail: l.galantini@caspur.it; Fax: +39 06490631; Tel: +39 0649913687 b Division of Physical Chemistry, Center for Chemistry and Chemical Engineering, Lund University, SE-221 00 Lund, Sweden c Department of Physics and CNISM, ‘‘Sapienza’’ University of Rome, P.le Aldo Moro 5, 00185 Rome, Italy w Electronic supplementary information (ESI) available: Synthesis of the b-L-PheC molecule; description of cryo-TEM, AFM, CD and SAXS measurements and gel SAXS interpretation; cryo-TEM images of the b-L-PheC gel; distribution of the heights of AFM images; SAXS spectra of b-L-PheC solutions at pH 1.1 and 55 1C; UV absorption and CD spectra of b-L-PheC solutions at pH 1.1 and at different tempera- tures. See DOI: 10.1039/c2cc36030f ChemComm Dynamic Article Links www.rsc.org/chemcomm COMMUNICATION Published on 29 October 2012. Downloaded by Lund University on 02/10/2013 23:34:04. View Article Online / Journal Homepage / Table of Contents for this issue