drug formulation and food chemistry

8/10/2019 Drug Formulation and Food Chemistry

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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/Calixarene


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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

drug formulation and food chemistry

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