# F127/Cisplatin Microemulsions: _In Vitro_, _In Vivo_ and Computational Studies
## 3 Results and Discussion
### Computational Results: The Interplay between Cis and Surfactant F127
Moreover, the distribution of HOMO on complex **B** has more \(\pi\) character in comparison to other complexes. As said, this complex has the largest binding energy among other complexes. It seems that this distribution of HOMO, which refers to division of electron charges, has an effect on the formation of stable complex **B** via HB interaction between Cis and atom O\({}_{6}\) of F127. Due to the important role of electron charge distribution on the stability of the drug-surfactant systems, it is necessary to survey atomic charges on the complexes and also free molecules Cis and F127. Results reveal that there is an overall CT in the complexes from F127 to Cis. The magnitude of negative charge that transfers to Cis is \(-0.046\), \(-0.009\), and \(-0.060\) e in the complexes **A**, **B**, and **C**, respectively. As can be seen, a decrease in the absolute value of such CT is consistent with an increase in the binding energies of the complexes. Thus, as the CT diminishes, the stability of the current drug-surfactant system increases. Charges of atoms that contribute to HB interactions are presented in Table 2 and denoted with q\({}_{\text{O}}\), q\({}_{\text{H}}\), and q\({}_{\text{N}}\). As can be seen, q\({}_{\text{O}}\) and q\({}_{\text{N}}\) values in the corresponding complexes are more negative than those in free molecules. Additionally, the positive value of q\({}_{\text{H}}\) is amplified with complex formation. Results indicate that the sum of q\({}_{\text{O}}\), q\({}_{\text{H}}\), and q\({}_{\text{N}}\) has a linear relation with the stability of the complexes. The sum of mentioned charges is \(-0.868\), \(-1.026\), and \(-1.047\) e in complexes **A**, **B**, and **C**, respectively. In fact, a decrease in the sum of negative charge on atoms involved in HB interaction is followed by the rise  
Figure 8: Distribution of HOMO and LUMO on the complexes. of stability of the complexes. Moreover, an increase in the positive value of \(\mathrm{q_{H}}\) in the complexes is associated with the increase of such stability. This outcome highlights the role of HB donors in the formation of stable drug-surfactant systems. Population analysis was surveyed using the NBO method to better understand electron charge transfer between molecular orbitals of HB donor and HB acceptor in the complexes. Thus, we calculated donor-acceptor stabilization energies (E(2) values) for the LpO to \(\sigma^{*}_{\mathrm{NH}}\) interaction. The E(2) value for this electron charge transfer is 19.87, 23.55, and 5.74 kcal mol\({}^{-1}\) in complexes **A**, **B**, and **C**, respectively. As can be seen, the trend of E(2) values is the same as that of the complexes' stability. As a result, electron charge transfer from lone pair of oxygen atom (LpO) of F127 to the anti-bonding molecular orbital of N-H (\(\sigma^{*}_{\mathrm{NH}}\)) in Cis has an effective role on the stability of the current drug-surfactant system. Topological properties of the complexes have been planned by the AIM method. The molecular graphs involving bond critical points (BCPs) and bond paths are shown in Figure 9. As can be observed, there are two weak HB interactions (C-H\(\cdots\)Cl) in complex **A**. The electron charge density values at BCPs of these interactions (\(\mathrm{\rho_{BCP}}\)) are 2.89 \(\times\) 10\({}^{-3}\) and 7.50 \(\times\) 10\({}^{-3}\) au. The \(\mathrm{\rho_{BCP}}\) value at the main HB is 3.93 \(\times\) 10\({}^{-2}\) au. Additionally, there are two weak HB interactions in complex **C** due to tendencies of both ammonia groups of Cis to atom O\({}_{7}\) of F127. The \(\mathrm{\rho_{BCP}}\) values related to these interactions are 1.69 \(\times\) 10\({}^{-2}\) and 1.57 \(\times\) 10\({}^{-2}\) au. However, interaction in complex **B** does not include any weak HB, and this complex has the larger binding energy. The \(\mathrm{\rho_{BCP}}\) value at HB interaction of this complex is 4.35 \(\times\) 10\({}^{-2}\) au. Hence, it can be suggested that the magnitudes of \(\mathrm{\rho_{BCP}}\) values directly influence the complexes' stability.