DFT STUDIES ON THE INTERACTIONS OF B-C59 NANOPARTICLE WITH CYCLOPHOSPHAMIDES

The structures of boron-doped fullerene B-C59 (1) as a drug delivery system, two derivatives of cyclophosphamide anticancer prodrug (2 and 3) as well as their covalently bonded structures 4 and 5 were optimized by DFT computations at B3LYP level of theory using 6-31G(d) basis set. Comparing compounds 4 and 5 reveals that the fluoro derivative (-22.8318 kcal/mol) is more stable than its chloro analogue (-22.0483 kcal/mol). The dipole moments of isolated drugs (~ 4.8, 5.2 D) have almost half values compared with those of their related compounds covalently bonded to the B-C59 (~ 9.7, 10.0 D) reflecting attachment of drugs on the B-C59 significantly enhances the polarity of the whole systems which is a desired property for drug delivery in biological media. The ΔGinteraction values are slightly more negative for compound 4 relative to 5 and the attachment of both drugs on the surface of B-fullerene is exergonic (ΔGinteraction 0) that means these are spontaneous reactions. Similarly, the ΔHinteraction values are negative for both compounds 4 and 5 reflecting these interactions are exothermic (ΔHinteraction 0). The density of states (DOS) spectra reveal that there are very strong hybridizations between the orbitals of B-C59 (1) and the drug molecules (2 and 3) so that they illustrate combinations of the spectra of both drugs and B-C59. Therefore, great interactions are happened quantitatively in terms of binding energies. The HOMO-LUMO band gaps of pristine B-C59 (1) and isolated drugs 2, 3 are near 2.3 and 2.7 eV, respectively while those of compounds 4, 5 are smaller (2.1 eV) indicating decrease in electrical conductivities of the isolated drugs/B-C59 upon interactions. The  values for 14N and 2H atoms are about 5 MHz and 255 KHz, respectively. The 35Cl and 37Cl nuclei exhibit NQCCs of about 70 and 55 MHz, respectively, with some greater values for compound 5 compared with those of 3. The oxygen atoms of P=O and P–O bonds display  values about 5.0 and 10.0 MHz, respectively