Related Experiment Video
Updated: Jun 4, 2025
11:00
Determination of the Gas-phase Acidities of Oligopeptides
Published on: June 24, 2013
11.1K
Comparison of Orthogonal Determination Methods of Acid/Base Constants with Meta-Analysis
Tamás Pálla1,2, Károly Mazák1,2, Dania Mohammed Alkhazragee1,2
1Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre utca 9, 1092 Budapest, Hungary.
International Journal of Molecular Sciences
|December 17, 2024
Summary
Accurate determination of acid/base constants is crucial for drug design. This study compares potentiometry and NMR titrations, finding NMR a reliable alternative for physicochemical characterization.
Area of Science:
- Analytical Chemistry
- Physical Chemistry
- Medicinal Chemistry
Background:
- Acid/base constants (pKa, log K) are vital for molecular physicochemical characterization.
- These constants significantly impact drug pharmacokinetics and pharmacodynamics.
- Potentiometric titration is the gold standard, but NMR titrations offer complementary structural insights.
Purpose of the Study:
- To conduct a meta-analysis of protonation constants from literature.
- To compare data obtained via potentiometry and NMR titrations.
- To assess the reliability and applicability of NMR titrations versus potentiometry.
Main Methods:
- Comprehensive literature data compilation for protonation constants.
- Comparative analysis of potentiometric and NMR titration results.
- Consideration of experimental variables like temperature and ionic strength.
Main Results:
- Assessed agreement between potentiometry and NMR titration methods.
- Evaluated the influence of experimental conditions on data consistency.
- Provided insights into the reliability of NMR titrations.
Conclusions:
- NMR titrations are a powerful alternative to potentiometry for determining acid/base constants.
- Results guide the selection of appropriate methods in drug design and development.
- This meta-analysis enhances understanding of spectroscopic techniques in analytical chemistry.
Related Concept Videos
01:30Titration of a Weak Acid with a Strong Base
2.1K
In titrating a weak acid with a strong base, different calculation methods are applied at various stages. Initially, the pH of a weak acid like acetic acid is calculated using its dissociation constant (Ka) and an ICE table. Upon addition of a strong base such as sodium hydroxide, a buffer forms, and its pH is determined using the Henderson-Hasselbalch equation. As more base is added and the titration reaches the halfway point, the pH becomes equal to the pKa of the acid, indicating equal...
2.1K
01:08Titration of a Weak Acid with a Weak Base
2.6K
Weak acids and bases do not undergo dissociation completely, and titrations between these two are rarely studied. When such studies are performed, say, for the titration of a weak acid with a weak base, the titration curve plots the change in pH as a function of the volume of base added. Take the titration of acetic acid with ammonia, for instance. During the titration, these two species form ammonium acetate and water, but the pH change is slow and gradual.
As a result, there is no simple...
As a result, there is no simple...
2.6K
01:17Solution Composition During Acid/Base Titrations
561
The titration of a weak acid with a strong base results in the formation of water and the conjugate base of the acid. For instance, titrating acetic acid with sodium hydroxide leads to the formation of water and sodium acetate. A solution of acetic acid and sodium acetate constitutes a buffer whose relative concentration at different stages of the titration is indicated by the α values, which represent percentages of the weak acid and its conjugate base.
The α0 and α1 values...
The α0 and α1 values...
561
02:29Relative Strengths of Conjugate Acid-Base Pairs
45.3K
Brønsted-Lowry acid-base chemistry is the transfer of protons; thus, logic suggests a relation between the relative strengths of conjugate acid-base pairs. The strength of an acid or base is quantified in its ionization constant, Ka or Kb, which represents the extent of the acid or base ionization reaction. For the conjugate acid-base pair HA / A−, the ionization equilibrium equations and ionization constant expressions are
45.3K
03:02Acid/Base Strengths and Dissociation Constants
60.2K
The relative strength of an acid or base is the extent to which it ionizes when dissolved in water. If the ionization reaction is essentially complete, the acid or base is termed strong; if relatively little ionization occurs, the acid or base is weak. There are many more weak acids and bases than strong ones. The most common strong acids and bases are listed below:
60.2K
01:16Titration in Nonaqueous Solvents
728
Most acid-base titrations are performed in an aqueous medium. In aqueous titrations, water competes with weaker acids or bases for proton donation or acceptance, leading to ambiguous endpoints in the titration curve. Water also affects the partial ionization of weak acids or bases. For example, water accepts a proton from acetic acid to form hydronium and acetate ions. The hydronium ion formed is a stronger acid than acetic acid, and the acetate ion is a stronger base than water. As a result,...
728