DNA-Based Assembly DOI: 10.1002/anie.201006992 Branched DNA That Forms a Solid at 95 8C** Arunoday Singh, Mariyan Tolev, Martin Meng, Konstantin Klenin, Oliver Plietzsch, ChristineI. Schilling, Thierry Muller, Martin Nieger, Stefan Bräse, Wolfgang Wenzel, and Clemens Richert* Control over the structure of materials may be achieved by using predictable interactions, such as base pairing. Base pairing between DNA strands is emerging as one of the most versatile design principles of nanoconstruction. [1] A range of hybridization [2] and folding motifs [3] of linear and circular DNA have been reported. The flexibility of the design has been further expanded by linking oligonucleotides to syn- thetic branching elements or “cores”. [4, 5] The resulting con- struct can have properties not found in natural DNA. This includes DNA-coated gold nanoparticles [6] that assemble into three-dimensional aggregates, the melting transitions of which are exceptionally sharp. [7] Nanoparticle size and linker structure affect the association behavior, [8] and crystal- lization may be induced in favorable cases. [9] For DNA hybrids with organic cores, the effect of linking the DNA to a branching element can be more dramatic still. Four-arm hybrid 1 (Scheme 1) with its tetrahedral core was recently shown to assemble into a macroscopic material, even though its oligonucleotide arms are just dimers. [10] The assembly process is sequence specific, as demonstrated by mismatch controls, but the UV-melting transitions are broad, not sharp as in the case of gold nanoparticles. Shortly after the publication of the unusually stable assemblies of 1, the first designed DNA crystals were reported. [11] The fact that the association of the rigid triangle motifs that serve as rigid “cores” in these crystals is also driven by no more than dimer “sticky ends” again suggests that the rules for 3D construction of periodic assemblies are quite different from those of linear DNA. [12] We have modeled the assembly processes of hybrids by using an effective coarse-grained model to better understand the effect of rigidity and core geometry on assembly. The theoretical results motivated the synthesis of new hybrids with greater propensity to assemble into three-dimensional structures. Herein, we report two such hybrids, namely 2 with six DNA arms and pseudo-octahedral core, and 3, which forms a material from micromolar aqueous solution at 95 8C. We performed Brownian dynamics simulations with geo- metric forms that hybridize via the ends of their arms as models for DNA hybrids. These uncharged, coarse-grained models can reflect some key properties, such as size, coordination, and energy of bond formation as a function of bond angle and distance. To observe the assembly processes, the simulations had to be performed at high concentration (3 mm), and environmental effects (such as salt concentration, Scheme 1. Structures of the DNA hybrids employed: (CG) 4 TPM (1), (CG) 6 HPX (2), and (CG) 4 TTPA (3). Abbreviations of cores are derived from those of the corresponding alcohols: TPM = tetrakis(hydroxyphe- nyl)methane, HPX = hexakis(hydroxyphenyl)-p-xylene, TTPA = tetrakis- (triazoylphenyl)adamantane. [*] A. Singh, M. Tolev, Prof. C. Richert Institut für Organische Chemie, Universität Stuttgart 70569 Stuttgart (Germany) Fax: (+ 49) 711-685-64321 E-mail: lehrstuhl-2@oc.uni-stuttgart.de M. Meng, O. Plietzsch, C.I. Schilling, Dr. T. Muller, Prof. S. Bräse Institute of Organic Chemistry and Center for Functional Nano- structures (CFN), Karlsruhe Institute of Technology (KIT) 76131 Karlsruhe (Germany) Dr. M. Nieger Laboratory of Inorganic Chemistry, Department of Chemistry University of Helsinki, 00014 Helsinki (Finland) Dr. K. Klenin, Priv.-Doz.Dr. W. Wenzel Institute for Nanotechnology Karlsruhe Institute of Technology (KIT) 76021 Karlsruhe (Germany) [**] This work was supported by CFN (project no. C5.01-03). We thank Harald Henning for contributing to the synthesis of (CC) 4 TTPA. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201006992. 3227 Angew. Chem. Int. Ed. 2011, 50, 3227 –3231  2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim