Computational Approaches for the Prediction of pKa Values  book cover
1st Edition

Computational Approaches for the Prediction of pKa Values

ISBN 9781138199910
Published October 18, 2017 by CRC Press
175 Pages 25 B/W Illustrations

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Book Description

The pKa of a compound describes its acidity or basicity and, therefore, is one of its most important properties. Its value determines what form of the compound—positive ion, negative ion, or neutral species—will be present under different circumstances. This is crucial to the action and detection of the compound as a drug, pollutant, or other active chemical agent. In many cases it is desirable to predict pKa values prior to synthesizing a compound, and enough is now known about the salient features that influence a molecule’s acidity to make these predictions.

Computational Approaches for the Prediction of pKa Values describes the insights that have been gained on the intrinsic and extrinsic features that influence a molecule’s acidity and discusses the computational methods developed to estimate acidity from a compound’s molecular structure. The authors examine the strengths and weaknesses of the theoretical techniques and show how they have been used to obtain information about the acidities of different classes of chemical compounds.

The book presents theoretical methods for both general and more specific applications, covering methods for various acids in aqueous solutions—including oxyacids and related compounds, nitrogen acids, inorganic acids, and excited-state acids—as well as acids in nonaqueous solvents. It also considers temperature effects, isotope effects, and other important factors that influence pKa. This book provides a resource for predicting pKa values and understanding the bases for these determinations, which can be helpful in designing better chemicals for future uses.

Table of Contents


Absolute pKa Calculations
Thermodynamic Cycles
Gas Phase Gibbs Free Energy Calculations
Solvation Gibbs Free Energy Calculations
Pitfalls and Lessons from the Literature
Concluding Remarks on Absolute pKa Calculations

Relative pKa Calculations

Quantitative Structure-Acidity Relationships (QSARs)
Basic Principles of the QSAR approach
Hammett and Taft Constants
The Search for Useful Quantum Chemical Descriptors
Alternative Approaches
Commercial and Free Programs

Oxyacids and Related Compounds
Alcohols, Phenols, and Carboxylic Acids
Phosphonic Acids
Hydroxamic Acids and Oximes

Nitrogen Acids
Aliphatic Amines
Azoles and Some Other Heterocyclics
Amino Acids
Pyridines and Related Heterocyclics
Purines and Pyrimidines

Additional Types of Acids
Carbon Acids
Inorganic Acids
Polyprotic Acids
Excited State Acids

Acids in Non-aqueous Solvents
Deuterium Oxide
Dimethyl Sulfoxide
Other Solvents and Commentary

Additional Factors Influencing Acidity and Basicity
Temperature Effects on Acidity
Steric Effects and Hydrogen Bonding
Isotope Effects


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George Shields, Ph.D., is currently a professor of chemistry and dean of the College of Arts and Sciences at Bucknell University. His research uses computational chemistry to investigate atmospheric and biological chemistry.

Paul Seybold, Ph.D., has been has been a faculty member and department chair (1999–2004) in the Department of Chemistry at Wright State University in Ohio and a visiting scholar and visiting professor at a number of universities in the United States and Europe. His research interests center on chemical and biochemical applications of quantum chemistry, molecular structure-activity relationships, luminescence spectroscopy, and cellular automata models of complex systems.