Supramolecular Chemistry PDF

# Supramolecule ## Supramolecular Chemistry Supramolecular chemistry is the chemistry of molecular assemblies held together by non-covalent bonds. This is chemistry beyond molecules. ### Host A large molecule having a convergent complementary binding site. For Example: Enzyme, synthetic cyclic c...

# Supramolecule ## Supramolecular Chemistry Supramolecular chemistry is the chemistry of molecular assemblies held together by non-covalent bonds. This is chemistry beyond molecules. ### Host A large molecule having a convergent complementary binding site. For Example: Enzyme, synthetic cyclic compounds. ### Guest A molecule or ion having divergent binding sites. For example: Monoatomic cation, simple inorganic anion, ion pair, sophisticated molecules like hormones, pheromones, neurotransmitters. ## Classification of Supramolecular Host-Guest Chemistry A supramolecular host-guest chemistry can be divided into two parts: 1. **Cavitands**: Hosts with some intramolecular cavity. A host-guest aggregate formed by a cavitand is termed as a cavitate. * Small molecules bind to the large molecule through covalent bonds and form a host-guest complex. * The host forms its own cavity. 2. **Clothrand**: Hosts with extramolecular cavity. * Large molecules crystallize to form an extramolecular cavity. * Small cations bind to the large molecules to form the host-guest complex. ## Examples of Cavitates 1. Cyclodextrin has a cone-shaped cavity. It binds to the guests through hydrophobic interactions and van der Waals forces. 2. Calixarene has a cone-shaped cavity. It binds to the guest through van der Waals forces and hydrophobic interactions. ## Self-Assembled Aggregates - Small molecules bind to large molecules through covalent synthesis. - Self-aggregates are formed through non-covalent bond formation. - These aggregates are called self-assembled complex. ## Classification of Supramolecules on Basis of Force - If the host and guest are linked together by electrostatic interactions, ion-ion, ion-dipole, and hydrogen bonding, this is termed as a complex. - They are held together by weak, less-specific, non-directional interactions like hydrophobic interactions, crystal clashed packing, and are termed as clathrate and cavitate. ## Classification of Supramolecular Host-Guest Complexes | Host | Guest | Interaction | Class | Example | | :------------------------- | :----------------------- | :-------------------------------------- | :-------------- | :------------------------- | | Crown ether | Alkali metal cation | Ion-dipole | Complex | [18]Crown-6 | | Spherand | Ally amine | H-bond | Complex | Spherand | | Cyclodextrin | Organic molecule | Hydrophobic/Cavitate (van der Waals) | Cavitate | Cyclodextrin | | Water | O.M (CH4) | Vander Waals/clathrate (crystal packing) | Clathrate | (H2O)4 (CH4) | | Calixarene | O.M (toluene) | Vander Waals/Cavitate | Cavitate | Calix[4]arene | ## Thermodynamic and Kinetic Stability - **Thermodynamic stability**: It is measured in the term of binding constant (K), association constant (Ka), dissociation constant (Kd), and stability constant (Kp). - **Kd**: Concentration under which the drug receptor dissociates. ## Nature of Supramolecular Interactions 1. **Ion-Ion interaction:** Opposite charges are interacting in a solid state. - It is the strongest interaction possible. - It is non-directional. - For example, ionic cubic lattice of solid NaCl. 2. **Ion-Dipole interaction:** The interaction between an ion and a dipole. - It is directional. - For example, the interaction between crown ether and an ion. - This interaction can be solid or liquid, depending on the nature of the molecules. 3. **Dipole-Dipole interaction:** The interaction between two dipoles. - It is directional. 4. **H-Bonding:** The interaction between hydrogen and an electronegative Atom like Oxygen, nitrogen, or fluorine. - Directional. 5. **π-π interactions:** The interaction between two π-systems. - It occurs between aromatic rings. - There are two types of π-π interactions: 1. **Face-to-face π-π interaction:** It involves electrostatic forces between electron-rich and electron-poor regions in the aromatic ring. 2. **Edge-to-face π-π interaction:** It involves van der Waals forces between the aromatic rings. 6. **Cation-π interaction**: The interaction between a cation and a π-system. - It occurs between a transition metal cation and an aromatic hydrocarbon like ferrocene and a π-system. - It is considered as a non-covalent interaction. - Even though π-π interactions have partially covalent character, this interaction is much more non-covalent. - This interaction is also seen between alkaline earth metal cations and aromatic hydrocarbons, with an interaction energy of 80 kJ/mol. 7. **Anion-π interactions:** The interaction between anion and a π-system. - This interaction occurs when an anion interacts with a π-system through electrostatic interactions. - This interaction is considered as a non-covalent interaction. - It is stronger than cation-π interactions. - This interaction is important for the binding of anions to aromatic molecules. ## Thermodynamic Selectivity * **Thermodynamic Selectivity:** - K_guest for a guest molecule. - K_guest is the selectivity of a host to a guest. - For example: Crown ether for K⁺ is 10⁶ M^-1 and for Na⁺ is 10⁴ M^-1. - Alkali metal ion is more selective than Sodium ion. ## Cooperativity **Cooperativity**: When two or more binding sites (ARS) on a host cooperate in this fashion to bind to a guest. * Such interaction when added to all the other small interactions from other interaction results in a significant binding energy and hence complex stability. * There are two types of cooperativity: 1. **Positive cooperativity**: Overall stability of the complex is greater than the sum of the energies of the interaction of the guest with binding GFs A and B individually. 2. **Negative cooperativity**: If unfavorable steric or electronic effects arising from the linking of A and B together into one host cause the overall binding free energy for the complex to be less than the sum of its parts, then the phenomenon. ## Chelate Effect **Chelate Effect**: Binding site cooperativity in a supramolecular host-guest interaction. * **Chelate effect** in energy term more generally arises from the intern of a two binding-site guest (A-B) with a bidentate host. The chelate effect can be expressed in terms of overall binding free energy. ## Macrocyclic Effect **Macrocyclic Effect:** This effect relates not only to the chelation of the quest or metal cation by multiple binding sites, but also to the organization of this binding site in space prior to the guest binding such that, the guest will enwrap around the guest or metal ion so as to get maximum binding energy. * **Macrocyclic Effect is greater than Chelate Effect**: For example: Cyclic hosts like carands are 10⁴ times more stable than acyclic hosts. * **The Intrastability due to Macrocyclic Effect:** - The macrocyclic effect can be seen in the interaction between a macrocyclic host and a guest molecule. - The macrocyclic host has a higher binding affinity for the guest molecule than an acyclic host. - This is due to the preorganization of the macrocyclic host, which allows the guest to bind more easily. * **Measurement of the Macrocyclic Effect:** - In the case of unmethylated 2+ complex, a macrocyclic host can be 10⁴ times more stable. - Both entropic and enthalpic contributions play a role in the macrocyclic effect. * **Entropic Effect:** The macrocyclic host is less conformationally flexible because of the restriction of their motion. * **Enthalpic Effect:** Macrocyclic hosts are less strongly solvated than acyclic hosts due to their less accessible surface area. ## Preorganization **Preorganization**: This means a host molecule undergoes conformational change upon guest binding, and this change can be unfavorable. * The host is already preorganized, meaning that it does not undergo conformational change when the guest binds. * The preorganization of the host is very important in supramolecular chemistry because it contributes to the stability of the host-guest complex. * The preorganization of the host can be achieved by incorporating macrocyclic or bicyclic structures. * Macrocyclic hosts are more preorganized than acyclic hosts. ## Podands - Acyclic hosts with pendant binding sites. - They have less affinity for binding cations. - They are more flexible and can engage in multiple bridged structures. ## Lariat Ethers * Crown ethers with a podand side-arm. * They have higher rigidity and preorganization than crown ethers. * They have a higher affinity for metallic cations. ## Cryptands * They are macro-bi-or-poly-cyclic. * They have a cage-like structure. * Synthesized through a high-dilution technique. * They are sold commercially under the trade name Kryptofix. * They are highly selective for potassium ions. * They are more stable than crown ethers. * For example: [2,2,2] cryptand. ## Spherands * They are 3D, spaced-filled molecular models. * Their cation-binding oxygen atoms are organized in an octahedral array. * For example: 3.33 spherand. ## Synthesis of Host * **High Dilution Synthesis**: When temperature is not assured, there is a higher chance of polymerization. * High dilution means using a small quantity of reactant and adding it dropwise to a large volume of solvent to ensure an adequate reaction time. * **Template effect**: The template effect is a kinetic effect that occurs when a template molecule is used to direct the synthesis of a macrocycle. * In the absence of a template, the synthesis of macrocyclic ligands is more difficult. ## Conclusion Supramolecular chemistry is a fascinating field that is still in its early stages of development. With the development of new synthetic methods and a deeper understanding of non-covalent interactions, supramolecular chemistry is poised to play an increasingly important role in various fields, including medicine, materials science, and energy.