Revealing the art and science of self-replicating rotaxanes

Supramolecular chemistry;Rotaxanes--Synthesis;Macrocyclic compounds;Molecular recognition

Hassan, Nurul Izzaty ; Philp, Douglas ; Philp, Douglas

University:University of St Andrews

Department:Chemistry (School of)

关键词: Supramolecular chemistry;    Rotaxanes--Synthesis;    Macrocyclic compounds;    Molecular recognition;   

Others  :  https://research-repository.st-andrews.ac.uk/bitstream/handle/10023/3128/NurulHassanPhDThesis.pdf?sequence=3&isAllowed=y

来源: DR-NTU

【 摘 要 】

This thesis reveals the strategies for the construction and replication of mechanicallyinterlocked molecules, particularly rotaxanes, which consist of a macrocyclic ring thatencircles a linear component terminated with bulky groups. The work highlights ourrecent research activities in exploring the recognition-mediated synthesis of this classof interlocked molecule and its amplification by replication. Our starting point is theminimal model of self-replication.The introductory chapters (Chapter 1 and 2) provide some background andsignificance to the study, which presents comprehensive review of the publishedwork carried out in the area of self-replication with existing examples from biomimeticand discrete synthetic assemblies. In Chapter 1, we mainly discuss the do and thedonʼts in designing successful self-replicating systems based on our own experiencein previous work. Our chief concerns in Chapter 2 are the understanding of thechemistry of the mechanical bond and the synthesis of rotaxanes by three means ofapproaches (clipping, threading and stoppering, and slippage). Attractive and usefulexamples are illustrated for each mechanism. Moreover, the definition and the rolesof templated-synthesis of interlocked molecules are described. Recent advances inthe understanding of the nature of the mechanical bond have also been introducedinto molecular electronic devices.Emphasis is placed in Chapter 3 upon the essential requirements for the design ofself-replicating rotaxanes, namely a recognition site, a reactive site and a bindingsite. These aspects are explained in the designed minimal model chosen in the past(Replication model 1) and the alternate proposed models (Replication model 2and Replication model 3). The importance of high association constant to providesubstantial amount of pseudorotaxane [L•M] precursors is exemplified in the simplekinetic model of rotaxane formation. The advantages and disadvantages of eachindependent minimal replication model are also summarized.In the self-replicating rotaxane frameworks, the principal strategy involves a selectionof an efficient macrocycle to accommodate the guest unit. Thus, Chapter 4exclusively describes the design, synthesis and binding properties of a series of macrocycle incorporating the hydrogen bond donors and/or hydrogen bond acceptorsmotif. In particular, the guests were designed and synthesised based on the mutualinteractions with the macrocycle framework and the binding experiments is describedin details. An account is provided of the problems faced in the synthetic attemptstowards the formation of these macrocycles. The novel macrocycle MEUdemonstrated a deficient binding performance with amide and urea compounds, andthus abandoned in later stages. The developed macrocycle MDG and MP have beenselected as our workhorse macrocycles, which successfully increase the bindingstrength in the pseudorotaxanes formation. We have learnt that the associationconstant, Kₐ can be manipulated by the changing the binding site of the guest orredesign the framework of the macrocycle itself.An exhaustive investigation of the performance of self-replicating rotaxanes focuseson Replication model 1 is demonstrated in Chapter 5. It was evident now that as aconsequence of low Kₐ, a substantial amount of thread is present over rotaxane. Theimplementation of the simple kinetic model of rotaxane formation is prevailed throughout this chapter. The position of the central reversible equilibrium in this modeleffectively resulted in a different reactivity of thread and rotaxane. Therefore, it isconcluded that the ratio of rotaxane and thread is sensitive to both the associationconstant for the [L•M] complex and to the ratio of k[subscript(rotaxane)]/k[subscript(thread)].The key marker for the efficiency of the rotaxane-forming protocol is the ratio ofrotaxane, R to thread, T. In previous chapter, the Kₐ for the [L•M] complex wasaround 100 M⁻¹ and k[subscript(T)] = 3 k[subscript(R)], which led to an unacceptably small [R]/[T] ratio. Wedemonstrated for the first time in Chapter 6, that it is possible to manipulate the Kₐfor the [L•M] complex by means of a change in temperature. Yields of a rotaxane canbe improved by employing a two-step capture protocol. Cooling a solution of thelinear and macrocyclic components required for the rotaxane increases thepopulation of the target pseudorotaxane, which is then captured by a rapid cappingreaction between an azide and PPh₃. The resulting iminophosphorane rotaxane canthen be manipulated synthetically at elevated temperatures. Following this, theseimines could be reduced readily to afford the stable amine rotaxane.Replication model 2 is subsequently proposed as alternate replication framework inChapter 7, which realised significant advantages over the first model. A number ofdesigns of a potential self-replicating rotaxane have been fabricated in order tointegrate self-replication with the formation of rotaxanes. An account is provided ofthe problems faced with the unanticipated larger cavity of the newly prepared acidrecognition macrocycles, and hence, force us to search for a new scaffold of thenitrone structures. Pleasingly, a substantial amount of rotaxane was present, mostlyas trans diastereoisomer. It is concluded that the resulting rotaxane structures maybe self-replicating through the recognition-mediated pathways from the preliminarykinetic experiments. Nonetheless, the remainder of the full kinetic analysis areprevented given a small quantity of the necessary building block.Chapter 8 reveals our recent efforts to demonstrate the notions behind the finalreplication scheme, Replication model 3. We have become aware that the reactivesite must be placed sufficiently far away from the binding site to inhibit the remotesteric effect through the proximity of the macrocyclic component. The design of novelnitrone structures is described in details. We bring together conclusions that can bedrawn from three designated replication models in Chapter 9. Experimental andsynthetic procedures of the target compounds and appropriate spectroscopicanalysis of the products are elaborated in Chapter 10.