PRESENTATION ON PHYSICOCHEMICAL PROPERTIES.pdf
- 1. By- Dr. Prerana B. Jadhav M. Pharm, Ph.D. Pharmaceutical Chemistry Assistant Professor, Sanjivani College of Pharmaceutical Education and Research, Kopargaon. Physicochemical Properties in Relation to Biological Action
- 2. • The physicochemical properties of molecules play vital role towards the specific behavior of compounds. • The drug molecules exhibit unique features by virtue of their physicochemical properties. • Physicochemical characteristics affect pharmacodynamic and pharmacokinetic behavior of drugs. • Physicochemical characteristics affect interactions of drug with biological receptor and this interaction is responsible for pharmacological action of drug molecule. • Partition coefficient, ionization, surface activity, solubility, chelation, hydrogen bonding, isosterism and partition coefficient, etc. are major physicochemical properties which affect biological behavior of drug.
- 3. 1. IONISATION • The property of any atom or molecule losing/gaining electron and acquiring charge. • The ionized form gives the medication strong water solubility, which is necessary for effective drug-receptor binding interactions, whereas the non-ionized form allows the drug to cross cell membranes. • As a result, a suitable mix of ionized and non-ionized forms is required for improved pharmacodynamic and pharmacokinetic properties. • Unionized: Lipophilic • Ionized: Hydrophilic
- 4. • Plays important role in Pharmacokinetics. • It involves ADME • Good balance of Ionised and Unionised is better for pharmacokinetics • Unionised Drug: Lipophilic, helps to cross cell membrane • Ionised : Hydrophilic, imparts better water solubility for drugs which is imp for binding interaction of drugs with its receptor.
- 5. 2. Solubility • Water makes up a large portion of all biological structures • All biochemical reactions rely on the dissolution of tiny molecules or the dispersion of macromolecular fragments in an aqueous phase. • Cells are composed primarily of non-aqueous lipid structures, such as plasma membranes and organelle membranes, which can dissolve either polar or non-polar hydrophobic molecules.
- 6. • The atoms and molecules of all organic substances are held together by various types of bonds (e.g., hydrogen bond, dipole-dipole, Vander Waals). • These forces are important in solubility because solubility is governed by solvent-solvent, solute-solute, and solvent-solute interactions. • Methods for Improving solubility • Complexation • Use of co – solvents • Employing surfactants • Structural modification
- 7. • Important relation to biological action • Drugs must be in solution and interact with receptors • Drugs must be in solution before it can be absorbed by biological membrane and show it’s activity • Bioavailability of drugs mainly depend on their solubility in the given solvent system.
- 8. 3. Partition coefficient • A partition coefficient is a measure of how a compound distributes between two immiscible liquids, like water and octanol, and is important in biological action because it indicates how a drug will cross a cell membrane and be absorbed.
- 9. • The partition coefficient is the ratio of the concentrations of a compound in two phases at equilibrium. It's a measure of how hydrophilic or lipophilic a compound is. • Biological action • A drug's partition coefficient is important for its absorption and distribution in the body. Drugs with a high partition coefficient can easily pass through biological membranes. • Rate of drug transfer is directly related to the lipophilicity of drug because biological membranes are lipophilic.
- 10. • Drug design • Knowledge of partition coefficients can help optimize existing drugs and design new ones. For example, a drug molecule should have a partition coefficient of 1–4 for effective transdermal or dermal application. • Experimental determination • The partition coefficient is determined by shaking a drug with equal parts of two immiscible solvents until equilibrium is reached. The content of the drug in one of the layers is then determined.
- 11. 4. Hydrogen Bonding • Hydrogen bond is an interaction in which a hydrogen atom bridges two electronegative atoms (in biological systems, usually nitrogen or oxygen). • It results from attractive force between hydrogen atom covalently bonded to very electronegative atom such as N, O. • Hydrogen bonding plays a critical role in biological systems in many ways, including: • Hydrogen bonds hold the two strands of a DNA helix together, and in proteins they hold α-helices and β- sheets together.
- 12. • The two types of hydrogen bonding are intermolecular and intramolecular, and they have different effects on a substance's melting point and solubility • Intermolecular Hydrogen Bonding • When hydrogen bonding takes place between different molecules of the same or different compounds, it is called intermolecular hydrogen bonding. • For example, hydrogen bonding in water, alcohol, ammonia etc.
- 13. Hydrogen bonding in Water
- 14. • Intramolecular Hydrogen Bonding • The hydrogen bonding which takes place within a molecule itself is called intramolecular hydrogen bonding.
- 15. • Intermolecular hydrogen bonding • Increases a substance's melting point, boiling point, solubility, viscosity, and surface tension. This is because hydrogen bonds are strong intermolecular forces that create stable molecules, making it harder to break them apart. • Intramolecular hydrogen bonding • Has the opposite effect of intermolecular hydrogen bonding, decreasing a substance's melting point and boiling point. This is because intramolecular hydrogen bonding prevents the association of ortho-substituted groups with other molecules. • Important for drug receptor interaction • Important in chemistry of genetic code: DNA
- 18. 5. Protein Binding • Protein binding is the interaction between drugs and host proteins, such as albumin, and it has a significant impact on biological action and drug pharmacokinetics: • Drug distribution: Protein binding affects how drugs are distributed and their bioavailability. • Drug effectiveness: Only unbound drugs are biologically active and can elicit a pharmacological response.
- 19. • Plasma protein binding refers to the degree to which medications attach to proteins within the blood. A drug's efficiency may be affected by the degree to which it binds. The less bound a drug is, the more efficiently it can traverse cell membranes or diffuse. • Common blood proteins that drugs bind to are human serum albumin, lipoprotein, glycoprotein, and α, β‚ and γ globulins.
- 20. • Protein binding can influence the drug's biological half-life. The bound portion may act as a reservoir or depot from which the drug is slowly released as the unbound form. Since the unbound form is being metabolized and/or excreted from the body, the bound fraction will be released in order to maintain equilibrium.
- 21. Chelation • Chelation is the process where an organic moiety binds a metal ion through two or more coordination bonds. • Metal complexes can be used to transport organic chemotherapeutic drugs to target organs • Chelation is a key component of enzyme functionality, especially when a metal cofactor is involved.
- 30. Ferguson principle • The Ferguson principle is a framework for understanding the relationship between the structure and activity of drugs, and how it relates to fatal drug toxicity. It's based on the observation that the ratio of partial pressure to saturated vapor pressure (P/P) is constant for a series of nonreactive toxicants or narcotics. • Used for • Calculates the fatal toxicity of drugs and related compounds • How it works • The median fatal concentrations (EC50) of different drugs are determined by their aqueous solubilities (S), and the ratio EC50/S is essentially constant • How it's used in toxicology • Separates or indicates possible mechanisms for acute toxic effects of chemicals • The Ferguson principle has been used in toxicology, but it hasn't been adequately tested because of the lack of a database with enough non-reactive and reactive chemicals. However, a theoretical framework has been presented that suggests the Ferguson principle can be extended to reactive chemicals.