Control of self-assembly and functionalisation of coordination cages

多面体配位笼是一类复杂的，已成为感兴趣的两个主要原因。(i)它们有吸引力的高度对称结构可以通过自组装方法制备，其中简单的组分在正确的条件下联合收割机结合以产生非常精细的多组分物质（参见图1）。来自数百个蛋白质亚基的病毒外壳的生物组装）。因此，它们充当了我们在人工系统中进行自组装能力的“试验台”。(ii)它们的大中心空腔可以作为各种小客体的大小和形状特定的宿主，提供一系列基于识别和结合特定分子的可能功能（传感，催化，运输）。然而，迄今为止，除了简单的不稳定组分自组装方法之外，几乎没有笼合成发展的例子。这项建议旨在扩大我们的能力，合成特定的笼型物种，有用的功能行为，在两个不同的和互补的方式。首先，我们将使用“子组件自组装”的技术，开发方法组装笼在一步一步的方式使用部分预制积木（“子组件”）。这些子组件可以基于三角形面，其可以以不同的方式交联以给出完整的多面体，正如三角形面板可以以不同的方式组合以给出四面体、三棱柱等。或者，这些子组件可以基于非常稳定的金属络合物片段，其几何形状确保它们将被并入多面体阵列的特定顶点位置，允许形成混合金属笼，其中一种类型的金属离子在某些顶点，而不同类型的金属离子在其它顶点。这种从预制子组件的逐步组装将极大地扩展我们控制所需形状和大小并具有内置功能的笼状复合物的合成的能力（发光，氧化还原活性，顺磁性）。其次，我们将研究在组装完成后为笼添加有用特性和功能行为的方法，通过将另外的单元共价连接到笼的外表面，所述笼将具有适当的外部导向的反应性基团（羟基、胺）。这将需要带有这些羟基或胺取代基的配体的初始合成以及它们用于形成笼的用途，所述笼将含有多达48个用于连接其它单元的外部定向位点。将研究各种基团的共价连接，包括：（i）荧光物质（以给出围绕中心笼芯的许多发光单元的阵列）;（ii）氧化还原活性片段（允许笼上的电荷通过外部单元阵列的简单氧化/还原而大量改变）;（iii）氢键位点（核碱基）或金属离子结合位点（吡啶基单元），以允许使用晶体工程方法形成固态的中空胶囊阵列，其将执行固体-状态主-客体化学;和（iv）具有已知细胞识别位点的寡肽序列，以允许发光笼被摄取到细胞中并在特异性识别位点结合，允许细胞的特异性靶向区域的基于发光的成像并可能将客体“有效载荷”递送到特异性细胞位点。

Polyhedral coordination cages are a class of complex that have become of interest for two major reasons.(i) Their attractive, highly-symmetric structures can be prepared by self-assembly methods in which simple components combine under the correct conditions to give remarkably elaborate multi-component species (cf. biological assembly of virus coats from hundreds of protein subunits). Accordingly they act as a 'test-bed' for our ability to perform self-assembly in artificial systems.(ii) Their large central cavities can act as size- and shape-specific hosts for a variety of small guest species, giving access to a range of possible functions (sensing, catalysis, transport) that are based on recognition and binding of a particular molecules.So far however there are almost no examples of the development of cage synthesis beyond the simple self-assembly-of-labile-components approach. This proposal aims to expand our ability to synthesis specific cage-type species, with useful functional behaviour, in two distinct and complementary ways.Firstly, we will use the techniques of 'subcomponent self-assembly' to develop ways to assembly cages in a step-by-stap manner using partially pre-formed building blocks ('subcomponents'). These subcomponents may be based on triangular faces which can be cross-linked in different ways to give complete polyhedra, just as a triangular panels can be combined in different ways to give tetrahedral, trigonal prisms, and so on. Alternatively these subcomponents may be based on very stable metal complex fragments whose geometry ensures that they will be incorporated into specific vertex sites of a polyhedral array, allowing formation of mixed-metal cages with metal ions of one type at some vertices and metal ions of a different type at the other vertices. Such stepwise assembly from pre-fabricated subcomponents would greatly extend our ability to control the synthesis of cage complexes of desired shapes and sizes and with built-in functionality (luminescence, redox activity, paramagnetism) at specific positions.Secondly, we will investigate ways to add useful properties and functional behaviour to cages after their assembly is complete, by covalent attachment of additional units to the external surface of the cages which will have appropriate externally-directed reactive groups (hydroxyl, amine). This will require initial synthesis of ligands bearing these hydroxyl or amine substituents and their use to form cages which will contain up to 48 externally-directed sites for attachment of other units. Covalent attachment of a wide range of groups will be investigated including:(i) fluorescent species (to give an array of numerous luminescent units around a central cage core); (ii) redox-active fragments (to allow the charge on the cage to be massively altered by simple oxidation / reduction of the array of external units); (iii) hydrogen-bonding sites (nucleobases) or metal-ion binding sites (pyridyl units) to allow formation using crystal-engineering methods of arrays of hollow capsules in the solid state which will perform solid-state host-guest chemistry; and (iv) oligopeptide sequences which have known cellular recognition sites, to allow uptake of luminescent cages into cells and their binding at the specific recognition sites, permitting luminescence-based imaging of specific targeted regions of a cell and possibly delivery of a guest 'payload' to a specific cell site.