Computational Approaches for the Prediction of pKa Values (QSAR in Environmental and Health Sciences)

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. Content: Introduction 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 Silanols Thiols Nitrogen Acids Aliphatic Amines Anilines Azoles and Some Other Heterocyclics Amino Acids Pyridines and Related Heterocyclics Purines and Pyrimidines Additional Types of Acids Carbon Acids Inorganic Acids Polyprotic Acids Superacids Excited State Acids Acids in Non-aqueous Solvents Deuterium Oxide Dimethyl Sulfoxide Acetonitrile Tetrahydrofuran 1,2-Dichloroethane Other Solvents and Commentary Additional Factors Influencing Acidity and Basicity Thermodynamics Temperature Effects on Acidity Steric Effects and Hydrogen Bonding Isotope Effects Conclusions Abstract: "The book describes how one can calculate the acidities and basicities of chemicals (pKa is the dissociation constant). Many drugs, industrial chemicals, biochemicals and pollutants dissociate to form new species under different conditions. The nature of the species present has a profound effect on how the species act, and it is important to be able to estimate which species will be present under different conditions. No other book summarizes how one can estimate the natures of the species present using modern theoretical methods. This book fills that need" "The pK[indice inférieur a] 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 pK[indice inférieur a] 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."--[Source inconnue] "The book describes how one can calculate the acidities and basicities of chemicals (pKa is the dissociation constant). Many drugs, industrial chemicals, biochemicals and pollutants dissociate to form new species under different conditions. The nature of the species present has a profound effect on how the species act, and it is important to be able to estimate which species will be present under different conditions. No other book summarizes how one can estimate the natures of the species present using modern theoretical methods. This book fills that need"-- Provided by publisher "The book describes how one can calculate the acidities and basicities of chemicals (pKa is the dissociation constant). Many drugs, industrial chemicals, biochemicals and pollutants dissociate to form new species under different conditions. The nature of the species present has a profound effect on how the species act, and it is important to be able to estimate which species will be present under different conditions. No other book summarizes how one can estimate the natures of the species present using modern theoretical methods. This book fills that need"-- Read more...