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Questions and Answers
What is true about the chemical species involved in the reaction [𝐴− ]/[𝐻𝐴] = 25 at pH = 5.9 ?
What is true about the chemical species involved in the reaction [𝐴− ]/[𝐻𝐴] = 25 at pH = 5.9 ?
For a given acid, if the pH is less than the pKa, which of the following is true?
For a given acid, if the pH is less than the pKa, which of the following is true?
What is the predominant form of a base with a pKa of 9.6 at pH = 7?
What is the predominant form of a base with a pKa of 9.6 at pH = 7?
Based on the content provided, what is the relationship between the pH value and the pKa value that is more significant regarding the ionization state of a functional group?
Based on the content provided, what is the relationship between the pH value and the pKa value that is more significant regarding the ionization state of a functional group?
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Which of the following is NOT a step in solving problems involving the relationship between pH and pKa?
Which of the following is NOT a step in solving problems involving the relationship between pH and pKa?
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Based on the provided content, what is the relationship between the pH and pKa for a base when the pH is equal to the pKa?
Based on the provided content, what is the relationship between the pH and pKa for a base when the pH is equal to the pKa?
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If a hypothetical molecule contains an acidic functional group with a pKa of 3.5 and a basic functional group with a pKa of 8.2, where would the pH need to fall for the acidic functional group to be predominantly ionized?
If a hypothetical molecule contains an acidic functional group with a pKa of 3.5 and a basic functional group with a pKa of 8.2, where would the pH need to fall for the acidic functional group to be predominantly ionized?
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Which of the following scenarios best represents the relationship between pH and pKa when a base is primarily unionized?
Which of the following scenarios best represents the relationship between pH and pKa when a base is primarily unionized?
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What does a low $pK_a$ value indicate about a functional group?
What does a low $pK_a$ value indicate about a functional group?
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If a functional group has a higher $pK_a$ value compared to another, what can be inferred?
If a functional group has a higher $pK_a$ value compared to another, what can be inferred?
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What is the pH of a solution primarily a measure of?
What is the pH of a solution primarily a measure of?
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Which of the following best describes how a solution's pH can change?
Which of the following best describes how a solution's pH can change?
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What does a $pK_a$ value represent regarding a functional group?
What does a $pK_a$ value represent regarding a functional group?
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Considering different body environments, where would you expect to find the highest pH value?
Considering different body environments, where would you expect to find the highest pH value?
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In the context of acids and bases, which of the following is correct regarding protonated and deprotonated forms?
In the context of acids and bases, which of the following is correct regarding protonated and deprotonated forms?
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If pKa=8, what percentage of the substance is in the ionized form when the $pKa$ is equal to the $pH$ (i.e. when $pKa$ = $pH$)?
If pKa=8, what percentage of the substance is in the ionized form when the $pKa$ is equal to the $pH$ (i.e. when $pKa$ = $pH$)?
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According to the Henderson-Hasselbalch equation, what is the relationship between pH, pKa, and the ratio of the ionized and unionized forms of an acid?
According to the Henderson-Hasselbalch equation, what is the relationship between pH, pKa, and the ratio of the ionized and unionized forms of an acid?
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A weak acid has a pKa of 6.5. At what pH will the concentration of the ionized form be equal to the concentration of the unionized form?
A weak acid has a pKa of 6.5. At what pH will the concentration of the ionized form be equal to the concentration of the unionized form?
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The Henderson-Hasselbalch equation can be used to determine:
The Henderson-Hasselbalch equation can be used to determine:
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What does the term 'pKa' represent?
What does the term 'pKa' represent?
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A base has a pKa of 9.0. If the pH is 8.0, what is likely to be the ratio of its unionized to ionized form?
A base has a pKa of 9.0. If the pH is 8.0, what is likely to be the ratio of its unionized to ionized form?
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If you change the pH of the solution from 4 to 7, for a molecule with a pKa of 6, what will happen to the ratio of ionized to unionized forms of an acid?
If you change the pH of the solution from 4 to 7, for a molecule with a pKa of 6, what will happen to the ratio of ionized to unionized forms of an acid?
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A drug with a pKa of 7.4 is in the blood at pH 7.4. Which statement is correct?
A drug with a pKa of 7.4 is in the blood at pH 7.4. Which statement is correct?
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Which of the following correctly describes the relationship between pH and pKa for an acidic molecule?
Which of the following correctly describes the relationship between pH and pKa for an acidic molecule?
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What happens to acidic functional groups when the pH is greater than the pKa?
What happens to acidic functional groups when the pH is greater than the pKa?
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What is the percent ionized of a functional group with a pKa of 8.9 at a physiological pH of 7.4?
What is the percent ionized of a functional group with a pKa of 8.9 at a physiological pH of 7.4?
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Which statement about quaternary ammonium functional groups is true?
Which statement about quaternary ammonium functional groups is true?
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At what pH level would an acidic functional group with a pKa of 4.5 be 80% ionized?
At what pH level would an acidic functional group with a pKa of 4.5 be 80% ionized?
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When the pH is less than the pKa, what happens to basic functional groups?
When the pH is less than the pKa, what happens to basic functional groups?
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If a drug molecule has more than one acidic functional group, what must be evaluated?
If a drug molecule has more than one acidic functional group, what must be evaluated?
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What is the ionization status of nonelectrolytes at physiological pH?
What is the ionization status of nonelectrolytes at physiological pH?
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What is a key feature of the Henderson-Hasselbalch equation in relation to drug ionization?
What is a key feature of the Henderson-Hasselbalch equation in relation to drug ionization?
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What must be done to ensure the acidic functional groups of methotrexate are highly ionized and water soluble?
What must be done to ensure the acidic functional groups of methotrexate are highly ionized and water soluble?
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What is the consequence of decreasing the urine pH on phenobarbital's renal elimination?
What is the consequence of decreasing the urine pH on phenobarbital's renal elimination?
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Which pKa value would indicate that a functional group is expected to be predominantly unionized in urine with a normal pH of 5 to 6?
Which pKa value would indicate that a functional group is expected to be predominantly unionized in urine with a normal pH of 5 to 6?
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What is the significance of the Rule of Nines in relation to the Henderson-Hasselbalch equation?
What is the significance of the Rule of Nines in relation to the Henderson-Hasselbalch equation?
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Which of the following measures the ratio of [Base Form]/[Acid Form] when determining percent ionization?
Which of the following measures the ratio of [Base Form]/[Acid Form] when determining percent ionization?
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What characteristic of the functional group should be identified before using equations to calculate ionization?
What characteristic of the functional group should be identified before using equations to calculate ionization?
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What describes the typical pH range of normal urine?
What describes the typical pH range of normal urine?
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Why is it recommended to verify the calculated ionization values with the given data?
Why is it recommended to verify the calculated ionization values with the given data?
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What is the relationship between pH, pKa, and the ratio of ionized and unionized forms of an acid?
What is the relationship between pH, pKa, and the ratio of ionized and unionized forms of an acid?
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If the percentage of the deprotonated form is found to be 99%, what would be the expected range for the pH-pKa value?
If the percentage of the deprotonated form is found to be 99%, what would be the expected range for the pH-pKa value?
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What formula is used to express the dissociation constant (Ka) in relation to the percentage of ionized form?
What formula is used to express the dissociation constant (Ka) in relation to the percentage of ionized form?
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How can the Henderson-Hasselbalch equation be utilized for the drug naproxen?
How can the Henderson-Hasselbalch equation be utilized for the drug naproxen?
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What is the typical pKa value for a drug with 50% ionized and 50% unionized forms in a physiological environment?
What is the typical pKa value for a drug with 50% ionized and 50% unionized forms in a physiological environment?
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For which functional group would you expect more than 50% of the species to be ionized in an acidic environment?
For which functional group would you expect more than 50% of the species to be ionized in an acidic environment?
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If an acid produces a low Ka, what can be inferred about its pKa value?
If an acid produces a low Ka, what can be inferred about its pKa value?
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In which scenario would a drug be predominantly in its protonated form?
In which scenario would a drug be predominantly in its protonated form?
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Study Notes
Topic 1: Solving pH and pKa Problems
- Junmei Wang, Associate Professor, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh
- Contact information included for the professor and course website
Why Do We Learn Principles of Medicinal Chemistry?
- Ibuprofen and Naproxen are structurally similar but have different durations of action.
- Naproxen is a longer-acting agent.
- Ibuprofen has 98% plasma protein binding, while naproxen has 99%.
- Ibuprofen pKa is 4.5, and Naproxen's is 4.15.
Reference Book for Medicinal Chemistry Section
- Basic Concepts in Medicinal Chemistry by Marc W. Harrold and Robin M. Zavod
- Textbook is available online through the university library database.
Learning Objectives
- Explain the similarities, differences, and interrelationships between pKa of a functional group and pH of an environment.
- Explain how the Henderson-Hasselbalch equation was constructed and how it can calculate pH values, pKa values, and the ratio of ionized to unionized functional groups.
- Solve both qualitative and quantitative pH/pKa problems.
Basic Concepts
- pH = -log[H+]
- pOH = -log[OH−]
- pH + pOH = 14
- Includes an example table relating hydrogen ion concentration to pH and pOH.
Calculating pKa
- HA + H₂O ⇌ H₃O⁺ + A⁻ (Actual equation)
- HA ⇌ H⁺ + A⁻ (Simplified form)
- Kₐ = [H⁺][A⁻]/[HA] (Dissociation constant)
- pKa = -log([H⁺][A⁻]/[HA])
Basic Concepts (Basic Functional Groups)
- pKa for basic functional groups: B: + H⁺ ⇌ B:H⁺
- Kₐ = ([H⁺][B:])/[B:H⁺]
- pKa = -log([H⁺][B:])/[B:H⁺]
Key Summary Points for pH and pKa
- pH value is a property of the environment.
- Low pH values indicate acidic environments, high pH values indicate basic environments, and pH 7.0 is neutral.
- Key pH values include Saliva (6.4), Stomach (2.0), Duodenum (5.4), Plasma (7.4), Urine (5.7).
- pKa value is a property of a specific acidic/basic functional group; generally constant.
- Low pKa values indicate strong acids or weak bases.
- High pKa values indicate weak acids or strong bases.
Henderson-Hasselbalch Equation
- Includes the equation pH = pKa + log ([A⁻]/[HA]) and related variations for acidic and basic functional groups.
Equilibria for Acids and Bases
- Includes representations of mono and diprotic acids and bases.
Application of Henderson-Hasselbalch Equation
- Example question and answer regarding the ionization of a functional group in urine.
- pKa of 4.5; urine pH of 5.9; primarily unionized.
Three Scenarios on the Relationship of pH and pKa
- Three scenarios representing relationships between pH and pKa for acids and bases
- Indicates the relative importance of differences in pH and pKa rather than exact values.
Solving Qualitative pH and pKa Problem
- Example problem with Amoxicillin showing predominant forms of two functional groups.
Key Summary Points on Solving Qualitative Problems
- Identification of acidic and basic functional groups and pka values is first.
- Solutions are possible when comparing pH and pKa values; the Henderson Hasselbalch Equation is not always required.
- Explains quantitative situations when pH=pKa; pH>pKa; pH<pKa.
Solving Quantitative pH and pKa Problem
- Example problem determining the % of ionized drug at a given pH.
Calculating the pH of an Environment
- Example problem to calculate the pH needed for specific ionization of a drug.
Calculating pKa of A Function Group
- Example problem to calculate the pKa of a functional group given its ionization percentage in a specific pH.
The Rule of Nines
- Table and example demonstrating how pH-pKa difference correlates with ratio.
Key Summary Points on Solving Quantitative Problems
- The Henderson-Hasselbalch equation relates pH, pKa and ratio.
- Initial steps for the solution include identifying the acid/base character and analyzing the relationship between pH/pKa.
- Calculating percentage ionization using the Henderson Hasselbalch equation and related concepts.
The Importance of pH and pKa in Drug Therapy
- Aqueous Solubility: High-dose methotrexate used for tumors; it can precipitate in the renal tubules if urine pH is not raised. Crucial to maintain high ionization as increased solubility; alkaline urine required.
- Duration of Action: Phenobarbital renal elimination is pH-dependent. Decreassed urine pH will lead to reabsorption decreased renal elimination.
- Influence on Drug Binding Interactions: Ionic bonds are formed between drugs and biological targets over a significant distance; can be the first step in attraction.
Key Summary Points Involving the Importance of pH and pKa Drug Therapy
- Urinary and gastric pH are variable, while blood and tissue pH remains constant.
- Alterations of functional groups alter drug properties, affecting solubility, bioavailability, adverse reactions, duration, and binding interactions.
In Class Practice Problems
- Series of application problems for students' practice. Illustrative questions and scenarios are presented along with the appropriate equations and examples.
Homework
- Questions with several real-world drug molecule examples in solution, allowing students to apply concepts learned in the lecture.
Homework - Continued
- Table with various pH environments and their corresponding ionization outcomes.
- Application exercise for naproxen and dyclonine.
L1: Homework - Continued
- Further homework exercises employing Henderson-Hasselbalch equations and the "Rule of Nines."
- Illustrative cases focused on naproxen and dyclonine.
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Description
Test your understanding of the relationships between pH, pKa, and the ionization states of acids and bases. This quiz covers fundamental concepts in acid-base chemistry, including the effects of pH on functional groups and the rules for determining predominance in ionic forms. Engage with questions that help clarify these essential biochemical principles.
