Doxorubicin is a drug used in cancer chemotherapy. It is an anthracycline antibiotic and it is commonly used in the treatment of a wide range of cancers. In this report, the molecular structure, binding energy Dipole Moment (DM), Gibbs free energy of solvation (
G (solvation))and some physico chemical properties of doxorubicin–PLGA complex of the conjugated complex were investigated using computational methods . A carboxylic acid end group of PLGA(poly(D,Llactic-co-glycolic acid)) was conjugated to a primary hydroxyl group of doxorubicin(complex A). On the other hand, a hydroxyl terminal group of PLGA was activated by p-nitrophenyl chloroformate and reacted with a primary amine group of doxorubicin for conjucation (complexB). Complex A and B are large molecules. For large reactive systems, the calculation of energies can be simplified by treating the active part with a high-level quantum mechanical (QM) ab initio or density functional. One such method is the original ‘‘Our-own-N-layer Integrated molecular Orbital, Molecular Mechanics ONIOM’’ approach. We used of this approach for optimization of complex A and B.