Lecture 2 Flashcards
What is supramolecular chemistry
It is a field of chemistry investigating molecular systems in which the components are held together reversibly by intermolecular forces, not by covalent bonds. Chemists in this field combine individual covalently bonded building blocks, designed to be held together by intermolecular forces.
This is depicted in notes (Fig 1.1)
What is complementary?
It is the concept that the binding site of a host must have a specific shape, size and position to recognize its quest
What are the possible hosts and their guests?
Hosts: Guest
Ligand Metal
Enzyme Substrate
Receptors Drugs or substrate
Antibody Antigen
In DNA how many hydrogen bonds form between the base pairs?
Between C and G forms 3 hydrogen bonds
Between A and T forms 2 hydrogen bonds
What is Valinomycin and its structure?
Vanilnomycin is a naturally occurring macrocyclic antibody that selectively transports potassium cations (K^+) across a mitochondrial membrane in the presence of sodium cations.
The potassium is complexed with the electronegative oxygen atoms of the ester groups and once it is enclosed it will be transported across the hydrophobic membrane.
The reason why valinomycin is needed is because the membrane is lipophilic (meaning it doesn’t allow charged species to flow across) and valinomycin is structured in a way where it has alkyl groups on its peripheral axis that are “Greasy” which provides the complex with solubility and allows transport K^+. Also, valinomycin has a lipophilic exterior.
Final note: The Valinomycin-K^+ complex is stabilized by six NCO—HN hydrogen bonds around the periphery of the Macrocycle.
Find the structure in notes (Fig 1.5 and 1.6)
What are the non-covalent interactions that hold supramolecular molecules together?
- Electrostatics (ion-ion, ion-dipole and dipole-dipole
- Hydrogen bonding
- hydrophobic and solvatophobic effects
- Pi-Pi stacking interactions
- Dispersion and induction forces (VdW)
They are arranged from strongest to weakest interactions. important to note that the hydrophobic effect doesn’t have a fixed strength so in a few cases the Pi-pi might be stronger.
The supramolecular chemists use the forces above in combination to maximize the selectivity and tunability of the new receptor and also increase the strength of the complex formed.
What are electrostatic interactions (quick recap)
- interactions based on the Coulombic attraction between opposite charges.
- Ion-ion interactions are not directional
- ion-dipole interactions are directional
What are Pi-Pi stacking forces?
They are forces that occur between systems containing aromatic rings. Attractive interactions (theorized to be electrostatic in nature) occur in either a face-to-face or face-to-edge manner (shown in Fig 1.8). For example, benzene crystallizes in a “hearing bone” arrangement maximising edge-to-face contacts
What is the hydrophobic effect?
It is the driving force for the association of apolar binding partners in an aqueous solution.
Basically, Water molecules around the apolar surfaces of a hydrophobic cavity arrange themselves in a structured array. Upon guest complication, the water molecules are released and become disordered. This leads to a favourable increase in entropy.
There is also believed to be an enthalpic component to the hydrophobic effect, where once the water molecules are dispersed they will form stronger hydrogen bonds between each other.
What is the application of chelating or microcrystals?
The are used to increase the strength of host-guest complexes. This is due to the high thermodynamic stability of these complexes.
Note chelate is literally any class of coordination or complex compounds consisting of a central metal atom attached to a ligand in a cyclic or ring structure
What is the chelate effect? (a detailed description)
It is the enhanced stability of a compound containing a chelate ring in comparison with a similar system containing fewer or no rings. This is shown in notes Fig 1.10
The effect is based on the enthalpic drive where the bonds by the chelating ligands are usually stronger. Some times also entropic since more disorder upon replacement of ligand.
Interestingly the chelate effect reaches its maximum at a 5-membered ring and starts to decrease from 6 onward. This is due to the increase of configurational entropy with increasing chain length.
The reason why the chelate 5-member ring is more stable with large metal ions compared with 6-membered rings is that the 5-membered ring has more space to incorporate the metal ion without disrupting the chelate bridge (coordination bond) Look at Fig 1.12.
So a 5-membered chelate ring containing a a large Pb^2+ cation is more stable than a 5-membered chelate ring containing a smaller Cu^2+ cation.
What is the macrocyclic effect?
It is an effect related to the chelate effect and referees to the increased thermodynamic stability of macrocyclic systems compared with their acyclic analogues.
The increased stability is caused by a combination of entropic and enthalpic effects differing from case to case with enthalpic frequently providing dominate effects:
- Macrocyclic hosts are less heavily solvated than their acyclic analogues and therefore less energy is required for desolvation (enthalpically favoured)
- Macrocyclic ligands are less flexible (due to the rigidity of the receptor) and consequently have less disorder to lose upon complication (entropic favoured)
- Macrocyclic ligands are also more chemically inter than their acyclic analogues (slower complexation and decomplexation)
What are the 3 questions that characterize a supramolecular system?
- What is the structure, is it planned?
- How rapidly is it formed (kinetics)?
- How strong are the interactions (thermodynamic)?
How do we find out what is the structure of the supramolecular system? (sorry i love wallahi)
We use the following techniques:
- Crystallography: It shows the binding sites, and if the complex is planned by the designer. It also gives information about the interactions that hold the guest in place. This is only valid in the solid state as factors such as crystal packing might affect the properties of the supramolecule.
- NMR: A simple experiment where first the NMR of the denatured host is shown. then the NMR is monitored as additions of aliquots of the guest begin. Binding will pertud the electron environment of the host which will be represented on the NMR (this is the titration method). NMR is also often used to find the stoichiometry of binding which is obtained from a method of continuous variation. (FIG 1.15)
-NOSEY (ask if required Page 10 of PDF shared)
- UV-visible spectroscopy: investing pi-electron systems as their spectra can be strongly perturbed by complexing.
- Mass Spec: Used to find the mass of the complex, but the ionization must be mild or the complex will break into multiple units instead of flying through the spectrometer as one discrete unit.
- Chromatography (Size exclusion Gel): where the largest molecules immigrate more rapidly. This is important for finding the aggregate mass.
How can we use NMR resonance to test the kinetics of macromolecules?
First, it is important to mention that complexation is a dynamic exchange between the bound and unbound forms of the host and we can use NMR to give insight into the kinetics of the macromolecule:
There is two situations:
- If the binding is kinetically fast compared with the frequency separation between the free and complexed host NMR resonances, then the host NMR resonance is observed as an average peak. on the addition of increasing quantities of guest, the time-averaged peak shifts continuously until the receptor is saturated. This gives a titration curve with a distant shape where the host would first be strongly perpetuated by the guest at first, but at higher concentration, it becomes statured by the guest and no longer perpetuated. This is shown in Fig 1.16a
- If the biding is kinetically slower compared to the NMR time scale, then the average time peak is not observed on guest addition. Instead, the resonances for host-free gradually diminished in intensity while the resonances of the guest-host complex grow. Fig1.16b
Note that in UV-Vis spec only slow exchange is exhibited due to its time scale being faster than diffusion-controlled processes.
How do we calculate the rate of complication at coalescence?
If the solution exhibiting slow exchange is heated, the two peaks will borden and merge. eventually, an intermediate point is reached between the slow and fast exchange at a single board peak. this is the point of coalescence and it is calculated by the equation shown in the notes.
What are all the equations that need to be known from this lecture?
This is found in the notes
How can NMR be used to provide thermodynamic data (the value of ka)?
Again similar to the kinetic data with this procedure, there is two situations to consider:
- If the reaction is kinetically slow, the relative concentration of host, guest, and host-guest complex can be obtained from the integration of the resonances. Dor a 1:1 complex, the calculation for Ka is quite easy since all of the concentrations are known.
- If the reaction is kinetically fast, the titration curve (like the one in 1.16a) contains all of the information required. The sharpness of the curve represents the affinity of the guest to the host. Computer programs are used to find the ka by using the non-linear least square method to fit the theoretical data of the complexation to experimental data.
Note that performing titration equations (mentioned in the above flash cards) at different temps gives different Ka’s which allows for the values of S and H to be obtained
What are other methods that give thermodynamic information about supramolecules?
Calorimetry - where the heat absorbed or evolved upon complex formation is measured. Once again the titration method is used with the temperature being recorded as a function of the amount of guest added. Obviously the heat change is linked to the thermodynamic quantities of complexation
Polarimetry - It is used for monitoring the binding constants of ionic guests in an aqueous solution. The enrnest equation (shown in notes) shows the relation of potential difference applied to the activity of a guest which can be approximated as its concentration. When the concentration is changed due to complexation then the potential difference will change. This potential change can be measured on an ion-selective electrode, and the response of this electrode will then be directly dependent on the degree of complexation of the guest ion. Then we perform titration by adding the guest and monitoring the change of potential of the solution, we can then analyze this data using computers to give the binding constant
What is the effect of the solvent in supramolecular chemistry?
As of yet, we have considered the solvent to be inert, which is far from the truth as the solvent plays an important role in the recognition process (as shown in Fig 1.17). If the solvent strongly solvates the host, guest, or complex, or if the solvent interacts strongly with itself, then this can have dramatic effects on the eq
What is desolvation and its effects?
Desolvation is the process of removing a solvent from a material in a solution.
Desolvation possesses unfavourable enthalpy (energy is required to break the bonds) and favourable entropy (increases in disorder on release of solvent)
What are the effects of solvent on the hydrophobic effect, electrostatic interactions and donor acceptor ability?
- The hydrophobic effect shows how a solvent influences teh molecular recognition. As mentioned the source of binding energy for this procedure is a combination of (entropic) liberation of water molecules about complexation and (enthalpic) and hydrogen bond formation between the water molecules. The water can also only solvate the large apolar surfaces of the host and the guest poorly. This makes the eq in Fig 1.17 go to the right
- Electrostatic interactions: The Dielectric constant of the solvent plays an important role in controlling binding strength. The dielectric constant measures its bulk polarity and reflects the dipole moment of an individual solvent molecule. The larger the dipole moment of a solvent the better charged species would dissolve in it. If this was applied to supramolecules with a charged host and guest in a polar solvent the strength of their attraction would decrease
- Donor-acceptor ability: There are a number of different empirical measures of a solvent’s ability to accept or donate protons. This ability plays a very important role in molecular recognition. For example, if the solvent is a very good proton donor it will solvate the cationic species and therefore compete against any receptor for such guests. The vice versa is true if the solvent is a good proton acceptor (in this case it’ll solvate the anionic species). The Gatmann donor and acceptor number provide a good scale for the solvent’s abilities. (Table 1.2)
Donor-acceptor ability is also of great importance in hydrogen bond recognition. If the solvent is a good hydrogen donor or acceptor, it will disrupt and weaken any recognition based on the formation of hydrogen bonds between the guest and the host.
What is a competitive solvent?
Solvents which strongly disrupt molecular recognition.
How can we use supramolecular chemistry to form functional devices
Figure 1.20 shows that is needed
