education

1. Presented by
Khondaker Afrina Hoque
ID -1114015, Reg-900048
Session:2011-12
Department of chemistry.
Comilla university.
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2. Presentation on
Supramolecular host-guest design
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3. Basic concepts
Supramolecular compound:
A molecular assembly where two or more molecule interacts each other via various
weak intermolecular interactions such as electrostatic interactions, metal
coordination, hydrogen bonding, π-π interactions and hydrophobic or solvophobic
effects.
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4. Host-guest chemistry:
A molecule (host) to produce a “host –guest” complex.
Interactions between host and guest are noncovalent .
Guest may be
:a monoatomic cation
:a simple inorganic anion
:A more sophisticated molecule such as hormone or neurotransmitter.
Host may possesses convergent binding site.
Guest may possesses divergent binding site.
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5. Design principles of supramolecular host
A number of non-covalent interactions play an major role in
building of supramolecular blocks are:
Ionic & dipolar interactions (stongest) .
• ion-ion interactions.
• Ion-dipole interactions.
• Dipole dipole interactions.
Hydrogen bonding.
Vander waals interactions.
Close packing.
Hydrophobic effects.(weakest)
Solvent effects.
Π-Interactions.
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6. Ion-dipolar interaction
ion-ion interaction:
•Stongest interaction.
•Nondirectional.
•Example:
•tetra butylammonium
chloride.
Ion_dipole interaction:
•Ion interacts with polar part
of the molecule
•Directional
•Example:alkali metal-crown
ether complexes.
dipole-dipole
interaction:
•Weaker then ion-dipole
•Example: typical with
organic carbonyl
compounds.
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7. Definitions:
A hydrogen bond may be regarded as a particular kind of dipole-dipole
interaction in which a hydrogen atom attached to an electronegative
atom is attracted to a neighboring dipole on an adjacent molecule or
functional group.
Properties:
•4-60kJ mol−1
•Directional, certain geometry.
•Solvent is defining factor when for H-bond.
•Orders the overall shape of a biological molecule.
•In DNA H-bond is sheltered by double helix-
structure.
Hydrogen bonding
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8. Sub catagories:
Strong: electron density deficiency in donor or excess electron density in a acceptor
or conformation forces donor & acceptor closer than normal H-bond.
Moderate: between neutral donor & neutral acceptor.
weak: when H is bonded to slightly more electronegative(C, Si) atom, or acceptor
contains Π electrons.
strong moderate weak
A-H---B interaction covalent electrostatic electrostatic
Bond energy(kjmol-1) 60-120 16-60 <12
Bond length
H---B
A---B
1.2-1.5
2.2-2.5
1.5-2.2
2.5-3.2
2.2-3.2
3.2-4.0
BOND ANGLES(◦) 175-180 130-180 90-150
examples H-F complexes Dimers of acids C-H H-bond
Table:
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9. •Vander waals forces(<5kjmol-1)
•Arises from fluctuation of electron distribution between species that are in close
proximity To one another.
•Proportinal to size of the molecules and inversly proportional to the sixth power of
distance.
•Define molecular shape and geometry.
Vander waals forces
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10. Π-Interactions
Edge-to-face π-interactions
Figure: edge-to-face interaction
Face-to-face π-interactions
Figure:Face-to-face π-interactions
Two catagories:
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11. Hydrophobic effect
•Relate the exclusion of larger or weakly
solvated (hydrophobic ) species from polar
media>
•Can be divided into enthalpic and entropic
components .
•Enthalpic effect: stabilization of polar
solvant excluded from the cavity upon guest
binding .(dominating) (-22kjmol-1)
•Entropic effect: combination of host and
guest results in disruption to the solvent
structure →entropic gain(-9kjmol-1)
•Example: binding of organic molecules by
cyclophanes and cyclodextrine in water.
Figure:Hydrophobic binding of
organic guests in aqueous solution.
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12. Solvation effect:
Polar solvents:
Compete for binding sites →hydrogen bond functionality→less binding constan magnitude.
Nonpolar solvents:
host-guest interactions are much more significant→more binding constant.
solvent Solvent type K(M-1)
CH2Cl2 Non-polar 240
CHCl2CHCl2 Non-polar
,large size
128000
Iso propanol polar 13
Tert-butyl alcohol polar 66
Table: influence of solvent on the binding constant of host
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13. In order to plan a suitable host for a target guest one should
consider several Parameters. they are:
For a host–guest interaction to occur the host molecule must posses
the appropriate binding sites for the guest molecule to bind to.
Selectivity
This selectivity can arise from a number of different factors, such as-
- complementarities of the host and guest binding sites
- pre-organisation of the host conformation
- co-operativity of the binding groups.
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14. As summed up by cram et al.” to complex , the host must have binding sites
which cooperatively contact and attract the binding site of the guest
without generating strong non-bonded repulsions”.
Example: The active site of an enzyme is complementary in size and shape
and is functionally compatible with the substrate.
Figure 1.2 The lock and key principle, where the lock represents
the receptor in which the grooves are complimentary to the key,
which represents the substrate.
The key-lock model
Induced-fit model
Figure 1.3 The induced-fit model of substrate binding. As the enzyme
and substrate approach each other, the binding site of the enzyme
changes shape, resulting in a more precise fit between host and
guest.
Complementarity
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15. Chelate, macrocyclic and macrobicyclic effects:
Chelate effect:
Metal complexes of bidentate ligands are significantly more stable than closly related
materials that contain unidentate ligands.
Example:
Due to both thermodynamic and kinetic effects.
Dependent on the size of the chelate ring.
Allosteric effect.
∆G=-49.4kjmol-1 ∆G=-104.4kjmol-1
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16. Macrocyclic effect:
Host system that are preorganised into
a large cycle shape form more stable
complexes.
Relates not only to the organisation of
the binding sites , but also the
organization of the binding sites in space
prior to the guest binding .
Macrobicyclic effect:
bicyclic hosts such as cryptands are
found to be even more stable than the
monocyclic corands .
Fig: the chelate , macrocyclic and
macrobicyclic effect.
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17. A host is said to be preorganised when it requires no significant
conformational change to bind a guest species.
Preorganisation:
•Macrocyclic, corand, more
preorganised.
•Rigid, favorable
•Less solvation
•Enthalpically favorable.(-
61.9kjmol-1)
•Entropy: less negative.
•logK=15.34
•Podand
•Flexible& unfavorable
•More solvated.
Enthalpically `unfavorable(-44.4kjmol-
1)
•(bond breaking occurs due to
solvation)
•logK=11.25
Preorganised macrocyclic host is 10000 time more capable of binding guest :
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The small amount of stabilisation energy gained by any one Non-
covalent interaction when added to all the other small
stabilizations from the other interactions (summative) results in
a signify cant binding energy and hence complex stability, this
phenomenon is called co-operativity.
Co-operativity:
Two types:
Positive co-operativity:if the overall stability of the complex is greater than the sum
of energies of the Interaction of the guest with binding groups than the result is
positive co-operativity.
Negative co-operativity:if unfavorable steric and electronic effects arising from the
linking of binding sites togather into one host Causes overall binding free energy for
the complex to be less than the sum of its parts than the phenomenon is termed
negative co-operativity.

19.  formation of kinetically labile complex is a fundamental criterion in the
definition of molecular hosts which allows the rapid exchange of guests.
Concept of anion host design
FACTORS WITCH AFFECT ANION COMPLEXATION
Prevailing interactions which take place in anion binding:
• hydrogen bonding
• ion-dipole and ion-ion interactions
•Vander waals force.
1. Size match between anion and host cavity.
2. Complementarity.
3. Anion and host charge and anion polarisability.
4. Solvent (polarity, hydrogen bonding and coordination ability), anion and host free
energies of solvation.
5. Anion basicity and host acidity.
6. Other kinetic, enthalpic and entropic contributions to the anion-host interactions.
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20. 1. Size match between anion and host cavity.
Anions are relatively large and therefore require receptors of considerably greater
size than cations.
2. Complementarity.
Even simple inorganic anions occur in a range of shapes and geometries.
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21. Complexes of 6H+ forms of nitrogen
macrobicycles with anions:
F- : tetrahedral binding; log K = 4.19
Cl- : octahedral coordination; log K = 3.0
N3- : log K = 4.3
I- : log K = 2.15
Fluoride Chloride Azide
3. Anions have high free energies of solvation compared to cations of similar size
and hence hosts for anions experience more competition from the surrounding
medium. For example, the standard free energies of hydration, ∆Ghydro, for F− and
K+ are −465 and −295 kJ mol−1, respectively.
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22. Concept of Cation host design:
Crown ethers :
•Preorganised .
•Selectivity for their binding strength to alkali and alkali earth metal.
•Also complexes with ammonium, guanadium & pyridinium etc.
Cryptates
•Analogues to crown ether.
•Bicyclic
•More metal cation binding ability than crown ether is due to the three
dimensional nature of their cavity.
Crown ether Cryptand
Applications: catalytic and medicinal application.
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THANKS TO ALL