A Comparative DFT Investigation of the Adsorption of Temozolomide Anticancer Drug over Beryllium Oxide and Boron Nitride Nanocarriers

Abstract

Herein, attempts were made to explore the adsorption prospective of beryllium oxide (Be₁₂O₁₂) and boron nitride (B₁₂N₁₂) nanocarriers toward the temozolomide (TMZ) anticancer drug. A systematic investigation of the TMZ adsorption over nanocarriers was performed by using quantum chemical density functional theory (DFT). The favorability of Be₁₂O₁₂ and B₁₂N₁₂ nanocarriers toward loading TMZ was investigated through A↔D configurations. Substantial energetic features of the proposed configurations were confirmed by negative adsorption (E _ads) energy values of up to -30.47 and -26.94 kcal/mol for TMZ•••Be₁₂O₁₂ and •••B₁₂N₁₂ complexes within configuration A, respectively. As per SAPT results, the dominant contribution beyond the studied adsorptions was found for the electrostatic forces (E _elst = -100.21 and -63.60 kcal/mol for TMZ•••B₁₂N₁₂ and •••Be₁₂O₁₂ complexes within configuration A, respectively). As a result of TMZ adsorption, changes in the energy of molecular orbitals followed by alterations in global reactivity descriptors were observed. Various intermolecular interactions within the studied complexes were assessed by QTAIM analysis. Notably, a favorable adsorption process was also observed under the effect of water with adsorption energy ( reaching -28.05 and -22.26 kcal/mol for TMZ•••B₁₂N₁₂ and •••Be₁₂O₁₂ complexes within configuration A, respectively. The drug adsorption efficiency of the studied nanocarriers was further examined by analyzing the IR and Raman spectra. From a sustained drug delivery point of view, the release pattern of TMZ from the nanocarrier surface was investigated by recovery time calculations. Additionally, the significant role of doping by heavy atoms (i.e., MgBe₁₁O₁₂ and AlB₁₁N₁₂) on the favorability of TMZ adsorption was investigated and compared to pure analogs (i.e., Be₁₂O₁₂ and B₁₂N₁₂). The obtained data from thermodynamic calculations highlighted that the adsorption process over pure and doped nanocarriers was spontaneous and exothermic. The emerging findings provide a theoretical base for future works related to nanocarrier applications in the drug delivery process, especially for the TMZ anticancer drug.

Figure 1

Illustration showing the adsorption of the temozolomide (TMZ) anticancer drug with Be₁₂O₁₂ and B₁₂N₁₂ nanocarriers within four orientations labeled from A to D.

Figure 2

An overview showing the optimum geometries for TMZ, Be₁₂O₁₂, and B₁₂N₁₂ systems combined with MEP maps with color scale (from −0.01 (red) to +0.01 (blue) au) and the calculated V_s,max/V_s,min values (kcal/mol).

Figure 3

Optimized TMZ•••nanocarrier complexes and MEP maps with color scale −0.01 au (red) to +0.01 au (blue) for configurations A↔D. The separation distances (d) are in Å.

Figure 4

QTAIM and NCI molecular graphs for the optimized TMZ•••nanocarrier complexes within configurations A↔D.

Figure 5

Patterns of HOMO and LUMO for the optimized TMZ, Be₁₂O₁₂, and B₁₂N₁₂ systems.

Figure 6

Patterns of HOMO and LUMO for the optimized TMZ•••nanocarrier complexes within configurations A↔D.

Figure 7

Graphed 2D TDOS diagrams for Be₁₂O₁₂ and B₁₂N₁₂ along with their corresponding complexes with TMZ within configuration A.

Figure 8

Diagrams of infrared (IR) and Raman spectra for the isolated nanocarriers and TMZ•••nanocarrier complexes within configuration A.