Atomic physicochemical parameters for three-dimensional-structure-directed quantitative structure-activity...

Area of Science:

• Computational Chemistry
• Medicinal Chemistry
• Structure-Property Relationships

Background:

• Atomic physicochemical properties are essential for 3D-structure-directed quantitative structure-activity relationships (QSAR).
• Previous work demonstrated the development of atomic parameters to evaluate molecular hydrophobicity (water-1-octanol partition coefficient).

Purpose of the Study:

• To report atomic values for molar refractivity.
• To develop and validate atomic parameters for molar refractivity prediction.
• To analyze the relationship between molar refractivity and hydrophobicity parameters.

Main Methods:

• A constrained least-squares technique was employed to evaluate 93 atomic values from 504 molecules.
• The developed atomic parameters were used to predict molar refractivities for 78 compounds.
• Linear relationship between atomic water-1-octanol partition coefficients and molar refractivities was assessed using correlation coefficients.

Main Results:

• The evaluated atomic molar refractivity values yielded a standard deviation of 1.269 and a correlation coefficient of 0.994.
• Predictions of molar refractivities for 78 compounds showed a standard deviation of 1.614 and a correlation coefficient of 0.994.
• A low correlation coefficient (0.322) was found between atomic water-1-octanol partition coefficients and molar refractivities for 89 atom types.

Conclusions:

• The developed atomic molar refractivity parameters are reliable for predicting molecular molar refractivity.
• The low correlation between molar refractivity and hydrophobicity suggests their complementary roles in modeling intermolecular interactions.
• Further analysis of the origin and interaction modeling capabilities of these physicochemical properties is warranted.