Raghupathi Krishna R, Guo Jing, Munkhbat Oyuntuya, Rangadurai Poornima, Thayumanavan S
Department of Chemistry, University of Massachusetts Amherst , Amherst, Massachusetts 01003, United States.
Acc Chem Res. 2014 Jul 15;47(7):2200-11. doi: 10.1021/ar500143u. Epub 2014 Jun 17.
Supramolecular assemblies formed from spontaneous self-assembly of amphiphilic macromolecules are explored as biomimetic architectures and for applications in areas such as sensing, drug delivery, and diagnostics. Macromolecular assemblies are usually preferred, compared with their simpler small molecule counterparts, due to their low critical aggregate concentrations (CAC) and high thermodynamic stability. This Account focuses on the structural and functional aspects of assemblies formed from dendrimers, specifically facially amphiphilic dendrons that form micelle or inverse micelle type supramolecular assemblies depending on the nature of the solvent medium. The micelle type assemblies formed from facially amphiphilic dendrons sequester hydrophobic guest molecules in their interiors. The stability of these assemblies is dependent on the relative compatibility of the hydrophilic and hydrophobic functionalities with water, often referred to as hydrophilic-lipophilic balance (HLB). Disruption of the HLB, using an external stimulus, could lead to disassembly of the aggregates, which can then be utilized to cause an actuation event, such as guest molecule release. Studying these possibilities has led to (i) a robust and general strategy for stimulus-induced disassembly and molecular release and (ii) the introduction of a new approach to protein-responsive supramolecular disassembly. The latter strategy provides a particularly novel avenue for impacting biomedical applications. Most of the stimuli-sensitive supramolecular assemblies have been designed to be responsive to factors such pH, temperature, and redox conditions. The reason for this interest stems from the fact that certain disease microenvironments have aberrations in these factors. However, these variations are the secondary imbalances in biology. Imbalances in protein activity are the primary reasons for most, if not all, human pathology. There have been no robust strategies in stimulus-responsive assemblies that respond to these variations. The facially amphiphilic dendrimers provide a unique opportunity to explore this possibility. Similarly, the propensity of these molecules to form inverse micelles in apolar solvents and thus bind polar guest molecules, combined with the fact that these assemblies do not thermodynamically equilibrate in biphasic mixtures, was used to predictably simplify peptide mixtures. The structure-property relationships developed from these studies have led to a selective and highly sensitive detection of peptides in complex mixtures. Selectivity in peptide extraction was achieved using charge complementarity between the peptides and the hydrophilic components present in inverse micellar interiors. These findings will have implications in areas such as proteomics and biomarker detection.
由两亲性大分子自组装形成的超分子聚集体被探索用作仿生结构，并应用于传感、药物递送和诊断等领域。与结构更简单的小分子对应物相比，大分子聚集体通常更受青睐，这是因为它们的临界聚集浓度（CAC）较低且热力学稳定性较高。本综述聚焦于由树枝状大分子形成的聚集体的结构和功能方面，特别是表面两亲性树枝状分子，它们根据溶剂介质的性质形成胶束或反胶束型超分子聚集体。由表面两亲性树枝状分子形成的胶束型聚集体将疏水性客体分子隔离在其内部。这些聚集体的稳定性取决于亲水性和疏水性官能团与水的相对相容性，通常称为亲水亲油平衡（HLB）。利用外部刺激破坏HLB可能导致聚集体解体，进而可用于引发诸如客体分子释放等驱动事件。对这些可能性的研究带来了（i）一种用于刺激诱导的解体和分子释放的稳健且通用的策略，以及（ii）一种蛋白质响应型超分子解体的新方法。后一种策略为影响生物医学应用提供了一条特别新颖的途径。大多数刺激敏感型超分子聚集体被设计为对诸如pH、温度和氧化还原条件等因素作出响应。这种兴趣的产生源于某些疾病微环境在这些因素方面存在异常这一事实。然而，这些变化是生物学中的次要失衡。蛋白质活性的失衡是大多数（如果不是全部）人类病理学的主要原因。在刺激响应型聚集体中，尚未有针对这些变化作出响应的稳健策略。表面两亲性树枝状大分子提供了探索这种可能性的独特机会。同样，这些分子在非极性溶剂中形成反胶束并因此结合极性客体分子的倾向，再加上这些聚集体在双相混合物中不会达到热力学平衡这一事实，被用于可预测地简化肽混合物。从这些研究中得出的结构 - 性质关系已导致对复杂混合物中的肽进行选择性和高灵敏度检测。利用肽与反胶束内部存在的亲水性成分之间的电荷互补性实现了肽提取的选择性。这些发现将对蛋白质组学和生物标志物检测等领域产生影响。
