الفهرس 
Chapter I: IntroductionOnly 14 pages are availabe for public view
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Abstract
Nanomaterials hold great promise for advancements in chemical, physical, and biomedical research. In particular, fullerene-like nanocarriers have sparked a great deal of interest in biomedical applications. Amongst, the potentiality of fullerene-like nanocarriers to be applied as drug delivery systems gained more interest. In this regard, the current thesis is dedicated to thoroughly providing a premier insight into the potentiality of various nanocarriers to be applied in various drug delivery processes of anti-COVID-19 and anti-cancer drugs through the use of a plethora of quantum mechanical calculations.
For the drug delivery process of anti-COVID-19 drugs, the tendency of aluminium nitride (Al12N12) fullerene-like nanocarrier to adsorb Favipiravir (FPV) anti-COVID-19 drug was investigated. All possible orientations were considered to thoroughly examine the ability of Al12N12 nanocarrier to engage into the drug delivery process. Hence, the most favourable configurations were denoted as N∙∙∙, O∙∙∙, and F∙∙∙Al interactions and named as A, B, C, D, and E. According to the results, Al12N12 showed high potentiality toward adsorbing FPV anti-COVID-19 drug within all studied configurations. Substantial negative Eads and Eint values were found for all optimized complexes. Symmetry-adapted perturbation theory (SAPT) revealed that the electrostatic force dominated all FPV∙∙∙Al12N12 configurations. Additionally, the alteration of electronic properties after FPV illustrates the occurrence of the adsorption process. Noticeably, the thermodynamic parameters confirmed the spontaneous and exothermic nature of all studied complexes through negative values of ΔG and ΔH. The favourability of studied complexes in the water phase was also confirmed with negative adsorption and solvation energies. Quantum theory of atoms in molecules (QTAIM) and noncovalent interaction (NCI) analyses were accomplished to unveil the nature of FPV∙∙∙Al12N12 complexes within configuration A, B, C, D, and E. IR and Raman spectra were generated for all optimized complexes along with isolated nanocarrier, ensuring the occurrence of the adsorption process. By the end, the obtained results of the FPV∙∙∙Al12N12 complexes were compared with FPV∙∙∙B12N12 analogues. Recovery time (τ) was calculated for all studied complexes confirming the ability of FPV anti-COVID-19 drug to be separated from the nanocarrier when it reaches the target site.
A novel clarification of the tendency of the B12N12 and Al12N12 fullerene-like nanocarriers to engage in the drug delivery process of Molnupiravir anti-COVID-19 drug was thoroughly assessed. Various quantum mechanical calculations were performed at M0-2X/6-311+G** level of theory. Electrostatic potential (ESP) analysis was executed for Molnupiravir, B12N12, and Al12N12 optimized systems. The nucleophilic nature was observed for Molnupiraivr anti-COVID drug, while electrophilic nature was observed for B12N12 and Al12N12 nanocarriers. The energetic findings revealed a preferential tendency of the studied nanocarriers to adsorb Molnupiravir anti-COVID-19 drug within different configurations. The occurrence of the adsorption process within Molnupiravir∙∙∙B12N12 and ∙∙∙Al12N12 complexes was confirmed through quantum theory of atoms in molecules (QTAIM), noncovalent interaction (NCI), symmetry-adapted perturbation theory (SAPT), electronic parameters, and global indices of reactivity calculations. Spontaneous and exothermic natures of the optimized complexes were confirmed by negative values of thermodynamic parameters. Further, the adsorption process was studied in water as well as gas phase, indicating that solvent enhanced the adsorption process. Along with the adsorption process, the drug release procedure was also executed in an acidic medium. Thence the difficulty of drug separation from the nanocarrier was examined by calculating recovery time (τ).
According to anti-cancer drugs, the adsorption process of Chlormethine anti-cancer over pure and Al-doped boron nitride fullerene-like nanocarriers (B12N12 and AlB11N12) was investigated. The adsorption process within CM∙∙∙B12N12 and ∙∙∙AlB11N12 complexes was studied in-depth using various quantum mechanical calculations. According to obtained results, the electrophilic and nucleophilic natures were affirmed for the studied nanocarriers and the drug, respectively. Favourable adsorption process within CM∙∙∙B12N12 and ∙∙∙AlB11N12 complexes was significantly unveiled by negative interaction (Eint) and adsorption (Eads) energy values. Electrostatic forces were deemed the predominant force, followed by induction from SAPT analysis. Alterations in electronic parameters indicated the favourable contributions of the Al doping process to delivering CM drug. Spontaneous and exothermic natures were affirmed for all optimized complexes by negative ΔG and ΔH values. Enhanced effect of solvent was highlighted by negative solvation energy values. The potentiality of CM drug to be released from nanocarriers was executed by recovery time (τ) values.
In the same brain area, the favourability of aluminium phosphide (Al12P12) fullerene-like nanocarrier to adsorb Mercaptopyridine (MCP) drug was elucidated by using DFT methods. According to ESP results, the existence of notable nucleophilic sites over the N and S atoms of MCP drug, while electrophilic ones were found around the Al atoms in the Al12P12 nanocarrier. Thence, the occurrence of the adsorption process was highlighted by negative adsorption energies. In the scope of SAPT results, the electronic forces dominated the studied adsorption process. from the FMOs outcomes, obvious changes in HOMO and LUMO distributions were found following the adsorption of MCP drug. Thermodynamic parameters affirmed the spontaneous and exothermic nature of the MCP∙∙∙Al12P12 complexes. Solvent effect was found to enhance the adsorption process through negative adsorption, and solvation energies. In a comparative way, the MCP∙∙∙Al12N12 complexes were examined and the obtained adsorption energies were compared with MCP∙∙∙Al12P12 counterparts. On the basis of adsorption energy, MCP∙∙∙Al12N12 complexes exhibit high adsorption energy values compared with MCP∙∙∙Al12P12 analogues. High adsorption of MCP∙∙∙Al12N12 complexes caused distortion in MCP drug structure, where hydrogen atom transferred from MCP to the Al12N12 nanocarrier. By the end, the recovery time (τ) values ensured the potentiality of MCP drug to be transferred from the Al12P12 nanocarrier.
The obtained results would be an efficient linchpin toward evolving the applications of nanomaterials in the drug delivery process. All calculations were executed using High-Performance Computer (HPC) located at CompChem Lab, Minia University, and supported by the Science and Technology Development Fund, STDF, Egypt, Grants No. 5480 & 7972.