Laporte Annechien A H, Reek Joost N H
Homogeneous, Supramolecular, and Bio-Inspired Catalysis, van 't Hoff Institute for Molecular Sciences (HIMS), Universiteit van Amsterdam (UvA), Science Park 904, 1098 XH Amsterdam, The Netherlands.
Chem Rev. 2025 Aug 13;125(15):7223-7274. doi: 10.1021/acs.chemrev.5c00047. Epub 2025 Aug 1.
Bioorthogonal reactions play a key role in controlled chemical transformations in living systems and are therefore applied to a diverse area of biological and medical applications. However, these applications can be limited by poor selectivity, slow kinetics under biological conditions, and intrinsic incompatibility between the introduced materials and the cellular environment. An emerging strategy for greater functional control over bioorthogonal transformations is the employment of supramolecular strategies or constructs. Herein, we focus on synthetic supramolecular systems that (i) improve biocompatibility by shielding reactive species within protective supramolecular constructs from harsh biological environments; (ii) allow for integration of subcellular targeting moieties; (iii) reduce toxicity; (iv) accelerate reaction rates through molecular preorganization; (v) explore entirely new tools, such as catalysis regulated by controlled stimuli at a functionalized surface. Through rational integration of these supramolecular strategies, bioorthogonal reactions could achieve enhanced precision, faster kinetics, and targeted reactivity within specific tissues, cells, or organelles, subsequently paving the way for further applications in chemical biology and therapeutic interventions.
生物正交反应在生命系统中的可控化学转化中起着关键作用，因此被应用于生物和医学应用的多个领域。然而，这些应用可能受到选择性差、生物条件下动力学缓慢以及引入的材料与细胞环境之间内在不相容性的限制。一种对生物正交转化进行更大功能控制的新兴策略是采用超分子策略或构建体。在此，我们专注于合成超分子系统，这些系统能够：（i）通过在保护性超分子构建体内将反应性物种与恶劣的生物环境隔离开来提高生物相容性；（ii）允许整合亚细胞靶向部分；（iii）降低毒性；（iv）通过分子预组织加速反应速率；（v）探索全新的工具，例如在功能化表面由可控刺激调节的催化作用。通过合理整合这些超分子策略，生物正交反应能够在特定组织、细胞或细胞器内实现更高的精度、更快的动力学和靶向反应性，从而为化学生物学和治疗干预的进一步应用铺平道路。
