State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences , Fuzhou 350002, P. R. China.
College of Chemistry, Fuzhou University , Fuzhou 350116, P. R. China.
J Am Chem Soc. 2015 Nov 11;137(44):14220-8. doi: 10.1021/jacs.5b09912. Epub 2015 Nov 2.
The research of systems chemistry exploring complex mixtures of interacting synthetic molecules has been burgeoning recently. Herein we demonstrate for the first time the coupling of molecular switches with a dynamic covalent reaction (DCR) and the modulation of created chemical cascades with a variety of inputs, thus closely mimicking a biological signaling system. A novel Michael type DCR of 10-methylacridinium perchlorate and monothiols exhibiting excellent regioselectivity and tunable affinity was discovered. A delicate balance between the unique reactivity of the reactant and the stability of the adduct leads to the generation of a strong acid in a thermodynamically controlled system. The dynamic cascade was next created via coupling of the DCR and a protonation-induced configurational switch (E/Z isomerization) through a proton relay. Detailed examination of the interdependence of the equilibrium enabled us to rationally optimize the cascade and also shed light on the possible intermediate of the switching process. Furthermore, relative independence of the coupled reactions was verified by the identification of stimuli that are able to facilitate one reaction but suppress the other. To further enhance systematic complexity, a second DCR of electrophilic aldehydes and thiols was employed for the reversible inhibition of the binary system, thus achieving the interplay of multiple equilibria. Finally, a fluorescence switch was turned on through coupling with the DCR, showcasing the versatility of our strategy. The results described herein should pave the way for the exploitation of multifunctional dynamic covalent cascades.
近年来，系统化学领域对相互作用的合成分子复杂混合物的研究蓬勃发展。在此，我们首次展示了分子开关与动态共价反应（DCR）的耦合，以及通过多种输入对所创建的化学级联进行调制，从而模拟生物信号系统。我们发现了一种新颖的迈克尔型 DCR，涉及高氯酸 10-甲基吖啶鎓和单硫醇，具有出色的区域选择性和可调亲和力。反应物的独特反应性和加合物的稳定性之间的微妙平衡导致在热力学控制的系统中生成强酸。通过 DCR 与质子诱导的构象开关（E/Z 异构化）的偶联，通过质子传递来创建动态级联。对平衡的相互依存关系的详细检查使我们能够合理地优化级联，也阐明了开关过程的可能中间体。此外，通过鉴定能够促进一个反应但抑制另一个反应的刺激物，证实了耦合反应的相对独立性。为了进一步提高系统的复杂性，采用了第二种亲电醛和硫醇的 DCR 来可逆抑制二元系统，从而实现了多个平衡的相互作用。最后，通过与 DCR 偶联实现荧光开关，展示了我们策略的多功能性。本文所述的结果应为多功能动态共价级联的开发铺平道路。
