Physicochemical properties in relation to biological activity Slide 44 Dr

Physicochemical properties in relation to biological

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Physicochemical properties in relation to biological activity Slide 44 Dr. Waleed A. Zalloum Water Solubility of Drugs The solubility of a drug molecule in water greatly affects the routes of administration that are available as well as its absorption, distribution, and elimination. Two key concepts to keep in mind when considering the water (or fat) solubility of a molecule are 1.the hydrogen bondforming potential of the functional groups in the molecule 2.the ionization of functional groups.
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Physicochemical properties in relation to biological activity Slide 45 Dr. Waleed A. Zalloum Lipophilicity (‘fat-liking’)is the most important physical property of a drug in relation to its absorption, distribution, potency, and elimination. Lipophilicity is often an important factor in all of the following, which include both biological and physicochemical properties: Solubility Enzyme / receptor binding Absorption Plasma protein binding Metabolic clearance Volume of distribution Biliary and renal clearance CNS penetration Storage in tissues Bioavailability Toxicity
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Physicochemical properties in relation to biological activity Slide 46 Dr. Waleed A. Zalloum The hydrophobic effect Molecular interactions why don’toil and water mix? HHHHHHHHHHHHOHHOHHHOHHOHHOHHOHHHOHOHHOHHHOOHHHOHHOHOHH
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Physicochemical properties in relation to biological activity Slide 47 Dr. Waleed A. Zalloum This is entropy driven (remember DG = DH TDS). Hydrophobic molecules are encouraged to associate with each other in water. Placing a non-polar surface into water disturbs network of water-water hydrogen bonds. This causes a reorientation of the network of hydrogen bonds to give fewer, but stronger, water-water H-bonds close to the non-polar surface.
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Physicochemical properties in relation to biological activity Slide 48 Dr. Waleed A. Zalloum This is entropy driven (remember DG = DH TDS). Hydrophobic molecules are encouraged to associate with each other in water. Placing a non-polar surface into water disturbs network of water-water hydrogen bonds. This causes a reorientation of the network of hydrogen bonds to give fewer, but stronger, water-water H-bonds close to the non-polar surface. Water molecules close to a non-polar surface consequently exhibit much greater orientational ordering and hence lower entropy than bulk water.
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Physicochemical properties in relation to biological activity Slide 49 Dr. Waleed A. Zalloum This principle also applies to the physical properties of drug molecules.If a compound is too lipophilic, it may be insoluble in aqueous media (e.g. gastrointestinal fluid or blood) bind too strongly to plasma proteins and therefore the free blood concentration will be too low to produce the desired effect distribute into lipid bilayers and be unable to reach the inside of the cell
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Physicochemical properties in relation to biological activity Slide 50 Dr. Waleed A. Zalloum Conversely, if the compound is too polar, it may not be absorbed through the gut wall due to lack of membrane solubility.
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