Induction And Control Of Supramolecular Chirality From Pillararenes And Tr(?)ger's Base-based Macrocycles

Chirality is the basic attribute of nature and a common phenomenon,ranging to an extent as large as the vortex of the universe and as small as the microscopic particles.The living entity is considered to be a special multi-level chiral system in the context that the basic biological molecules making up the living body such as amino acids,polysaccharides,and enzymes are all chiral molecules.Humans inherently live in a chiral environment,and the study of chirality being an integral part is inseparable from our lives.The exploration of the chiral world immensely helps humans to recognize the intricacies on the origin of life in a broader dimension,bringing in value based applications in life sciences,pharmacy and materials science.In recent years,chiral supramolecular systems developed based on the"chiral supramolecular self-assembly"strategy have been profoundly used in asymmetric synthesis,chiral recognition,chiral catalysis,chiral separation,chiral material science and other fields.Being an important branch of chiral supramolecular systems,chiral macrocyclic compounds have exhibited outstanding results in many relevant research fields with a perspective to enrich the application of chiral macrocyclic molecules in the field of supramolecular chirality.At the outset,supramolecular system with cyclodextrin based on pillared aromatic hydrocarbons have been researched in the present work aiming at chiral induction,chiral reversal,chiral regulation,etc.In addition,a series of novel nitrogen-centered chiral Tr(?)ger's Base-based dimeric macrocycles have been designed and synthesized,sequentially embarking on the influence of nitrogen-centered chirality on solid accumulation behavior by crystal engineering,and eventually stepping towards preliminary preparations for the construction of higher-level supramolecular chiral systems.The concise research contents and results of the research work are presented as follows:In the first part,the study on host-guest interaction between dynamically racemic water-soluble pillar[5]arene(WP5)and amino acid derivatives revealed planar chiral characteristics(p R or p S).The conformational chirality of WP5 was found to be induced by nineteen different L-amino acid ethyl ester hydrochlorides(L-AA-OEt).Among them,L-Arg-OEt could induce the p R conformation of WP5,in contrast to the p S conformation of WP5 induced by eighteen other L-AA-OEt.Significantly,Gly-OEt devoid of chiral center was unable to induce the conformational chirality of WP5.This indicates that the change in enantiomer ratio of WP5 influencing dynamic conversion upon induction of chiral amino acid derivatives.The most stable spatial configuration of WP5 with L-Ala-OEt or L-Arg-OEt was analyzed through UV spectral,2D NMR spectral analysis and theoretical calculations,further established by determining inclusion ratio,binding constant and,thus aiding the systematic discussion on the complex formed.Studies have proven that the two complex structures p S-WP5(?)L-Ala-OEt and p R-WP5(?)L-Arg-OEt are the most stable state.It could be reasoned that the"N-terminal"or"C-terminal"of amino acid binding to the WP5 cavity aids selective chiral recognition.Prevalently,L-AA-OEt tend to bind their"carbon-terminal"ester group to the WP5 cavity,thereby inducing the p S-WP5conformation.L-Arg-OEt stands unique in its structure differing from that of conventional amino acids,specifically portraying the guanidine unit in the direction of"N-terminal".This structural attribute benefits its penetration into the cavity of WP5through a strong binding effect thereby inducing chiral reversibility to p R-WP5.This hints specific chiral recognition ability of L-Arg-OEt.L-Arg(pbf)-OEt,used as the control molecule in the study,possesses a large steric hindrance group in the"N-terminal"direction of L-Arg-OEt inducing reversal of chirality of WP5.The work offered in this chapter opens up the research on the use of pillar[5]arene as chiral sensor,and enriches the prospects of chirality in pillar[n]arene research.The second part is in continuation of the work performed in the previous chapter and is focused on exploring the inversion of conformational chirality between WP5and WP6 with amino acids as chiral guests.The study revealed that water-soluble pillar[5,6]arenes,WP5 and WP6 can induce the p R or p S conformation through the association of"N-terminal"or"C-terminal"regions of L-AA-OEt.By detecting the CD signal induced by WP5 or WP6,the chiral conformation induced by either terminal of amino acid can be identified.Firstly,the CD signals of WP6 with 17different L-AA-OEt as chiral guest revealed induction of dynamic racemic mixtures.The studies corroborate well affirming with the chiral induction results of 17L-AA-OEt on WP5 as in the previous chapter.The classification and analysis of the CD signal disclosed the degree of matching of the amino acid"N-terminal"substituent with the cavity of WP5 or WP6 thereby directly affecting the chiral induction results.Considering chiral moieties,L-Phe-OEt and L-Arg-OEt as apt candidates for WP5 and WP6 bearing different cavity sizes,chiral reversal behavior has been generated.Through UV spectral,2D NMR spectral studies and theoretical calculations,the inclusion ratios,binding constants,and the most stable spatial configuration of the complexes between L-Phe-OEt,L-Arg-OEt and WP5 or WP6were analyzed systematically.The results show that the difference in the binding mode of the chiral amino acid through"N-terminal"or"C-terminal"with the water-soluble pillar[n]arene change the chiral environment of the water-soluble pillar[n]arene,thus affecting the reversal of the induced CD signal.In addition,this article summarizes the relationship between the size of amino acid derivatives and the induced WP5 chiral signal strength.For the L-AA-OEt whose"N-terminal"is an alkyl chain,the strength of the CD signal mainly depends on the occupied volume of the"N-terminal"substituents.In this work,racemic water-soluble pillar[5,6]arene WP5 and WP6 was used as a chiral sensor,which provides the possibility of detecting the conformational chirality induced by"N-terminal"or"C-terminal"amino acid derivatives.The third part deals with the dynamic reversibility of the supramolecular self-assembly strategy used to accommodate the amphiphilic tetrastyrene derivative(TPEA),?-cyclodextrin(?-CD)and WP5 through self-assembly leading to two topological structures of Pseudo[4]rotaxane or nanoparticles,and the switch is accompanied by hierarchical chiral transfer.Firstly,the CD and fluorescence spectrum were used to study the formation of pseudo[4]rotaxane?-CD(?)TPEA complex with TPEA.?-CD used as the chiral host molecule induced chirality in the self-assembled structures.Addition of 0.20 equiv.of WP5?-CD(?)TPEA,lead to dissociation of?-CD(?)TPEA and,favoring WP5 to form WP5(?)TPEA aggregates resulting in aggregation-induced luminescence effect,which in turn causes a significant increase in TPEA fluorescence emission.Since the assembly is aloof of the chiral environment of?-CD,neither WP5 nor TPEA exhibited chirality.The increase in molar ratio of WP5 to 2.0 eq,brought about dissociation of the aggregate WP5(?)TPEA.Moreover,the three components of TPEA,?-CD and WP5 can form Pseudo[4]rotaxane structure TPEACD(WP5)₂ through orthogonal self-assembly.At this juncture,not only can it induce the chirality of TPEA,but under the influence of the?-CD chiral environment,WP5 can adaptively adjust its dominant conformation to match the chiral configuration of?-CD.This results in secondary chirality being transferred,generating the conformational chirality of p R-WP5.This work provides a simple and effective strategy for a deeper understanding of the transfer process between supramolecular chirality and combinations of different morphologies.In the fourth part,considerate of the V-shaped skeleton of Tr(?)ger's Base and the chiral nature of the nitrogen center,through a one-step cyclization reaction,a class of approximately square Tr(?)ger's Base-based dimeric macrocycles(T1-T3)were successfully constructed.The cavity size and chiral configuration of T1-T3 were characterized,and the effect of ring cavity size on the ability to enclose solvent molecules was also discussed.In addition,the optical isomer resolution of the T2 was carried out to obtain the crystals of three stereoisomers R_4N-T2,S_4N-T2,and R_2NS_2N-T.The solid-state stacking results of the crystals indicate that the two isomers of opposite chirality have flanking benzene rings parallel to each other to form a one-dimensional chain arrangement.The two isomers of the same chirality can form a very beautiful supramolecular helix through selective self-assembly,indicating that the self-recognition and self-repulsion behavior of the nitrogen-centered chirality has a great influence on its accumulation form.Finally,it was found that the two diastereomers rac-T2 and R_2NS_2N-T2 have selective adsorption capacity for the solvents acetone and dichloromethane,indicating that different chiral combination modes of Tr(?)ger's Base-based dimeric macrocycle T2 can be used as functional separation materials.It is believed that the special shape of the host molecule based on Tr(?)ger's base will further enrich the study of chiral supramolecular macrocycles.In summary,the present research work reflects chiral macrocyclic molecules as the research theme based on the supramolecular chiral assembly strategy,unfolding the study of chiral transfer and chiral reversal behavior at the molecular level,also as specific chiral sensor for amino acids.In addition,an intelligent system utilizing stoichiometric ratio that fine tunes the topological structure and the resultant chirality of the assembly has been highlighted.The interplay of morphology of self-assembled supramolecular structures and the hierarchical chiral transfer behavior switch was established to rationalize the functional design for the future.Finally,a new type of nitrogen-centered chiral macrocyclic molecule was developed and designed.In the solid-phase system,the effects of nitrogen-centered chirality on the ring structure distribution,assembly stacking method,and the ability to contain guests were greatly explored.It is hoped that the above research work can provide a reference for the research and development of the supramolecular chiral field and pave way for vivid applications.