Control Of Multiple Hydrogen Bonding Interactions For Precise Non-covalent Synthesis

Self-assembly occurs in nature in various forms,from protein folding and lipid bilayer formation at the molecular level to establishing entire biological systems on Earth.Organisms assemble diverse building blocks through non-covalent interactions to form biological macromolecules with specific structures and functions,such as nucleic acids(DNA,RNA),proteins,and polypeptides.These natural biological macromolecules all have extremely complex but precise spatial structures.These delicate structures are indispensable from the precise control of the self-assembly process,and endow the biological macromolecules with special properties and unique functions.Among them,deoxyribonucleic acid(DNA),as a crucial genetic material,carries the genetic information of living organisms.Any changes in the DNA base sequence pairing process will bring inaccuracy to the process of identification,replication,and transmission,which may affect the normal function of the human body.Inspired by nature,scientists have long been eager to achieve the non-covalent and precise synthesis of artificial objects by employing self-assembly,so as to reach or even surpass the high complexity and specific functionality of biological macromolecules,which require the delicate design of building elements and precise control of the selfassembly process.For synthetic systems,achieving precise synthesis of complex and ordered structures is still a big challenge.At present,most studies use covalent synthesis to achieve precise synthesis.For instance,click chemistry,with high efficiency and selectivity,is highly recommended by chemists.Nevertheless,this method only works for a handful of reactions.In contrast,the synthesis based on non-covalent bonds has plenty of advantages,such as diverse methods,simple building blocks,easy synthesis,and functionalization.The research content of this thesis is the precise synthesis based on non-covalent interactions.Among the numerous non-covalent interactions,metal coordination interactions are used as the driving force to assemble into ordered structures in most cases due to their strong bond energy and good directionality.However,in living systems,only trace amounts of metallic elements exist.Hydrogen bonding is the basic driving force for the formation of biological macromolecules such as proteins,nucleic acids and polysaccharides.Hydrogen bonds are thought to be essential in recognition and molecular interactions.In DNA,guanine(G)and cytosine(C)pair through triple hydrogen bonds,while adenine(A)and thymine(T)pair through double hydrogen bonds,ultimately forming a double helix.Hydrogen bonding has significant directionality,reversibility and saturation,as well as a certain bonding strength,which can be used as a driving force of assembly for the construction of complex supramolecular systems with specific structures and functions.Intending to learn from biological systems,chemists have constructed a series of self-assembled systems with multiple hydrogen bonds.However,the stability of self-assembly systems with multiple hydrogen bonding is often affected by various factors,such as the number of hydrogen bonding sites,secondary electrostatic interactions,and allostery of hydrogen bonding units.Building blocks are the molecular basis of self-assembly structures,and the accuracy of building blocks will directly affect the precise synthesis of self-assembled structures.Therefore,we hope to find an effective method to solve the problem of how to control the stability of the hydrogen bonding interactions,and develop a definite building unit with multiple hydrogen bonding sites,to accurately synthesize complex supramolecular structures.The detailed work are as follows:1.Precision of supramolecular structures by controlling multiple hydrogen bonding interactionsMultiple hydrogen-bonding ureidopyrimidinone(UPy)units have certain complementarity,cheap raw materials,easy derivatization,strong dimerization ability,and many other advantages.Therefore,the UPy unit can be used as an important building block to build various supermolecular structures driven by multiple hydrogen bonding interactions.Meanwhile,an important feature that cannot be ignored of this system is that there is an equilibrium of two different kinds of proton tautomers in nonpolar or weak polar solvent.They are the 4[1H]-pyrimidinone(keto)isomer and the pyrimidin-4-ol(enol)isomer,respectively.The former forms DDAA-AADD dimer through self-complementary quadruple hydrogen bonding interactions,while the latter forms DADA-ADAD dimer.Because of the existence of the inherent tautomerization of this heterocyclic ring-based system,there are various isomers in supramolecular assemblies based on this building block,which makes supramolecular structures very complicated in essence.In this part,we propose a reasonable and simple supramolecular strategy to pre-organize the dimerization behavior of UPy molecule,that is,using intramolecular hydrogen bonding interactions to limit the intramolecular movement of proton,control keto-enol tautomerism,and fix the hydrogen bonding sites to arrange in a specific way,thus the UPy derivative 1 exists as only a 4[1H]-pyrimidinone tautomer in solution and in the solid state,which gives rise to the generation of a single DDAA-AADD dimeric array.According to Jorgensen’s theory of secondary electrostatic interactions,the DDAA-AADD dimer with quadruple hydrogen bonding interactions shows higher stability and stronger binding ability than the DADA-ADAD dimer because of the two secondary electrostatic attraction interactions.Then,we synthesized the building block 5 containing two molecule 1,and found that the building block 5 self-assembled into ordered supramolecular structure with exclusive DDAA-AADD dimeric arrays in solution.Here,we have controlled the precise arrangement of hydrogen bonding sites of the UPy system,and provided a specific multiple hydrogen bonding driving force for the precise synthesis of selfassembled structures.2.Construction of two-dimensional assemblies in aqueous media based on multiple hydrogen bondsIn addition to the quadruple hydrogen bonding system with DDAA-AADD dimeric array,another kind of self-complementary quadruple hydrogen bonding system with DADA-ADAD type hydrogen bonding sites is also often used to construct supramolecular structures.In the previous work,we have successfully controlled the DDAA-AADD dimerization of the UPy system through a supramolecular strategy.Based on the previous work,we hope to realize the DADA-ADAD dimerization of UPy system with the same strategy.Therefore,in this part,we effectively controlled the enol isomer of UPy molecule through the weak intramolecular hydrogen bonding interactions,and formed DADA-ADAD dimeric array in both solution and solid state.Unlike the work in part 1,the UPy derivative we obtained here not only undergos the dimerization through precisely controlled quadruple hydrogen bonding interactions,but also undergos π-π interactions with the introduced aromatic group to stabilize hydrogen-bonded dimmers.Currently,most studies based on hydrogen bonding were carried out in organic solvents,because water molecules as competitive molecules can severely interfere with the self-assembly process.To achieve precise structural control and high stability,many important biological processes(e.g.DNA assembly,protein folding)protect directional hydrogen bonding imteractions from water molecules by forming hydrophobic regions.Excitingly,we found that the enol monomer molecule designed and synthesized in this part would continuously form a region similar to the sandwich structure during the self-assembly process,and the quadruple hydrogen bonding interactions would be just shielded in the hydrophobic region formed by aromatic stacking interactions and resulting in dimerization,thus avoiding the interference of water molecules.This research shows that we have synthesized a definite multiple hydrogen-bonded building block,which further realizes the precise self-assembly driven by multiple hydrogen bonds in aqueous medium.3.Controllable assembly of two-dimensional monolayered structures driven by hydrogen bonding interactionsTwo-dimensional monolayered nanostructures are important materials with large specific surface area and abundant active sites,which have many potential applications.The preparation of monolayered two-dimensional nanostructures remains a challenge without templates or confined space.In the previous part of this work,we provide a kind of multiple hydrogen bonding unit with definite structure,and realize the precise construction of the sheet structures.In this part,we hope to control the assembly process by controlling the direction of multiple hydrogen bonding driving force,and construct a single layer self-assembled structure with specific spatial arrangement.Therefore,we took 2,5-bis(amino)terephthalate as the precursor,the crystal structure shows that the molecule has strong intramolecular and intermolecular hydrogen bonding interactions.On the basis of its structural characteristics,we designed and synthesized molecule 1by introducing leucine at both ends to provide hydrogen bonding interactions in the other direction.In the process of self-assembly,the building block 1 has a specific spatial orientation of its hydrogen bonding driving forces,which can be assembled along the x-axis and y-axis to form a two-dimensional monolayered structure with specific spatial arrangement.Through various microscopic imaging experiments and comparison with the self-assembled structure of reference molecule,it is proved that controllable self-assembly of two-dimensional monolayered structure can be realized by controlling the spatial orientation of hydrogen bonding driving forces during the self-assembly process.In this part,we have successfully constructed the monolayered nanosheets with large specific surface area,which provides ample scope for further chemical modification and functionalization.