Bonding of Phosphoramides onto B-C59 Nanostructure as Drug Delivery Systems

The structures of boron-doped fullerene B-C59 (1), as a drug delivery system (DDS), two phosphoramides (2 and 3), which are analogous to the cyclophosphamide anticancer prodrug, as well as their covalently bonded structures to B-C59 (4 and 5) were optimized by DFT computations at the B3LYP level of theory using 6-31G(d) basis set. Comparing compounds 4 and 5 revealed that the chloro derivative (-1429544.59 kcal mol-1) is more stable than its bromo analogue (-1429531.23 kcal mol-1). The isolated drugs had almost half dipole moment values compared to those of their corresponding covalently bonded compounds with B-C59. This reflects that the attachment of drugs to B-C59 has considerably enhanced the polarity of the drug-carrier systems which is a desired property for drug delivery in biological media. The negative ΔGinteraction values for the compounds 4 and 5 confirmed that the attachment of both drugs on the surface of B-C59 has been spontaneously taken place. The negative ΔHinteraction values for both compounds 4 and 5 indicated that these interactions are exothermic (ΔHinteraction < 0). The density of states (DOS) spectra disclosed that there are very strong hybridizations between the orbitals of B-C59 and the drug molecules. The oxygen atoms of P=O and P-O bonds revealed  values about 5.0 and 10.0 MHz, respectively that might be due to more positive oxygen atoms in P-O bonds that had a greater interaction with EFG tensor. It was established that the DDS 4 is preferred for the cancer therapy applications due to its greater Ebinding, ΔHinteraction and ΔGinteraction values compared to those of DDS 5.