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Functionalisable metallo-cages as nano-vessels

可功能化的金属笼作为纳米容器

基本信息

批准号：
EP/J001325/1
负责人：
Michaele Hardie
金额：
$ 60.34万
依托单位：
University of Leeds
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2011
资助国家：
英国
起止时间：
2011 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FJ001325%2F1
关键词：
Functionalisable metallo cages nano vessels

项目摘要

In this proposal we will be investigating the self-assembly of metallo-supramolecular species and their use as post-construction vessels for chemical space applications. Utilisation of chemical space will ultimately address a variety of important objectives including creation of nano-scale vessels akin to artificial enzymes for performing unusual organic chemistry including catalytic transformations, and organising biologically relevant molecules in an artificial environment. The final area will give important information regarding the fundamental nature of the interactions between biological molecules, which may facilitate modelling studies, and may offer a new route to investigating more complex, higher order, structural motifs. We will be utilising molecular dynamics simulations to better understand the behaviour of guest molecules inside the metallo-cages, and to inform the design of the subsequent generation of functional cages.Self-assembly involves molecular or ionic components ("building blocks") arranging themselves into more complicated assemblies through reversible interactions between them. Self-assembled systems have well-defined architectures and geometric and interactional design of the building blocks can be used to promote formation of desired assemblies. In this proposal we are targeting discrete hollow cage-like assemblies with significant internal space. In some instances, we will be functionalising the insides of these cages in order to promote functionality such as catalysis, and binding/ordering of guest molecules.The building blocks that we will be using include the pyramidal-shaped cyclotriveratrylenes (CTVs) which offer hydrophobic binding sites for guest molecules, and we will be developing a new class of folded tetrapodal ligands that can be easily functionalised. Furthermore, CTV derivatives are often chiral and are known to form topologically complicated metallo-supramolecular assemblies. A topologically complicated assembly is one which displays mechanical inter-linking or threading, for example.Many discrete cages exist in solution and we will be developing their use as nano-scale reaction vessels for performing chemical reactions on guest molecules included inside the cages. A chemical included inside a cage is in a different environment to one outside of a cage in free solvent, and hence will show different chemistry. This is due to both the restricted space inside a cage and the specific interactions between the cage host and chemical guest. We will be designing mixed-ligand cages that allow for different types of interactions with chemical guests, hence an enhanced ability to control spatial orientation, and therefore regio/stereo-chemistry of the guests. For example, the product distribution of 1,3-dipolar coupling reactions could be manipulated or altered through reaction in a confined space. Oxidative reactions using the cages as catalysts will also be investigated.The novelty of the cage environment will be demonstrated, in solution, by the (NMR) detection and characterisation of interactions between guest molecules, and guest/host molecules. To this end small biologically relevant systems such as complementary deoxydinucleotides sequences will be incorporated and their base-pairing monitored. A DNA tetramer (the i-motif) will be studied to probe the effect of, for example, molecular crowding in the cage. Latterly it will be of interest to note whether the chiral interiors impose any 'order' on the DNA systems, permitting dipole-dipole couplings to be measured and analysed structurally. Such measurements are generally only accessible through the use of ordered media, such as lipids, and provide structural data not otherwise available from solution phase studies.

在本提案中，我们将研究金属超分子物种的自组装及其作为化学空间应用的建造后容器的用途。化学空间的利用将最终解决各种重要目标，包括创建类似于人工酶的纳米级容器，用于执行不寻常的有机化学，包括催化转化，以及在人工环境中组织生物相关分子。最后一个区域将提供有关生物分子之间相互作用的基本性质的重要信息，这可能有助于建模研究，并可能为研究更复杂，更高阶的结构基序提供新的途径。我们将利用分子动力学模拟来更好地了解金属笼中客体分子的行为，并为后续功能笼的设计提供信息。自组装涉及分子或离子组分（“构建块”）通过它们之间的可逆相互作用将自己排列成更复杂的组装体。自组装系统具有明确定义的架构，并且构建块的几何和互穿设计可用于促进所需组件的形成。在该提案中，我们的目标是具有显著内部空间的离散中空笼状组件。在某些情况下，我们将功能化这些笼子的内部，以促进功能，如催化，和客体分子的结合/排序。我们将使用的构建块包括为客体分子提供疏水结合位点的圆形cytrotriveratrylenes（CTV），我们将开发一类新的折叠四足配体，可以很容易地功能化。此外，CTV衍生物通常是手性的，并且已知形成拓扑复杂的金属-超分子组装体。拓扑结构复杂的组装体是一种显示机械互连或螺纹的组装体。许多离散的笼状结构存在于溶液中，我们将开发它们作为纳米级反应容器的用途，用于对笼状结构中的客体分子进行化学反应。笼内包含的化学品与游离溶剂中笼外的化学品处于不同的环境中，因此将显示不同的化学性质。这是由于笼内的有限空间和笼主体与化学客体之间的特定相互作用。我们将设计混合配体笼，允许不同类型的相互作用与化学客人，因此增强控制空间取向的能力，因此区域/立体化学的客人。例如，1，3-偶极偶联反应的产物分布可以通过在有限空间中的反应来操纵或改变。使用笼作为催化剂的氧化反应也将被调查。笼环境的新奇将被证明，在解决方案中，通过（NMR）检测和表征客体分子之间的相互作用，和客体/主体分子。为此，将纳入小的生物相关系统，如互补脱氧二核苷酸序列，并监测其碱基配对。将研究DNA四聚体（i基序）以探测例如笼中分子拥挤的效应。后来，它将是有趣的注意是否手性内部强加任何“秩序”的DNA系统，允许偶极偶极耦合进行测量和分析结构。这种测量通常只能通过使用有序介质（如脂质）进行，并提供溶液相研究无法获得的结构数据。