AN ANALYSIS OF THREE FUNCTIONALS IN ORCA QUANTUM CHEMISTRY SOFTWARE TO PREDICT SELECTION OF A NEW LAB-MADE POLYMER FOR DOXORUBICIN ANTI-CANCER DRUG DELIVERY CARRIER APPLICATION

Doxorubicin (DOX) is a cancer drug that is crucial for treating cancer, and its use is hindered by toxicity and other delivery issues. The electronic-structure predictions were made by density functional theory and compared in this study. It was obtained through three density functional theory methods: r²SCAN/6-31G*, ωB97X-D/6-31G*, and PBE0/6-31G* for the calculation of the electronic properties of DOX, a laboratory made polymer, and its polymer-DOX conjugate. The energies of HOMO and LUMO, the energy gap between HOMO and LUMO (ΔE), distribution of frontier molecular orbitals and global chemical reactivity descriptors were considered for the analysis. All three functionals yielded considerable electronic reorganization upon conjugation, but the size of the reorganization computed was highly dependent on the functional used. The ΔE values obtained for the conjugate were 0.3215, 4.6746, and 0.2975 eV for r²SCAN, ωB97X-D and PBE0 respectively, which were much lower than those of the corresponding isolated systems. The frontier electronic structure redistribution was also revealed by FMO distributions after polymer-DOX conjugation. Conjugate chemical hardness decreased and softness increased when compared to the isolated polymer in all cases, and the r²SCAN and PBE0 models predicted the greatest changes. The two r²SCAN and PBE0 have a close agreement for the conjugates and they predict a similar frontier-orbital separation for the system under study, while the separation predicted by ωB97X-D is significantly larger. The results show that the electronic properties of the polymer-DOX conjugate are dependent on the functional used. The results enable a molecular-level comparison of the polymer-drug electronic structure.