DOI: 10.1002/chem.201202342 MolecularDescription of the Propagation of Chirality from Molecules to Complex Systems: Different Mechanisms Controlled by Hydrophobic Interactions Fabrizio Marinelli,* [a] Alessandro Sorrenti, [b, c] Valentina Corvaglia, [b] Vanessa Leone, [a] and Giovanna Mancini* [b, c] Introduction Most chiral systems in nature are found in only one of their mirror-image forms, this being true from the level of mole- cules to that of complex biological systems, such as the spiral shell of snails and some climbing plants, which show a preferential handedness in their spiraling and twining, re- spectively. The break of chiral symmetry raises a number of questions regarding its origin, the propagation of chirality from simple molecules to complex biological systems, and the mechanisms of such propagation. [1–7] Many reports suggest that hydrogen-bond, p–p stacking, cation–p, and Coulombic interactions play a pivotal role in the propagation of chirality. [8–10] Investigations of model sys- tems, such as aggregates of amphiphilic molecules, [11–17] sug- gested, in some cases, that hydrophobic interactions also might control the transfer of chirality from the components to the aggregates. [12, 18] Because hydrophobic interactions control many processes that involve biomolecules, for exam- ple, processes occurring in cell membranes, it is conceivable that they could have been involved in the propagation proc- esses responsible for the chiral homogeneity of complex bio- logical systems. However, the role of such interactions in the transfer of chirality has been elusive and difficult to depict until now. This lack of understanding might also be due to the lack of a detailed molecular inspection of chirality prop- agation in model systems such as dye/surfactant heteroag- gregates, which are excellent models for investigating the transfer of chirality. [19] An atomistic description would better define the role of hydrophobic interactions in these process- es and it would shed light on the mechanisms responsible for chiral homogeneity in nature. Herein, a combined exper- imental (based on absorption spectroscopies) and theoreti- cal approach allowed the description of the molecular inter- actions underlying the transfer of chirality from the chiral cationic surfactants (S)- and (R)-N,N-dimethyl-N-(1-phenyl- ethyl)hexadecan-1-ammoniumbromide, SC16 and RC16, and (S)-N,N-dimethyl-N-(1-phenylethyl)dodecan-1-ammo- niumbromide, SC12 (Scheme 1) to the aggregates they form with Congo Red (CR). Furthermore, it is shown that the ex- pression of chirality depends on a fine balance between electrostatic and hydrophobic interactions. Abstract: In this work a combined the- oretical and experimental approach was used to elucidate and describe at the molecular level the basic interac- tions that drive the transfer of the chiral information from chiral surfac- tant molecules to dye/surfactant assem- blies. It was found that both hydropho- bic interactions and relative concentra- tions strongly influence the chiroptical features of the heteroaggregates. In particular it was observed that, depend- ing on the length of the surfactant hy- drophobic chain, the chiral information is transferred to the dye by stabilizing an enantiomer either of a chiral con- former or of a chiral topological ar- rangement. These findings underline the role of hydrophobic interactions in the transfer of chirality and provide an example of the potential of in silico simulations for providing an accurate description of the process of chirality propagation. Keywords: chirality transfer · circu- lar dichroism · hydrophobic interac- tions · metadynamics · self-assem- bly [a] Dr. F. Marinelli, + Dr. V. Leone Theoretical Molecular Biophysics Group Max Planck Institute of Biophysics Max-von-Laue Strasse 3, 60438 Frankfurt am Main (Germany) Fax: (+ 49) 69-6303-4502 E-mail: Fabrizio.Marinelli@biophys.mpg.de [b] Dr. A. Sorrenti, + V. Corvaglia, Dr. G. Mancini CNR, Istituto di Metodologie Chimiche (IMC) and Dipartimento di Chimica Università degli Studi di Roma “La Sapienza” P.le A. Moro 5, 00185 Roma (Italy) Fax: (+ 39) 06-4904-21 E-mail : giovanna.mancini@uniroma1.it [c] Dr. A. Sorrenti, + Dr. G. Mancini Centro di Eccellenza Materiali Innovativi Nanostrutturati per Applicazioni Chimiche Fisiche e Biomediche (CEMIN) Via Elce di Sotto 8, 06123 Perugia (Italy) [ + ] Contributed equally to this work. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201202342. Chem. Eur. J. 2012, 00,0–0 # 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim These are not the final page numbers! ÞÞ &1& FULL PAPER