*3.1.3.1 Theoretical approach and basis set used in the molecular calculations*

In the calculations with the nitrofuran compounds (**Figure 1**), quantum–chemical approaches were used [81–87]. We use Becke's three-parameter hybrid methods [81], the Lee-Yang-Parr (LYP) correlation functional [82], B3LYP and Becke's 1988 functional (BLYP) [83], Hartree-Fock (HF) method [84], Austin model 1 (AM1) method [85], Parametric Method Number 3 (PM3) [86], and standard basis sets [87] available in the Gaussian program package. In 5-nitrofuran-2-aldoxim, geometry optimization was carried out by B3LYP/6-21G, B3LYP/6-21G\*, B3LYP/6-31G, B3LYP/6-31-G\*, BLYP/6-21G, BLYP/6-21G\*, BLYP/6-31G, BLYP/6-31G\*, HF/6- 21G, HF/6-21G\*, HF/6-31G, and HF/6-31G\* approaches [81–84] and basis sets [87] and AM1 and PM3 approaches [85, 86] . The calculations were performed to find the approach and basis set that would present the best compromise between

*Cheminformatics and Its Applications*

set as implemented in the Gaussian program package. The electrostatic potential is obtained through the calculation of a set of punctual atomic charges so that it represents the possible best quantum molecular electrostatic potential for a set of points defined around the molecule [76, 77]. The charges derived from electrostatic potential present the advantage of being, in general, physically more satisfactory than the charges of Mülliken [78], especially with regard to biological activity. The quantum–chemical descriptors employed and obtained with the Gaussian 98 program package [69] were total energy of molecules (TE), highest occupied molecular orbital (HOMO) energy, one level below to highest occupied molecular orbital (HOMO–1) energy; lowest unoccupied molecular orbital (LUMO) energy, one level about lowest unoccupied molecular orbital (LUMO+1) energy, HOMO energy–LUMO energy (gap energy), total dipole moment (μ), Mulliken's electronegativity (χ), atomic charges on the Nth atom (QN), molecular hardness (HD),

The physicochemical descriptors obtained with ChemPlus module [79] were total surface area (TSA), molecular volume (VOL), molecular refractivity (MR),

Molecular holistic (MH) descriptors were included with the purpose of representing different sources of chemical information in terms of molecular size, symmetry, and distribution of atoms in molecules. Also, we include topologic indices, connectivity indices, geometric descriptors, 3D-MoRSE descriptors, and Moriguchi octanol–water partition coefficient (MlogP). These descriptors were calculated with

**52**

**Figure 2.**

and molecular softness (MS).

the Dragon software [80].

and molecule hydration energy (MHE).

*2D molecular structure for nitrofurans (training set).*

computational time and accuracy of the information relative to the experimental data. The experimental structure of 5-nitrofuran-2-aldoxim molecule was retrieved from the Cambridge Structural Database CSD [72]. PCA and HCA techniques were used to compare the computed structures with different methods/basis sets of quantum chemistry with the experimental structure of 5-nitrofuran-2-aldoxim molecule to identify the appropriate method and the basis set for further calculations. The analyzes were carried out on an auto-scaled data matrix with dimension 26 × 5, where each row was associate 26 computed and 1 experimental geometry, and each column represented one of 5 geometrical parameters of the 5-nitrofuran-2-aldoxim molecule (bond lengths and bond angles). In order to compute all structures and perform calculations to obtain the molecular properties, the HF/6-31G method has selected (see Results and discussion section); the initial geometries of the nitrofurans (**Figures 2** and **3**) were built with the optimized geometry of the 5-nitrofuran-2-aldoxim molecule selected by PCA and HCA techniques. A conformational analysis for each compound was carried out with the MM+ algorithm [79], and the lowest energy conformation was submitted to a conformational search with the Gaussian program.

## **3.2 Results and discussion**
