Stereochemistry and Biological Activity
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Questions and Answers

What are molecules with the same molecular formula but different spatial arrangements called?

  • Diastereomers
  • Stereoisomers (correct)
  • Isomers
  • Enantiomers

    • Which type of stereoisomerism involves non-superimposable mirror images?

  • Diastereomers
  • Geometric isomers
  • Enantiomers (correct)
  • Racemic mixtures

    • Which statement is true regarding the therapeutic properties of stereoisomers?

  • Stereoisomers cannot exhibit different biological activities.
  • Enantiomers always have the same effects in biological systems.
  • Only one stereoisomer of a racemic mixture may be active. (correct)
  • All stereoisomers have identical properties.

    • What is the first step in determining the absolute configuration of a stereogenic center?

    <p>Assign priorities to the ligands based on atomic number.</p> Signup and view all the answers

    If the sequence of ligands from 1 to 3 is counterclockwise during configuration assignment, what designation is given?

    <p>S (sinister)</p> Signup and view all the answers

    What type of isomers are E/Z alkene isomers considered?

    <p>Geometric isomers</p> Signup and view all the answers

    What is the lowest priority substituent in determining absolute configuration?

    <p>Hydrogen</p> Signup and view all the answers

    Which of the following correctly describes diastereomers?

    <p>They are non-superimposable and non-mirror images.</p> Signup and view all the answers

    What does a higher ability of an enantiomer to bind to receptor sites indicate about its potency?

    <p>The enantiomer acts on more binding sites.</p> Signup and view all the answers

    Which of the following statements about enantiomers is true?

    <p>Enantiomers differ in their interaction with polarized light.</p> Signup and view all the answers

    Which is the correct implication of the Easson-Stedman Hypothesis regarding drug-receptor interactions?

    <p>Three intermolecular interactions are necessary for drug efficacy.</p> Signup and view all the answers

    What does the R, S designation indicate about a compound?

    <p>It indicates the configuration of substituents around a chiral center.</p> Signup and view all the answers

    What characterizes a racemate?

    <p>An equal mixture of two enantiomers.</p> Signup and view all the answers

    How does the configuration (R or S) relate to optical rotation?

    <p>R and S have no relation to the direction of rotation.</p> Signup and view all the answers

    In the context of chirality, which statement about amino acids is true?

    <p>All amino acids are L-isomers and are chiral.</p> Signup and view all the answers

    When determining priority in the R and S nomenclature, which functional group has the highest priority?

    <p>-COOH</p> Signup and view all the answers

    Which is true about the enantiomers of dexchlorpheniramine?

    <p>The S-(+)-isomer is 200 times more potent than the R-(-)-isomer.</p> Signup and view all the answers

    What connection exists between the isomers of fluoxetine?

    <p>Only the S isomer demonstrates anti-migraine effects.</p> Signup and view all the answers

    What major problem did the drug thalidomide cause?

    <p>The S isomer resulted in significant toxicity.</p> Signup and view all the answers

    What distinguishes the enantiomers of dextropropoxyphene and levopropoxyphene?

    <p>Levopropoxyphene does not have analgesic properties.</p> Signup and view all the answers

    Which statement is correct regarding the pharmacological activities of enantiomers?

    <p>They can have opposite effects on biological activity.</p> Signup and view all the answers

    What is a potential drawback of using racemic drug mixtures?

    <p>Inactive components may lead to side effects.</p> Signup and view all the answers

    Which of the following statements is incorrect regarding the activities of nebivolol's isomers?

    <p>Neither isomer has therapeutic efficacy.</p> Signup and view all the answers

    Which enantiomer of picenadol acts as a narcotic antagonist?

    <p>(-)-isomer</p> Signup and view all the answers

    At a pH of 8.0, what percentage of molecules exist in the ionized form?

    <p>50%</p> Signup and view all the answers

    What percentage of amobarbital is in the unionized form at pH 2.0?

    <p>100%</p> Signup and view all the answers

    At a pH of 7.4, what is the ratio of [A-] to [HA] according to the calculations?

    <p>1:0.25</p> Signup and view all the answers

    What pH value indicates that the acid form predominates to 99.7%?

    <p>5.5</p> Signup and view all the answers

    What is the correct relationship between pH and pKa when pH is 6 log units below pKa?

    <p>Unionized form is dominant</p> Signup and view all the answers

    Which electronic effect is significant in determining the behavior of functional groups?

    <p>Resonance effect</p> Signup and view all the answers

    What is the total concentration of both the conjugate base and acid form when the pH is set at 7.4?

    <p>1.25</p> Signup and view all the answers

    Which of the following statements is true regarding the ionized form at pH 7.4?

    <p>20% in ionized form</p> Signup and view all the answers

    What determines the acid-base properties of a functional group?

    <p>Protonation state</p> Signup and view all the answers

    Which property is NOT associated with the solubility effects of drugs?

    <p>Molecular symmetry</p> Signup and view all the answers

    If the pKa of a compound is 6, what is the pH where the acid form is fully ionized?

    <p>2.0</p> Signup and view all the answers

    In the Henderson-Hasselbalch equation, what does pKa represent?

    <p>Dissociation constant of the acid</p> Signup and view all the answers

    Which factor influences the chirality of a molecule?

    <p>Absence of symmetry</p> Signup and view all the answers

    Which aspect is critical in predicting the behaviors of drugs in biological systems?

    <p>Functional group reactivity</p> Signup and view all the answers

    What is primarily affected by the steric effects of a functional group in drug design?

    <p>Shape and size interactions</p> Signup and view all the answers

    Which relationship in drug chemistry does the Henderson-Hasselbalch equation help explain?

    <p>Relationship between pH and ionization of drugs</p> Signup and view all the answers

    What is the percentage of ionization of phenylpropanolamine at a pH of 2.0?

    <p>99.99%</p> Signup and view all the answers

    How does urine alkalinization affect the excretion of acidic drugs like acetylsalicylic acid?

    <p>Increases the ionized state of the drug.</p> Signup and view all the answers

    At what pH does phenylpropanolamine display 99.7% ionization?

    <p>pH 5.5</p> Signup and view all the answers

    What is a consequence of Ecstasy's charged character once it accepts a proton?

    <p>It becomes difficult to cross biological membranes.</p> Signup and view all the answers

    What is the primary reason that phenylpropanolamine is highly ionized in the stomach?

    <p>The pH of the stomach is low.</p> Signup and view all the answers

    What is the approximate pH required for urine alkalinization to enhance drug excretion?

    <p>Above 7.5</p> Signup and view all the answers

    Why is there more than 50% nonionized drug in the plasma at pH 7.4?

    <p>The pH is slightly lower than the pKa.</p> Signup and view all the answers

    What happens to the ionized form of phenylpropanolamine at pH 8.0?

    <p>It becomes less ionized than at pH 2.0.</p> Signup and view all the answers

    Which enantiomer of dexchlorpheniramine is significantly more potent?

    <p>S-(+)-isomer</p> Signup and view all the answers

    What effect does the S-isomer of fluoxetine have compared to the racemic mixture?

    <p>It works effectively for anti-migraine treatment.</p> Signup and view all the answers

    Which statement regarding thalidomide is accurate?

    <p>The S-isomer was used to treat advanced leprosy.</p> Signup and view all the answers

    What is true about the pharmacological activities of the enantiomers of nebivolol?

    <p>One is a β-blocker and the other is a vasodilating agent.</p> Signup and view all the answers

    Which of the following statements is true regarding the isomers of dextropropoxyphene and levopropoxyphene?

    <p>Dextropropoxyphene is an analgesic, while levopropoxyphene is an antitussive agent.</p> Signup and view all the answers

    In how many cases can enantiomers have opposite effects?

    <p>Only in specific cases like picenadol.</p> Signup and view all the answers

    What challenge is associated with separating enantiomers in drug production?

    <p>It often requires complex chemical transformations.</p> Signup and view all the answers

    What is a major reason for selling drugs as racemic mixtures?

    <p>Combining isomers may enhance overall drug activity.</p> Signup and view all the answers

    What is the effect of the pH being below pKa on weak acids?

    <p>They remain un-ionized and can easily diffuse through membranes.</p> Signup and view all the answers

    In the environment of the stomach with a pH of 2, which statement is true regarding the absorption of drugs?

    <p>Most acids can diffuse through the membrane while most bases cannot.</p> Signup and view all the answers

    What characterizes a molecule with multiple asymmetric carbons concerning optical isomers?

    <p>It produces 2n optical isomers where n is the number of chiral centers.</p> Signup and view all the answers

    What is the outcome for acidic drugs when the pH is greater than the pKa?

    <p>They are predominantly un-ionized.</p> Signup and view all the answers

    Which property of functional groups helps determine a drug’s biological response?

    <p>Chemical properties of functional groups</p> Signup and view all the answers

    When analyzing the ionization of basic drugs, what occurs when the pH is lower than the pKa?

    <p>They predominately exist in an ionized form.</p> Signup and view all the answers

    How does the Henderson-Hasselbalch Equation relate to the ionization of drugs?

    <p>It calculates the percentage of ionization based on pH and pKa.</p> Signup and view all the answers

    What is the significance of chirality in drug design with respect to adverse effects?

    <p>Different enantiomers may have varying therapeutic and toxic effects.</p> Signup and view all the answers

    Study Notes

    Stereochemistry and Biologic Activity

    • The Easson-Stedman Hypothesis states that drug-receptor interactions require a minimum of three points of contact for optimal binding.
    • Enantiomers are non-superimposable mirror images of each other.
    • A racemate is an equal mixture of two enantiomers.
    • All amino acids are chiral molecules and exist as L-isomers.
    • Proteins are also chiral and their interactions with enantiomers of chiral drugs can lead to different binding sites.

    Types of Stereoisomers

    • Enantiomers: Non-superimposable mirror image isomers.
    • Diastereomers: Non-superimposable, non-mirror image isomers. They have more than one chiral center.
    • Geometric Isomers: Diastereomers that are E/Z alkene isomers.

    Determining Absolute Configuration (R/S Convention)

    • The R/S convention is used to describe the spatial arrangement of ligands around a stereogenic center.
    • R (rectus): Clockwise order of ligands when viewed with the lowest priority group in the back.
    • S (sinister): Counterclockwise order of ligands when viewed with the lowest priority group in the back.

    Assigning R/S Configuration

    • Assign priorities to the four ligands based on atomic number, with higher atomic number = higher priority.
    • Rotate the molecule so the lowest priority ligand is pointing away from the viewer.
    • Determine the direction of the remaining three ligands (1-3). Clockwise = R, Counterclockwise = S.

    Enantiomeric Specificity in Biological Activity

    • One enantiomer may be more potent than the other: S-(+)-isomer of dexchlorpheniramine is 200 times more potent than the R-(-)-isomer.
    • Both enantiomers may be active, but one contributes to toxicity: R isomer of fluoxetine shows cardiac side effects while the S isomer is effective for anti-migraine effects.
    • One enantiomer may be responsible for side effects and toxicity: (S)-isomer of thalidomide caused birth defects, while the (R)-isomer was converted to (S)-isomer in vivo.
    • Enantiomers may have different therapeutic activities: Darvon (2R, 3S-(+)-dextropropoxyphene) is an analgesic, while Novrad (2S,3R-(-)-levopropoxyphene) is an antitussive.
    • Enantiomers may have opposite effects: (+)-isomer of picenadol is an opiate agonist, the (-)-isomer is an antagonist, and the racemate is a partial agonist.
    • Two enantiomers may have synergistic pharmacological activities: (+)-isomer of nebivolol is a -blocker, and the (-)-isomer is a vasodilating agent.

    Separation of Enantiomers

    • It can be expensive to separate enantiomers.
    • About one-third of drugs are sold as racemic mixtures, even though only one enantiomer may be active or even cause adverse effects.

    Functional Groups

    • Functional groups (FGs) are parts of compounds or drugs that provide specific characteristics and behaviors, allowing them to produce biological responses.
    • FGs influence a compound's or drug's properties through electronic, steric, and acid-base effects.
    • Electronic Effects: Include resonance and inductive effects which influence the distribution of electron density within a molecule. Resonance involves the delocalization of electrons, while inductive effects involve the polarization of electron density.
    • Steric Effects: Relate to the spatial arrangement of atoms and functional groups, influencing the molecule's shape and how it interacts with other molecules.
    • Acid-base Properties: Determine how a compound interacts with protons (H+). Acidic FGs donate protons, while basic FGs accept protons.

    Henderson-Hasselbalch Equation

    • This equation relates the pH of a solution to the pKa of a weak acid or base and the ratio of ionized to un-ionized forms.
    • Weak Acids: The equation is pKa = pH + log ([acid]/[conjugate base]), where pKa is the negative logarithm of the acid dissociation constant.
    • Weak Bases: The equation is pH = pKa + log ([base]/[conjugate acid]).

    Chirality and Stereochemistry

    • The orientation of functional groups in three-dimensional space defines a molecule's stereochemistry.
    • Asymmetric Carbon (chiral carbon): A carbon atom bonded to four distinct substituents.
    • Molecules with 'n' asymmetric carbons result in 2^n optical isomers.
    • Enantiomers: Stereoisomers that are non-superimposable mirror images of each other.
    • Enantiomers can have different biological activities:
      • One enantiomer can be significantly more potent than the other.
      • Both isomers could be active but only one contributes to toxicity.
      • One enantiomer could produce undesirable side effects and toxicity.
      • Enantiomers can have opposite therapeutic activities.
      • Two enantiomers can have synergistic pharmacological activities.

    Separation of Enantiomers

    • About a third of drugs are sold as racemic mixtures, containing equal amounts of both enantiomers.
    • Separating enantiomers can be costly.
    • Inactive enantiomers might contribute to side effects.

    Acid-base Properties and Absorption

    • Ionized forms of drugs have difficulty crossing biological membranes, while un-ionized forms can easily diffuse.
    • Weak acids: At pH below their pKa, they are predominantly in the un-ionized form, readily crossing membranes.
    • Weak bases: At pH below their pKa, they are predominantly in the ionized form, making membrane crossing difficult.
    • The pH of the environment influences a drug's absorption. For example, in the stomach (low pH), weak acids are absorbed, while weak bases are less absorbed.

    Pharmacist Alert

    • Drug Trapping in the Stomach: Weakly basic drugs, like morphine, are trapped in the stomach due to ionization.
    • Urine Alkalinization: Increasing urine pH above the pKa increases the ionized form of acidic drugs, promoting their excretion. For instance, aspirin (acetylsalicylic acid) excretion is enhanced by urine alkalinization.
    • Urine Alkalinization for Poison Elimination: Administering sodium bicarbonate or oral tablets to raise urine pH (>7.5) can enhance the elimination of certain poisons like mecoprop, methotrexate, phenobarbital, and salicylate.
    • Ecstasy (MDMA) Absorption: Ecstasy, a weak base, is poorly absorbed in the stomach due to ionization. In the small intestine (more alkaline), it readily crosses membranes.
    • Rule of Thumb for Absorption: Weak acids are more likely to be absorbed in a low pH environment (stomach), while weak bases are more likely to be absorbed in a higher pH environment (small intestine).
    • Percentage of Ionization: The Henderson-Hasselbalch equation can be used to calculate the percentage of ionization for a drug at a specific pH.

    Summary of Key Points

    • Functional groups determine the properties and biological activity of a compound or drug.
    • The Henderson-Hasselbalch equation predicts the ionization state of a drug based on its pKa and the pH of the surrounding environment.
    • Chirality plays a crucial role in drug activity and side effects.
    • Enantiomers can exhibit different biological properties, including potency, toxicity, and therapeutic effects.
    • The pH of the environment influences drug absorption, with weak acids favored in low pH environments, and weak bases favored in high pH environments.

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    Description

    This quiz covers essential concepts in stereochemistry, focusing on drug-receptor interactions and the classification of stereoisomers. Explore the Easson-Stedman Hypothesis, enantiomers, diastereomers, and the R/S convention for determining absolute configuration. Test your knowledge on how these concepts apply to biologically active compounds.

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