LONGO ET AL . VOL. 7 ’ NO. 11 ’ 9933–9939 ’ 2013 www.acsnano.org 9933 October 16, 2013 C 2013 American Chemical Society Reversible Chirality Control in Peptide- Functionalized Gold Nanoparticles Edoardo Longo, Andrea Orlandin, Fabrizio Mancin, Paolo Scrimin, * and Alessandro Moretto * Department of Chemical Sciences, University of Padova, Via Marzolo 1, 35131 Padova, Italy C hirality of gold nanoparticles is an intriguing property that only recently has started to become the focus of investigation. The role of the passivating monolayer in affecting it has not been fully understood yet. Peptide-functionalized gold nanoparticles 1À3 constitute appealing supramolecular systems for their ability to mimic natural proteins. By confining on the surface of a cluster of gold atoms several copies of a peptide, a nanosystem that re- sembles a protein in size (a few nanometers), shape (globular), and, possibly, function may be obtained. 4 Peptide-functionalized gold nanoparticles have been used, inter alia, in catalysis, 5À8 selective protein recognition, 9,10 drug delivery, 11,12 and gene transfection. 13,14 However, in spite of the chiral properties deriving from the helical conformation and the configuration of the constituent amino acids, chirality in peptide-functionalized gold nanoparticles has been little explored. After the first observation by Whetten 15 of optical activity of glutathione (a tripeptide)- passivated gold nanoparticles, the few other examples are constituted by peptide nano- tubes, 16 cysteine, 17,18 and unstructured peptides. 19 It is now well accepted that chirality in such nanosystems may derive from 19,20 (a) the chiral arrangement of the metal cluster of the gold core; (b) the binding of the thiolates on the gold surface to form chirally arranged staples (a bridged binding motif involving gold and sulfur); 21 and (c) the chirality of the surrounding monolayer of passivating organic molecules. Peptide se- quences rich in C R -tetrasubstituted R-amino acids are known to stabilize the metallic cluster of gold nanoparticles in very polar solvents. 22,23 This is likely associated with their strong propensity to fold into rather robust 3 10 - or R-helix conformations. We argued that these properties could be exploited to address: (a) peptide folding behavior when bound to the surface of a gold nanoparticle; (b) the role of the indivi- dual amino acids and the secondary struc- ture of the sequence in inducing chiroptical properties to the passivated nanoparticles. RESULTS AND DISCUSSION In this view, we synthesized by conven- tional solution protocols seven peptides with Aib (R-amino isobutyric acid) and L-Ala alter- nating residues and N-mercaptopropionyl (mpr-) N-termination (P2À8; see Figure 1). Even sequences are characterized, at the N-terminus, by an Aib amino acid, while odd * Address correspondence to paolo.scrimin@unipd.it, alessandro.moretto.1@unipd.it. Received for review July 23, 2013 and accepted October 15, 2013. Published online 10.1021/nn403816a ABSTRACT We report the induction of chiroptical properties in 2 nm diameter gold nanoparticles passivated with short peptides characterized by the Aib-L-Ala repetition in their sequence. The nanoparticles present relevant ECD signals in the 300À650 nm wavelength region, corresponding to the gold nanoparticle's quantized electronic structure. Although the only chiral amino acid present in the peptide sequences is L-Ala, the particles show mirror image spectra like those of enantiomers according to the number of amino acids in the main chain (odd or even). Such a behavior appears to be strongly influenced by the secondary structure assumed by the peptides when passivating the nanoparticles and vanishes when the sequence is long enough to assume a 3 10 -helix conformation. Moreover, chirality control is a reversible process and can be deactivated or reactivated by increasing or decreasing the temperature. KEYWORDS: chiral gold nanoparticle . peptide gold nanoparticle . helical peptide . circular dichroism . supramolecular chemistry ARTICLE