Supporting Information

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1 Supporting Information Copyright Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2013 More than Meets the Eye: Conformational Switching of a Stacked Dialkoxynaphthalene Naphthalenetetracarboxylic diimide (DAN NDI) Foldamer to an NDI NDI Fibril Aggregate Cameron Peebles, Rebecca Piland, and Brent L. Iverson* [a] chem_ _sm_miscellaneous_information.pdf

2 General methods: All commercially available chemicals were purchased from Aldrich, Fisher Scientific or Novabiochem/EMD/Merck unless otherwise indicated. 1 H and 13 C NMR spectra were taken on a Varian Unity Plus 400 spectrometer at 400 MHz in CDCl 3 or d 6 -DMSO. All amphiphilic foldamer purification was done on a Waters HPLC system equipped with a 2996 photodiode array detector and Grace-Vydac C18 peptide semi-preparatory reverse phase column. Transition electron microscopy (TEM) was performed on a FEI Tecnai microscope operating at 80 kv. Circular dichroism (CD) was done on a Jasco J-815 circular spectropolarimeter. Atomic force microscopy (AFM) was taken on a Digital Instruments Dimension 3100 atomic force microscope with silicon tips (NSC14/AIBS, MicroMasch) in tapping mode. Synthesis of Fmoc-Asp(OtBu)-NDI-CO 2 H and Fmoc-Leu-DAN-CO 2 H: Synthesis of the starting monomers for Fmoc-based solid phase synthesis, Fmoc-Asp(OtBu)-NDI-CO 2 H and Fmoc-Leu-DAN-CO 2 H, were synthesized and characterized according to previously published literature. [1] Solid Phase Synthesis: Both amphiphilic foldamers were all synthesized using standard Fmocbased solid phase peptide synthesis protocols. Our starting resin was Fmoc Wang resin and our monomers (3eq.) were Fmoc-Asp(OtBu)-NDI-CO 2 H and Fmoc-Leu-DAN-CO 2 H utilizing PyBOP (3 eq.) as a coupling additive and DIPEA (6 eq.) as base in NMP. Fmoc deprotection was performed using a 20% (v/v) piperidine solution in DMF. Capping with acetic anhydride (1:1 Ac2O: CH2Cl2) was performed after each monomer coupling step. Cleavage of the crude foldamer off the resin was performed with a 95:5 TFA/H2O solution. RP-HPLC purification of the crude foldamers was performed on a Waters HPLC system equipped with a 2996 photodiode array detector and Grace-Vydac C18 peptide semi-preparatory reverse phase column. Mobile phase solution consisted of a gradient of 25% B to 40% B over 60 minutes, where A is 10mM ammonium acetate buffer (ph 5.6) and B is 100% acetonitrile. Compound elution was monitored at a UV wavelength of 298nm. After lyopholization, purified foldamers were de-salted using Waters C-18 Sep-Pak cartridges. Tetrameric amphiphilic foldamer: The tetramer was synthesized using Fmoc-DAN-Leu-CO 2 H and Fmoc-Asp(OtBu)-NDI-CO 2 H monomers and followed the above stated protocol for standard Fmoc-based solid phase synthesis and RP-HPLC purification. Ac(Leu-DAN-Asp-NDI) 2 Gly- CO 2 H. ESI-MS (negative mode) calculated for C 96 H 103 N 13 O 27 (M+2H): m/z , found Hexameric amphiphilic foldamer: The hexamer was synthesized using Fmoc-DAN-Leu-CO 2 H and Fmoc-Asp(OtBu)-NDI-CO 2 H monomers and followed the above stated protocol for standard Fmoc-based solid phase synthesis and RP-HPLC purification. Ac(Leu-DAN-Asp-NDI) 3 Gly- CO 2 H. ESI-MS (positive mode) calculated for C 142 H 151 N 19 O 39 (M+2H): m/z , found

3 Figure S1. DAN and NDI monomer titration experiment. Ratios of 1,5-dimethoxynaphthalene (D) and 1,4,5,8-tetracarboxylic naphthalenedimethylimide (N) are given. As ratio of D to N increases to 1:1, peak corresponding to electronic transitions across N short axis (232 nm) becomes shoulder of larger peak at 223 nm corresponding to electronic transitions across D. Figure S2. Foldamer 1 overlaid spectra. CD spectra of aedamers confronted with UV spectra of foldamers. CD before heating (blue line), and CD after heating (red line), UV after heating (black line).

4 Figure S3. Foldamer 2 overlaid spectra. CD spectra of aedamers confronted with UV spectra of foldamers. CD before heating (blue line), and CD after heating (red line), UV after heating (black line). Figure S4. Amphiphilic foldamers 1 (left) and 2 (right) TEM images (after heating) showing stick and wrap behaviour of fibrils.

5 Figure S5. Foldamer 1 AFM topography (after heating) image showing ubiquitus height profiles among fibrils. References [1] Bradford, V.J.; Iverson, B.I. Amyloid-like Behavior in Abiotic, Amphiphilic Foldamers. J. Am. Chem. Soc. 2008, 130,