*3.2.1 Quantum–chemical approach and basis set selection for the description of the geometries of nitrofurans*

The advantage in using the PCA and HCA techniques in this step was that all structural information are considered simultaneously and it takes into account the correlations among them. **Table 1** shows the theoretical and experimental structural information (bond lengths and bond angles) of the geometry of the 5-nitrofuran-2-aldoxim molecule. It was used with the aim to select using PCA and HCA techniques, which quantum–chemical approach and basis set give results closest to the experimental data [72].

The first two principal components explain 86.02% of the original information as follows: PC1 = 58.01% and PC2 = 28.02%. The PC1 versus PC2 scores plot is shown in **Figure 4**, from which it can be seen that the methods are discriminated into two classes according to PC2. The semiempirical approaches (AM1 and PM3) are at the top of the graph, while the other theoretical (HF, BLYP, and B3LYP) approaches and experimental data are at the bottom. Moreover, it can be seen that the HF/6-31G approach/basis set is the closest to the experimental data, indicating that they should be used in the development of this work.

Also, to investigate the most appropriate approach and basis set for further calculations, we used HCA. **Figure 5** shows the dendrogram obtained with complete linkage method; from this figure, we conclude that the theoretical approaches are distributed in a similar way as in PCA, i.e., HCA confirmed the PCA results. Moreover, we can observe that the HF/6-31G approach/basis set is closer to the experimental data therefore being the most suitable to carry out this work.

#### *3.2.2 MEP maps for compounds of the training set*

**Figure 6** shows the MEP maps for the nitrofurans in the training set. The analysis of these maps reveals that the most active compounds, in general, have the following characteristics:

(i) Compounds with an unsaturation and presenting O atom neighboring the carbonyl in the carbonic chain present greater electron density in the proximities of the furan ring with the decrease of the chain size. In these compounds (**4, 5,** and **6**), MEP

**55**

**Approaches/basis set**

**Geometric parameters** Bond length (Å)

C C2 3 C4C5 C C1 2 C O1 1 C O4 1 C N4 1

N

N

C C1 5 C N5 2

N

O

H4 1 Bond angle (°)

C O1 C1 4 O C1 C1 2 O C1 C1 5 C C5 C1 2 C N5 O2 2 C O1 C1 4

N

O2 H4 1

100.7

100.8

103.6

102.7

99.3

99.8

102.0

101.6

102.4

103.7

102.1

106.9

115.2

116.7

112.2

107.9

110.0

109.5

110.6

107.1

109.2

108.5

109.8

108.8

109.6

111.2

111.4

122.8

120.4

127.8

121.2

120.6

121.8

121.3

121.2

120.7

121.9

121.4

122.0

120.9

120.1

121.7

129.7

128.8

135.6

131.2

131.0

130.9

130.4

131.3

131.1

131.1

130.5

131.3

130.9

130.6

130.9

119.5

120.4

114.1

119.3

118.7

119.8

119.5

119.2

118.8

119.7

119.6

119.5

119.4

118.5

119.8

110.6

110.7

110.2

109.5

110.2

109.2

110.1

109.5

110.0

109.2

109.9

109.1

109.6

110.7

109.4

105.2

106.0

104.8

105.3

105.6

106.0

106.1

104.7

105.3

105.5

105.8

105.4

106.3

105.8

106.9

105.3

106.3

104.5

1.47

1.40

1.44

1.39

1.50

1.42

1.47

1.41

1.44

1.37

1.40

1.36

1.31

1.39

1.38

O2 4

1.29

1.28

1.29

1.28

1.32

1.31

1.31

1.30

1.26

1.25

1.26

1.25

1.31

1.29

1.27

1.43

1.44

1.43

1.44

1.44

1.45

1.44

1.45

1.45

1.46

1.45

1.46

1.45

1.45

1.45

1;29

1.23

1.27

1.23

1.32

1.26

1.30

1.26

1.26

1.20

1.23

1.20

1.20

1.22

1.22

O1 3

1.28

1.23

1.26

1.23

1.31

1.25

1.29

1.25

1.24

1.19

1.22

1.19

1.19

1.21

1.22

O1 2

1.41

1.43

1.41

1.43

1.43

1.44

1.43

1.48

1.40

1.43

1.41

1.42

1.46

1.47

1.42

1.41

1.43

1.41

1.43

1.43

1.44

1.43

1.49

1.40

1.43

1.40

1.42

1.45

1.48

1.42

1.38

1.35

1.38

1.35

1.41

1.37

1.40

1.37

1.36

1.37

1.35

1.33

1.40

1.38

1.35

1.40

1.37

1.39

1.36

1.42

1.39

1.42

1.38

1.37

1.39

1.37

1.33

1.34

1.37

1.37

1.38

1.38

1.38

1.38

1.39

1.39

1.40

1.39

1.35

1.35

1.35

1.35

1.33

1.38

1.36

1.36

1.36

1.37

1.37

1.38

1.38

1.39

1.38

1.34

1.39

1.34

1.34

1.40

1.39

1.34

1.42

1.42

1.42

1.42

1.43

1.47

1.43

1.42

1.43

1.43

1.43

1.43

1.43

1.43

1.41

**B3LYP/6-**

**B3LYP/6-**

**B3LYP/6-**

**B3LYP/6-**

**BLYP/6- 21G**

**BLYP/6- 21G\***

**BLYP/6- 31G**

**BLYP/6- 31G\***

**HF/6- 21G**

**HF/6- 21G\***

**HF/6- 31G**

**HF/6- 31G\***

**AM1**

**PM3**

**Exp [72]**

> **21G**

**21G\***

**31G**

**31G\***

*Molecular Electrostatic Potential and Chemometric Techniques as Tools to Design Bioactive…*

*DOI: http://dx.doi.org/10.5772/intechopen.89113*


#### *Molecular Electrostatic Potential and Chemometric Techniques as Tools to Design Bioactive… DOI: http://dx.doi.org/10.5772/intechopen.89113*

*Cheminformatics and Its Applications*

each compound was carried out with the MM+

*of the geometries of nitrofurans*

closest to the experimental data [72].

that they should be used in the development of this work.

*3.2.2 MEP maps for compounds of the training set*

following characteristics:

**3.2 Results and discussion**

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

conformation was submitted to a conformational search with the Gaussian program.

The advantage in using the PCA and HCA techniques in this step was that all structural information are considered simultaneously and it takes into account the correlations among them. **Table 1** shows the theoretical and experimental structural information (bond lengths and bond angles) of the geometry of the 5-nitrofuran-2-aldoxim molecule. It was used with the aim to select using PCA and HCA techniques, which quantum–chemical approach and basis set give results

The first two principal components explain 86.02% of the original information as follows: PC1 = 58.01% and PC2 = 28.02%. The PC1 versus PC2 scores plot is shown in **Figure 4**, from which it can be seen that the methods are discriminated into two classes according to PC2. The semiempirical approaches (AM1 and PM3) are at the top of the graph, while the other theoretical (HF, BLYP, and B3LYP) approaches and experimental data are at the bottom. Moreover, it can be seen that the HF/6-31G approach/basis set is the closest to the experimental data, indicating

Also, to investigate the most appropriate approach and basis set for further calculations, we used HCA. **Figure 5** shows the dendrogram obtained with complete linkage method; from this figure, we conclude that the theoretical approaches are distributed in a similar way as in PCA, i.e., HCA confirmed the PCA results. Moreover, we can observe that the HF/6-31G approach/basis set is closer to the experimental data therefore being the most suitable to carry out this work.

**Figure 6** shows the MEP maps for the nitrofurans in the training set. The analysis of these maps reveals that the most active compounds, in general, have the

(i) Compounds with an unsaturation and presenting O atom neighboring the carbonyl in the carbonic chain present greater electron density in the proximities of the furan ring with the decrease of the chain size. In these compounds (**4, 5,** and **6**), MEP

*3.2.1 Quantum–chemical approach and basis set selection for the description* 

algorithm [79], and the lowest energy

**54**


**Table 1.**

**57**

**Figure 4.**

**Figure 5.**

*semiempirical and semiempirical not.*

*semiempirical and semiempirical not.*

*Molecular Electrostatic Potential and Chemometric Techniques as Tools to Design Bioactive…*

*Score plots of the two first PCs, PC1 and PC2, for the separation of the approaches basis sets into classes:* 

maps show negative regions ranging from −82.99 to −4.87 kcal/mol. In the most active compound (**6**), as can be seen, the most negative values are in the nitro group, the O atom of the furan ring and the O atoms of the ester group (red and yellow). Also, the MEP maps of these compounds exhibit positive regions between the +4.54 and + 76.96 kcal/ mol values (green and blue). Compounds with double unsaturation, containing N atom next to the carbonyl, raise the electronic density with the increase of the carbonic chain. In the most active compound (**7**), the MEP map shows a region of negative values between −77.74 and − 1.31 kcal/mol, with the electron density concentrating mainly on the atoms of the nitro group, on the O atom of the furanic ring and on the N and O atoms of the amide group (red and yellow). According to the MEP map, these compounds pres-

*Dendrogram obtained with HCA technique for the separation of the approach basis set into two classes:* 

(ii) Compounds with double unsaturation, containing O atom neighboring the carbonyl, raising the carbon chain, increase the electron density in the atoms of the

ent positive MEP between +5.64 and 61.21 kcal/mol (green and blue).

*DOI: http://dx.doi.org/10.5772/intechopen.89113*

*Experimental and theoretical structural parameter of the 5-nirofuran-2-aldoxime.*
