Control of self-assembly and functionalisation of coordination cages

多面体配位笼是一类引起人们兴趣的配合物，主要有两个原因。(i)它们吸引人的、高度对称的结构可以通过自组装方法制备，在这种方法中，简单的组分在适当的条件下结合起来，形成非常复杂的多组分物种（例如，由数百个蛋白质亚基组成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我组装能力的“试验台”。（ii）它们巨大的中心腔可以作为各种小客物种的大小和形状特定的宿主，从而基于识别和结合特定分子实现一系列可能的功能（传感、催化、运输）。然而，到目前为止，除了简单的自组装不稳定组件的方法之外，几乎没有开发笼式合成的例子。这一提议旨在扩大我们的能力，合成特定的笼型物种，具有有用的功能行为，在两种不同的和互补的方式。首先，我们将使用“子组件自组装”技术来开发使用部分预成型构建块（“子组件”）逐步组装笼的方法。这些子组件可以基于三角形面，这些三角形面可以以不同的方式交联以得到完整的多面体，就像三角形面板可以以不同的方式组合以得到四面体、三角棱镜等一样。或者，这些子组件可以基于非常稳定的金属复合碎片，其几何形状确保它们将被合并到多面体阵列的特定顶点位置，从而允许形成混合金属笼，在某些顶点具有一种类型的金属离子，而在其他顶点具有不同类型的金属离子。这种由预制子组件逐步组装的方法将极大地扩展我们控制笼状配合物合成所需形状和尺寸的能力，并在特定位置具有内置功能（发光、氧化还原活性、顺磁性）。其次，我们将研究在其组装完成后，通过在具有适当的外部定向反应基团（羟基，胺）的笼的外表面附加单元的共价附着，为笼添加有用的性能和功能行为的方法。这将需要最初合成带有这些羟基或胺取代基的配体，并使用它们形成包含多达48个外部定向位点的笼，用于连接其他单元。将研究各种基团的共价附着，包括：(i)荧光物种（在中心笼核心周围形成众多发光单元阵列）；（ii）氧化还原活性片段（允许通过简单的氧化/还原外部单元阵列来大规模改变笼上的电荷）；（iii）氢键位点（核碱基）或金属离子结合位点（吡啶基单位），以允许使用晶体工程方法在固态中形成空心胶囊阵列，从而进行固态主客体化学；（iv）具有已知细胞识别位点的寡肽序列，允许将发光笼吸收到细胞中并在特定识别位点结合，允许对细胞的特定目标区域进行基于发光的成像，并可能将来宾“有效载荷”递送到特定细胞位点。

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.