Adsorption of Chlormethine Anti-Cancer Drug on Pure and Aluminum-Doped Boron Nitride Nanocarriers: A Comparative DFT Study

Abstract

The efficacy of pure and aluminum (Al)-doped boron nitride nanocarriers (B₁₂N₁₂ and AlB₁₁N₁₂) in adsorbing Chlormethine (CM), an anti-cancer drug, was comparatively dissected by means of the density functional theory method. The CM∙∙∙B₁₂N₁₂ and ∙∙∙AlB₁₁N₁₂ complexes were studied within two configurations, A and B, in which the adsorption process occurred via N∙∙∙ and Cl∙∙∙B/Al interactions, respectively. The electrostatic potential affirmations confirmed the opulent ability of the studied nanocarriers to engage in delivering CM via two prominent electrophilic sites (B and Al). Furthermore, the adsorption process within the CM∙∙∙AlB₁₁N₁₂ complexes was noticed to be more favorable compared to that within the CM∙∙∙B₁₂N₁₂ analog and showed interaction and adsorption energy values up to -59.68 and -52.40 kcal/mol, respectively, for configuration A. Symmetry-adapted perturbation theory results indicated that electrostatic forces were dominant in the adsorption process. Notably, the adsorption of CM over B₁₂N₁₂ and AlB₁₁N₁₂ nanocarriers exhibited predominant changes in their electronic properties. An elemental alteration was also revealed for the softness and hardness of B₁₂N₁₂ and AlB₁₁N₁₂ nanocarriers before and following the CM adsorption. Spontaneity and exothermic nature were obviously observed for the studied complexes and confirmed by the negative values of thermodynamic parameters. In line with energetic manifestation, Gibbs free energy and enthalpy change were drastically increased by the Al doping process, with values raised to -37.15 and -50.14 kcal/mol, respectively, for configuration A of the CM∙∙∙AlB₁₁N₁₂ complex. Conspicuous enhancement was noticed for the adsorption process in the water phase more than that in the gas phase and confirmed by the negative values of the solvation energy up to -53.50 kcal/mol for configuration A of the CM∙∙∙AlB₁₁N₁₂ complex. The obtained outcomes would be the linchpin for the future utilization of boron nitride as a nanocarrier.

Keywords: Chlormethine; DFT calculations; anti-cancer drug; boron nitride nanocarriers; thermodynamic parameters.

Figure 1

Pictorial representation for the adsorption process of the Chlormethine (CM) anti-cancer drug over pure and aluminum (Al)-doped boron nitride (B₁₂N₁₂ and AlB₁₁N₁₂) nanocarriers through configurations A and B.

Figure 2

Optimized structures and molecular electrostatic potential (MEP) maps supplemented with electrostatic potential extrema (V_s,min/V_s,max, in kcal/mol) of CM, B₁₂N₁₂, and AlB₁₁N₁₂. The color scale changes from red (−0.01) to blue (+0.01) au.

Figure 3

Optimized structures of CM∙∙∙B₁₂N₁₂ and ∙∙∙AlB₁₁N₁₂ optimized complexes within configurations A and B (at M06-2X/6-311+G** level of theory) along with molecular electrostatic potential (MEP) maps. MEP maps are plotted using electron density envelopes of 0.002 au. The color scale varies from −0.01 (red) to +0.01 (blue) au. Intermolecular distances (d) within the optimized complexes are given in Å.

Figure 4

Bar chart presenting the physical components (i.e., electrostatic (E_elst), induction (E_ind), dispersion (E_disp), and exchange (E_exch)) of the total SAPT0 energies for the CM∙∙∙B₁₂N₁₂ and ∙∙∙AlB₁₁N₁₂ optimized complexes in configurations A and B.

Figure 5

Visualized QTAIM and 3D NCI diagrams of the optimized CM∙∙∙B₁₂N₁₂ and ∙∙∙AlB₁₁N₁₂ complexes in configurations A and B. In QTAIM diagrams, red dots represent the location of BCPs and BPs. Three-dimensional NCI isosurfaces are graphed with a reduced density gradient value of 0.50 au and colored from blue to red according to sign (λ₂)ρ ranging from −rangi (blue) to 0.020 (red) au.

Figure 6

Diagrams of HOMO and LUMO distributions of CM, B₁₂N₁₂, and AlB₁₁N₁₂ systems.

Figure 7

Diagrams of HOMO and LUMO distributions of the optimized CM∙∙∙B₁₂N₁₂ and ∙∙∙AlB₁₁N₁₂ complexes within configurations A and B.

Figure 8

Density of states (DOS) plots for the B₁₂N₁₂ and AlB₁₁N₁₂ nanocarriers before and after the adsorption process of CM within the CM∙∙∙B₁₂N₁₂ and ∙∙∙AlB₁₁N₁₂ complexes within configurations A and B.