Podcast
Questions and Answers
What is the molecular weight of α1-acid glycoprotein?
What is the molecular weight of α1-acid glycoprotein?
Which type of drugs primarily bind to α1-acid glycoprotein?
Which type of drugs primarily bind to α1-acid glycoprotein?
What is the primary mechanism by which lipoproteins bind drugs?
What is the primary mechanism by which lipoproteins bind drugs?
Which globulin is known for binding steroidal drugs?
Which globulin is known for binding steroidal drugs?
Signup and view all the answers
What effect does protein binding have on drug distribution?
What effect does protein binding have on drug distribution?
Signup and view all the answers
Which of the following drugs is mainly eliminated by glomerular filtration?
Which of the following drugs is mainly eliminated by glomerular filtration?
Signup and view all the answers
What role does hemoglobin play in drug binding?
What role does hemoglobin play in drug binding?
Signup and view all the answers
What is a significant effect of protein binding on drug metabolism?
What is a significant effect of protein binding on drug metabolism?
Signup and view all the answers
What is the primary effect of renal failure on drug binding?
What is the primary effect of renal failure on drug binding?
Signup and view all the answers
Which protein is primarily responsible for binding acidic and neutral drugs?
Which protein is primarily responsible for binding acidic and neutral drugs?
Signup and view all the answers
How does aging influence drug binding in the elderly?
How does aging influence drug binding in the elderly?
Signup and view all the answers
What happens to drug binding when albumin becomes saturated?
What happens to drug binding when albumin becomes saturated?
Signup and view all the answers
What effect does inflammatory states have on basic drug binding?
What effect does inflammatory states have on basic drug binding?
Signup and view all the answers
How many binding sites does albumin possess for drug molecules?
How many binding sites does albumin possess for drug molecules?
Signup and view all the answers
What type of drugs does α1-acid glycoprotein primarily bind?
What type of drugs does α1-acid glycoprotein primarily bind?
Signup and view all the answers
What physiological condition is linked to low drug binding capacity in neonates?
What physiological condition is linked to low drug binding capacity in neonates?
Signup and view all the answers
What does protein-ligand binding kinetics primarily describe?
What does protein-ligand binding kinetics primarily describe?
Signup and view all the answers
What is the main assumption of the lock-and-key model?
What is the main assumption of the lock-and-key model?
Signup and view all the answers
Which model assumes that the binding site in a protein can change shape upon ligand interaction?
Which model assumes that the binding site in a protein can change shape upon ligand interaction?
Signup and view all the answers
Which interaction occurs between charged amino acids and oppositely charged ligand molecules?
Which interaction occurs between charged amino acids and oppositely charged ligand molecules?
Signup and view all the answers
What do the kinetic rate constants $k_{on}$ and $k_{off}$ represent in protein-ligand binding?
What do the kinetic rate constants $k_{on}$ and $k_{off}$ represent in protein-ligand binding?
Signup and view all the answers
What is a characteristic of the conformational selection model?
What is a characteristic of the conformational selection model?
Signup and view all the answers
Which type of interaction is characterized by dipole-dipole forces?
Which type of interaction is characterized by dipole-dipole forces?
Signup and view all the answers
At equilibrium, what does the equation $k_{on}[P][L] = k_{off}[PL]$ signify?
At equilibrium, what does the equation $k_{on}[P][L] = k_{off}[PL]$ signify?
Signup and view all the answers
What characterizes a bound drug in relation to its activity?
What characterizes a bound drug in relation to its activity?
Signup and view all the answers
How does lipophilicity affect protein drug binding?
How does lipophilicity affect protein drug binding?
Signup and view all the answers
Which protein is predominantly responsible for drug binding in plasma?
Which protein is predominantly responsible for drug binding in plasma?
Signup and view all the answers
What does competition between drugs for binding sites refer to?
What does competition between drugs for binding sites refer to?
Signup and view all the answers
What role does physiological pH play in drug binding?
What role does physiological pH play in drug binding?
Signup and view all the answers
Which factor significantly impacts drug binding related to the drug itself?
Which factor significantly impacts drug binding related to the drug itself?
Signup and view all the answers
What happens when there is a small change in a medication that is extensively protein bound?
What happens when there is a small change in a medication that is extensively protein bound?
Signup and view all the answers
Regarding the affinity for binding components, what is a key factor?
Regarding the affinity for binding components, what is a key factor?
Signup and view all the answers
What is the first parameter estimated in the analysis of complexation?
What is the first parameter estimated in the analysis of complexation?
Signup and view all the answers
Which method uses the change in pH to indicate complex formation?
Which method uses the change in pH to indicate complex formation?
Signup and view all the answers
What phenomenon does the Distribution Method measure in complexation?
What phenomenon does the Distribution Method measure in complexation?
Signup and view all the answers
What is the effect of caffeine on the solubility of Para-aminobenzoic acid (PABA)?
What is the effect of caffeine on the solubility of Para-aminobenzoic acid (PABA)?
Signup and view all the answers
What does a nonlinear relationship in physical properties suggest when two species are mixed?
What does a nonlinear relationship in physical properties suggest when two species are mixed?
Signup and view all the answers
Which example illustrates the solubility method of complexation analysis?
Which example illustrates the solubility method of complexation analysis?
Signup and view all the answers
How is the stability constant of a complex commonly estimated?
How is the stability constant of a complex commonly estimated?
Signup and view all the answers
What does the Continuous Variation method assess when two species are mixed?
What does the Continuous Variation method assess when two species are mixed?
Signup and view all the answers
What is generally studied using absorption spectroscopy in the context of complexation?
What is generally studied using absorption spectroscopy in the context of complexation?
Signup and view all the answers
What information does the complex [C0(NH3)6] +3 provide?
What information does the complex [C0(NH3)6] +3 provide?
Signup and view all the answers
What characterizes a protein-bound drug?
What characterizes a protein-bound drug?
Signup and view all the answers
Which type of bond is typically involved in reversible protein binding?
Which type of bond is typically involved in reversible protein binding?
Signup and view all the answers
Which of the following is NOT a function of proteins?
Which of the following is NOT a function of proteins?
Signup and view all the answers
Irreversible protein binding may lead to which of the following outcomes?
Irreversible protein binding may lead to which of the following outcomes?
Signup and view all the answers
What are the main components of human plasma proteins?
What are the main components of human plasma proteins?
Signup and view all the answers
Which spectroscopy method is NOT listed as a technique to determine complexation?
Which spectroscopy method is NOT listed as a technique to determine complexation?
Signup and view all the answers
Study Notes
Complexation and Protein Binding
- Complexation is the interaction between a metal ion and a ligand.
- Polypyridyl ligands fit well with large metal ions.
- Extended aromatic systems are useful sensors for metal ions.
- Benzo groups lead to more preorganized ligands.
- Steric clashes between ortho H atoms and adjacent polypyridyl groups can destabilize the complex.
Analysis of Complexation
- Involves estimating the stoichiometric ratio of ligand:metal and the stability constant of the complex.
- pH titration is a method to determine complexation. The change in pH indicates complex formation.
- Chelation of cupric ion by glycine, for example, can be represented as: Cu² + 2NH3 CH2CH2 COO- = Cu(NH2CH2COO)2 + 2H+.
- Two protons formed during the reaction cause a decrease in pH.
Distribution Method
- The distribution behavior of a solute between two immiscible liquids is expressed by a distribution coefficient or partition coefficient.
- When a solute complexes with an added substance, the solute distribution pattern changes based on the nature of complex.
- The stability constant can be estimated.
- Example: Iodine complex with Potassium iodide.
Solubility Method
- Using the change in solubility profile as a criterion to analyze complexation.
- When components in a mixture form a complex, solubility may increase or decrease.
- Example: Estimation of complexation of para-aminobenzoic acid (PABA) and caffeine.
Continuous Variation Method
- Physical properties, such as UV absorbance, dielectric constant, refractive index, and spectrophotometric extinction coefficient are characteristics of a species.
- A change in property suggests complex formation.
- If no complexation occurs, the property value is additive and shows a linear relationship.
- Complexation leads to a nonlinear relationship in property value.
Spectroscopy Method
- Studying donor-acceptor or charge transfer complexation using absorption spectroscopy in the visible/UV range..
- The complex will have different UV absorbance from its individual components.
- Other methods for determining complexation include nuclear magnetic resonance (NMR), infrared spectroscopy (IR), polarography, and X-ray diffraction.
Question Examples
- Identify the central metal ion, ligand and coordination number in the complex [CO(NH3)6]+3.
- Identify the central metal ion, ligand and coordination number in the complex [Cr(H2O)6]+3.
Protein Binding
- The complex formed by drug interaction with proteins.
- Human plasma is composed of many known proteins.
- Proteins are made of approximately 20 amino acids.
- Functions include maintaining osmotic pressure, proper pH, immune reactions (antibodies), transport, enzymatic function (enzymes or hormones), cell growth/tissue maintenance, and catalyzing metabolism reactions.
Protein Binding - Types
- Protein binding can be reversible or irreversible.
- Reversible binding involves weak bonds like hydrogen bonds, hydrophobic bonds, and van der Waals forces.
- Irreversible binding is rare and results from covalent bonding (can cause toxicity).
Protein-Ligand Binding Kinetics
- Describes protein-ligand association/dissociation.
- Binding is based on protein-ligand affinity and kinetics arising from contacts/collisions and molecular diffusion.
- P + L <=> PL (Protein and ligand can form a complex)
Protein-Ligand Binding Models
- Common models like lock-and-key, induced-fit, and conformational selection are suggested.
- Lock-and-key model: Protein and ligand are rigid, with perfectly matched binding interfaces.
- Induced-fit model: Binding site is flexible and the interacting ligand induces a conformational change in the binding site.
- Conformational selection model: The native state of protein exists in a vast conformational ensemble.
Mechanisms of Interactions (Protein-small molecules)
- Hydrogen bonding between donor and acceptor functional groups in amino acid sequences.
- Electrostatic interactions between charged amino acids and oppositely charged ligand molecules.
- Van der Waals interactions (dipole-dipole, dipole-induced dipole, dispersion forces).
- Hydrophobic interactions between nonpolar groups in the presence of water molecules.
Implications of Protein Binding
- Bound drugs are inactive; free drugs are active.
- Free drugs distribute to organs and tissues.
- Bound drugs act as reservoirs, and a small change in concentration can have a significant impact.
- Drug-related factors (physicochemical characteristics): Lipophilicity increases binding extent. -Concentration of drug in the body changes protein binding process.
- Affinity of the drug to the binding component depends on the degree of attraction or affinity of the protein molecule or tissues towards drug moieties.
- Protein/tissue related factors (physicochemical characteristics): This is related to the characteristics of proteins.
Patient-Related Factors Affecting Protein Binding
- Neonates have lower albumin content; thus, more free drug.
- Elderly patients have lower albumin content; thus, more free drug.
- Inter-subject variability (individual differences)
Disease States Affecting Protein Binding
- Renal failure can decrease albumin content leading primarily to increased binding.
- Hepatic failure can decrease albumin synthesis and thus decreased binding.
- Inflammation can lead to increases in some protein concentrations changing the drug binding capacity.
Protein Binding Locations
- Protein binding can occur intracellularly and extracellularly.
- Common proteins that bind drugs include human serum albumin (HSA), alpha-1-acid glycoprotein, lipoproteins, and blood cells.
Binding of Drug to Specific Proteins
- Drugs can bind to HSA, with albumin possessing four binding sites.
- Alpha-1-acid glycoprotein (orosomucoid) binds by hydrophobic bonds; basic drugs bind in acidic regions.
- Lipoproteins bind by hydrophobic bonds (lipid core).
- Globulins (cortisol binding globulin, transferrin, ceruloplasmin) bind steroids, vitamins, and metals.
- Blood cells (hemoglobin) bind lipophilic ligands.
Significance/Effects of Protein Binding
- Absorption: Protein binding decreases free drug concentration.
- Distribution: Bound drug does not cross barriers (BBB, placental, glomerulus);
- Metabolism: Protein binding can decrease metabolism; unbound drug is metabolized.
- Elimination: Only unbound drug is eliminated.
Other Considerations
- Diseases/disorders change protein status (used as biomarkers).
- Lipoproteins transport hydrophobic drugs.
- Protein binding inactivates drugs; a sufficient concentration at the receptor site is needed for action.
- Drug-protein complex acts as a reservoir; and continuously provides free drug.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Test your knowledge on the principles of complexation and protein binding. Explore topics like metal ion interactions with ligands, stability constants, and methods for analyzing complex formation. Perfect for students in chemistry or biochemistry courses.
