EFFECT OF CARBOXYL AND CARBOXAMIDE SUBSTITUENT GROUPS ON FLUORINATED PYRAZINE SPECIES WITH ANTITUBERCULAR ACTIVITIES

The NBO study reveals the high stability of the acid species due to the two DET and DET interactions not observed in the amide LP* LP LP* species. The AIM analysis supports the high stabilities of both C2 conformers due to the halogen bonds formation where the topological properties are higher for the acid species, in very good concordance with the higher total energy observed by NBO calculations. The frontier orbitals predict a higher reactivity for the amide species while the descriptors evidence the higher nucleophilicity and electrophilicity indexes for the acid species. On the other hand, the C2-N3 stretching mode in FP is predicted at higher wavenumbers than pyrazine while in the acid and amide species this stretching mode is predicted with partial double bond at lower wavenumbers. The tentative assignments for the acid and amide species were performed. The force constants calculated show strongly dependence from their geometrical parameters. Maximiliano A. Iramain Cátedra de Química General, Instituto de Química Inorgánica, Facultad de Bioquímica. Química y Farmacia, Universidad Nacional de Tucumán, Ayacucho 471, (4000) San Miguel de Tucumán, Tucumán, Argentina Silvia Antonia Brandán Cátedra de Química General, Instituto de Química Inorgánica, Facultad de Bioquímica. Química y Farmacia, Universidad Nacional de Tucumán, Ayacucho 471, (4000) San Miguel de Tucumán, Tucumán, Argentina www.worldwidejournals. com 613 Figure 1. Theoretical structures of pyrazine, F-pyrazine, 3fluoropyrazine-2-carboxilic acid and 3-fluoropyrazine-2carboxamide in gas phase by using the hybrid B3LYP/6-311++G** level of theory. RESULTS AND DISCUSSION OPTIMIZATIONS IN GAS PHASE The calculated total energies, dipole moments and volume variation for the two optimized P structures, FP and, the two C1 and C2 conformers of FPCOOH and FPCONH can be seen in Table 2 1 while in Figure 2 are represented the modifications observed on these properties when the F atom is incorporated to pyrazine ring and, then when the COOH and CONH groups are incorporated to 2 fluoropyrazine. Obviously, the energies values increase with the group, as expected because increase the numbers of atoms while, for both pyrazine species the energies are the same independently of the symmetry. In relation to the dipole moment values the carboxylic species present the higher value, being C2 the most voluminous species of FPCOOH while for FPCONH the higher 2 volume is observed for C1. Note that both most stable C2 conformations of FPCOOH and FPCONH have the higher dipole 2 moment values, as also was observed in other species [33-37]. This way, such observations could probably be related to the higher stabilities of the species as a consequence of their higher dipole moments. On the other side, pyrazine has dipole moment null and when the F atom is incorporate to the ring structure clearly increases the dipole moment of pyrazine to 1.70 D. Figure 3 shows the orientations and magnitudes of the vectors corresponding to the dipole moments of FP, FPCOOH and FPCONH species where we can easily observe the change in size 2 and direction, especially when the group change from FP to FPCOOH and from FPCOOH to FPCONH . The higher dipole 2 moment value observed for the carboxylic acid species can be explained because the electronegativity of OH group is between 3.51 [38] and 2.68 [39] where for the carboxy group it is reported values between 3.49 [38] and 2.8 [39] while the amino group present lower values, which are between 2.61 [38] and 2.42 [39]. These results show clear structural differences between the acid and amide species being the C2 conformer of FPCOOH most polar and voluminous. When the populations are analyzed from Table 1 we observed that the energies differences existent between both conformers of FPCOOH and FPCONH are high and, as a 2 consequence only the C2 conformers are expected in both species. Figure 2. Calculated total energies, dipole moments and volume variation for the pyrazine, F-pyrazine, 3-fluoropyrazine-2carboxilic acid and 3-fluoropyrazine-2-carboxamide structures in gas phase by using the hybrid B3LYP/6-311++G** level of theory. TABLE  1 Calculated total energies (E), dipole moments (μ), volume and populations for pyrazine (P), F-pyrazine (FP), 3-fluoropyrazine-2carboxilic acid (FPCOOH) and 3-fluoropyrazine-2-carboxamide (FPCONH ) in gas phase. 2 Figure 3. Orientations and magnitudes of the vectors corresponding to the dipole moments of FP, FPCOOH and FPCONH species in gas phase by using the hybrid B3LYP/62 311++G** level of theory. PARIPEX INDIAN JOURNAL OF RESEARCH Volume-6 | Issue-9 | September-2017 | ISSN 2250-1991 | IF : 5.761 | IC Value : 79.96 B3LYP/6-311++G** method Species E (Hartrees) E (kJ/mol) μ (D) V 3 ( ) Pop % P (D ) 2h -264.3873 0.00 0.0 77.7 100 P (C ) S -264.3873 0.0 78.4 FP -363.3611 0.00 1.70 86.8 100 Acid C1 -552.2794 22.58 4.87 117.5 0.0 Acid C2 -552.2880 0.00 6.25 120.2 100 Amide C1 -532.4131 14.43 2.69 124.6 0.3 Amide C2 -532.4186 0.00 5.44 116.7 99.7 614 www.worldwidejournals. com PARIPEX INDIAN JOURNAL OF RESEARCH Volume-6 | Issue-9 | September-2017 | ISSN 2250-1991 | IF : 5.761 | IC Value : 79.96 www.worldwidejournals. com 615 Parameters a B3LYP/6-311++G** Pyrazincarboxamide Pyrazine F-pyrazine F-pyrazine-2-carboxil acid F-pyrazine-2-carboxamide form δ form C1 C2 C1 C2 b Exp c Exp