DOI: 10.1002/chem.200800988 Metal-Directed Dynamic Formation of Tertiary Structure in Foldamer Assemblies: Orienting Helices at an Angle Nicolas Delsuc, [a] Marie Hutin, [c] Victoria E. Campbell, [b] Brice Kauffmann, [a] Jonathan R. Nitschke,* [b] and Ivan Huc* [a] A number of non-natural folding oligomers—or folda- ACHTUNGTRENNUNGmers—have been shown to adopt well-defined helical or ex- tended conformations resembling the secondary structures of biopolymers. [1] Interest in foldamers stems from the pros- pect that if the forms of biopolymers can be mimicked, their functions may be mimicked as well and even be further ex- panded, thereby opening the perspective of countless appli- cations. Thus, one major line of development in foldamer chemistry is the investigation of function; for example, bio- logical activity [2, 3] and molecular-recognition properties. [4, 5] However, even in nature, isolated secondary structures ach- ieve little function relative to tertiary or quaternary struc- tures. Another line of foldamer development and a major challenge in synthetic chemistry is thus to elaborate strat- egies to design, produce, and characterize artificial, folded objects composed of several non-natural secondary ele- ments. Key steps recently taken in this direction have al- lowed the first characterizations of artificial “tertiary” or “quaternary” folded motifs in the solid state. [6] In this en- deavor, the objective is not simply to reproduce natural pat- terns using non-natural scaffolds, but also to explore pat- terns that do not exist in nature. Here we report on the use of metal complexes as dynamic connection elements be- tween oligomeric helical segments. Specifically, a metal com- plex was used to connect and define the relative orientation of two helices, as does a turn structure in proteins, but at an unconventional angle. A tetrahedral Cu I ion was shown to impart a roughly perpendicular orientation between two helices, whilst an octahedral Fe II center oriented two helices in an almost parallel fashion. Aromatic oligoamides (AOAs) of 8-amino-2-quinoline carboxylic acid adopt particularly stable helical conforma- tions in the solid state and in a wide variety of solvents. [7] They provide a firm foundation upon which to build in mod- ular fashion towards large multi-helical, folded architectures. Several reports describe the irreversible covalent attachment of AOAs. [6a, 8] Alternatively, dynamic linkages that let the system self-organize facilitate synthesis and allow one to use thermodynamic equilibration to probe a given systems in- trinsic preferences. [9] We thus set out to explore the use of reversible linkages based on metal complexes to connect AOAs. The dynamic formation of imine–Cu I complexes from amines, 6-methyl-2-formylpyridine and Cu I (Scheme 1) [10] was well-suited for this purpose, because it is simple to implement and because the two levels of reversi- [a] Dr. N. Delsuc, Dr. B. Kauffmann, Dr. I. Huc Institut EuropØen de Chimie et Biologie UniversitØ de Bordeaux—CNRS UMR5248 and UMS3033 2 rue Robert Escarpit, 33607 Pessac (France) Fax: (+ 33) 540002215 E-mail: i.huc@iecb.u-bordeaux.fr [b] V.E. Campbell, Dr. J. R. Nitschke Department of Chemistry, University of Cambridge Lensfield Road, Cambridge CB2 1EW (UK) Fax: (+ 44) 1223-336017 E-mail : jrn34@cam.ac.uk [c] Dr. M. Hutin DØpartement de chimie organique UniversitØ de Genve—Sciences II 30 quai Ernest-Ansermet, 1211 Genve 4 (Switzerland) Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.200800988. Scheme 1. Equilibrium between 1 and tetrahedral Cu I complex 2. Helical chirality (P/M) and chirality at the metal center (L/D) result in a mixture of three racemic pairs of diastereomers for 2 : PLP/MDM (2a), PDP/ MLM (2b), and PLM/PDM (2c).  2008 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim Chem. Eur. J. 2008, 14, 7140 – 7143 7140