SUPRAMOLECULAR CHEMISTRY

CHEMISTRY OF SUPRAMOLECULES by VARINDER KHEPAR (PhD Chemistry), Punjab Agricultural University, Ludhiana, PUNJAB, INDIA

1. Chemistry of Supramolecules VARINDER KHEPAR DEPARTMENT OF CHEMISTRY 1

2. C ontents HISTORY INTRODUCTION CRAM’S HOST- GUEST CHEMISTRY COOPERATIVITY MOLECULAR SELF-ASSEMBLY MOLECULAR RECOGNITION AND COMPLEXATION MECHANICALLY-INTERLOCKED MOLECULAR ARCHITECTURES BIOMIMETICS MOLECULAR IMPRINTING TECHNIQUES MOLECULAR MACHINERY PROPERTIES APPLICATIONS 2

3. HISTORY In 1967, Pedersen observed that crown ether showed molecular recognition. Cram established, host–guest chemistry, where the host molecule can accommodate another guest molecule. In 1978, Lehn proposed the term “Supramolecular C hemistry ”. In 1987, Pedersen, Cram and Lehn received the Nobel Prize in Supramolecular Chemistry 3

4. Nobel Prize in 1987: Pederson C , Cram D J, Lehn J M. Supramolecular chemistry, a term introduced by Jean- Marie Lehn, is “ chemistry beyond the molecule ”, i.e. the chemistry of molecular assemblies using noncovalent bonds . 4

5. INTRODUCTION “ Supramolecular chemistry” - “chemistry beyond the molecule” According to Dr. Lehn, who invented the term, a supermolecule formed by the association of two or more chemical species held together by intermolecular forces, like.. Hydrogen bonding, hydrophobic interactions and coordination. 5

6. Focuses on non-covalent bonding interactions of molecule. • Forces include hydrogen bonding, ion-ion, dipole-dipole, ion-dipole, vander Waals forces, pi-pi interaction. Bhalla V (2018) Supramolecular Chemistry From Molecule to Molecular Machines. Resonance 272-90 . 6

7. Konovalov A I and Antipin I S (2008). Supramolecular systems based on calixarenes . Mendeleev Commun . 18 (5), 229–237.  7

8. CRAM’S HOST- GUEST CHEMISTRY Suprachem involves the a molecule (a host) binding another molecule (a guest) via. Noncovalent binding or complexation . Cram’s (1988) states that, “ The host is any molecule or ion whose binding sites converge in the complex while the guest is any molecule or ion whose binding sites diverge. The supramolecule complex is a highly structued assembly of host and guest molecules through multiple contact points on common surface. 8

9. Bhalla V (2018) Supramolecular Chemistry From Molecule to Molecular Machines. Resonance 272-90 . 9

10. Host-guest classification Host Guest Interaction Crown ether Metal cation Dipole Cryptands Alkyl ammonium cation H-bonding Cyclodextrin Organic molecule Vander Waal Water Organic molecule/ halogen Vander Waal Calixarene Organic molecule Vander Waal Cyclotrivera - trylene (CTV) Organic molecule Vander Waal 10

11. Crown ethers Crown ethers are consist of a cyclic ring containing several ether groups. Crown ethers strongly bind to certain cations , forming complexes through oxygen atoms. Resulting cations form salts, that are soluble in nonpolar solvents.  Useful in phase transfer catalysis. https://en.wikipedia.org/wiki/Crown_ether 11

12. Cryptands Cryptands  are a family of synthetic bicyclic and polycyclic  multidentate ligands for a variety of cations . Cryptands bind the guest ions using both nitrogen and oxygen donors. The complex between the cationic guest and the cryptand is called a cryptate . https://en.wikipedia.org/wiki/Cryptand 12

13. Cyclodextrins   Cyclodextrins  are a family of cyclic oligosaccharides. Consists of a  macrocyclic  ring of glucose subunits joined by α-1,4  glycosidic bonds. The three main types of cyclodextrins : α - cyclodextrin : 6 glucose subunits β - cyclodextrin : 7 glucose subunits γ - cyclodextrin : 8 glucose subunits https://en.wikipedia.org/wiki/Cyclodextrin 13

14. 14 α - cyclodextrin

15. Calixarene A  calixarene  is a  macrocycle compounds capable of assuming a basket (or ' calix ') shaped conformation. Calixarenes have hydrophobic cavities that can hold smaller molecules or ions. Calixarene  nomenclature involves counting the number of repeating units in the ring e.g. calix [4] arene has 4 units in the ring and a calix [6] arene has 6. https://en.wikipedia.org/wiki/Calixarene 15

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17. Cyclotriveratrylene CTV is an  macrocyclic organic compound with the formula [C 6 H 2 (OCH 3 ) 2 CH 2 ] 3. The compound is related to  calixarenes  in terms of its host–guest properties and its synthesis. When two CTV units are connected though molecular spacers a molecular box is formed called a  cryptophane . https://en.wikipedia.org/wiki/Cyclotriveratrylene 17

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19. COOPERATIVITY IN SUPRAMOLECULAR COMPLEXES Non-covalent interactions are much weaker in comparison to covalent interactions. Due to cooperative interactions (non-covalent), the free energy change ( δG ) is either decreased or increased over the interaction steps in a reaction If the free energy is decreased it is called positive cooperativity while an increase in the free energy change suggests negative cooperativity . 19

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21. Systems generated through interaction of : Monovalent guest and a multivalent host - intermolecular cooperativity Multivalent receptors and multivalent guests – intramolecular cooperativity Binding of a bivalent guest with a tetravalent receptor - interannular cooperativity 21

22. Bhalla V (2018) Supramolecular Chemistry From Molecule to Molecular Machines. Resonance 272-90. 22

23. MOLECULAR SELF-ASSEMBLY Molecules adopt a defined arrangement without external influences. There are two types of self-assembly— intermolecular self-assembly and intra-molecular self assembly. The term molecular self-assembly refers to intermolecular self-assembly, while the intramolecular analog is more commonly called folding. 23

24. Intermolecular self-assembling Intermolecular self-assembling exist in biological systems (naturally occurring double helical form of DNA). In DNA two single strands are held together by a number of hydrogen bonds. Involves acidic hydrogen atoms (hydrogen bonding donor), oxygen (hydrogen bonding acceptor) and nitrogen atoms (hydrogen bonding acceptor), in order to maintain the double helical structure 24

25. In this double helix guanine (G) forms triple hydrogen bonds with cytosine (C) and adenine (A) forms double hydrogen bonds with thymine (T). Guanine selectively interacts with cytosine because the G-C complex is much more stable than G-T complex which would form only one hydrogen bond. Adenine exclusively forms complex with thymine because adenine would form no hydrogen bonds with cytosine. X-ray diffraction studies revealed that the hydrogen bonds holding G-C and A-T complexes are about the same length (2.9±0.1 Å). 25

26. Bonding in DNA 26

27. Intra-molecular self-assembly or folding Occurs in foldamers . Foldamer is a discrete chain molecule that folds into a conformationally ordered state in solution. The structure of a foldamer is stabilized by non-covalent interactions. Foldamers are studied with the main goal of designing large molecules with predictable structures. 27

28. MOLECULAR RECOGNITION AND COMPLEXATION Specific binding of a guest molecule to a complementary host molecule to form a host guest complex. The molecules are able to identify each other using direct non-covalent interactions. 28

29. Molecular recognition between crown ether and a specific ion Crown ethers are macrocyclic polyethers . Oxygen atoms forms complex with alkali metal through electrostatic interactions. The size of ring opening determines the size of metal ion that can be accomodated . 29

30. Cation Ionic radius (A ) Cavity radius (A ) K+ 2.66 2.6-3.2 Na+ 1.80 1.7-2.2 Li+ 1.20 1.2-1.5 Kalsi P S and kalsi J P (2007) Bioorganic, Bioinorganic and Supramolecular Chemistry. New Age International (P) Ltd., Publishers Pp 228-30. 30

31. MECHANICALLY-INTERLOCKED MOLECULAR ARCHITECTURES Consist of molecules that are linked only as a consequence of their topology. E.g. Molecular Borromean rings three macro cycles are interlocked in such a way that breaking any macrocycle allows the others to disassociate. 31

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33. Biomimetics is the knowledge borrowed from natural systems to solve scientific problems. Synthetic supramolecular systems are designed to copy functions of biological systems. Used to learn about both synthetic implementation and biological systems i.e. enzyme mimics. Manna A K (2015) Supramolecular Chemistry-Concepts and Applications. Int. J. Sci. Res. 4 (4), 892-99. 33

34. MOLECULAR IMPRINTING TECHNIQUES 34

35. Obtained cavity can work as a selective binding site I . Then template molecule is removed from the matrix. It leaves a cavity complementary in size and shape to the template 35

36. Manna A K (2015) Supramolecular Chemistry-Concepts and Applications. Int. J. Sci. Res. 4 (4), 892-99. 36

37. MOLECULAR MACHINERY 37

38. Defined as any discrete number of molecular components that produce quasimechanical output in response to specific input. These molecular machines are capable of showing controlled repetitive motion and function at the nanoscale . Such materials have great potential in the field of nanotechnology. Macromolecular machines frequently perform tasks essential for life such as DNA replication and ATP synthesis 38

39. Artificial molecular machines (AMMs) refer to molecules that are artificially designed and synthesized whereas biological molecular machines can commonly be found in nature.  https://en.wikipedia.org/wiki/Molecular_machine 39

40. PROPERTIES IONOPHORES PHASE TRANSFER CATALYSIS PHOTORESPONSIVE ALLOSTERIC SWITCH 40

41. IONOPHORES Ionophores are compounds capable of binding and transporting certain metal cations viz. K + , Na + etc . Gramicidin – induces the transport of K + and Na + ions Valinomycin - induces the transport of K + across the mitochondrial membrane. 41

42. PHASE TRANSFER CATALYSIS 18-crown-6 acts as phase transfer catalyst. It catalyzes the reaction by transfer the metal ion. E.g. KMnO 4 is not soluble in non-polar solvent like benzene. KMnO 4 can be dissolved in benzene by adding 18-crown-6. 42

43. Crown ether binds K + ion in its cavity and dissolved in benzene. 43

44. PHOTORESPONSIVE Conformational changes occurs in photochemical reactions. E.g. Azobenzene system can undergo cis -trans isomerism. On cis form is capable to form complexes with K + ion whereas off trans form is unable to form complexes with K + ion. 44

45. Kalsi P S and kalsi J P (2007) Bioorganic, Bioinorganic and Supramolecular Chemistry. New Age International (P) Ltd., Publishers Pp 276-77. 45

46. ALLOSTERIC SWITCH Binding at one site generates the conformational change, resulting in change the binding ability at the second site. Eg . Bipyridyl macrocyclic system. 46

47. APPLICATIONS Development of New Materials Efficient Catalysis Medicinal Green Chemistry High-Tech Devices 47

48. DEVELOPMENT OF NEW MATERIALS Large structures can be readily accessed using bottom-up synthesis as they are composed of small molecules requiring fewer steps to synthesize. Thus most of the bottom-up approaches to nanotechnology are based on supramolecular chemistry 48

49. EFFICIENT CATALYSIS Non-covalent interactions are extremely important in catalysis Binding reactants into conformations suitable for reaction Lowering the transition state energy of reaction. 49

50. MEDICINAL Development of new pharmaceutical therapies by understanding the interactions at a drug binding site. Supramolecular chemistry providing encapsulation and targeted release mechanisms 50

51. HIGH-TECH DEVICES Develop new functions that cannot appear from a single molecule. These functions also include magnetic properties, light responsiveness and synthetic ion channels etc. 51

52. GREEN CHEMISTRY Supramolecular chemistry also has application in green chemistry where reactions proceeds in the solid state directed by non-covalent bonding. They reduce the need for solvents during the production of chemicals. 52

53. SUMMARY Supramolecular chemistry is “chemistry beyond the molecule”, i.e. The chemistry of molecular assemblies using noncovalent bonds. Pedersen, cram and lehn received the nobel prize for chemistry in 1987. Suprachem involves the a molecule ( a host) binding another molecule ( a guest) via. Noncovalent binding or complexation . Non-covalent interactions are much weaker in comparison to covalent interactions. In molecular assembly, molecules adopt a defined arrangement without external influences. Intermolecular self-assembling exist in biological systems while intera occurs in foldamers Synthetic supramolecular systems are designed to copy functions of biological systems in biomimetics . Second nobel prize in December 2016 for the design and synthesis of molecular machines. Supramolecules exhibits properties- ionophores , phase transfer catalysis, photoresponsive and allosteric switch. There are number of applications of supramolecules viz. development of new materials, efficient catalysis, medicinal, green chemistry and high-tech devices 53

54. Thank you 54