## 3 Results and Discussion
### Chemical Reactivity Parameters and Charge Transfer Descriptor  
Once the most stable conformation and the schematic structure of the active site between NtMGAM and ligands (ACA, MAY, and LUT) were defined, an analysis of reactivity in each ligand was carried out by means of the chemical reactivity descriptors, namely, the ionization potential (IP), electron affinity (EA), chemical hardness (\(\eta\)), electronegativity (\(\chi\)), electrophilicity (\(\omega\)) and chemical potential (\(\mu\)). The values of these properties are shown in Table 2. As can be seen, the highest value of EA is 1.80 eV corresponding to the MAY ligand, which means that it forms an anion easier than the other ligands. On the opposite, according to the IP values reported, the ligand most prone to lose electrons was LUT with 6.35 eV. According to the \(\eta\) value of 2.27 eV, the MAY molecule could interact stronger with NtMGAM than the other compounds studied here. The chemical potential (\(\mu=-\chi\)) represents the tendency of a molecule to attract or transfer electrons. This is an important parameter in the calculation of the charge transfer descriptor. Electronegativity values were reported suggesting that MAY (\(\chi=4.07\) eV) has the highest tendency to attract electrons. Electrophilicity (\(\omega\)) represents the stabilization energy when a system is saturated by the surrounding electrons. According to our results, MAY has the highest electrophilicity, which is in accordance with the highest binding energy for the MAY-NtMGAM coupling obtained by molecular docking. The \(\mu\) and \(\eta\) were calculated in all the residues involved in the active site of the analyzed protein. In the same way, the charge transfer between the ligands and the amino acids was determined with the charge transfer parameter (\(\Delta\)N) (see Equation (4)). The values of \(\mu\), \(\eta\), and \(\Delta\)N are shown in Table 3. According to the notation employed in Equation (4), \(\mu_{A}\) is the chemical potential of the ligands ACA, MAY, and LUT; and \(\mu_{B}\) is the chemical potential for the amino acids of the active site. Similarly, \(\mu_{A}\) and \(\eta_{B}\), represent the chemical hardness values for ligands and amino acids of the active site, respectively [46]. \(\Delta\)N represents the fraction of the transferred electron from one system to another [46]. These kinds of interactions are primary indicators of specificity, rate control, and reversibility in many biochemical reactions [72]. Additionally, this is a first step to understand the oxidative damage process in the active site produced by the ACA, MAY, and LUT ligands, allowing for identifying their behavior and biological activity with the NtMGAM. The characterization of oxidative damage by the charge transfer values had been previously used by some authors, in order to describe the oxidative and reductive reactions in other molecular systems as DNA bases [45; 46]. A positive value of \(\Delta\)N indicates that the ligand acts as an electron acceptor, while a negative value of \(\Delta\)N indicates that the ligand acts as an electron donor. Therefore, the ACA in the presence of the amino acids Asp203, Thr205, Asp327, Asp443-Met44, and Asp542, acted as an electron acceptor, while with the rest of the amino acids, it worked as an electron donor. Furthermore, the MAY molecule in presence of all amino acids behaved as an electron donor. Finally, the LUT ligand in the presence of all amino acids acted as an electron acceptor. Hence, the oxidative damage in the active site decreases in the order LUT > MAY > ACA. \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline
**Ligand** & **EA** & **IP** & \(\eta\) & \(\chi\) & \(\omega\) & \(\mu\) \\ \hline ACA & 0.21 & 6.14 & 2.97 & 3.17 & 1.70 & \(-\)3.17 \\ MAY & 1.80 & 6.34 & 2.27 & 4.07 & 3.65 & \(-\)4.04 \\ LUT & 1.70 & 6.35 & 2.32 & 4.03 & 3.49 & \(-\)4.03 \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Reactivity parameters of docked ligands at M06/6-31G(d) level theory.