Complexation and Protein Binding Quiz

Complexation and Protein Binding

• Organic molecules are held together by weak forces like hydrogen bonds, van der Waals forces, and donor-acceptor interactions. Covalent bonds are not typically involved.
• Charge transfer complexes result when one molecule polarizes another, creating ionic interactions or charge transfer.
• Donor-acceptor complexes rely more on London dispersion forces and dipole-dipole interactions for stability.
• Many organic complexes are too weak to separate from solutions as distinct compounds.
• Disulfiram, clomethiazole, and tolnaftate possess N-C-S moieties.
• Interactions involving iodine atoms may result from charge transfer, inhibiting thyroid function.
• Caffeine, sulfonamides, and barbiturates form complexes via dipole-dipole forces and hydrogen bonding between polarized carbonyl groups.
• Quinhydrone complexes (benzoquinone and hydroquinone) are used in pH determinations due to the formed complex.
• Picric acid forms complexes, like Butesin picrate, combining antiseptic and anesthetic properties.
• Pharmaceutical additives like polyethylene glycols (PEGs), carboxymethyl cellulose (CMC), and carbowaxes can form complexes with other drugs (e.g., tannic acid, salicylic acid, phenols).
• Interactions can cause negative side effects from incompatibilities, like precipitates, flocculates, or delayed absorption.
• CMC and amphetamine show poor absorption.
• Ajmaline absorption is improved by complexation with polyvinylpyrrolidone (PVP).
• Caffeine complexes with acidic drugs such as sulfonamides and barbiturates.
• Benzocaine, procaine, and tetracaine form complexes with caffeine.
• Caffeine complexation can enhance drug solubility, mask bitter taste, improve stability.
• Caffeine can reduce benzocaine metabolism.
• Benzodiazepine efficacy is reduced by caffeine combination.
• Inclusion complexes (occlusion compounds) trap one component within the crystal lattice of another.
• Channel complexes are formed by crystallization of host molecules, creating channels specific for guest molecules.
• Host molecules are tubular, such as deoxycholic acid, urea, or thiourea.
• Guest molecules are typically long, unbranched compounds.
• Starch-iodine complexes are formed within channels.
• Layer complexes include alternating layers of guest and host molecules, where guest molecules are trapped within the layers.
• Clays, like montmorillonite, can trap hydrocarbons and alcohols in this way.
• The stability of clathrates depends on the structure's strength.
• Warfarin sodium USP is a clathrate example that crystallizes as a white powder.
• Monomolecular inclusion molecules contain one guest molecule trapped in a host molecule's cavity.
• Cyclodextrins are cyclic oligosaccharides, and are produced from starch.
• The interior of CD cavities is hydrophobic (CH2), while the exterior is hydrophilic (OH).
• CD complexation does not involve covalent bonds, but utilizes hydrophobic interactions.
• A-CD, B-CD, and Y-CD complex contain 6, 7, and 8 glucose units; B-CD and Y-CD are generally more beneficial to drug applications due to larger cavities.
• Aqueous solubility is improved by complexation with CD.

CD Complex Applications

• Enhanced solubility: Retinoic acid solubility is significantly increased by complexation with β-CD.
• Enhanced dissolution: Famotidine and Tolbutamide dissolve better when combined with β-CD.
• Enhanced stability: Aspirin, ephedrine, and testosterone experience improved stability when complexed with β-CD.
• Sustained release: Ethylated β-CD is used to manage the release of diltiazem.

Applications of Complexation

• Solubility: Drugs like caffeine enhance solubility of PABA.
• Dissolution: β-cyclodextrin improves Phenobarbital dissolution.
• Physical State: β-cyclodextrin converts liquid nitroglycerin into a solid complex.
• Stability: β-cyclodextrin provides stability to Vitamin A and D.

Chemical and Other Considerations

• Chemical stability: Complexation may inhibit undesirable chemical reactions, such as the hydrolysis of benzocaine.
• Partition coefficient: Complexation improves the partition coefficient of drugs like permanganate.
• Absorption and bioavailability: Complexing with cations like calcium or magnesium reduces absorption of some drugs (like tetracyclines).
• Reduced toxicity: Complexation of certain drugs (indomethacin and barbiturates) with β-cyclodextrin to reduce ulcerogenicity.
• Drug activity: 8-hydroxy quinoline complexes with iron (Fe) exhibit improved antimalarial activity.
• Anti-tuberculosis activity: Para-amino-salicylic acid complexes with copper (Cu) exhibit improved anti-tuberculosis activity.
• Metal poisoning antidote: Dimercaprol (BAL) and EDTA are used as antidotes for metal poisoning and blood preservation.
• Assay of drugs: Complexometric titrations are employed to analyze drugs containing metal ions.
• Reduced Volatility: Cyclodextrins stabilize volatile drugs, preventing unpleasant odors.

Test your understanding of complexation and protein binding concepts in organic chemistry. This quiz covers the interactions between organic molecules, including hydrogen bonds, charge transfer complexes, and donor-acceptor interactions. Explore specific examples such as caffeine and disulfiram to solidify your knowledge.