Finding and developing effective targeted drug delivery systems has emerged as an attractive approach for treating a wide range of diseases. In the present study, the potential of alkaline earth metal functionalized porphyrin-like porous C24N24 fullerenes for delivering 5-fluorouracil (5FU) anticancer drug is assessed using density functional theory calculations. The goal is to evaluate how the addition of alkaline earth metals to C24N24 enhances the adsorption capabilities of this system towards 5FU drug. The adsorption energies and charge transfers are determined in order to evaluate the strength of the interaction between the 5FU and fullerene surfaces. According to the results, adding alkaline earth metals increases the drug's adsorption energy on the C24N24 fullerene. In all cases, the drug molecule interacts with the metal atom through its CO group. Furthermore, the adsorption strength of the 5FU increases with metal atom size (Ca > Mg > Be), which is connected to the polarizability of these atoms. The adsorption energies of 5FU are shown to be highly sensitive on solvent effects and the acidity of the environment. The adsorption strength of 5FU decreases within the solvent (water), allowing it to be released more easily. The moderate adsorption energies and short desorption times of 5FU imply that it is reversibly adsorbed on the functionalized fullerenes.

The band gap of the heterostructure determines the withstand voltage. It is very important to regulate the band gap of heterojunctions and to investigate their electrical properties by applying external electric field. Based on density functional theory (DFT), ZnO/GaN vertical heterostructures with two stacking configurations (AB/BA and AB/AB, named H1 and H2, respectively) are constructed. The external electric field and vacancy defects of Zn, Ga, O and N atoms (VZn, VGa, VO and VN) are applied to analyze the electrical properties. The band gap can be tuned from 2.07 eV to 0 eV in H1 and 1.53 eV-0 eV in H2. As the electric field increases, H1 has stronger withstand voltage (-0.84-0.56 V/Å) than H2 (-0.26-0.26 V/Å). In addition, the structures deform obviously with the effect of vacancy defects, but remain stable. The presence of VGa and VN enables H1 and H2 to exhibits metal conductivity and VO change the band types of H1 and H2 from direct to indirect. The results of charge density difference (CDD) prove that a zero potential region and a weak electric field occur at the position of VZn and VO, respectively. Likewise, the external electric field is applied to the defective heterostructures. The bandgap also exhibits strong tunability, and the heterostructure with VO has the largest electric field modulation width. The above results indicate that ZnO/GaN exhibits excellent electrical properties with the influence of VO, which represents potential applications in electronic devices.

By developing next-generation lithium-ion batteries (LIBS), demand for exploring novel anode materials with exclusive electrochemical features and ultra-high capacity is increasing. In the current research, first-principles theory, and density functional theory (DFT) calculations were conducted to extensively investigate and compare the capability of three different borophene nanolayers, including striped, β12, and χ3 borophene, as a novel candidate for anode electrode in LIBs. We first predicted the most preferential Li atom adsorption sites on the three borophene structures. The predicted average formation energies for striped, β12, and χ3 borophene were obtained 3.123, 3.184, and 3.216 eV, respectively. The positive value of formation energy exhibits the sufficient stability of the structures. Moreover, the negative adsorption energy proved that Li atom insertion on all borophene monolayers is thermodynamically favorable. In order to simulate the lithiation process, we gradually increased the concentration of Li atoms. We found that the fully lithiated striped, β12 and χ3 borophenes could provide ultra-high specific capacities of 1700, 1983, and 1859 mAh/g, respectively. Structural analysis proved that the surface area expansion rate of the striped borophene in a fully lithiated state was 1%, which was lower than those of β12 and χ3 borophene with 3.33% and 2.63%, respectively. The analyses of electronic properties confirmed that borophenes were inherently metallic and superior ion conductive agents, even after fully lithiated state. Ion diffusion was studied using Nudged elastic band method and the value of diffusion energy barrier ranged from 0.03 to 0.36 eV which was lower than other promising 2D anode materials. Furthermore, open-circuit voltage results demonstrated that the electronic potential of modeled borophenes was low enough to be in the acceptable range of under 1.2V. All these reports exhibited that borophene nanolayers with excellent specific capacity and superior conductivity were desired candidates for anode materials of next generation LIBs.

A theoretical study on the reaction mechanisms of the addition of transition metal oxo complexes of the type MO3Cl (M = Mn, Tc, and Re) to tetramethylethylene (TME) is presented. Theoretical calculations using B3LYP/LACVP* and M06/LACVP* (LACVP* is a combination of the 6-31G(d) basis set along with LANL2DZ pseudopotentials on the metallic centres) were performed and the results are discussed within the framework of reaction energetics. The nature of the stability of the reaction mechanisms was equivalent for both theories. However, the M06/LACVP* simulations generally had slightly lower energies and shorter bond lengths compared to the B3LYP/LACVP* computations. Furthermore, it was observed that the reaction does not proceed via the stepwise reaction mechanism due to kinetic and thermodynamic instabilities. Epoxidation was also found to occur via the [2 + 2] concerted reaction mechanism for the MO3Cl (M = Tc and Re) whereas the permanganyl chloride complex epoxidizes TME via the [2 + 1] concerted reaction mechanism on the singlet potential energy surface (PES). Dioxylation was observed to proceed via the [3 + 2] route for the addition of MO3Cl (M = Tc and Re) and TME. Results indicate that all reaction surfaces were unselective except for the permanganyl chloride catalyzed surface which leads to the formation of epoxides exclusively. Changes in temperatures from 298.15 K to 373.15 K, resulted in kinetically and thermodynamically unstable reaction pathways as the activation and reaction energies increased generally. On the singlet PES, the rate constant calculations showed that the [3 + 2] catalyzed surface reaction mechanism leading to dioxylation was faster than the [2 + 2] mechanism in cases where plausible. Theoretical values from the global reactivity parameters, namely the chemical hardness, chemical potential, electrophilic and nucleophilic indices, are in good correlation with the DFT activation and reaction energies at both levels of theories. Thus, as the electrophilic nature of the metal decreases from Mn to Re, so do the activation and reaction energies increase from Mn to Re, indicating that the higher the electrophilicity of the metal centre, the more spontaneous the oxidation reaction.

The [3 + 2] cycloaddition (32CA) reaction of benzonitrile oxide (BNO) with 4-substituted 4-hydroxy-2-cyclopentenone has been investigated using molecular electron density theory (MEDT) at the Density Functional Theory (DFT) B3LYP/6-31G (d), M06/6-311G (d,p) and M06-2X/6-311++G (d,p) levels. The present theoretical computations indicate that the reaction of BNO with 4-substituted 4-hydroxy-2-cyclopentenones is via [3 + 2] cycloaddition, where the three atom component (TAC) chemo-selectively adds across the alkene functionality in the 2-cyclopentenones (Path A). Analysis of the electrophilic PA+ and nucleophilic PA- Parr functions at the different reaction sites in the alkene counterpart indicates that the aryl nitrile oxides add across the atomic centers with the highest Mulliken atomic spin densities. The results reported in this study are in good agreement with previous experimental work. The GEDT calculations unravel the low polar character of the [3 + 2] cycloaddition reactions. This reaction occurs with poor enantioselectivity, but a high degree of stereo-, peri-, diastereo, and regioselectivity is seen for the reaction of the BNO with 4-hydroxy-4-methyl-2-cyclopentenones. The regioselectivity of the reactions is the same in all the solvents investigated.

Through an use of three functionals (B3PW91, B3LYP and BP86) associated to a generic basis set LanL2DZ for transition metals (as well as halogen atoms) and 6-311+G (d,p) for others atoms, an examination of the bonding properties of a series of mononuclear half-sandwich nd7 transition metal (anticancer) complexes based on N∩N dendritic scaffolds (L) has been done. Collectively, complexes studied have adopted the piano-stool environment. An examination of the performance of each functional has shown that for the most reliable geometrical analysis of Metal-Nitrogen and Metal-Halogen bonds, the B3LYP and B3PW91 functionalities are suitable respectively. Regardless of the halogen ligand adopted, the B3LYP metal-nitrogen bond lengths are the most widely overestimated. A correlation has been built between the retained charge on each divalent transition metal cation and its metal ion affinity (MIA). Topological examinations reveal the higher instability of metal-N bonds compared to metal-X ones (X = Cl and Br). By the mean of the energy decomposition analysis, a predominant electrostatic character of metal … halogen and [LCP]- … [MX]+ interaction has been demonstrated. The transition metal atom … (hydrophobic) surface (Cp*) interaction is most pronounced for the chloride rhodium complexes of rhodium (combined with (E)-N-(pyridin-2-ylmethylene) Propan-1-amine and 2,2'- dipyridylketone ligands and iridium combined with 2,2'- dipyridylketone ligand. The charge decomposition analysis displays the weakening of the [Formula: see text] bonds in the studied complexes.

Here, the electronic transport characteristics of the 1,3,3-trimethylindolino-6'-nitrobenzopyrylospiran were studied by using NEGF and DFT methods. By being exposed to UV or visible light, this molecule can change from its MC to SP states. The titled structure was optimized at B3LYP/6-311++G(d,p) level of theory. To obtain conductivity results, the electrons of metal and organic atoms were approached by the single-plus polarization (SZP) for single-zeta and double-plus polarization (DZP) for double zeta basis sets, respectively. We examined some factors in this study, including various molecule geometries, the type of surface materials (Platinum, gold, and silver), the switching ratio, the gap between HOMO and LUMO levels, and the transmission spectra, at different bias voltages. The outcomes show that conductivity transforms from an off-state (high resistance) to an on-state as the molecule switches from MC to SP form (low resistance).

Roxadustat, a small-molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase domain 2 (HIF-PHD2) has been recently overruled by the American Food and Drug Administration (FDA) in Phase 3 clinical trials. This study provides insights into the dynamics of Roxadustat with PHD2 and proposes two FDA-approved drugs; Pemetrexed and Valrubicin to treat chronic kidney disease (CKD). Role of chemical scaffolds such as synthetic pyrimidine-based antifolate is found critical for PHD2 inhibitory activity, which is concurrent with the experimental findings for stimulating Endogenous erythropoietin (EPO) gene expression. Furthermore, Fe+2 and Mn+2 in solution are essential for imparting structural stability to the screened carboxylic and non-carboxylic acid drugs. Comparative analysis of FDA-approved drugs namely, Roxadustat, two-hit carboxylic, and non-carboxylic-acid type compounds (Pemetrexed and Valrubicin), as well as the control ligands (KU1 and 4JR), unveil structural dynamics of Roxadustat and its failure. However, the proposed FDA compounds, Pemetrexed and Valrubicin, used to treat mesothelioma, non-small cell lung cancer, and bladder cancer should be subjected to in vitro analysis for renal anemia.

In this quantum mechanistic study, density functional theory computations at the B3LYP hybrid level of theory, in addition to triple zeta basis set 6-311G (d, p), were utilized to investigate the chemoselectivities and regioselectivities of the [3 + 2] cycloaddition reaction of phenyl (2-thienyl) thioketone (B1) derivatives with nitrile oxide (B2) and diazopropane derivatives (B3). From the computations obtained, the reactions of nitrile oxide and diazopropane derivatives with phenyl (2-thienyl) thioketone proceed through an asynchronous one-step mechanism. The initial [3 + 2] cycloaddition reaction of B1 and B3 is followed by a nitrogen extrusion which is also highly asynchronous. Despite the steric and electronic effects of the substituent on the energetics, the reaction center is selectively observed at the thiocarbonyl site of B1. A study of the Parr functions at the different reaction sites in B1 indicates the addition of B2 and B3 via the atomic centers with the largest Mulliken atomic spin densities. These results show that the thiocarbonyl site is the most reactive center compared to the other ethylene groups on B1, irrespective of the three atom components used. The global electron density transfer results are in agreement with the selectivity and activation barriers observed in the reaction. Our results agree well with experimental observations.

Nature plays a major role in the development of new drugs which helps in preventing and treating human diseases. Anti-obesity compound database (AOCD) contains comprehensive information on all published small molecules from natural sources with anti-obesity potential targeting pancreatic lipase (PL), appetite suppressant (AS) and adipogenesis (AD). Presently the database contains 349 compounds isolated from 307 plants, 26 marine and 16 microbial sources. Users can query the AOCD database (https://aocd.swmd.co.in/) in several ways. The database was divided into three datasets (PL, AS and AD) to perform chemoinformatic analysis using Platform for Unified Molecular Analysis (PUMA), which were analyzed based on molecular descriptors, scaffold diversity and structural fingerprint diversity. Chemoinformatics study inferred the PL dataset has the highest diversity of compounds based on the Euclidean distance on molecular properties, scaffold diversity and pairwise similarity on fingerprint diversity. This study would hasten the process of anti-obesity drug discovery.

Based on the density functional theory (DFT) computations, we investigated the hydrogen storage performances of alkali metal (Li) and transition metal (Co) decorated the defective GaN nanosheets. Fundamental aspects including the interaction properties, bonding characteristics, adsorption ability, frontier orbital, HOMO-LUMO energy gaps, natural bond orbital (NBO) analysis, projected densities of states (PDOS) and statistical thermodynamic stability have been demonstrated to analyze the interaction properties of H2 molecules. As a theoretical strategy, non-covalent interactions (NCI) and the atoms in molecules (QTAIM) descriptors were performed to depict weak interactions. The LiN-GaN and CoN-GaN systems and the H2 uptake capacity revealed to be 7.78% and 5.55%, respectively. Our results demonstrated that H2 molecules are introduced sequentially on the Li and Co that functionalized both sides of VN-GaN nanosheets yielded the gravimetric densities up to 8.158% (2Co-VN-GaN) that well above the gravimetric DOE achieve. The 2LiN-GaN and 2CoN-GaN are energetically more effective for the H2 adsorption, stable and preferred than pristine GaN nanosheet. Additionally, two binding mechanisms including polarization of the hydrogen molecules and σ orbitals hybridization of H2 molecules have been investigated to explain the interaction of H2 molecules. The hydrogen desorption enthalpy and desorption temperatures of hydrogen molecules, indicating the H2 molecules are easy to desorb from Li and Co decorated defective GaN nanosheets. These results suggest the possibility of an excellent and promising nanostructural material to improve the performance of hydrogen storage for in fuel cells application at ambient temperature.

Nanoribbons with different edge functionalization display interesting electronic properties for various device applications. It requires the necessity of exploring the novel passivating elements commensurate to various technological applications. In this direction, here we have compared the effect of H and F-passivation on the edges of zigzag SiC nanoribbons (ZSiCNR) using density functional theory based calculations. Remarkably, present study reveals that F could be used as an effective passivating element for ZSiCNR similar to widely explored H-passivations. Various possible combinations of F/H are found to have stable structural integrity for practical applications. The effect of F-adatom adsorption is also discussed which present peculiar electronic properties. The half-metallic behavior is observed to be realized via F-adsoprtion which is further confirmed with the transport calculations. The obtained negative differential resistance along the spin dependent electron transport pledges towards wide spread applications of considered ZSiCNR interacting with F.

Procathepsins, inactive precursors of cathepsins are present in the extracellular matrix (ECM) and in lysosomes. Their active forms are involved in a number of biologically relevant processes, including bone resorption, intracellular proteolysis and regulation of programmed cell death. These processes might be mediated by glycosaminoglycans (GAGs), long unbranched periodic negatively charged polysaccharides. GAGs are also present in ECM and play important role in anticoagulation, angiogenesis and tissue regeneration. GAGs not only mediate the enzymatic activity of cathepsins but can also regulate the process of procathepsin maturation, as it was shown for procathepsin B and S. In this study, we propose the molecular mechanism underlying the biological role of GAGs in procathepsin S maturation and compare our findings with computational data obtained for procathepsin B. We rigorously analyse procathepsin S-GAG complexes in terms of their dynamics, free energy and potential allosteric regulation. We conclude that the GAG binding region might have an effect on the dynamics of procathepsin S structure and so affect its maturation by two different mechanisms.

The repolarizing current (Ikr) produced by the hERG potassium channel forms a major component of the cardiac action potential and blocking this current by small molecule drugs can lead to life-threatening cardiotoxicity. Understanding the mechanisms of drug-mediated hERG inhibition is essential to develop a second generation of safe drugs, with minimal cardiotoxic effects. Although various computational tools and drug design guidelines have been developed to avoid binding of drugs to the hERG pore domain, there are many other aspects that are still open for investigation. This includes the use computational modelling to study the implications of hERG mutations on hERG structure and trafficking, the interactions of hERG with hERG chaperone proteins and with membrane-soluble molecules, the mechanisms of drugs that inhibit hERG trafficking and drugs that rescue hERG mutations. The plethora of available experimental data regarding all these aspects can guide the construction of much needed robust computational structural models to study these mechanisms for the rational design of safe drugs.