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Supramolecular Chemistry
From Molecule to Molecular Machines
Vandana Bhalla
Supramolecular chemistry as defined by Lehn ‘chemistry be- yond the molecule’ focuses on the development of functional complex architectures through non-covalent interactions. The year 2017, marked the fiftieth anniversary of the serendipi- tous discovery of crown ethers. Since then, the field is grow- ing, and due to the e ff orts of various researchers now it is pos- sible to have some control over the arrangement of things on a small scale. In this review article, the concept of supramolec- ular chemistry, cooperativity responsible for interactions, tech- niques for determination of thermodynamic parameters of cooperativity, and the contribution of supramolecular chem- istry to nanotechnology is described.
Introduction
Supramolecular chemistry has been defined by phrases such as ‘chemistry beyond the molecule’, ‘chemistry of molecular as- semblies and of the intermolecular bond’, and ‘non-molecular chemistry’. The main objective of supramolecular chemistry is to design and develop novel functional systems by joining multi- ple chemical components through non-covalent interactions. The year 2017, marked the fiftieth anniversary of publication of first paper in the field of supramolecular chemistry and the thirtieth an- niversary of the first Nobel Prize awarded in this field. The Nobel Prize awarded to Jean-Marie Lehn, Donald J Cram, and Charles J Pedersen in 1987, established supramolecular chemistry as a dis- Keywords Non-covalent interactions, self-assembly, molecular mo- tors, cooperativity, fluorescent chemosensors.
cipline which is now being explored in various areas such as drug development, sensors, catalysis, nanoscience, molecular devices etc. Over the last few decades, the discipline of supramolecular chemistry has emerged as a multidisciplinary domain providing
Receptor-analyte affinity^ opportunities to researchers is nature inspired and at the heart of many biological processes such as enzyme-substrate, antibody-antigen interactions.
working in different areas such as chemical science, biological science, physical science, material science and so on. On the whole, supramolecular chemistry focuses on two over- lapping areas, ‘supramolecules’ and ‘molecular assemblies’. A supramolecule is a well-defined discrete system generated through interactions between a molecule (receptor or host) having con- vergent binding sites such as donor atoms, sites for formation of hydrogen bonds and sizable cavity, and another molecule (ana- lyte or guest) having divergent binding sites such as hydrogen bond acceptor atoms ( Figure 1). The receptor can be a macro- molecule or aggregates and the analyte may be ions (cations and anions) or molecules. For designing a receptor molecule, knowl- edge of several interactions such as structural/functional informa- tion, energetics of the binding event, complementarity of molec- ular shapes etc., is needed at molecular level. Receptor-analyte affinity is nature inspired and at the heart of many biological pro- cesses such as enzyme-substrate, antibody-antigen interactions. On the other hand, well-defined molecular assemblies are gener- ated by spontaneous self-assembly of multiple components un- der the given set of conditions. The guiding force for the self- assembling process originates from molecular binding events. In the nutshell, for the generation of ordered molecular assemblies, operation is supramolecular but approach is molecular. Recently, self-assembly process has been utilized for generation of func- tional nanoarchitectures of different shapes and morphologies [1]. This is one of the fastest-growing fields, and over the past decade, supramolecular chemistry has contributed significantly towards the development of nanotechnology. At the interface of these two disciplines – supramolecular chemistry and nanotechnology – lies the domain of nanochemistry.
Historical Background
The famous phrase of Louis Pasteur, “chance favors the prepared mind”, reflects the curiosity of Charles J Pederson’s prepared
Supramolecular Interactions and Cooperativity in Supramolec- ular Complexes
The whole range of non-covalent interactions such as coulombic interactions, hydrogen bonding, charge transfer complexes, van der Waals forces, and hydrophobic effect strongly affect the struc- ture and properties of supramolecular systems. Non-covalent in- teractions are much weaker in comparison to covalent interac- tions ( Table 1). However, the small stabilization gained by one weak interaction when added to all small stabilizations from the other interactions leads to the generation of a stable architec-
Box 1. Organic Chemistry vs. Supramolecular Chemistry
A dream target of nature inspired synthesis is to prepare ‘smart’ functional molecules which are so de- signed that they themselves are ‘able to generate correct architectures’. Despite the excellent contribution of modern organic chemistry towards the development of highly complex materials, the synthetic routes are multistep and tedious. On the other hand, the principles of supramolecular chemistry can be applied to prepare well-defined large and complex architectures in a few steps. Furthermore, most of the organic reactions are kinetically controlled and irreversible. Due to irreversible reaction conditions, there is no pos- sibility of correction of any ‘mistake’ during the product formation. Moreover, the final product may not be the most stable product. For preparing designed molecules, it is important to understand the mechanism of organic reactions. Interestingly, the key point of supramolecular chemistry is doing the synthesis under ther- modynamically controlled conditions rather than kinetically controlled conditions. Due to thermodynamic control, all the steps are reversible and the final product is the most stable product. The interactions and the newly formed bonds are weak. Thus, they can break and reform till most stable structure is achieved. If any ‘misconnection’ is there, it can be self-corrected as shown in Figure A [5]. Self-corrected product is stable while least stable product is formed by misconnection.
Figure A. The left panel shows the misconnection and the right shows the self-corrected molecule.
Interaction Strength (kJ mol −^1 ) Covalent Bond 200– Ion-Ion 100– Ion-Dipole 50– Dipole-Dipole 5– Hydrogen Bonding 4– Cation-π 5– π–π 0– van der Waals < 5 (variable depending on surface area) Hydrophobic Related to solvent-solvent interaction energy
Table 1. Supramolecular interaction classified under various categories.
ture or stable host-guest complex. The formation of a complex via supramolecular interactions is fast, facile and more stable as compared to that prepared by using principles of organic chem- istry (see Box 1). Multivalent binding has added advantages of high binding strength, reversibility of binding process, and due to the organization of binding sites in the space, geometry of supramolecular complex can be controlled. Moreover, multiva- lency effect ensures the formation of discrete supramolecular sys- tems rather than oligomers. Thus, the interactions between a re- ceptor (host) and analyte (guest) strongly depends on multiple binding. On the other hand, in case of self-assembled polymeric supramolecular systems cooperative interactions between multi- ple chemical components are needed. Due to these cooperative interactions (non-covalent in supramolecular systems) or coop- erativity, the free energy change (Δ G ) is either decreased or in- creased over the subsequent interaction steps in a reaction as com- pared to the first step. If the free energy (^) Very interestingly, many supramolecular architectures are very stable than what would be expected from the presence of chelate/positive cooperativity alone.
change is decreased it is called positive cooperativity while an increase in the free en- ergy change suggests negative cooperativity. The positive coop- erativity of multiple binding sites present on the host molecule to bind a guest molecule in a way is chelate effect. Very inter- estingly, many supramolecular architectures are very stable than what would be expected from the presence of chelate/positive co- operativity alone. In general, in discrete supramolecular systems,
Experimental Techniques to Determine Thermodynamic Pa- rameters of Cooperativity
The selection of correct experimental techniques to determine various thermodynamic parameters such as ΔG to determine co- operativity or binding strength is very important. The selection of technique is based on the selection of physical property of the receptor that fits the concentration range which brings maximum change in the equilibria under examination. The most commonly used experimental techniques for the determination of binding strength between receptor and guest (supramolecular titration) are as follows:
1. NMR Titration Method : This is one of the most popular meth- ods for supramolecular titration studies. It is very much suitable for providing the information about the small structural changes generated in the receptor in the presence of guest. However, this technique is not suitable for systems having high association con- stants (K > 105 M−^1 ). This is also not a preferred method for the intramolecular chelate systems because the interactions involved in these systems lie in slow exchange region. 2. Absorption and Emission Spectroscopic Techniques : The ab- sorption studies (UV-vis studies titration studies) provide limited information about structural changes involved during the bind- ing event, however, the absorption experiments are more useful for thermodynamic analysis. The UV-vis spectroscopy is advan- tageous because of the operational simplicity of the instrument, high equilibrium constants, and (^) ITC is a direct technique to measure heat changes involved in a binding event. However, it provides no information about the heat changes involved at the molecular level, and thus ITC is not an independent technique and always requires the support of another technique to explain the binding event.
with a suitable chromophore, the studies can be carried out at micromolar concentrations. Simi- larly, fluorescence spectroscopy is another powerful technique for the investigation of cooperative interactions due to its high sensi- tivity, operational simplicity, and low background interferences.
3. Isothermal Titration Calorimetry (ITC) Method : ITC is a more convenient method to determine binding/association stoi- chiometry (n), binding/association constant (K), Gibbs free bind- ing/association energy, binding/ association enthalpy and bind- ing/association entropy. ITC is a direct technique to measure heat
changes involved in a binding event. However, it provides no in- formation about the heat changes involved at the molecular level, and thus ITC is not an independent technique and always requires the support of another technique to explain the binding event.
Signaling Binding Events with Fluorescent Chemosensors
The important binding^ Fluorescence spectroscopy events of supramolecular chemistry can be conveniently signaled through light signals emitted by tailormade molecular devices.
is an active tool in various fields of modern science and medicine, including clinical diagnostics, biotech- nology, molecular biology and biochemistry, materials science, and analytical and environmental chemistry. Especially for sens- ing and visualization of analytes, fluorescence spectroscopy of- fers significant advantages over other measurement methods, such as microelectrodes, NMR, atomic absorption spectroscopy, and spectrophotometry due to its operational simplicity, detection limit down to single molecules, ‘on-off’ switchability, high resolution and visualization, and the possibility of human-molecule commu- nication. The important binding events of supramolecular chem- istry can be conveniently signaled through light signals emitted by tailormade molecular devices. Fluorescence based molecular devices are important because their emission can be switched be- tween two distinguishable states in presence of external stimuli. In addition, fluorescence is a useful spectroscopy in which the fluorescence signals may be monitored as excitation and emis- sion spectra, intensities, intensity ratios, lifetimes, and even as anisotropy. There are several approaches for designing fluorescence- based materials. Most commonly used approach is depicted in Figure 4. Sousa, Czarnik, and de Silva are pioneer workers in this field. They reported a variety of fluorescent chemosensors prepared by connecting fluorophore with the crown-based recep- tor units. They demonstrated that crown/azacrown when linked to fluorophore showed quenching of the molecular emission due to photoinduced electron transfer (PET) from lone pair of the ben- zylic heteroatoms of the receptor unit [7]. Interestingly, emis- sion of such systems can be revived by the binding of receptor unit with a guest/analyte through chelation enhanced emission enhancement phenomenon (CHEF) as shown in Figure 5 [8]. In-
ane/catenane based systems have been developed. Molecular Walkers : Molecular walkers have been developed to show directional transport at molecular level. The molecule should
Box 2. Signaling Binding Events with Fluorescent Chemosensors in Aqueous Media
Development of chemosensors which show high emission in aqueous media is very important. However, in most of the cases, fluorescence is quenched or weakened due to exciton coupling, excimer formations, and excitation energy migration to the impurity traps. In 2001 Tang et al ., reported the term ‘aggregation- induced emission (AIE)’ materials for such kind of molecules [9]. Unlike other fluorophores showing quenching effect, these molecules show no emission in organic solvent. Amazingly, upon raising the water content, the molecules aggregate and show strong fluorescence. This feature is attributed to the availability of easily rotatable phenyl rings attached to the central core through C-C bond, also called ‘rotors’. In solution phase, these rotors are in rotating mode around their vertical axis due to which the energy of approaching photon is dissipated with a non-radiative pathway. Hence, less energy is absorbed by the molecule due to which the molecule is non-luminescent in solution state. But when a bad solvent is added to the solution, the molecule gets aggregated due to poor solubility on the molecular level, and rotation of the rotors is restricted due to the close packing in aggregated state which blocks the non-radiative pathways. This results in the release of excitation energy with radiative pathways to raise the luminescence of the molecule as in Figure B.
Figure B. Fluorescence turned on due to restricted intramolecular rotation by aggregation formation.
Most of the reported AIE sensors are based on design of molecules which are freely soluble in aqueous/organic media. These molecules undergoes coordination driven aggregation in the presence of analytes. As a result, restriction in intramolecular rotation and hence enhancement in fluorescence emission intensity was observed. The AIE strategy offers advantages such as high selectivity, sensitivity, facile fabrication, ready functionalization, excellent stability, high signal-to-noise ratio, low background interference as well as the simplicity of the fluorescence technique.
Figure 5. Photoin- duced electron transfer phenomenon.
Figure 6. Operation of the first small-molecule walker system by Leigh. Changes in the pH induce the mi- gration of the walker unit from one end of the track to the other by a ‘passing-leg’ mechanism.
fulfill essential requirements such as processivity (there should be minimum one contact point of molecule with the track during the whole operation) and directionality (molecule walker should move towards one end). Moreover, molecular walker must show autonomous, progressive and repetitive operation. Leigh’s group developed the first small molecule-based molecular walker in 2001 [10]. This walker worked on ‘passing leg’ mechanism. The walker has two feet – disulphide foot and hydrazine foot. Both the ‘feet’ bind reversibly with the track through covalent bonds and are highly sensitive to pH. Under basic conditions, disulphide foot becomes labile; however hydrazine foot remains covalently attached to the track. On the other hand, under acidic conditions, hydrazine foot becomes labile, and disulphide foot remains cova- lently attached as shown in Figure 6.
Rotaxane Based Molecular Machine : Rotaxanes [11] consist of axels threaded through one or two rings ( Figure 7). Since rotax- ane based systems have interlocked components. The exchange of these components with bulk is practically impossible without
Figure 8. Catenane deriva- tive consists of two (or more) macrocycles threaded through each other.
Conclusion
The key feature of supramolecular chemistry is its ability to re- organize and exchange molecules till the correct combination of building blocks is selected from a collection of different molec- ular components for the development of thermodynamically and kinetically favored supramolecular entity. Now, the biggest ques- tion is to where supramolecular chemistry is heading to? The an- swer to this query is very simply provided by Prof Lehn. Supramolec- ular chemistry is significantly contributing towards the growth of molecular chemistry, and hence a new type of adaptive chemistry is evolving. This chemistry aims at allowing reorganization and selection in self-organisation to attain adaptation at the molecular as well as supramolecular level.
Suggested Reading
[1] H Dugas, Bioorganic Chemistry: A chemical Approach to Enzyme Action , 3rd edition Springer private limited India, 2007. [2] C J Pedersen, Cyclic Polyethers and Their Complexes With Metal Salts, J. Am. Chem. Soc ., Vol.89, No.26, pp.7017–7036, 1967.
[3] D J Cram, T Kaneda, R C Helgeson, G M Lein, Spherands – Ligands Whose Binding of Cations Relieves Enforced Electron-electron Repulsions, J. Am. Chem. Soc ., Vol.101, No.22, pp.6752–6754, 1979. [4] B Dietrich, J M Lehn, J P Sauvage, Cryptates-XI Complexes Macrobi- cycliques, Formation, Structure, Properties, Tetrahedron , Vol.29, No.11, pp.1647–1658, 1973, [5] E V Anslyn, D A Dougherty, Modern Physical Organic Chemistry , University Science Books, California, 2006. [6] L K S Krbek, C A Schalley, P Thordarson, Assessing Cooperativity in Supramolecular Systems, Chem. Soc. Rev ., Vol.46, No.9, pp.2622–2637, 2017. [7] J Li, D Yim, W-O Jang, J Yoon, Recent Progress in the Design and Appli- cations of Fluorescence Probes Containing Crown Ethers, Chem. Soc. Rev ., Vol.46, No.9, pp.2437–2458, 2017. [8] A P de Silva, S A de Silva, Fluorescent Signalling Crown Ethers; ‘Switching On’ of Fluorescence by Alkali Metal Ion Recognition and Binding in situ , J. Chem. Soc. Chem. Commun ., Vol.0, No.23, pp.1709–1710, 1986. [9] J Mei, N L C Leung, R T K Kwok, J W Y Lam, B Z Tang, Aggregation- Induced Emission: Together We Shine, United We Soar, Chem. Rev ., Vol.115, No.21, pp.11718–11940, 2015. [10] S Kassem, T Leeuwen, A S Lubbe, M R Wilson, B L Feringa, D A Leigh, Artificial Molecular Motors, Chem. Soc. Rev ., Vol.46, No.9, pp.2592. [11] E A Neal, S M Goldup, Chemical Consequences of Mechanical Bonding in Catenanes and Rotaxanes: Isomerism, Modification, Catalysis and Molecular Machines for Synthesis, Chem. Commun ., Vol.50, No.40, pp.5128–5142, 2014.
