Abstract:
Owing to the mortalities caused by cancer and a high number of cases reported globally
there are continuous studies on improving the cancer treatment methods. This study
focuses on enhancing the therapeutic potential of g-C3N4 through surface modification
by doping this carrier sheet with alkali metals like Li, Na, and K using DFT for the
efficient delivery of 5-Fluorouracil. The interaction energies of the optimized geometry
are calculated by the computational method B3LYP-D3, and the results indicate an
obvious improvement in the interaction between the drug and the carrier sheet. The Ead
values in the case of Li@g-C3N4-5FU complex in the gas phase and the aqueous phase
are -10.21eV, and -3.23eV respectively and these values make this complex the most
stable one as compared to g-C3N4-5FU, Na@g-C3N4-5FU and K@g-C3N4-5FU
complexes. The frontier molecular orbital analysis indicates a significant decrease in
the band gap after the doping of alkali metals from the HOMO-LUMO gap value of
3.7eV to 0.81eV in the case of g-C3N4-5FU and Li@g-C3N4-5FU respectively. This
reduced band gap supports the idea of doping the carrier sheet with Li. The IRI and
QTAIM analyses show the weak forces of interaction between the doped carrier sheets
and the drug molecule and the presence of Van der Walls forces of attraction. To check
the behavior of these complexes inside the body and to estimate the ease of unloading
the drug upon reaching the targeted sites the complexes are also studied in the
environment of low pH by the protonation of these complexes. It is observed that when
the complexes are in the acidic medium the values of interaction energies decrease
significantly. For instance, in the case of Li@g-C3N4-5FU complex the the Ead value
decreases from -10.21eV to -4.9eV when the acidic medium is provided. This decrease
in energy value shows that the carrier can easily release the drug when it reaches the
cancer cells. In conclusion, the modification of the surface of the Graphitic Carbon
Nitride greatly increases the therapeutic potential of g-C3N4 as a carrier for the delivery
of 5-Fluorouracil in cancer treatment and this theoretical model can help the
experimentalists to enhance the precision in the delivery of the drug to reduce its side
effects in the surrounding healthy cells.
