The physicochemical properties of three new glucuronide paclitaxel prodrugs have been evaluated using Hartree fock (HF) and Density Functional Theory (DFT) calculations. Linked to the 2'-OH of the drug by a carbonate function, they include a self-immolative spacer bearing an arylnitro or arylamino group between the drug and the glucuronic acid residue. Our investigation include: geometrical parameters of glucuronide-paclitaxel conjugates, Gibbs free energy of solvation (
Gsolvation), binding energy and Dipole Moment (DM) of prodrugs, beside some properties such as partition coefficient, polarizibility, hydration energy and etc. Our results indicate that the glucuronide-paclitaxel conjugates mentioned above can be used to improve anticancer activity and water-solubility of paclitaxel.