Quantum-Chemical Parameters for Studying the Structure – Ionization-Constant Relationship of N-Substituted Mono(Di)Halo(H)Anthranilic Acids and Their Amides and Hydrazides

Accurate Estimation of pKb Values for Amino Groups from Surface Electrostatic Potential (VS,min) Calculations: The Isoelectric Points of Amino Acids as a Case Study

“…Therefore, accurately characterizing this H-bond can be helpful in accurately predicting the corresponding equilibrium constants. The idea that the formation of a hydrogen bond is the first step to occur during an acid−base equilibrium has led to density functional theory (DFT) calculations being performed with explicit water molecules interacting with the solute, 15,16 as well as multicomponent regression models involving various quantum chemical descriptors, 17,18 genetic algorithms, 19 combined DFT-molecular dynamics (MD) simulations, 20,21 general QM/MM hybrid methods, 2222 or continuous constant pH MD simulations. 23 These linear and multiple regression methods have been previously employed to correlate molecular quantum-chemical quantities calculated at the DFT level with other thermodynamic equilibrium constants beyond pK a like the octanol/water partition coefficients, Log P. 24 Dissociation of a protic acid in water occurs initially through the formation of a hydrogen-bonded species between the acid and the solvent, and similarly, the abstraction of a proton from the hydronium cation by a Lewis base will initiate with their interaction via a H-bond.…”