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Host-Guest Interaction
in Drug Formulation andFood Chemistry
Lecturer: Dr. Richard Fairman
Part I
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Introduction
What is Host Guest Interaction? Host-Guest Interactions are where two or more molecules, a host
and a guest, are involved in non-bonding interactions to form asupramolecular complex. This interaction is greater thanelectrostatic forces.
The hostis the molecule or ion whose binding sites converge in thecomplex and the guestis the molecule or ion whose binding sites
diverge in the complex.
Examples of biological hostguest complexes include enzymesubstrate complexes, antigenantibody complexes, and drugreceptor complexes.
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Importance of Host-Guest Interactions in
Drug Delivery
Macrocyclic hosts represent an important class of drug delivery vehiclesbecause they are able to sequester drugs within their structure, providing a
steric barrier to drug degradation/deactivation.
Size of macrocycle can control rate of drug release and binding strength of
host-guest complex.
The resulting complex has increased stability and greater selectivity that
may lead to less side effects Only three types of macrocycles have been studied extensively in drug
delivery.
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Common Hosts
Extensively studied hosts are:
Cyclodextrins
Cucurbiturils
Calixarenes
Others are:
Metallocrowns
Porphyrin
Crown ethers
Cyclotriveratrylenes
Cryptophanes
http://en.wikipedia.org/wiki/Calixarenehttp://en.wikipedia.org/wiki/Calixarene8/10/2019 Drug Formulation and Food Chemistry
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Cyclodextrin (CD)
CDs are natural products formed due the decomposition of starch via
bacteria and it is composed of seven D(+)-glucopyranose units linkedthrough -(1->4) glycosidic bonds.
CD complexation involves the CD as host molecule with a cavity that
entraps one drug molecule as a the guest.
Central cavity of CD is hydrophobic and the outer surface is
hydrophilic.
Formation of the complex, is via a variety of non-covalent forces likeVander wall forces, hydrophobic interaction, and dipole movement
are responsible.
CDs are often used as active site analogs for enzymes and are used to
aid the absorption of drugs in the body.
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Applications of Cyclodextrins
Table 1: Pharmaceutical applications of CDs showing Functions and
Guest-End Products.
Functions Guest-End Products
Improve taste and smell Prostaglandins, Alkylparabens
Improve bioavailability Aspirin, Barbiturates, Non-steroidal anti-
inflammatories
Reduce irritation tostomach
Non-steroidal anti-inflammatory agents
Improve solubility Prostaglandins, Steroids, Benzodiazepines
Chemical Stabilization
a) Hydrolysis Prostacyclin, Aspirin, Atropine
b) Oxidation Aldehydes, Epinephrine
c) Photolysis Vitamins, Ubiquinones
d) Dehydration Prostaglandins
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Table 2: Food applications of CDs showing Functions and Guest-EndProducts.
Functions Guests End-Products
Masking of taste/odour - Juices, Soy milk, Boiled rice
Reduce volatility Ethanol Food preservatives
Emulsification Oils & Fats Margarine, cake, Whip cream
Stabilization Flavours, SpicesColours & Pigments
Mustard paste, Cakes, Cookies,Dried/Pickled vegetables
Improvement ofquality
- Hard candy, Cheese, Soy sauce,Canned citrus fruits & juices
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Cucurbit[n]urils (CB[n])
CBs are sysnthesized with either 5, 6, 7, 8 or 10 glycoluril units.
Encapsulation of drugs within the homologues CB[6], CB[7] or CB[8] can
impart enhanced chemical and physical stability, improve drug solubility andcontrol drug release.
Forms an inclusion compound with the important cancer fighting drug
oxaliplatin
Examples of drugs (guests) studied with CBs are paracetamol, memantine,cisplatin and coumarin.
Used in tablets for oral delivery and inserts for nasal delivery.
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Calixarenes
Calixarenes are macrocyclic compounds of phenolic units linked bymethylene or sulfur groups at the 2,6-positions and with defined
upper and lower rims and a central annulus.
Efficient host molecules in molecular recognition
Proven to be useful for detoxification caused by xenobiotics.
Research has shown calixarenes are not regularly used as guests due
to medium toxicity level leading to inhibition of cell growth
T iti M t l
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Transition MetalCompounds as
Catalysts for OrganicReactions
Dr. Arvind KumarPart II
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Transition Metal Catalysts A catalyst is a substance that increases the rate of a reaction but it is
not itself consumed.
The transition metals are the group of metals in the middle section ofthe periodic table. They are divided into three groups - the first row,
second row and third row transition metals.
Many of the transition metals behave as catalysts, either as the metal
itself or as a compound.
Catalysts change the rate of a reaction, but do not alter the position
of equilibrium.
Desired properties of a catalysts are:
Selectivity- production of high yield of desired product.
Life time- able to survive through a large number of catalytic cycles.
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Types of Catalysts
Homogeneous Catalysts: They are present in the same phase as thereagents. That is all reagents are in solution together in the same
solvent, or all are gases.
Heterogeneous Catalysts: They are present in a different phase from
that of the reactants. For example a solid catalyst and a solution, or asolid and gases.
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Catalytic Uses Of The First Row Transition Metals
TITANIUM Ti
Titanium is important for its use as a component of the Ziegler Nattacatalysts used in the polymerisation of alkenes.
VANADIUM V
Vanadium(V) oxide is the catalyst in the production of SO3 from SO2in the manufacture of sulphuric acid - the Contact process.
IRON Fe
Iron is the catalyst used in the Haber process to manufacture NH3.
COBALT Co
Cobalt compounds are also used as catalysts in the OXO process forthe formation of aldehydes, and hydrogenation and dehydrogenationprocesses.
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NICKEL Ni
Nickel is well known as a useful catalyst for hydrogenation andother reactions in the lab and industry, often in a form calledRaney Nickel that is as the very finely divided.
Rhodium-Rh
Used as catalytic converters and also in industrial processes asWilkinsons catalyst.
Rhodium is used as an alloying agent for hardening and improvingthe corrosion resistance of platinum and palladium.
Palladium (Pd)
Palladium is also widely used in catalytic reactions in industry,such as in hydrogenation of unsaturated hydrocarbons.
In jewelry and in dental fillings and crowns. But themain use of palladium, along with rhodium and platinum, is in thethree-way catalytic converters in car exhaust systems.
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Catalytic Cycles
Catalysis is a cycle of reactions that involves the consumption ofreactants, formation of products and regeneration of the catalytic
species.
The catalytic cycle operates in the principle of microscopic
reversibility
Energetics of catalytic cycles is based on the catalyst increasing the
rate of processes by introducing new pathways with lower energies ofactivation.
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Catalytic Steps for Homogeneous Catalysis (a) Ligand coordination and dissociation: Catalytic cycle requires
facile coordination of reactants to metal ions and equally facile loss
of products. (b) Insertion and elimination: The migration of alkyl and hydride
ligands to unsaturated ligands (Migratory insertion). The reverse of
insertion is elimination (-hydrogen elimination)
(c) Nucleophilic attack on coordinated ligands: The coordination ofligands (CO, alkenes) to metals in positive oxidation states results in
the activation of coordinated C atoms towards attack by nucleophile. (d) Oxidative addition and reductive elimination:Oxidative addition
of a molecule AX to a complex brings about dissociation of the A X
bond and coordination of the two fragments
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Examples of Transition Metals used
as Catalysts in Catalytic Cycles
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Catalytic Cycle for Pd-catalyzed Decarbonylative
Trifluoromethylation using Trifluoroacetic Esters as CF3Sources.
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Rhodium used as Wilkinsons Catalyst in Hydroformylation
Reaction
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Cobalt used as Catalyst in
Hydroformylation Reaction
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Group Members
Sheeriza Ali
Kristy Mohammed