1 Template Directed Assembly of Polyoxothiometalate Scaffolds into Nanomolecular Architectures Hong-Ying Zang, Haralampos N. Miras, De-Liang Long, Benjamin Rausch and Leroy Cronin* Polyoxometalates (POMs) represent some of the largest non- biologically derived molecules (1-6 nm) and exhibit a diverse variety of structures, [1-3] assembled from a large ‘virtual combinatorial library’ of building blocks. [4] Whilst many tungsten POMs can be built in a controlled way, the designed assembly of giant molybdates is harder due to the inherent lability of the resulting compounds. [5] However, the thiometalate aqua cation [Mo2O2S2(H2O)6] 2+ has been explored systematically by Cadot et al. [6,7] who showed that a large variety of planar ring clusters could be templated by organic ligands, and recently reported by us in the assembly of a Mӧbius strip. [5b] Yet, thus far it has been difficult to devise routes to use such ring-based clusters as building blocks to move from planar to stereo architectures. [5] The key problem with developing new approaches to nanosized clusters, especially in polyoxometalate chemistry, is due to the lack of structural stability of reactive building blocks. To address this we reasoned that the [Mo2O2S2] 2+ cation, containing two Mo atoms could act as a highly effective linking unit, especially when templated by a highly symmetrical structure-directing anions such as squarate. 5d Herein we show that in the presence of excess of molybdate with [Mo2O2S2] 2+ and squarate, it is possible to cut the rings into fragments that can allow tessellation into stereo clusters, yielding much larger, protein sized polyoxothiometalates, resulting in an unprecedented new family of compounds. Consequently, we deduced that this combination of building units would lead to a new family of architectures because, under reducing conditions, the molybdate-based building blocks can form a vast array of combinatorial units. This indeed proved correct since altering the pH value, the ratio of the starting material, and the counter cations resulted in a family of related structures, representing a new assembly paradigm whereby ‘open’ rings of [(Mo2O2S2)3(OH)4(C4O4)] (type A building blocks) can be combined with [Mo5O18] 6- (type B building blocks) and in some cases [(Mo2O2S2)2(OH)2(C4O4)] (type C building blocks) and [Mo2O2S2] 2+ units (type D building blocks) to construct an unprecedented library of new compounds (1-5, Figure 1); 1: {Mo45} = {A5B3} = {[(Mo2O2S2)3(OH)4(C4O4)]5(Mo5O18)3} 18- , 2: {Mo47} = {A5B3D1} = {[(Mo2O2S2)3(OH)4(C4O4)]5(Mo5O18)3(Mo2O2S2) (H2O)4]} 16- , 3: {Mo55} = {A5B3C2D1} = {[(Mo2O2S2)3(OH)4 (C4O4)]5(Mo5O18)3[(Mo2O2S2)5(OH)8(C4O4)2]} 20- , 4: {Mo96}= {A9B6C3} = {[(Mo2O2S2)3(OH)4(C4O4)]9[(Mo2O2S2)2(OH)2 (C4O4)]3(Mo5O18)6} 36- (previously reported in ref 11). The assembly of the system is dependent on the nature of the alkali- metal cations used; under the same pH condition used in the synthesis of 4, but in the presence of Cs + instead of K + , compound 5 is formed. It is a highly symmetrical structure {Mo68} = {A8B4} {[(Mo2O2S2)3(OH)4(C4O4)]8(Mo5O18)4} 24- . This new assembly method is explained in Figure 2 which shows the formation of compound 5. Notably the key building block is the unique isomer of the lacunary Lindqvist-type [Mo5O18] 6- POM (Figure S3a and S3b) which is generated in-situ and acts as a convergent scaffold linking unit. Further, it is important to note that the special geometry of the [Mo5O18] 6- unit acts as a 90° ‘hinge’ allowing rings to be connected both horizontal and perpendicular to the plane that defines the overall macrocyclic cluster structure. [8] It is interesting to see that this orthogonal assembly is also found in many biological systems. [9,10] Figure 1. Representation of the polyoxothiometalate building blocks used for the construction of compounds 1 - 5. The vertical view of the [(Mo2O2S2)3(OH)4(C4O4)] building block (A) is represented by the red arc and the parallel view by the red ribbon. The [(Mo2O2S2)2(OH)2(C4O4)] (C) is denoted by the blue angle while the [Mo5O18] 6- synthon (B) by the yellow arrow (the squarate anions are omitted for clarity). Nanosized POMcycles DOI: 10.1002/anie.200((will be filled in by the editorial staff)) [] H.-Y. Zang, Dr. H. N. Miras, Dr. D.-L. Long, B. Rausch and Prof. L. Cronin*, WestCHEM, School of Chemistry, The University of Glasgow, University Avenue, Glasgow G12 8QQ, UK. Fax: (+44)-141-330-4888; Tel: (+44)-141-330-6650 E-mail: lee.cronin@glasgow.ac.uk Homepage: http://www.croninlab.com [] We thank the EPSRC, the Chinese Scholarship Council, WestCHEM and the University of Glasgow for supporting this work. LC thanks the Wolfson Foundation & Royal Society of London for a merit award. We thank Dr Jun Yan for help with the structure solutions, Dr Phil Kitson for the movie showing the self-assembly and Dr Roy McBurney for useful comments. Supporting information containing a movie, syntheses, IR, UV, CV, MS analysis for this article is available on the WWW under http://www.angewandte.org or from the author.