Global Reactivity Indices Research Articles

DFT Study on Mechanism and Regioselectivity in Pd(II)‐Catalyzed Dehydrogenative Heck Olefination of Selenophenes

AbstractThe present study deals with the theoretical investigation of mechanistic and regiochemical aspects of the Pd(II)‐catalyzed dehydrogenative Heck olefination of selenophenes. The detailed reaction mechanism was established, and the roles of the catalyst and regioselectivity were well rationalized. Our results clearly showed that the whole reaction involves a concerted metalation‐deprotonation (CMD) process between the C2 site of selenophene and Pd(OAc)2 in the first catalytic cycle. Afterward, the olefin coordinates to the palladium, followed by a regioselective 1,2‐migratory insertion to form a C─C bond. Then, β‐hydride elimination would give the final 2‐monoolefinated product. Subsequently, the second catalytic cycle generates the symmetrical 2,5‐diolefinated selenophene product. Another key finding of this study is that selenophene and its monoolefinated product act as nucleophiles, while the catalyst behaves as an electrophile. A global reactivity index (GRI) analysis revealed that the nucleophilicity (Nk) of C2, C3, C4, and C5 atoms in selenophene plays an important role in controlling the reaction selectivity at these sites. However, the distortion energies play a more important role in controlling the selectivity of reactions at the olefin C sites.

Regioselectivity study of 1,3-dipolar cycloaddition of 2-azido-N-(4-diazenylphenyl)acetamide with terminal alkyne through DFT analysis

The mechanism and regioselectivity of 1,3-dipolar reaction of 2-azido-N-(4-diazenylphenyl) acetamide and an alkyne have been studied in gas phase and in DMSO using the B3LYP-GD3 functional and 6-31G(d,p) basis set. The reaction followed a one-step mechanism with asynchronous TSs. The calculated global reactivity indices calculated revealed, among other things, the nucleophile character of the 2-azido-N-(4-diazenylphenyl)acetamide and the electrophile character of the alkyne (4-bromo-2-chloro-1-ethynylbenzene), in addition to an electron transfer from the 4-bromo-2-chloro-1-ethynylbenzene towards the 2-azido-N-(4-diazenylphenyl) acetamide. The calculated local reactivity indices predicted the formation of the 1,4-triazole, with the most nucleophilic nitrogen and the most electrophilic carbon favoring its formation. However, analysis of the activation energies and thermochemistry parameters showed that the 1,5 triazole is energetically favorable and more stable under thermodynamic control. Bond order analysis coupled with bond formation evolution and the solvent effect was further investigated to support and highlight the asynchronicity in bond formation and the regioselectivity of the reaction, respectively.

Density Functional Theory Rationalization of the Mechanism, Selectivity, and Role of Substituents in Au(I)-Catalyzed Synthesis of Pyrazolines and Dihydropyridines.

A comprehensive theoretical investigation into the gold-catalyzed synthesis of polysubstituted pyrazolines and dihydropyridines from imines and methyl phenylpropiolate was conducted in this study. Three imines with distinct substituents were selected as model reactants. The computational outcomes reveal that four-membered intermediates generated from aza-enyne metathesis significantly affect the reaction selectivity. For nitrogen-centered NHCO2Me substituents (series A), an outward ring opening occurs during the metathesis of the aza-alkyne. This leads to the formation of Z-butadiene intermediates and ultimately to pyrazoline products. Conversely, with an aromatic substituent at the nitrogen site (series B and C), an inward ring opening takes place. This results in E-butadiene intermediates and the synthesis of dihydropyridine derivatives. The dihydropyridine product's configuration is determined by the aromatic ring's substituent. Electron-donating groups tend to directly form 1,4-dihydropyridine through a 6π electrocyclization (series B). In contrast, strong electron-withdrawing substituents initially undergo azayne metathesis, followed by 6π electrocyclization to produce 1,2-dihydropyridine products (series C). Furthermore, the distinctive selectivities were investigated in depth using global reactivity index and distortion/interaction methods. This research may contribute to the design of more effective and selective protocols to access pyrazolines, dihydropyridines, and related compounds.

Theoretical investigations of some isolated compounds from Calophyllum flavoramulum as potential antioxidant agents and inhibitors of AGEs

In this paper, we have attempted a theoretical calculation of some plant-isolated compounds as potential inhibitors of oxidative stress and Advanced Glycation Endproducts (AGEs). Herein, theoretical reactivity indices based on the CDFT theory were computed to explore the reactivity of five isolated products from Calophyllum flavoramulum. Global reactivity indices based on HOMO and LUMO energy such as electronic chemical potential, hardness, electrophilicity and the local reactivity descriptors Parr function, molecular electrostatic potentials(MEP), electrostatic potential (ESP) and thermodynamic parameters for the studied compounds are computed and discussed using DFT method and two functionals B3LYP and CAM-B3LYP with 6-31 G(d,p) basis set. The free radical scavenging activity mechanisms (HAT, SET-PT, and SPLET) of some of the isolated products with DPPH are also presented in this work. SET-PT mechanism of the antiradical activity is found to be thermodynamically favorable. Furthermore, a molecular docking study with RAGE receptor and AtGSTF2 enzyme was conducted, in which flavonoids 4 and 5 show a low binding affinity with −8.42 and −10.49 kcal/mol for RAGE, −8.67 and −9.00 kcal/mol for AtGSTF2. After the encouraging outcomes from the molecular docking study, the 4-AtGSTF2 and 5-RAGE complex were subjected to 200 ns molecular dynamics simulation using Desmond, where both studied systems exhibited remarkable stability throughout the 200 ns simulations. Also, the MM-GBSA method was measured by calculating the binding free energy using the individual energy components. Finally, the ADMET predictions were assessed to anticipate the behavior of a drug candidate within the human body.

Comparative Study of Docking Tools for Evaluation of Potential Copper Metallodrugs and Their Interaction with TMPRSS2

COVID-19 has caused over seven million deaths globally due to its high transmission rate. The virus responsible for the disease requires a transmembrane protease serine type II (TMPRSS2-7MEQ) to infiltrate host cells and has been linked to several cancers, particularly prostate cancer. To investigate COVID-19 potential therapies, a series of Casiopeina-like copper complexes containing 1,10-Phenanthroline and amino acids were investigated as TMPRSS2 inhibitors. The molecular structures of twelve Phenanthroline copper complexes were calculated, and their global reactivity indices were analyzed using DFT and conceptual DFT methods. Three molecular docking algorithms were employed to identify the most effective inhibitors by examining their interactions with amino acid residues in the target protein’s catalytic activity triad (Asp345, His296, and Ser441). All complexes are docked above the catalytic site, blocking the interaction with substrates. The Phenanthroline complexes showed better interactions than the Bipyridine complexes, likely due to increased hydrophobic contacts. Analogs’ cationic nature and amino acids’ basic side chains bring them near the active site by interacting with Asp435. The top complexes in this study contain Ornithine, Lysine, and Arginine, making them promising alternatives for researching new drugs for COVID-19 and cancers like prostate cancer.

Investigating the electronic properties of edge glycine/biopolymer/graphene quantum dots

This study systematically investigated four types of graphene quantum dots (GQDs) AHEX, ZTRI, ZHEX, and ATRI, and their interactions with glycine to form GQD-glycine complexes. Utilizing density functional theory (DFT) and the PM6 semiempirical method, the study analyzed electronic properties and structure-activity relationships. Global reactivity indices were calculated using Koopmans’ theorem, and quantitative structure-activity relationship (QSAR) parameters were assessed via SCIGRESS 0.3. The study further explored interactions using density of states (DOS) and quantum theory of atoms in molecules (QTAIM) analyses. Key findings revealed that glycine interaction significantly increased the total dipole moment (TDM) and decreased the HOMO/LUMO energy gap (ΔE) for the GQD-glycine complexes. Notably, ZTRI/glycine showed a TDM of 4.535 Debye and a reduced ΔE of 0.323 eV, indicating enhanced reactivity. Further interactions with cellulose, chitosan, and sodium alginate identified the ZTRI/glycine/sodium alginate composite as the most reactive, with a TDM of 8.020 Debye and the lowest ΔE of 0.200 eV. This composite also exhibited the highest electrophilicity index (56.421) and lowest chemical hardness (0.145 eV), underscoring its superior reactivity and stability. DOS analysis revealed that biomolecules contributed the most to molecular orbitals, with carbon atoms contributing the least. QTAIM analysis confirmed the greater stability of the ZTRI/glycine/sodium alginate complex compared to other studied composites. These results highlight the enhanced reactivity and stability of GQDs when interacting with glycine and sodium alginate.

Thermodynamic Study of Mehtylene Blue Adsorption and Photocatalytic Degradation on The N‐Doped TiO2 Thin Films: A DFT and Experimental Study

AbstractN‐Doped TiO2 coatings (N‐TiO2) were synthesized and characterized. The effect of the doping process on the physical‐chemical properties and photocatalytic efficiency of Methylene Blue (MB) under visible light irradiation were studied. The bare TiO2 showed only anatase crystalline structure. Furthermore, after the doping process, a slight transition from anatase to rutile was verified. The HRXPS confirmed that the doping process was effective. The N2 sorption using the BET assay showed a slight increase in surface area after the doping process. MB adsorption kinetic showed also a slight increase for doped TiO2 films, showing as best fitting the Langmuir model. Furthermore, a modification on the electronic structure was observed, showed by the modification of the optical absorption profile in the doped material. The results showed that the MB adsorption on N‐TiO2 thin films was endothermic (▵H=11 kJ mol−1) and a spontaneous process (▵G=−6.45 kJ mol−1). We performed DFT calculations to three simulated doped‐structures. The Gap value, the global reactivity indexes and, the Fukui function isosurfaces are presented. Finally, the scavenger tests suggested that and OH⋅ could be the main ROS driving the photocatalytic process.

Zinc isoporphyrin from [Zn(4-Cl)TPP]: Synthesis, characterization, density functional theory and molecular docking studies

Zinc isoporphyrin from [Zn(4-Cl)TPP]: Synthesis, characterization, density functional theory and molecular docking studies

Synthesis, characterization and DFT study of Ti(IV) phthalocyanines with quinoline groups.

The synthesis, characterization, and electronic properties of 4-((7-methoxyquinolin-4-yl)oxy), 4-(quinolin-2-ylthio), and 4-((7-(trifluoromethyl)quinolin-4-yl)thio) peripherally substituted oxo-titanium phthalocyanines are described for the first time. The structures of the compounds were determined by UV-Vis, FTIR, 1H NMR, and MALDI-TOF mass spectrometry. Electronic spectra and molecular and electronic properties of compounds were calculated by Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TD-DFT) methods. Solvent effects on the electronic, geometric, and reactivity properties of the compounds were also investigated. Global and local reactivity indices and Molecular Electrostatic Potential surfaces of compounds were calculated. The reactivities and electronic structures of molecules vary depending on the solvent and substituents. It has been found that the synthesized compounds can be used for different purposes such as dye-sensitized solar cells and photodynamic therapy applications.

Mechanisms and Origins of Regio- and Stereoselectivities in NHC-Catalyzed [3 + 3] Annulation of α-Bromoenals and 5-Aminoisoxazoles: A DFT Study.

Density functional theory (DFT) calculations were conducted to explore the mechanisms and origins of regio- and stereoselectivities underlying the [3 + 3] annulation reaction between α-bromoenals and 5-aminoisoxazoles with N-heterocyclic carbene (NHC) as the catalyst. The reaction occurs in nine steps: (1) nucleophilic addition of NHC to α-bromoenal, (2) Breslow intermediate formation through 1,2-proton transfer, (3) debromination, (4) α,β-unsaturated acyl azolium intermediate formation via 1,3-proton transfer, (5) addition of α,β-unsaturated acyl azolium intermediate to 5-aminoisoxazole, (6) deprotonation, (7) protonation, (8) ring closure, and (9) elimination of NHC. For the fifth step, 1,2-addition suggested in the experiment was not supported by our results. Instead, we found that Michael addition is energetically the most feasible pathway and the stereo-controlling step that preferentially provides the S-configuration product. DFT-computed results and experimental findings agree well. Analysis of distortion/interaction reveals that lower distortion energy leads to stability of the transition state corresponding to the S-configuration product. Global reactivity index analysis indicates that the behavior of the NHC catalyst differs significantly before and after the Breslow intermediate debromination. Before debromination, the nucleophilicity of α-bromoenal is enhanced by addition to NHC. However, after debromination, the α,β-unsaturated acyl azole generates and acts as an electrophilic reagent.

DFT studies on N-(1-(2-bromobenzoyl)-4-cyano-1H-pyrazol-5-yl)

In this work, molecular descriptors of N-(1-(2-bromobenzoyl)-4-cyano-1H-pyrazol-5-yl) halogenated benzamides (1a-h) have been computed using a quantum chemical technique through DFT. Prior work involved the synthesis of compounds (1a-h) and the assessment of their anticancer activity on breast, colon, and liver tumors: MCF-7, HCT-116, and HepG-2 cell lines respectively. Since 1a, 1b, and 1d showed the most potential anticancer impact, their ability to inhibit EGFRWT was investigated. Based on the biological data, 1b inhibited EGFRWT the most. According to the docking evaluation, an H-bond with the threonine residue was one of the main non-covalent contacts between 1b and the EGFRWT active site residues. PES, MESP, HOMOs, LUMOs, energy band gap, global reactivity indices [electron affinity (A), ionization energies (I), electrophilicity index (ω), nucleophilicity index (ε), chemical potential (μ), electronegativity (χ), hardness (η), and softness (S)], condensed Fukui functions, NBO, and NCIs are the molecular descriptors of 1a-h that were computed using DFT technique. According to the theoretical investigation results, compounds (1a-h) might have anticancer effects; these findings are consistent with the biological findings from our previous research. Compound 1b had the lowest binding energy, according to an assessment of the binding energies between the threonine and the three most active compounds (1a, 1b, and 1d). This is consistent with the outcomes of the docking study and the biological examination of the influence of 1a, 1b, and 1d on EGFRWT.

Deciphering the adsorption and sensing performance of Al24N24 and B24N24 nanoclusters as a drug delivery system for nitrosourea anticancer drug: A DFT insight

Deciphering the adsorption and sensing performance of Al24N24 and B24N24 nanoclusters as a drug delivery system for nitrosourea anticancer drug: A DFT insight

Computational studies on a selection of phosphite esters as antioxidants for polymeric materials.

Phosphite esters, a class of organo-phosphorus compounds, are widely used as non-discolouring antioxidants in many polymeric products. Apart from normal radical scavenging, they prevent the splitting of hydroperoxides (ROOH), one of the initial products of autoxidation, from forming extremely reactive free radicals such as alkoxy (RO.) and hydroxy (.OH) radicals. The inherent molecular properties of antioxidants and the chemistry of their action are essential for researchers working in this field of science. Four organo-phosphorous compounds well-known for their antioxidant activity are selected here for theoretical analysis: Tri(m-methylphenyl) phosphite (m-TMPP), Tri(4-methyl-2,6-di-tert-butylphenyl) phosphite (TMdtBPP), Tri(allylphenyl) phosphite (TAPP) and Tri(mercaptobenzothiazoyl) thiophosphate (TMBTTP). The antioxidant activity exhibited by these compounds is theoretically verified, and the results are consistent with the available experimental data. Such theoretical predictions offer advantages in scientific research, particularly when researchers need to select certain molecules as antioxidants for experiments from a pool of molecular systems. The chemical computations presented in this report are done in Gaussian 16 program package. The procedure of density functional theory (DFT) with the model chemistry B3LYP/6-31G(d,p) is used to generate computational data. Global reactivity indices, thermochemical data, Fukui functions, molecular electrostatic potential and NMR spectra are computed for the chosen molecular systems from their optimized geometries.

Theoretical study of [3 + 3] annulation reaction of bromoenal with β-tetralone catalysed by N-heterocyclic carbene

N-heterocyclic carbenes (NHCs) are effective organocatalysts, which are widely used in various cycloaddition reactions. Among them, the [3 + 3] cycloaddition reaction type can be used for the synthesis of six-membered ring, which is also one of the most important methods for the formation of carbon–carbon bonds in organic chemistry. In this paper, a possible reaction pathway for the stereoselective [3 + 3] cycloaddition of bromoenal and β-tetralone have been investigated at the M06-2X/6–31G(d,p)/IEFPCM(THF) level. Our suggested mechanism includes binding of the NHC to bromoenal, 1,2-proton transfer, debromination, 1,3-proton shift, Michael addition, protonation, deprotonation and cyclisation, and NHC regeneration. The stereochemistry of the reaction is determined by the Michael addition step, and the favourable pathway generates the R-configurational dihydropyranone. Furthermore, through the use of global reactivity indexes (GRIs), we are able to demonstrate that the nucleophilicity of the bromoenal is increased by the NHC. The mechanistic insights gained in this work should be helpful in the rational design of potential catalysts for analogous reactions.

Analyzing a series of ligands against malaria through the application of molecular docking, molecular quantum similarity, and reactivity indices

Background The primary goal of this research is to underscore the significance of molecular docking in the context of malaria drug discovery. Molecular docking plays a crucial role in comprehending the interactions between prospective drugs and the target proteins found in Plasmodium parasites. The study delves into the docking interactions of various compounds, emphasizing the necessity of stabilizing the active site to formulate potent and selective drugs. Methods The research focuses on highlighting compound-specific interactions with residues, stressing the importance of stabilizing the active site to design drugs tailored to specific target proteins. Inhibiting the function of these target proteins disrupts the life cycle of the malaria parasite. Quantum Similarity Analysis, utilizing Overlap and Coulomb operators, is employed to identify electronic similarities. The resulting quantum similarity values guide subsequent chemical reactivity analysis. Global reactivity indices such as chemical potential, hardness, softness, and electrophilicity contribute to drug design by showcasing compound-specific indices that underscore the significance of stability and electrophilicity. Fukui functions are utilized to visualize regions for stabilization, providing insights crucial for potential malaria treatment. Results The enhancement of drug-target binding affinity is observed through stabilizing interactions in the active site. Understanding electrophilicity at the active site emerges as a critical factor in drug design and selectivity. The rational manipulation of electrophilic interactions holds promise for developing potent and selective drugs against malaria. Consequently, the integration of molecular docking, quantum similarity analysis, and chemical reactivity indices offers a comprehensive approach to malaria drug discovery. Conclusions The study identifies potential lead compounds, emphasizing the crucial role of stabilizing the active site. Additionally, it sheds light on electronic considerations vital for the design of effective and resistance-resistant drugs. The insights provided by Fukui functions into regions susceptible to -H bond formation make these compounds promising candidates for malaria treatment.

Anticancer Effects of Abietane Diterpene 7α-Acetoxy-6β-hydroxyroyleanone from Plectranthus grandidentatus and Its Semi-Synthetic Analogs: An In Silico Computational Approach.

The abietane diterpenoid 7α-acetoxy-6β-hydroxyroyleanone (Roy) isolated from Plectranthus grandidentatus demonstrates cytotoxicity across numerous cancer cell lines. To potentiate anticancer attributes, a series of semi-synthetic Roy derivatives were generated and examined computationally. ADMET predictions were used to evaluate drug-likeness and toxicity risks. The antineoplastic potential was quantified by PASS. The DFT models were used to assess their reactivity and stability. Molecular docking determined cancer-related protein binding. MS simulations examined ligand-protein stability. Additionally, network pharmacology was used to identify potential targets and signaling pathways. Favorable ADME attributes and acceptable toxicity profiles were determined for all compounds. Strong anticancer potential was shown across derivatives (Pa 0.819-0.879). Strategic modifications altered HOMO-LUMO gaps (3.39-3.79 eV) and global reactivity indices. Favorable binding was revealed against cyclin-dependent kinases, BCL-2, caspases, receptor tyrosine kinases, and p53. The ligand exhibited a stable binding pose in MD simulations. Network analysis revealed involvement in cancer-related pathways. In silico evaluations predicted Roy and derivatives as effective molecules with anticancer properties. Experimental progress is warranted to realize their chemotherapeutic potential.

Sites and Zones of Maximum Reactivity of the most Stable Structure of the Receptor-binding Domain of Wild-type SARS-CoV-2 Spike Protein: A Quantum Density Functional Theory Study

Today, it is well known that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has four types of proteins within its structure, between them the spike protein (S). The infection mechanism is carried out by the entry of the virus into the human host cell through the S protein, which strongly interacts with the human cell receptor angiotensin-converting enzyme 2 (ACE2). In this work, we propose an atomic model of the Receptor Binding Domain (RBD) of the S spike protein of the wild-type SARS-CoV-2 virus. The molecular structure of the model was composed of 50 amino acids that were chemically bonded, starting with Leucine and ending with one amino acid Tyrosine. The novelty of our work lies in the importance of knowing the sites and zones of maximum reactivity of the RBD from the fundamental levels of quantum mechanics considering the atomic structure of matter. For this, the local and global reactivity indices of the RBD were calculated, such as frontier orbitals, Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO), Fukui indices, chemical potential, chemical hardness, electrophilicity index; with this, it will be possible to know what type of molecules are more likely to interact with the RBD structure, and in this way, new knowledge will be generated at the quantum, atomic and molecular level to inhibit the virulent effects of wild-type SARS-CoV-2. Finally, in order to identify the functional groups within the most stable structure and thereby verify the future reactions that can be carried out between the RBD structure and biomolecules, the Infrared (IR) absorption spectrum was calculated. For this work, we used Material Studio v6.0 which uses the density functional theory (DFT) implemented in its DMol3 computational code. The IR spectrum was obtained using the Spartan ‘94 computer code. One novelty would be that we found nine amino acids more that could make the RBD and ACE2 binding further the already known. Thus, the Mulliken charge distribution indicates that the highest concentrations of positive and negative charge are found in the zones 477S, 478T, 484E, and 501N amino acids letting ionic or Van der Waals possible interactions with other structures.

Evaluating the corrosion inhibition potential of two innovative N-benzyl-5-bromo isatin derivatives for carbon steel in alkaline environments: insights from DFT, SAR and toxicology

DFT-derived global reactivity indices, structure-activity relationships (SAR), and toxicity parameters have been used to correlate between the corrosion inhibition role of two N-benzyl-5-bromo isatin derivatives namely N-benzyl-5-bromo-3-[(imine aceto) urea]-2-oxo indole (ISAO) and N-benzyl-5-bromo-3-[(imine aceto) thiourea]-2-oxo indole (ISAS) against carbon steel corrosion in an alkaline environment and their electronic properties at molecular scale as well as understanding their impacts on human health. The computed global reactivity indices and SAR parameters establish a direct correlation with previously reported experimental data. Mulliken charge analysis provides helpful insights into the atoms responsible for electronic transfer. The predicted toxicological parameters suggest that the tested corrosion inhibitors pose no significant risk to human health.

Synthesis of Indole-Linked Thiadiazoles and their Anticancer Action against Triple-Negative Breast Cancer.

With a lack of targeted therapy and significantly high metastasis, heterogeneity, and relapse rates, Triple-Negative Breast Cancer (TNBC) offers substantial treatment challenges and demands more chemotherapeutic interventions. In the present study, indole-endowed thiadiazole derivatives have been synthesized and screened for antiproliferative potency against the triple-negative breast cancer MDA-MB-231 cell line. Compound 4 h, possessing chlorophenyl moiety, displays the best anticancer potency (IC50: 0.43 μM) in the cell viability assay. The title compounds demonstrate substantial docking competency against the EGFR receptor (PDB ID: 3POZ), validating their in-vitro ant proliferative action. With a high docking score (-9.9 to -8.7 kcal/mol), the indole hybrids display significant binding propensity comparable to the co-crystallized ligand TAK-285 and occupy a similar strategic position in the active domain of the designated receptor. The quantum and electronic properties of the integrated templates are evaluated through DFT, and optimal values of the deduced global reactivity indices, such as energy gap, electronegativity, ionization potential, chemical potential, electrophilicity, etc., suggest their apt biochemical reactivity. The indole hybrids show near-appropriate pharmacokinetic efficacy and bioavailability in the in-silico studies, indicating their candidacy for potential drug usage. Promising in-vitro anticancer action and binding interfaces project indole conjugates as potential leads in addressing the TNBC dilemma.

In silico design of a new Podophyllotoxin derivative with potent anti-tubulin activity

Nowadays, there is an increasing focus on cancer as a major cause of death. Therefore, comprehending the chemical reactivity, geometric and electronic structures of inhibitors can aid in the development of better quality and more efficient drugs. In this study, we propose a hybrid compound of Podophyllotoxin (PPT) and vitamin C (VC) as an anti-cancer agent. The PPT and its derivatives are well-known for their anti-tubulin properties. The geometry optimisation and calculation of global chemical reactivity indices (µ = −3.836 eV, η = 2.402 eV, S = 0.416 eV, and ω = 3.061 eV) were performed using the M06/6-311++G (d, p) level of theory. The global reactivity descriptors predict that the PPT-VC compound has more nucleophilic properties compared to Etoposide and Teniposide compounds. Furthermore, the PPT-VC compound exhibits a lower HOMOPPT-VC–LUMOSWCNT gap and a higher adsorption energy (−37.4 kJ mol−1) in the encapsulation process than other derivatives into SWCNT, providing additional evidence of its nucleophilic nature as an effective anti-tubulin agent. Therefore, the PPT-VC@SWCNT compound can be considered a reliable drug delivery system (DDS). Molecular docking analysis reveals that the best cavity of tubulin has an interaction energy of −102.1 kJ mol−1, involving both bonding and non-bonding interactions.