Quantitative Activity Structure Relationship (QSAR) of a Series of Azetidinones Derived from Dapsone by the Method of Density Functional Theory (DFT)

Abstract

This QSAR study, which involved a series of Azetidinones derived from 4,4'-diaminodiphenylsulfone (dapsone), yielded two models based on molecular descriptors and the antibacterial activities Escherichia coli and Staphylococcus aureus.The molecular descriptors were obtained by applying the methods of quantum chemistry at the B3LYP/6-31G (d) level. The statistical indicators of the first model which is a function of the Escherichia coli activity are: the coefficient of determination R<sup>2</sup> equals 0.992, the standard deviation S equals 0.342, the Fischer coefficient F equals 185.088 and the cross-validation coefficient Q<sup>2</sup><sub>CV</sub> equals 0.992. Those of the second model showing the activity of Staphylococcus aureus are: the regression coefficient R<sup>2</sup>= 0.987, a standard deviation S=0.193, the Fischer coefficient F=114.955 and the cross-validation coefficient Q<sup>2</sup><sub>CV</sub>= 0.987. These models have good statistical performances. The quantum descriptors of dipole moment (μ), global softness (σ) and electronegativity (χ) are responsible of the antibacterial activity of the Azetidinones derived from dapsone. In addition, the dipole moment is the priority descriptor for the prediction of the antibacterial activity of the studied compounds. The Eriksson et al. acceptance criteria used for the test set is verified. The values of the dtheo/dexp ratio of the theoretical and experimental activities for the test set tend towards unity.

Study of Reactivity and Molecular Stability by the Density Functional Theory Method on 2,3-Dihydro -1H-Perimidine: Comparative Analysis

“…However, the lowest vacant molecular orbital (LUMO) is perceived to be the lowest orbital containing free places that can accept electrons. These frontier orbitals therefore play an important role in the qualitative interpretation of chemical reactivity [19]. While the energy of HOMO is directly related to ionization potential, that of LUMO is directly related to electron affinity.…”

“…The energy difference between HOMO and LUMO, called the energy gap, is an important stability factor for structures. The energy difference (EHOMO-ELUMO) makes it possible to characterize the chemical reactivity and the kinetic stability of the molecule [19]. A molecule with a high energy difference (ΔE) is less polarizable and is generally associated with low chemical reactivity and high kinetic stability [20].…”

DFT Study of Molecular Stability and Reactivity on Some Hydroxamic Acids: An Approach by Hirshfeld Population Analysis

“…Some theoretical descriptors related to DFT have been predisposed to predict chemical reactivity. The energy of the lowest unoccupied molecular orbital (ELUMO), electronegativity (χ), the energy of the highest occupied molecular orbital (EHOMO), the softness (s), the hardness (η), and the electrophilicity ( ) [21]. These descriptors are all determined from the optimized molecules.…”

Combining of DFT and QSAR Results to Predict the Antibacterial Activity of a Series of Azetidinones derived from Dapsone as Inhibitors of Bacillus Subtilis and Pseudomonas Aeruginosa

“…Concerning all the studied descriptors, the analysis of the bivariate data, that is to say the calculation of the partial correlation coefficient between each of the pairs of the whole descriptors is (inferior) less than 0.70 (aij <0.70) , Which means that these different descriptors are independent from each other's [39,40].…”