Subscriber access provided by READING UNIV
Communication
Kinetically Controlled Stepwise Self-Assembly of AuI-Metallopeptides in Water Benedict Kemper, Lydia Zengerling, Daniel Spitzer, Ronja Otter, Tobias Bauer, and Pol Besenius J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b08189 • Publication Date (Web): 22 Dec 2017 Downloaded from http://pubs.acs.org on December 22, 2017
Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.
Page 1 of 10 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
Journal of the American Chemical Society
Kinetically Controlled Stepwise Self-Assembly of AuIMetallopeptides in Water Benedict Kemper, Lydia Zengerling, Daniel Spitzer, Ronja Otter, Tobias Bauer, Pol Besenius* Institute of Organic Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10–14, 55128 Mainz, Germany Supporting Information Placeholder ABSTRACT: The combination of attractive supramolecular I
interactions of a hydrophobic Au -metallopeptide with the shielding effect of flexible oligoethylene glycol chains provides access to a stepwise self-assembly of a AuI-metalloamphiphile in water. Kinetic control of the supramolecular polymer morphology is achieved using a temperature-dependent assembly protocol, which yields low dispersity supramolecular polymers (metastable state I) or helical bundled nanorods (state II).
The supramolecular polymerization of molecular building blocks is a promising approach for the construction of functional nanostructures.1 Such complex architectures are formed by chemically encoded self-assembly based on multiple non-covalent and reversible interactions.2 Traditionally, synthetic supramolecular polymerizations have been considered as equilibrium structures and investigations into the kinetic pathways of product formation have been largely neglected.3 This is surprising since the field of DNA-directed supramolecular assemblies have exploited multistep kinetic pathways in order to guide structure formation of colloids and nanoparticles.4 Recently, a number of pioneering studies have identified pathway selection and the power of kinetic control in steering the structure and function of supramolecular polymers and materials,5 for applications from organic electronics6 to cellular adhesion.7 Meijer and coworkers studied the pathway complexity of chiral oligophenylvinylenes in organic solvents, where temperature protocols could determine the selfassembly into kinetically or thermodynamically controlled aggregates, with opposite handedness.5d The groups of Sugiyasu and Takeuchi reported on a living supramolecular polymerization using functionalized porphyrins that assemble into either kinetically stable J-type or thermodynamically stable H-type aggregates.8 De Cola and coworkers presented an example of a PtIImetalloamphiphile, which upon dissolution in water/dioxane mixtures spontaneously self-assembles into spherical, redemitting nanoparticles.9 This kinetically trapped state slowly interconverts into anisotropic green-emitting assemblies before the thermodynamic stable state consisting of blue-emitting microcrystalline structures is obtained. In water, the key to success in the preparation of supramolecular nanostructures is to combine hydrogen bonding, Coulombic forces, π–π stacking and dispersive interactions, with solvophobic shielding.10 Based on our previous strategy of frustrated growth using dendritic peptide amphiphiles11 and the surface confined assembly of supramolecular copolymers,12 we designed amphiphilic AuI-metallopeptides. AuIcomplexes have prompted renewed interest in the field of luminescent materials,13 homogeneous catalysis,14 where many of the unique chemical and physical properties arise due to the soft nature of the gold(I) metal ion and its ability to undergo aurophilic
interactions,15 a van der Waals-like interaction between closedshell gold(I) centers. We here report the kinetically controlled supramolecular polymerization of a AuI-metallopeptide into metastable nanorods at room temperature. Upon heating these nanorods undergo thermal fibrillation to form dimeric bundles. The discotic AuI-metalloamphiphile 1 was synthesized in a convergent approach. First, the hydrophobic C3-symmetrical diphenylalanine core bearing the chlorido(diphenylphosphane)gold(I) complex was prepared based on peptide coupling chemistry, using a carboxylic acid functionalized diphenylphosphane gold(I) complex (see SI). Secondly, the anionic ligand exchange of the chlorido ligand in the AuI-complex with the hydrophilic thiol carrying a tetraethylene glycol dendron, was followed by NMR spectroscopy in degassed DMF-d7 and DIPEA as base. Disappearance of the thiol triplet in the 1H NMR as well as a shift from 𝛿=31.0 ppm (P-AuI-Cl) to 𝛿=34.8 ppm (P-AuI-S) in the 31P{1H} NMR, provided evidence for the successful ligand exchange. Using the same procedure, we synthesized further derivatives of AuI-metalloamphiphile 1, containing one or three phenylalanines per side arm (molecules 2 and 3, respectively).
Figure 1. C3-symmetrical AuI-metalloamphiphile 1 (A) and its self-assembly in water into 1D supramolecular nanorods and intertwined fibrils (B). We first decided to study the temperature-dependent selfassembly of the discotic AuI-monomer 1 using circular dichroism (CD) spectroscopy (Figures 2-3). Due to changes in the secondary structure during the supramolecular polymerization process, CD is a powerful tool to investigate the self-assembly of peptidic amphiphiles and chiral supramolecular monomers into ordered supramolecular polymers.11 The amphiphile 1 quickly dissolves in the cold phosphate buffer. Note, that 1 was isolated form a solution in DMF, where it is molecularly dissolved as clearly shown in the NMR measurements during the characterization (Figures S42-S44). In 5 °C buffer, the CD spectrum shows a weak negative CD band at λ=213 nm (state 0, Figure 2), which is very similar to the CD spectrum of a molecularly dissolved species obtained in a CH3CN/H2O (1:1) solvent mixture (Figure S3). Upon increasing
ACS Paragon Plus Environment
Journal of the American Chemical Society 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
the temperature from 5 °C to 25 °C using 5 °C intervals, the CD spectra change significantly. A strong (λ=219 nm) and a weak (λ=250 nm) negative CD band is observed (state I, Figure 2). This is indicative of the formation of ordered supramolecular polymers. In temperature-dependent transmission electron microscopy (TEM) experiments we were able to assign this first assembly state I to anisotropic nanorod-like structures. Surprisingly, when we increased the temperature further to above room temperature, we observed a transition to a second state, with a different CD signature. In the CD spectrum at 60 °C (state II, Figure 2), a weak negative band at λ=219 nm and a positive band at λ=237 nm is observed. These results are indicative of a change in the secondary structure of the peptidic core due to a rearrangement of the supramolecular assemblies, in agreement with reports on redshifted β-sheet signals due to a twisting of fibrillar structure formation.16 TEM micrographs of state II reveal the presence of dimer helical bundles. Note, that at temperatures T>70 °C, the solutions become turbid most likely due to dehydration of the tetraethylene glycol chains. This behavior has been ascribed to a lower critical solution effect, often observed for PEGylated macromolecular structures in water.17 The clouding of the solution is fully reversible after cooling the solution to temperatures T
