CAPÍTULO II. MARCO METODÓLOGICO
ENFOQUE CUANTITATIVO
In recent years, there has been a significant development in supramolecular chemistry. The emergence of molecular machinery and highly complex self-assembled structures are becoming more apparent. As a result of such research, a number of advances have materialised in the use of such structures in nanotechnology. Interlocked compounds such as catenanes and rotaxanes are one such area of importance.76 Rotaxanes in particular are receiving much interest in new research as they have the ability to act as molecular machines and switches,77 valves, insulated wires,78 drug delivery vehicles,79 wheels,80 scaffolds81 and in nanoelectronics.82 Exploiting the week intermolecular forces we have seen many examples of the synthesis of these structures come to light over the last three decades.
1.7.1 Valves
Stoddart78, has developed rotaxanes that are able to act as valves, trapping and releasing molecules under chemical and light control. These then have applications in sensors and controlled drug release. Using pH stimulation and competitive binding in order to control ‘gatekeeper supermolecules’, the openings of nanosized pores on silica particles were able to be regulated.
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1.7.2 Wheels
Investigating configurational entropy of protein-ligand interactions to measure complex stability, Smithrud80 used host-guest complexes, rather than the traditional lock-and-key or induced-fit model. Rotaxane axles act as the synthetic hosts, with bulky calixarenes and cyclophanes used as ‘stoppers’. Attaching functional groups to the macrocycle (wheel) allowed guest recognition. The host-guest association was measured in both water and DMSO. The binding sites were arranged over several parts of the axle to create a relationship between guest association and conformational changes that occur as the wheel moves between each site. The hosts use several conformations to bind guests so are excellent models of protein binding domains. From these studies, an increase in entropy of binding has been observed on addition of the wheel to the host. Increasing motion of the wheel is thought to be where this originates from, showing favourable configurational entropy which aids complex formation.
1.7.3 Molecular Switches
The relative movement of the interlocked components of a rotaxane can be modulated in a controlled manner in the development of molecular switches and shuttles. There is great interest is such complexes with research into several methods of stimulation including chemical, electrochemical and photochemical processes. Stoddart et al83 reported one of the first [2]rotaxanes to act as a ‘molecular shuttle’. They described the complex as a tetracationic “bead” that shuttles between two identical “stations”. It consisted of a CBPQT4+
macrocycle acting as the “bead” on a polyether thread with hydroquinol units to act as the “stations”. The ends of the rotaxane were stoppered by large triisopropylsilyl groups preventing the macrocycle from slipping off. (Scheme 1.11) The shuttling motion was temperature dependant with a large free energy of activation (13 kcal mol-1). Changes in the rate of the macrocycle shuttling were measured using variable temperature 1H NMR.
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Scheme 1.11 Stoddart’s first example of a molecular shuttle.A molecular shuttle has recently been reported by Li and co-workers84 to drive a multilevel fluorescence switch. It is a [2]rotaxane prepared by a thermodynamically controlled, template induced clipping method. The thread has two recognition sites which are separated by a phenyl unit, these are -NH2
+
- and an amide. When protonated, the macrocycle binds to the -NH2
+
- region through a variety of non-covalent interactions. When the ammonium ion is deprotonated, the macrocycle prefers to hydrogen bond to the amide region. Addition of either Li+ or Zn2+ ions to the system then controls the movement from one recognition site to the other. All three processes result in a fluorescent response (Figure 1.8) and it is pH dependant and reversible.
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Figure 1.8 A pH switchable molecular switch.The Stoddart group have successfully synthesised a bistable [2]rotaxane which can be controlled thermodynamically. The macrocyclic ring structure is the π electron deficient CBPQT4+ ring and the axle contains two different π electron accepting moieties which are a TTF and DNP units. The CBPQT4+ macrocycle was threaded onto an axle with two terminating azide groups. The bulky stoppers were attached in a ‘CuAAC’ reaction to give the bistable [2]rotaxane. The position of the macrocycle could be controlled via oxidation and reduction of the TTF unit (Scheme 1.12).85
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Scheme 1.12 Schematic of a bistable [2]rotaxane.A more recent example of this molecular switch has been created by Stoddart.86 They have further developed the bistable [2]rotaxane with a CBPQT4+ π electron deficient macrocycle and the axle again containing the TTF and DNP units. Located in the central part of the axle is a 3,5,3’,5’-tetramethylazobenzene (TMeAB) unit which is photoactive and can change between its cis and trans conformations. In the axle’s neutral form the CBPQT4+ macrocycle resides over the more π electron rich TTF unit. Upon oxidation the CBPQT4+ is ‘switched’ to
the DNP moiety. The ‘switching’ process is also controlled by the photo induced isomerisation of TMeAB unit. When in the trans configuration the CBPQT4+ macrocycle can move freely between stations. Once in the cis configuration the macrocycle now has a much larger energy barrier to overcome due to steric hindrance which provides further control of the macrocycle position.