Li Hao research group of Zhejiang University: dynamic chemical self-assembly based on oxime

Author: Li Hao research group recently, Li Hao research group, Department of chemistry, Zhejiang University has made new progress in water phase self-assembly The related research results were published in angel.chem.int.ed (DOI: 10.1002 / anie 201811025) under the title of "dynamic ovalent self assembly based on oxygen condensation" One of the works is Shen Libo, a doctoral student in the Department of chemistry, Zhejiang University The synthesis of three-dimensional complex molecules has always been a difficulty in chemical research There are many steps and time-consuming in the total synthesis of irreversible chemical reactions Scientists have developed a kind of supramolecular self-assembly method based on Dynamic Bond, which uses the reversible formation and disconnection of dynamic covalent bond, metal coordination bond and supramolecular noncovalent bond to find the most stable state of thermodynamics This means that some target molecules with complex topological structure can be obtained by one pot method with high yield through reasonable design of target molecular structure Before that, Li Hao's research group used the dynamic nature of imine bond to synthesize a tetrahedral molecule (yield > 99%) efficiently by one pot method, and used tetrahedral molecule to bind white phosphorus molecule to realize the protection of white phosphorus molecule, so that it can exist stably in oxygen environment for no less than three months This means that self-assembled molecules can be used as a kind of "molecular capsule" to store and transport high-energy, flammable and explosive guest molecules safely Relevant research results were published in angelw Chem Int ed (2017, 56, 14545, one work: Jiao Tianyu and Chen Liang, Ph.D., Department of chemistry, Zhejiang University) and J org Chem (2018, 83, 12404, one work: Jiao Tianyu, Ph.D., Department of chemistry, Zhejiang University) However, the biggest obstacle to the use of imine bond is its poor stability Due to the electrophilic nature of the imine chemical bond, in the aqueous solution environment, the water molecule and the imine bond are prone to electrophilic addition reaction, resulting in the hydrolysis of the imine bond (Fig 1a) To solve the compatibility between aqueous solution and dynamic covalent bond is an urgent problem in the study of self-assembly, because water is the medium of life Only when the stability of the assembly in aqueous solution system is realized, these self-assembled molecular systems can realize their supramolecular functions in the life system In order to solve this problem, Li Hao group developed a new type of dynamic covalent bond for dynamic covalent self-assembly by using a class of derivatives of imines, that is, through the quantitative condensation of hydrazone (- C = N-N -) in aqueous solution, the self-assembly of hydrazone in aqueous solution was realized The reason why hydrazone is more stable than imine is that the lone pair electron pair of nitrogen atom connected with imine has resonance phenomenon (- C-N = n + -), so that the carbon atom has partial negative charge, so it has relatively weak electrophilicity Therefore, the reaction constant of hydrazone and water molecule addition reaction is reduced Using this dynamic covalent reaction compatible with aqueous solution, the research team synthesized a series of molecules with complex structures (nature chem 2015, 7, 1003; J am Chem SOC 2018, 140, 5955, one work: Wu Guangcheng, Ph.D., Zhejiang University; org Lett 2018, 20, 2356, one work: Zhang Yang, Ph.D., Zhejiang University; chem Commun 2018, 54, 3138, the first work: Zhang Yang, Ph.D., Department of chemistry, Zhejiang University; chem Commun 2018, 54, 5106, the first work: Wang Caiyun, Ph.D., Department of chemistry, Zhejiang University) Fig 1 Different kinetic stability of imine bond and its derivatives However, hydrazone system also has disadvantages - in solution environment (especially in acid), hydrazone chemical bond is also unstable The chemical bond is constantly subject to decomposition / formation exchange reaction (Fig 1b), so the self-assembled molecular system formed by hydrazone condensation is often unstable Once the thermodynamic driving force (such as hydrophobic effect) for its formation is lost, these molecules are easy to decompose Furthermore, Li Hao's group solved this problem by using the kinetic inertia of oxime bond (- C = N-O -) Firstly, the formation of oxime bond is reversible in strong acid environment; secondly, oxime bond is irreversible in neutral and weak acid environment (Fig 1c) It is mainly because the decomposition of imine bond and hydrazone bond usually starts from the protonation of C = n bond (- C = NH + - N -) - the double bond obtains protons and positive charges, which is conducive to electrophilic addition reaction The C = n bond of oxime bond is connected with the oxygen atom with higher electronegativity The electron absorption effect of oxygen atom greatly reduces the basicity of nitrogen, so the difficulty of protonation of the latter is enhanced The thermodynamic exchange reaction of oxime bond is forbidden because it can't form protonated cation intermediate The researchers found that, despite the loss of thermodynamic driving force such as hydrophobic effect, an interlocking molecule containing oxime bond (such as alkanes) can hardly see any decomposition phenomenon when heated in DMSO solvent at 80 ℃ for 8 hours, so it can realize dynamic chemical self-assembly process in aqueous solution (Fig 2) Fig 2 These studies on the structure of sodehydrocarbons formed by oxime bond condensation (source: angelw Chem Int ed.) are supported by Zhejiang University, China Natural Science Foundation, Zhejiang Natural Science Foundation and the central organization department The research results are also strongly supported by Professor Pan Yuanjiang's research group A review of previous reports: Li Hao research group, Department of chemistry, Zhejiang University: Coulomb driven heterogeneous free radical pairing JACS: Li Hao research group, Zhejiang University realizes the green separation of phenanthrene and anthracene