Revealing the art and science of self-replicating rotaxanes
Abstract
This thesis reveals the strategies for the construction and replication of mechanically
interlocked molecules, particularly rotaxanes, which consist of a macrocyclic ring that
encircles a linear component terminated with bulky groups. The work highlights our
recent research activities in exploring the recognition-mediated synthesis of this class
of interlocked molecule and its amplification by replication. Our starting point is the
minimal model of self-replication.
The introductory chapters (Chapter 1 and 2) provide some background and
significance to the study, which presents comprehensive review of the published
work carried out in the area of self-replication with existing examples from biomimetic
and discrete synthetic assemblies. In Chapter 1, we mainly discuss the do and the
donʼts in designing successful self-replicating systems based on our own experience
in previous work. Our chief concerns in Chapter 2 are the understanding of the
chemistry of the mechanical bond and the synthesis of rotaxanes by three means of
approaches (clipping, threading and stoppering, and slippage). Attractive and useful
examples are illustrated for each mechanism. Moreover, the definition and the roles
of templated-synthesis of interlocked molecules are described. Recent advances in
the understanding of the nature of the mechanical bond have also been introduced
into molecular electronic devices.
Emphasis is placed in Chapter 3 upon the essential requirements for the design of
self-replicating rotaxanes, namely a recognition site, a reactive site and a binding
site. These aspects are explained in the designed minimal model chosen in the past
(Replication model 1) and the alternate proposed models (Replication model 2
and Replication model 3). The importance of high association constant to provide
substantial amount of pseudorotaxane [L•M] precursors is exemplified in the simple
kinetic model of rotaxane formation. The advantages and disadvantages of each
independent minimal replication model are also summarized.
In the self-replicating rotaxane frameworks, the principal strategy involves a selection
of an efficient macrocycle to accommodate the guest unit. Thus, Chapter 4
exclusively describes the design, synthesis and binding properties of a series of macrocycle incorporating the hydrogen bond donors and/or hydrogen bond acceptors
motif. In particular, the guests were designed and synthesised based on the mutual
interactions with the macrocycle framework and the binding experiments is described
in details. An account is provided of the problems faced in the synthetic attempts
towards the formation of these macrocycles. The novel macrocycle MEU
demonstrated a deficient binding performance with amide and urea compounds, and
thus abandoned in later stages. The developed macrocycle MDG and MP have been
selected as our workhorse macrocycles, which successfully increase the binding
strength in the pseudorotaxanes formation. We have learnt that the association
constant, Kₐ can be manipulated by the changing the binding site of the guest or
redesign the framework of the macrocycle itself.
An exhaustive investigation of the performance of self-replicating rotaxanes focuses
on Replication model 1 is demonstrated in Chapter 5. It was evident now that as a
consequence of low Kₐ, a substantial amount of thread is present over rotaxane. The
implementation of the simple kinetic model of rotaxane formation is prevailed through
out this chapter. The position of the central reversible equilibrium in this model
effectively resulted in a different reactivity of thread and rotaxane. Therefore, it is
concluded that the ratio of rotaxane and thread is sensitive to both the association
constant 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 of
rotaxane, R to thread, T. In previous chapter, the Kₐ for the [L•M] complex was
around 100 M⁻¹ and k[subscript(T)] = 3 k[subscript(R)], which led to an unacceptably small [R]/[T] ratio. We
demonstrated for the first time in Chapter 6, that it is possible to manipulate the Kₐ
for the [L•M] complex by means of a change in temperature. Yields of a rotaxane can
be improved by employing a two-step capture protocol. Cooling a solution of the
linear and macrocyclic components required for the rotaxane increases the
population of the target pseudorotaxane, which is then captured by a rapid capping
reaction between an azide and PPh₃. The resulting iminophosphorane rotaxane can
then be manipulated synthetically at elevated temperatures. Following this, these
imines could be reduced readily to afford the stable amine rotaxane.
Replication model 2 is subsequently proposed as alternate replication framework in
Chapter 7, which realised significant advantages over the first model. A number of
designs of a potential self-replicating rotaxane have been fabricated in order to
integrate self-replication with the formation of rotaxanes. An account is provided of
the problems faced with the unanticipated larger cavity of the newly prepared acid
recognition macrocycles, and hence, force us to search for a new scaffold of the
nitrone structures. Pleasingly, a substantial amount of rotaxane was present, mostly
as trans diastereoisomer. It is concluded that the resulting rotaxane structures may
be self-replicating through the recognition-mediated pathways from the preliminary
kinetic experiments. Nonetheless, the remainder of the full kinetic analysis are
prevented given a small quantity of the necessary building block.
Chapter 8 reveals our recent efforts to demonstrate the notions behind the final
replication scheme, Replication model 3. We have become aware that the reactive
site must be placed sufficiently far away from the binding site to inhibit the remote
steric effect through the proximity of the macrocyclic component. The design of novel
nitrone structures is described in details. We bring together conclusions that can be
drawn from three designated replication models in Chapter 9. Experimental and
synthetic procedures of the target compounds and appropriate spectroscopic
analysis of the products are elaborated in Chapter 10.
Type
Thesis, PhD Doctor of Philosophy
Description
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