Evaluating hydrogen-bond donor strength.

Area of Science:

• Physical Chemistry
• Computational Chemistry
• Drug Discovery

Background:

• Accurate modeling of biological interactions requires understanding solute properties like hydrogen-bond donor (HBD) strength.
• Solvent choice significantly influences solute partitioning and interaction modeling.
• Octanol and chloroform are common solvents with distinct properties affecting solute interactions.

Purpose of the Study:

• To develop a quantitative parameter for measuring the hydrogen-bond donor (HBD) strength of solutes.
• To establish a method for modeling biological interactions based on solute HBD strength.
• To compare the HBD donating capabilities of various solutes using a novel parameter.

Main Methods:

• Utilizing the partitioning of solutes between octanol and chloroform (log P(oct) and log P(clf)).
• Accounting for solute excess alkane affinity (XAA) and molecular volume.
• Calculating the difference between log P(oct) and log P(clf) to determine the effective HBD sum, termed epsilon alpha.

Main Results:

• Octanol's HBA oxygen and alkane character favor solutes with HBD groups and excess alkane affinity.
• Chloroform's lower cavity formation energy favors larger solutes.
• The parameter epsilon alpha effectively measures the sum of HBD, correlating with Abraham's operator alpha(2)(H).

Conclusions:

• The epsilon alpha parameter provides a reliable measure of solute HBD strength.
• This parameter aids in predicting and modeling solute behavior in biological systems.
• The findings offer a refined approach to understanding solute-solvent interactions and their biological implications.