Toward Efficient Drug Delivery through Suitably Prepared Metal-Organic Frameworks: A First-Principles Study

With the goal in mind of developing new and much-improved drug delivery regimes for the important anticancer agent, tamoxifen; the interactions of tamoxifen with strategically modified organic linkers from IRMOFs-14 and -16 (nontoxic, high-loading, nanomaterials belonging to the metal organic framework family) have been investigated and elucidated by means of spin-component scaled second-order Moller-Plesset perturbation theory (SCS(MI-MP2) and density functional theory. The strategic replacement of a hydrogen atom with a hydroxyl moiety in the organic linker of IRMOE-14 and IRMOF-16 was critical for gaining key acid base and hydrogen-bond interaction sites. The magnitudes of the maximum interaction energies with tamoxifen were found to be 16.16 kcal/mol for the modified IRMOF-14 and 18.32 kcal/mol for the modified IRMOF-16. Secondary pi-pi type interactions of tamoxifen with the modified IRMOF-16 have also been identified, the strongest of which has an energy of between 3.0 and 5.3 kcal/mol. The type and magnitude of these combined noncovalent interactions affords appreciable multipoint binding without overbinding as is desirable for such drug delivery systems.