Taft’s steric constant MCQs With Answer

Taft’s steric constant (Es) is a core concept in physical organic and pharmaceutical chemistry, quantifying steric hindrance of aliphatic substituents and helping predict how bulky groups affect reaction rates and mechanisms. This resource for B.Pharm students covers how Es is measured from ester hydrolysis kinetics, its use alongside the polar constant (σ*) in the Taft equation, interpretation of Taft plots, and practical applications in structure–activity relationships (SAR), drug metabolism, and rational ligand design. Emphasis is on distinguishing steric from electronic effects and applying Es to optimize pharmacokinetic and synthetic outcomes. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. What does Taft’s steric constant (Es) primarily quantify?

• The electron-withdrawing ability of a substituent
• The steric hindrance of an aliphatic substituent measured from reaction kinetics
• The aromatic resonance stabilization
• The acidity of a proton adjacent to the substituent

Correct Answer: The steric hindrance of an aliphatic substituent measured from reaction kinetics

Q2. Taft originally derived Es values from kinetic studies of which reaction class?

• Electrophilic aromatic substitution
• Ester hydrolysis reactions
• Free radical polymerization
• Oxidative coupling

Correct Answer: Ester hydrolysis reactions

Q3. In the Taft equation log(k/k0) = ρ*σ* + δEs, what does the δ coefficient describe?

• Sensitivity of the reaction rate to polar effects
• Sensitivity of the reaction rate to steric effects
• The intrinsic rate constant for the uncatalyzed reaction
• The entropic contribution to the activation energy

Correct Answer: Sensitivity of the reaction rate to steric effects

Q4. Which parameter in Taft analysis represents polar (electronic) effects for aliphatic substituents?

• Es
• ρ (rho)
• σ* (sigma star)
• χ (electronegativity)

Correct Answer: σ* (sigma star)

Q5. For a reaction where δ is large and positive, how does increasing Es for a substituent affect the rate?

• Rate increases dramatically
• Rate is unchanged
• Rate decreases significantly due to steric hindrance
• Rate changes unpredictably

Correct Answer: Rate decreases significantly due to steric hindrance

Q6. Which of the following lists correctly orders substituents from most to least sterically demanding (typical Es trend)?

• H > Me > Et > i-Pr > t-Bu
• t-Bu > i-Pr > Et > Me > H
• Me > Et > i-Pr > t-Bu > H
• H > t-Bu > i-Pr > Et > Me

Correct Answer: t-Bu > i-Pr > Et > Me > H

Q7. Which statement best distinguishes Es from Hammett σ parameters?

• Es measures electronic effects in aromatic rings; Hammett σ measures steric hindrance.
• Es quantifies steric effects for aliphatic substituents; Hammett σ quantifies electronic effects for aromatic substituents.
• Es and Hammett σ are interchangeable descriptors for any substituent.
• Es measures solvent polarity while Hammett σ measures basicity.

Correct Answer: Es quantifies steric effects for aliphatic substituents; Hammett σ quantifies electronic effects for aromatic substituents.

Q8. When plotting log(k/k0) versus Es for a series of substituents, what information is obtained from the slope?

• The magnitude of electronic stabilization
• The sensitivity of the reaction to steric hindrance
• The absolute activation energy
• The solvent dielectric constant

Correct Answer: The sensitivity of the reaction to steric hindrance

Q9. A B.Pharm student compares two substituents with similar σ* but different rates. What is the most likely explanation?

• The reaction is governed only by solvent effects
• Steric differences (Es) cause the rate difference
• Experimental error; identical σ* must give identical rates
• Differences arise from aromaticity changes

Correct Answer: Steric differences (Es) cause the rate difference

Q10. Which application in drug design most directly uses Taft’s steric constant?

• Predicting electronic absorption spectra
• Optimizing synthetic yields of polymers
• Rationalizing how bulky substituents affect metabolic stability and enzyme access
• Calculating pKa values of aromatic acids

Correct Answer: Rationalizing how bulky substituents affect metabolic stability and enzyme access

Q11. Which experimental factor can change measured Es values for a substituent?

• Change in solvent polarity or reaction mechanism
• The molecular weight of the substituent only
• Ambient room lighting during the experiment
• The brand of glassware used

Correct Answer: Change in solvent polarity or reaction mechanism

Q12. Which reaction type is most affected by steric hindrance quantified by Es?

• SN2 nucleophilic substitutions at crowded centers
• Homogeneous electron transfer reactions with distant centers
• Gas-phase unimolecular decomposition of noble gases
• Electrochemical reduction of metal ions

Correct Answer: SN2 nucleophilic substitutions at crowded centers

Q13. If a student wants to separate steric and polar contributions to a reaction rate, which approach is most appropriate?

• Use only Hammett σ values
• Use the Taft equation combining σ* and Es terms
• Ignore substituent effects entirely
• Measure only equilibrium constants

Correct Answer: Use the Taft equation combining σ* and Es terms

Q14. Why is Taft’s Es especially useful for aliphatic substituents rather than aromatic substituents?

• Aliphatic substituents never exhibit electronic effects
• Es was derived from kinetic studies on aliphatic systems where steric, not resonance, dominates
• Aromatic substituents are too small to measure
• Es values are identical for all aromatic substituents

Correct Answer: Es was derived from kinetic studies on aliphatic systems where steric, not resonance, dominates

Q15. Which descriptor is a commonly used alternative or complement to Taft Es for steric effects?

• pKa
• Charton steric parameter (ν) or Verloop steric parameters
• Partition coefficient only
• Optical rotation

Correct Answer: Charton steric parameter (ν) or Verloop steric parameters

Q16. A Taft plot shows poor linear correlation between log(k/k0) and Es for a series. Which is the best interpretation?

• The series is dominated by polar or electronic effects not captured by Es
• Es values are universally inaccurate
• The reaction is independent of all substituent effects
• All substituents have identical steric size

Correct Answer: The series is dominated by polar or electronic effects not captured by Es

Q17. In structure–activity relationships (SAR), how can Es help medicinal chemists?

• By predicting UV–Vis spectra of new compounds
• By guiding substitution to reduce steric clashes with a biological target or metabolic enzymes
• By replacing in vitro testing completely
• By determining the absolute stereochemistry of chiral centers

Correct Answer: By guiding substitution to reduce steric clashes with a biological target or metabolic enzymes

Q18. Which position of a substituent is most relevant when applying Taft’s Es?

• Substituents on a distant aromatic ring unrelated to the reactive center
• Aliphatic substituents directly adjacent (α) to the reaction center
• Counterions in the reaction medium
• Terminal methyl groups far from functional groups

Correct Answer: Aliphatic substituents directly adjacent (α) to the reaction center

Q19. Which experimental observation would most strongly suggest steric control rather than electronic control?

• Rate correlates with σ* but not Es
• Rate correlates with Es but not σ*
• Rate does not change with substituent size or electronics
• Solubility changes with substituent polarity

Correct Answer: Rate correlates with Es but not σ*

Q20. How does Taft’s σ* differ conceptually from Hammett σ?

• σ* applies to aliphatic systems and quantifies polar effects; Hammett σ applies primarily to aromatic systems
• σ* measures steric bulk while Hammett σ measures mass
• σ* and Hammett σ are identical but named differently
• σ* applies only to gas-phase reactions

Correct Answer: σ* applies to aliphatic systems and quantifies polar effects; Hammett σ applies primarily to aromatic systems

Q21. A substituent shows a high Es but a strongly electron-withdrawing σ*. What combined effect might you expect on a nucleophilic acyl substitution?

• Only increased rate due to electronics, sterics irrelevant
• Competing effects: electronics may accelerate while sterics slow the reaction; net rate depends on ρ* and δ
• Complete inhibition of reaction regardless of magnitudes
• No effect on rate at all

Correct Answer: Competing effects: electronics may accelerate while sterics slow the reaction; net rate depends on ρ* and δ

Q22. Which of the following is a limitation of using Es in medicinal chemistry?

• Es values are universally accurate for all solvents and mechanisms
• Es does not account for conformational flexibility, solvent-specific interactions, or long-range effects
• Es replaces the need for computational docking studies
• Es measures only electronic resonance effects

Correct Answer: Es does not account for conformational flexibility, solvent-specific interactions, or long-range effects

Q23. Which observation supports using Taft analysis to rationalize drug metabolism?

• Bulky substituents at a metabolized site slow enzymatic hydrolysis
• Drug melting point correlates with Es perfectly
• All bulky drugs are inactive biologically
• Es predicts color changes on metabolism

Correct Answer: Bulky substituents at a metabolized site slow enzymatic hydrolysis

Q24. If log(k/k0) versus σ* shows a strong linear correlation but adding Es improves the fit, what does this indicate?

• Electronic effects alone fully explain the reaction
• Both polar (σ*) and steric (Es) effects influence the reaction rate
• Steric effects can be ignored
• The data are invalid

Correct Answer: Both polar (σ*) and steric (Es) effects influence the reaction rate

Q25. Which of the following best describes how Es values are typically used in practical medicinal chemistry projects?

• As one quantitative descriptor among many for SAR and optimization of binding and metabolism
• As the sole determinant of oral bioavailability
• To predict protein secondary structure
• To determine exact binding free energy without experiments

Correct Answer: As one quantitative descriptor among many for SAR and optimization of binding and metabolism

Q26. Which of these substituents would you expect to have the smallest Es (least steric hindrance)?

• Tert-butyl
• Isopropyl
• Methyl
• Phenyl at α-position

Correct Answer: Methyl

Q27. How can computational methods complement experimental Es values?

• By estimating steric maps, molecular volumes or conformational ensembles to rationalize Es trends
• By completely replacing kinetic experiments with no validation
• By changing fundamental definitions of Es
• By predicting elemental composition only

Correct Answer: By estimating steric maps, molecular volumes or conformational ensembles to rationalize Es trends

Q28. In a Taft analysis, which axis would you use to plot substituent steric constants to obtain the steric sensitivity coefficient?

• Plot Es on the x-axis and log(k/k0) on the y-axis to obtain δ as the slope
• Plot temperature on the x-axis and Es on the y-axis
• Plot pH on the x-axis and log(k/k0) on the y-axis
• Plot σ* on the x-axis for steric sensitivity

Correct Answer: Plot Es on the x-axis and log(k/k0) on the y-axis to obtain δ as the slope

Q29. Which experimental strategy would best separate steric from electronic effects when designing a compound series?

• Vary substituents that change both size and electronics identically
• Design two parallel series: one varying steric bulk with similar electronics, another varying electronics with similar steric size
• Change only the solvent and ignore substituents
• Use only bulky substituents in all positions

Correct Answer: Design two parallel series: one varying steric bulk with similar electronics, another varying electronics with similar steric size

Q30. For a medicinal chemist, which combined use of parameters provides the most complete initial picture of substituent effects on reactivity?

• Only molecular weight and melting point
• Taft Es for sterics and σ* (or other electronic parameters) for polar effects
• Only partition coefficient (log P)
• Only infrared stretching frequencies

Correct Answer: Taft Es for sterics and σ* (or other electronic parameters) for polar effects

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