Small Molecule Self-Assembly in Aqueos Media

在亚细胞水平上，人类和其他生物一样，通过自我组装的过程，构建和编排了无数维持健康生命所必需的结构。细胞实际上是非常复杂的超分子实体，采用超分子纳米结构。然而，不适当的自组装也会导致诸如阿尔茨海默氏症、镰状细胞性贫血等疾病。因此，掌握水介质中的分子自组装可以在开发新的诊断和治疗方法方面取得巨大进展。超分子化学提供了一种有吸引力的策略，通过在分子构建块中编程适当的信息来构建自制纳米结构。到目前为止，超分子化学在有机介质中通过自组装构建复杂分子机制方面取得了重大进展，但在水介质中的研究相对滞后。仍然有相对较少的例子，离散的合成超分子是基于小分子单独通过非共价相互作用结合在一起。在开发合适的识别基序方面存在差距，这些基序易于制作并在水环境中提供鲁棒和可靠的自我识别特性。对高特异性、高亲和力识别g -四重体DNA （QDNA）的有效配体的开发也存在空白。我们建议通过制造小分子鸟嘌呤(G)衍生物（目标1）和研究它们在水中的自组装（目标2）来填补这些空白。由此产生的超分子的有用性将通过它们作为自组装配体（SALs）用于QDNA的特异性识别而得到强调（目的3）。由于QDNA在端粒功能和某些致癌基因的调控中可能发挥的作用，QDNA一直是研究的热点。随后的超分子应该通过开发更好的诊断探针和治疗方法来进一步实现我们扩大纳米医学分子“工具箱”的长期目标。

At the subcellular level, humans like other organisms build and choreograph the countless structures essential to maintaining a healthy life by the process of self-assembly. Cells are in fact, enormously complex supramolecular entities that employ supramolecular nanoconstruction. Yet, improper self- assembly can also lead to diseases such as Alzheimer's, sickle-cell anaemia, etc. Therefore, mastering molecular self-assembly in aqueous media can lead to great advances in developing novel diagnostics and therapeutics. Supramolecular chemistry offers an attractive strategy for constructing self-made nanostructures by programming the appropriate information in their molecular building blocks. So far, supramolecular chemistry has made significant advances in constructing complex molecular machinery by self-assembly in organic media, but studies in aqueous media have lagged behind. There are still relatively few examples of discrete synthetic supramolecules based on small molecules held together solely with non-covalent interactions. There is a gap in the development of appropriate recognition motifs that are easy to make and offer robust and reliable self-recognition properties in aqueous environments. There is also a gap in the development of efficacious ligands that recognize G-quadruplex DNA (QDNA) with high specificity and affinity. We propose to fill these gaps by making small molecule guanine (G) derivatives (Aim 1) and studying their self-assembly in water (Aim 2). The usefulness of the resulting supramolecules will be highlighted by their use as self-assembled ligands (SALs) for the specific recognition of QDNA (Aim 3). QDNA is the subject of intense studies due to its putative role in telomere function and in the regulation of some oncogenes. The ensuing supramolecules should further our long-term goal of expanding nanomedicine's molecular 'toolbox' by developing better diagnostic probes and therapeutics.