2.1. Drug Design by Quantum Mechanical Calculations

All electronic calculations were carried out using Gaussian 09 program package [37]. The initial geometry of 3D structure of mitoxantrone (D) was taken from PubChem Open Chemistry Database [38]. The structure of mitoxantrone was fully optimized by density functional theory employing Becke's (B3) [39, 40] exchange functional combining Lee, Yang, and Parr's (LYP) correlation functional [41]. For all modified drug molecules (D1–D10), Cramer and Truhlar's MidiX basis set was employed [42]. MidiX basis set is originally developed from the Huzinaga MidiX basis and applied to H, C-F, S-Cl, Br, and I atoms. The MidiX basis set is comparatively smaller than the popular 6–31G(d,p) and can provide excellent geometries and charge balances with reasonable computational time and accuracy [43].

After optimization, subsequent vibrational frequency calculation was performed in order to confirm that the stationary points correspond to minima on the potential energy surface. Electronic energies, enthalpies, Gibb's free energies, dipole moments, and partial charge analysis were also explored for all optimized-energy geometries. Molecular orbital calculations were performed at the same level of theory. Hardness and softness of all drugs were also determined from the energies of frontier HOMOs and LUMOs. Considering Parr and Pearson interpretation [43–45] of DFT and Koopmans theorem [46] on the correlation of ionization potential (I) and electron affinities (E) with HOMO and LUMO energies (ε), hardness (η) and softness (S) of the drugs were calculated according to the following equation: