pH-Responsive Nanoparticle Superlattices with Tunable DNA Bonds Jinghan Zhu, †,‡,⊥ Youngeun Kim, †,‡,⊥,∥ Haixin Lin, ‡,§ Shunzhi Wang, ‡,§ and Chad A. Mirkin* ,†,‡,§ † Department of Materials Science and Engineering, ‡ International Institute for Nanotechnology, § Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States * S Supporting Information ABSTRACT: Stimuli-responsive nanomaterials with re- configurable structures and properties have garnered significant interest in the fields of optics, electronics, magnetics, and therapeutics. DNA is a powerful and versatile building material that provides programmable structural and dynamic properties, and indeed, sequence- dependent changes in DNA have already been exploited in creating switchable DNA-based architectures. However, rather than designing a new DNA input sequence for each intended dynamic change, it would be useful to have one simple, generalized stimulus design that could provide multiple different structural outputs. In pursuit of this goal, we have designed, synthesized, and characterized pH- dependent, switchable nanoparticle superlattices by utilizing i-motif DNA structures as pH-sensitive DNA bonds. When the pH of the solution containing such superlattices is changed, the superlattices reversibly undergo: (i) a lattice expansion or contraction, a consequence of the pH-induced change in DNA length, or (ii) a change in crystal symmetry, a consequence of both pH-induced DNA “bond breaking” and “bond forming” processes. The introduction of i-motifs in DNA colloidal crystal engineering marks a significant step toward being able to dynamically modulate crystalline architectures and propagate local molecular motion into global structural change via exogenous stimuli. A s a highly programmable material, DNA has proven useful for chemically arranging nanoscale building blocks into complex and functional colloidal crystalline materials. 1−3 The basis for such materials, programmable atom equivalents (PAEs), are typically composed of a nanoparticle core with synthetic oligonucleotides densely coating the surface so they are forced into an upright orientation. PAEs are unique material building blocks, in which the core “atom” identity (nanoparticle shape, size, and composition) and “DNA bonds” (sequence, length, strength, and density) can be independently tuned. 4 Importantly, the sequence-speci fic interactions between oligonucleotides allow one to program the assembly of nanoparticle superlattices with control over the crystal lattice parameter, 3 symmetry, 4 and habit. 5 In certain cases, the DNA that defines such superlattices can be intentionally designed to be stimuli-responsive, resulting in structures that respond to small molecule chemical cues (oligonucleotides 6,7 or inter- calators 8 ) or changes in osmotic pressure 9 or dielectric media. 10 These stimuli can lead to profound changes in the structure or crystallization path, and have been used to systematically explore and manipulate optoelectronic properties in epitaxially grown crystalline thin films and free-standing single crystals. 11 Indeed, learning how to chemically control the interactions of the nanoparticles within such superlattices is of paramount importance to eventually make use of them in optically active devices. Changes in pH have been used as the stimulus to effect actuation in molecular motors, 12−14 biological sensors, 15,16 and a variety of molecular switchable DNA-based architectures, 17,18 and although pH (i.e., proton environment) is one of the most extensively used triggers to effect both chemical and physical changes in material-based systems in general, 14,19,20 it has yet to be explored in the context of DNA-driven crystal engineering strategies. In this work, we explore how pH-responsive i-motifs can be synthetically incorporated into DNA bonding elements to control nanoparticle lattice formation, crystallization path, and crystal structure. An i-motif (Figure S1) is a cytosine-rich DNA strand that forms a quadruplex structure in acidic conditions (e.g., pH 5), but extends into a single strand configuration under basic conditions (e.g., pH 8). 14 Therefore, with an i-motif, one can interchangeably access a “contracted” or an “extended” state simply by changing pH. 13,18 We hypothesized that in a nanoparticle superlattice, the change in DNA length would directly translate into a controllable change in interparticle distance, resulting in a programmable change in the crystal lattice constant. In addition, we explored how the folding and unfolding of an i-motif can be used to completely break one set of bonds while initiating the formation of a new set, thereby altering the crystallization path and ultimate crystal structure. In proof-of-concept experiments, pH-responsive PAEs were constructed by first functionalizing colloidal gold nanoparticles with a dense shell of “anchor” oligonucleotides bearing a terminal propylthiol (Figure S2). 4 Complementary “linker” oligonucleotides were then hybridized to the “anchor” strands such that each PAE had its own unique set of linker strands. A typical linker strand was composed of three different regions: (i) a recognition region, an 18-base pair sequence fully complementary to the anchor strand, (ii) a spacer region, through which the overall length of the linker strand is modulated, and (iii) a sticky end region, a short single-stranded DNA that enables bonding between PAEs via hybridization. In this work, we synthesized and explored two types of pH- responsive PAEs, expandable and reconfigurable, by incorpo- rating an i-motif structure at two distinct positions in the spacer region within the linker DNA (Figure S3). Received: March 12, 2018 Communication pubs.acs.org/JACS Cite This: J. Am. Chem. Soc. XXXX, XXX, XXX-XXX © XXXX American Chemical Society A DOI: 10.1021/jacs.8b02793 J. Am. Chem. Soc. XXXX, XXX, XXX−XXX