Organic molecular complexes
—Organic molecular complexes held together by weak forces of the donor-acceptor type or hydrogen bond
—For example, dimethylaniline & 2,4,6-trinitroanisole are two compounds that react in the cold to give a molecular complex
—Conversely, these two compounds react at high temperature to form a salt in which the components molecules are held together by primary valence bond
—Numerous organic complexes are so weak that they cannot be separated from their solution as specific compounds. they are frequently hard to identify by chemical or physical means
—Theses molecular complexes are referred to as charge transfer complexes.
—Difference between a charge transfer and donor-acceptor complex is that in the former type, resonance makes the major contribution to complex action, while in the latter, dispersion forces and dipole-dipole interaction contribute more to the stability of the complex.
—These complexes are bond together by van der waals force, dipole-dipole interaction and hydrogen bonding, but lacking charge transfer are known as molecular complexes
—The charge transfer complexes are of much importance in the field of pharmacy e.g. 1:1 charge transfer complexes formed by iodine with drugs like clomethiazole, disulfiram and tolnaftate
—Each of these drugs holds nitrogen –carbon-Sulphur moiety and complex results form the transfer of charge from the pair of free electrons on the nitrogen and or Sulphur atoms of these drugs to antibonding orbital of iodine atom.
—Therefore thyroid action in the body can be inhibited by molecules containing the N-C=S moiety via tying up iodine. The organic molecular complexes may further be divided into the following types.
A.Polymer-types complexes
B.Caffeine and other drug complexes
C.Picric acid-type complexes
D.Quinhydrone-type complexes
Polymer-types complexes
—Several types of polymers also form complexes with specific types of drugs.
—Carboxymethylcellulose, polyethylene glycols, polystyrene and many similar polymers containing nucleophilic oxygen might form complexes with various drugs
—The incompatibilities of certain polyether's, such as the carbowaxes, pluronics, and tweens with tannic acid, salicylic acid and phenol may also be due to these types of polymer complexes interactions.
—The incompatibilities may be marked as flocculate, precipitate, delayed biological absorption, and loss of preservative action or another undesirable physical, chemical, and pharmacological effects
—Crosspovidone is a cross-linked insoluble polyvinyl pyrolidone (PVP). It is able to bind various drugs such as acetaminophen, benzocaine, benzoic acid, tannic acid and papaverine hydrochloride to form polymer-types complexes.
—The interaction is mainly due to the phenolic group on the drugs and dipolar and porous organization of crospovidone.
—Crosspovidone is used as a disintegrant in pharmaceutical granules and tablets. It does not obstructs the gastrointestinal absorption of drugs because the binding of drugs is reversible.
—Polymer-drug complexes are mainly employed to modify biopharmaceutical parameters of drugs. E.g. the dissolution rate of ajmaline is enhanced by complexation with PVP
—The interaction is attributed to the aromatic ring of ajmaline and the amide group of PVP to yield a dipole-dipole induced polymer type of complex
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Agent / drugs
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Polymers
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Polyethylene glycol
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Resorcinol, catechol, salicylic acid,
p-hydroxybenzoic acid
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Povidone ( polyvinyl pyroldone, PVP)
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Salicylic acid, p-hydroxybenzoic acid, phenobarbital
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Sodium carboxymethyl cellulose
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Procaine, quinine, pryribenzarine
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Oxytetracycline & tetracycline
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Sodium-p-aminobenzoate
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Caffeine & Other Drugs Complexes
—Complexation between drug and the complexing agent can improve or impair drug absorption and bioavailability
—Caffeine has been found to form complexes with many types of drugs
—Higuchi and his associates were the first to investigate the complexation of caffeine with a number of acidic drugs.
—They pointed out the interaction between caffeine and drugs such as sulphonamides or barbiturate by a dipole-dipole or a hydrogen bonding between the polarized carbonyl groups of caffeine and the hydrogen atom of the acid. also, secondary interaction probably occurs between the nonpolar parts of the molecules, and the resultant complex is squeezed out of the aqueous phase due to the higher internal pressure of water
—Complexation of esters such as benzocaine, procaine, and tetracaine with caffeine has also been by Higuchi, and he suggested that, in the caffeine molecules, comparatively a positive center exist that serves as a possible site of complexation
—Caffeine makes complexes acid, such as gentisic acid, are less soluble that caffeine alone. Such insoluble complexes provide caffeine in the form that makes its normally bitter taste and should serve as a suitable state for chewable tablets. These chewable tablets offer an extended release of the drug with improved taste
Picric acid complexes
—Picric acid is 2,4,6-trinitrophenol and its pKa is 0.38.
—Picric acid reacts with strong bases to form salts and with weak bases to form molecular complexes.
—Butesin picrate, a yellow powder most probably is a 2:1 complex, which is insoluble in water but soluble in organic solvents.
— The possible use of butesin picrate is as a 1% ointment for burns and painful skin abrasions.
—Bustesin picrate combine the antiseptic property of picric acid and anesthetic property of butesin
Quinhydrone complexes
—Quinhydrone complexes are formed by mixing alcoholic solutions of equimolar quantities of benzoquinone and hydroquinone and theses complexes deposit as green crystals.
—The 1:1 complex formed between benzoquinone and hydroquinone might have resulted from the overlap of the pi-framework of the electron-rich hydroquinone molecules.
—Highest overlap between the pi-frameworks is anticipated if the aromatic rings are parallel and are oriented in such a way as to have their centers directly above on another
—Once an aqueous solution is saturated with quinhydrone, the complex dissociates into an equal amount of quinine and hydroquinone. This is used as an electrode in the determination of pH.
—Hydrogen bonding may contribute to stabilizing this complex, but it is not the individual path of association, because hydroquinone dimethyl ether also forms a colored adduct with quinone. A remarkable quinone is obtained from salicylic acid, which readily oxidizes and yields blue-black quinhydrone compound
—Quinohydrone compounds are valuable chemical, which is useful as electronic-donor-acceptor complexes in liquid crystal displays, as bactericides in the petroleum industry for inhibiting the growth of sulfate-reducing bacteria, as components of sulphuric acid-based pickling solutions for steel, components in oxidation-reduction electrodes, and as components in antifriction compositions based on polyethylene and powdered iron