The role of organoaluminum and electron donors in propene insertion on the Ziegler-Natta catalyst.

Alkyl aluminium plays a primary role in activating Ti within Ziegler-Natta (ZN) catalysts for propylene polymerization. We performed density functional calculations to explore the additional roles of AlEt3 and AlEt2Cl, in conjunction with diisobutyl phthalate (DIBP) internal donor and dicyclopentyl dimethoxysilane (DCPDMS) external donor, to enhance the stereoselectivity of propene insertion. Based on our calculated adsorption energies on the (MgCl2)13/TiCl2iBu cluster model for the ZN catalyst, the presence of DIBP on the cluster essentially facilitated AlEt2Cl adsorption while AlEt2Cl also promoted the adsorption of DIBP. The reaction between AlEt3 and DIBP on the cluster led to the extraction of DIBP, creating an available site for DCPDMS adsorption. While the stereoselectivity, represented by the difference in the activation energies between 1,2-re and 1,2-si insertions of propene, was negligible on the cluster containing only DIBP, it became significant on the clusters containing both AlEt2Cl and DIBP (and DCPDMS). AlEt2Cl plays a pivotal role in imposing steric effects near the Ti active site, thereby increasing stereoselectivity. Our findings suggest the importance of including AlEt2Cl alongside DIBP (and DCPDMS) in the ZN cluster model to investigate stereoselective propene insertion. Considering AlEt2Cl adsorption and AlEt3 reaction with internal donors is essential in developing Ziegler-Natta catalysts.

Unraveling Structural and Acidic Properties of Al-SBA-15-supported Metal Phosphates: Assessment for Glucose Dehydration.

5-Hydroxymethylfurfural (5-HMF) synthesized through glucose conversion requires Lewis acid (L) site for isomerization and Brønsted acid (B) site for dehydration. The objective of this work is to investigate the influence of the metal type of Al-SBA-15-supported phosphates of Cr, Zr, Nb, Sr, and Sn on glucose conversion to 5-HMF in a NaCl-H2 O/n-butanol biphasic solvent system. The structural and acid property of all supported metal phosphate samples were fully verified by several spectroscopic methods. Among those catalysts, CrPO/Al-SBA-15 provided the best performance with the highest glucose conversion and 5-HMF yield, corresponding to the highest total acidity of 0.65 mmol/g and optimal L/B ratio of 1.88. For CrPO/Al-SBA-15, another critical parameter is the phosphate-to-chromium ratio. Moreover, DFT simulation of glucose conversion to 5-HMF on the surface of the optimized chromium phosphate structure reveals three steps of fructose dehydration on the Brønsted acid site. Finally, the optimum reaction condition, reusability, and leaching test of the best catalyst were determined. CrPO/Al-SBA-15 is a promising catalyst for glucose conversion to high-value-added chemicals in future biorefinery production.

Unraveling the Adsorption Behavior of Thymol on Carbon and Silica Nanospheres for Prolonged Antibacterial Activity: Experimental and DFT Studies.

Functionalization of thymol (Thy) on nanocarriers is a key step in achieving prolonged antimicrobial activity. This requires nanomaterials with uniform particle diameters and suitable thymol sorption. Herein, hollow carbon (HC) and SiO2-carbon core-shell (SiO2@C) were investigated due to their diverse morphologies and ease of surface modification. HC (14 ± 1 nm size) and SiO2@C (10 ± 1.5 nm size) were synthesized by the Stöber method before thymol was loaded by incipient wetness impregnation. Nanoparticle physicochemical properties were characterized by advanced techniques, including X-ray photoelectron spectroscopy (XPS) and near-edge X-ray absorption fine structure (NEXAFS). Adsorption energies of thymol on the carbon and SiO2 surfaces were elucidated by density functional theory (DFT) simulations. Moreover, the in vitro thymol release profiles and antibacterial activity were evaluated. The experimental results indicated that the oxy-carbon surface species of HC led to longer thymol release profiles than the -OH group of SiO2@C. The DFT calculations revealed that the weaker physical interaction of thymol on HC was better for drug release than that on SiO2@C. Thus, a longer thymol release profile of HC with hollow structures showed better antibacterial performance against Gram-positive bacteria Staphylococcus aureus than that of SiO2@C with core-shell structures. This work confirms the important role of carbon morphology and specific functional groups in thymol release profiles for the further development of inhibition products.

Self-calcifying lipid nanocarrier for bone tissue engineering.

BACKGROUND: A nanoemulsion with specific surface properties (such as charge and functional groups) can initiate the deposition of calcium phosphate (CaP) on its surface, leading to formation of CaP nanoparticles with a lipid core. The lipid core can carry lipophilic compounds based on the function of the nanoemulsion. Therefore, a dual purpose nanoemulsion of lipid nanoparticles (LNPs) exhibiting self-calcifying and carrier abilities can be developed. METHODS: We employed an emulsification process to formulate LNPs with a specific charged surface. The LNPs were tested for their ability to calcify in simulated body fluid and encapsulate cholecalciferol (a model of active compound). The self-calcifying LNP was successfully fabricated using the emulsification process and stabilized using a mixture of polysorbate 80 and polysorbate 20. RESULTS: The LNPs incubated in simulated body fluid bound to calcium and phosphate, subsequently forming CaP on the particle surface and resulting in approximately 180-nm CaP spheres with a lipid core. The LNPs facilitated calcium phosphate deposition in the collagen scaffolds. In addition, LNPs can be used as carriers of lipophilic compounds without impeding the self-calcifying ability.

Ti4-Decorated B/N-doped graphene as a high-capacity hydrogen storage material: a DFT study.

The adsorption properties of the hydrogen atom on our newly designed materials were investigated using density functional theory (DFT) calculations, focusing on the role of dopants in modulating the binding properties of the metal. We proposed decorating Ti4 on pristine, B- and N-doped graphene surfaces for preparing a large-capacity hydrogen-storage device. Computational results indicate that the doping of B on graphene enhances the interaction between the metal cluster and the supporting substrate with a very strong binding energy of -6.45 eV, which is the strongest interaction among our proposed catalysts. This binding energy prevents the aggregation and formation of Ti-metal clusters. Dissociative chemisorption of the first H2 molecule occurs on all materials. Metal hydrides preferentially exhibit strong hybridization between the H-1s and Ti-3d orbitals. Furthermore, Ti4 decorated B-graphene is the most effective, with a high capacity of hydrogen adsorption which could be released under practical conditions. We confirmed that eight H2 molecules could stably adsorb on Ti4/BGr with six reversible hydrogen adsorptions. Our proposed B-doped graphene-based material, Ti4/BGr, offers high cluster-stability on the substrate with high-capacity hydrogen storage compared to various other surfaces in the previous work. Therefore, Ti4 decorated B-graphene is a promising candidate material for use as a reversible hydrogen storage material.

Cavity Closure of 2-Hydroxypropyl-ß-Cyclodextrin: Replica Exchange Molecular Dynamics Simulations.

2-Hydroxypropyl-ß-cyclodextrin (HPßCD) has unique properties to enhance the stability and the solubility of low water-soluble compounds by inclusion complexation. An understanding of the structural properties of HPßCD and its derivatives, based on the number of 2-hydroxypropyl (HP) substituents at the α-d-glucopyranose subunits is rather important. In this work, replica exchange molecular dynamics simulations were performed to investigate the conformational changes of single- and double-sided HP-substitution, called 6-HPßCDs and 2,6-HPßCDs, respectively. The results show that the glucose subunits in both 6-HPßCDs and 2,6-HPßCDs have a lower chance of flipping than in ßCD. Also, HP groups occasionally block the hydrophobic cavity of HPßCDs, thus hindering drug inclusion. We found that HPßCDs with a high number of HP-substitutions are more likely to be blocked, while HPßCDs with double-sided HP-substitutions have an even higher probability of being blocked. Overall, 6-HPßCDs with three and four HP-substitutions are highlighted as the most suitable structures for guest encapsulation, based on our conformational analyses, such as structural distortion, the radius of gyration, circularity, and cavity self-closure of the HPßCDs.

Biological Evaluation and Molecular Dynamics Simulation of Chalcone Derivatives as Epidermal Growth Factor-Tyrosine Kinase Inhibitors.

Targeted cancer therapy has become a high potential cancer treatment. Epidermal growth factor receptor (EGFR), which plays an important role in cell signaling, enhanced cell survival and proliferation, has been suggested as molecular target for the development of novel cancer therapeutics. In this study, a series of chalcone derivatives was screened by in vitro cytotoxicity against the wild type (A431 and A549) and mutant EGFR (H1975 and H1650) cancer cell lines, and, subsequently, tested for EGFR-tyrosine kinase (TK) inhibition. From the experimental screening, all chalcones seemed to be more active against the A431 than the A549 cell line, with chalcones 1c, 2a, 3e, 4e, and 4t showing a more than 50% inhibitory activity against the EGFR-TK activity and a high cytotoxicity with IC50 values of < 10 µM against A431 cells. Moreover, these five chalcones showed more potent on H1975 (T790M/L858R mutation) than H1650 (exon 19 deletion E746-A750) cell lines. Only three chalcones (1c, 2a and 3e) had an inhibitory activity against EGFR-TK with a relative inhibition percentage that was close to the approved drug, erlotinib. Molecular dynamics studies on their complexes with EGFR-TK domain in aqueous solution affirmed that they were well-occupied within the ATP binding site and strongly interacted with seven hydrophobic residues, including the important hinge region residue M793. From the above information, as well as ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties, all three chalcones could serve as lead compounds for the development of EGFR-TK inhibitors.

Computational screening of chalcones acting against topoisomerase IIα and their cytotoxicity towards cancer cell lines.

Targeted cancer therapy has become one of the high potential cancer treatments. Human topoisomerase II (hTopoII), which catalyzes the cleavage and rejoining of double-stranded DNA, is an important molecular target for the development of novel cancer therapeutics. In order to diversify the pharmacological activity of chalcones and to extend the scaffold of topoisomerase inhibitors, a series of chalcones was screened against hTopoIIα by computational techniques, and subsequently tested for their in vitro cytotoxicity. From the experimental IC50 values, chalcone 3d showed a high cytotoxicity with IC50 values of 10.8, 3.2 and 21.1 µM against the HT-1376, HeLa and MCF-7 cancer-derived cell lines, respectively, and also exhibited an inhibitory activity against hTopoIIα-ATPase that was better than the known inhibitor, salvicine. The observed ligand-protein interactions from a molecular dynamics study affirmed that 3d strongly interacts with the ATP-binding pocket residues. Altogether, the newly synthesised chalcone 3d has a high potential to serve as a lead compound for topoisomerase inhibitors.

Influence of hydrogen spillover on Pt-decorated carbon nanocones for enhancing hydrogen storage capacity: A DFT mechanistic study.

We used density functional theory (DFT) to investigate hydrogen adsorption and diffusion on platinum-decorated carbon nanocones (Pt-CNCs). The curvature presented in the conical section of CNC materials affects the Pt binding stability. The role of Pt atoms as an active catalyst for H2 adsorption and dissociation has been investigated in perfect Pt-4CNC and defect Pt-v4CNC systems. Then, the spillover mechanism of dissociated hydrogen atoms in Pt-v4CNC is explored via two reaction steps: (i) H-migration from Pt to carbon atoms and (ii) H-diffusion via the C-C route throughout the CNC surface. Our results show that the presence of the hydrogen atom on the Pt catalyst can efficiently induce the H-diffusion process through the C-C surface, and the Pt-H bond significantly facilitates the H-migration from C-H bonds near to the active Pt catalyst to the adjacent carbon atom with an energy barrier <0.5 eV under ambient conditions. Altogether, the theoretical results support the concept of the spillover mechanism as a key process for enhancing the hydrogen storage capacity of metal-decorated CNCs. These results improve our understanding about the hydrogen spillover mechanism and the catalytic reactions which are very important for the development of highly efficient hydrogen storage materials.

Investigation of Functional Graphene/Cypermethrin Pesticide Molecules by Using Density Functional Theory Calculation.

Graphene has received tremendous interest owing to its excellence excellent in electrical conductivity and very high specific surface area. In this work, density functional theory (DFT) is used in order to investigate optical and electrical properties of functionalized graphene which interacted with cypermethrin pesticide molecules. The structures of graphene and pesticide were designed and optimized with M06-2x/6-31G(d,p) method of calculation. Graphene was functionalized by carboxyl, amine and hydroxyl groups to investigate the cypermethrin molecules. The binding energy, band spectra, optical properties and electron distribution of complexes were analyzed. The results reveal that the functionalized graphene with hydroxyl group can highly improve the interaction between graphene and cypermethrin with the lowest binding energy.

Controllable encapsulation of α-mangostin with quaternized ß-cyclodextrin grafted chitosan using high shear mixing.

In this study, the inclusion complex formation between α-mangostin and water-soluble quaternized ß-CD grafted-chitosan (QCD-g-CS) was investigated. Inclusion complex formation with encapsulation efficiency (%EE) of 5, 15 and 75% can be varied using high speed homogenizer. Tuning %EE plays a role on physicochemical and biological properties of α-mangostin/QCD-g-CS complex. Molecular dynamics simulations indicate that α-mangostin is included within the hydrophobic ß-CD cavity and being absorbed on the QCD-g-CS surface, with these results being confirmed by Fourier transform infrared (FTIR) spectroscopy. Probing the release characteristics of the inclusion complex at various %EE (5%, 15% and 75%) in simulated saliva (pH 6.8) demonstrated that α-mangostin release rates were dependent on % EE (order 5% > 15% > 75%). Additionally, higher antimicrobial and anti-inflammation activities were observed for the inclusion complex than those of free α-mangostin due to enhance the solubility of α-mangostin through the inclusion complex with QCD-g-CS.

Effects of shape, size, and pyrene doping on electronic properties of graphene nanoflakes.

Effects of size, shape, and pyrene doping on electronic properties of graphene nanoflakes (GNFs) were theoretically investigated using density functional theory method with PBE, B3PW91, and M06-2X functionals and cc-pVDZ basis set. Two shapes of zigzag GNFs, hexagonal (HGN) and rhomboidal (RGN), were considered. The energy band gap of GNF depends on shape and decreases with size. The HGN has larger band gap energy (1.23-3.96 eV) than the RGN (0.13-2.12 eV). The doping of pyrene and pyrene derivatives on both HGN and RGN was also studied. The adsorption energy of pyrene and pyrene derivatives on GNF does not depend on the shape of GNFs with energies between 21 and 27 kcal mol-1. The substituent on pyrene enhances the binding to GNF but the strength does not depend on electron withdrawing or donating capability. The doping by pyrene and pyrene derivatives also shifts the HOMO and LUMO energies of GNFs. Both positive (destabilizing) and negative (stabilizing) shifts on HOMO and LUMO of GNFs were seen. The direction and magnitude of the shift do not follow the electron withdrawing and donating capability of pyrene substituents. However, only a slight shift was observed for doped RGN. A shift of 0.19 eV was noticed for HOMO of HGN doped with 1-aminopyrene (pyNH2) and of 0.04 eV for LUMO of HGN doped with 1-pyrenecarboxylic acid (pyCOOH). Graphical Abstract HOMO and LUMO Energies of pyrene/pyrene derivatives doped Graphene Nanoflakes.

Host-guest interactions between sildenafil and cyclodextrins: Spectrofluorometric study and molecular dynamic modeling.

Sildenafil (SF) was included in cyclodextrins (CD) to enhance its solubility. Spectrofluorometry was used to confirm the complexation constant (stability constant). The orientations of SF inside the ß-CDs and γ-CDs were fully illustrated. Molecular dynamics simulations were performed on two inclusion complexes (ß-CD/SF and γ-CD/SF) in the aqueous system. The polar methylpiperazine group was found to locate inside the ß-CD cavity, both in the wide and narrow side and was positioned 2°A from the center. In contrast, the methylpiperazine group did not fit well within the γ-CD cavity. Moreover, these results also confirmed hydrogen bonding that the highest number of bonding formed between the polar methylpiperazine sulfonyl structure and the hydroxyl group of ß-CD. The simulated binding free energy of the methylpiperazine-ß-CD inclusion complex (-6.01kcal/mol), featured a large contribution from electrostatic and van der Waals forces, which was the most stable complex. The association constant of ß-CD/SF (12.3) was higher than γ-CD/SF (3.3) and confirmed with in silico measurements of binding free energy. In summary, SF forms a stable complex with ß-CD.

Comparison of Implicit and Explicit Solvation Models for Iota-Cyclodextrin Conformation Analysis from Replica Exchange Molecular Dynamics.

Large ring cyclodextrins have become increasingly important for drug delivery applications. In this work, we have performed replica-exchange molecular dynamics simulations using both implicit and explicit water solvation models to study the conformational diversity of iota-cyclodextrin containing 14 α-1,4 glycosidic linked d-glucopyranose units (CD14). The new quantifiable calculation methods are proposed to analyze the openness, bending, and twisted conformation of CD14 in terms of circularity, biplanar angle, and one-directional conformation (ODC). CD14 in GB implicit water model (Igb5) was found mostly in an opened conformation with average circularity of 0.39 ± 0.16 and a slight bend with average biplanar angle of 145.5 ± 16.0°. In contrast, CD14 in TIP3P explicit water solvation is significantly twisted with average circularity of 0.16 ± 0.10, while 29.1% are ODCs. In addition, classification of CD14 conformations using a Gaussian mixture model (GMM) shows that 85.0% of all CD14 in implicit water at 300 K correspond to the elliptical conformation, in contrast to 82.3% in twisted form in explicit water. GMM clustering also reveals minority conformations of CD14 such as the 8-shape, boat-form, and twisted conformations. This work provides fundamental insights into CD14 conformation, influence of solvation models, and also proposes new quantifiable analysis techniques for molecular conformation studies in the future.

pH-controlled doxorubicin anticancer loading and release from carbon nanotube noncovalently modified by chitosan: MD simulations.

In the present study, we describe here the pH condition activating doxorubicin (DOX) anticancer drugs loading and release over single-wall carbon nanotube (SWNT) non-covalently wrapped with chitosan (CS). The possibility of drug displacement on DOX/CS/SWNT nanocarrier was investigated using molecular dynamics simulations. The drug loading and release were monitored via displacement analysis and binding energy calculations. The simulated results clearly showed that the drugs well interacted with the CS/SWNT at physiological pH (pH 7.4), where CS was in the deprotonated form. Contrastingly, in weakly acidic environments (pH 5.0-6.5) which is a pH characteristics of certain cancer environments, the protonated CS became loosen wrapped around the SWNT and triggered drugs release as a result of charge-charge repulsion between CS and drug molecules. The obtained data fulfil the understanding at atomic level of drug loading and release controlled by pH-sensitive polymer, which might be useful for further cancer therapy researches.

How strong is the edge effect in the adsorption of anticancer drugs on a graphene cluster?

The adsorption of nucleobase-analog anticancer drugs (fluorouracil, thioguanine, and mercaptopurine) on a graphene flake (C54H18) was investigated by shifting the site at which adsorption occurs from one end of the sheet to the other end. The counterpoise-corrected M06-2X/cc-pVDZ binding energies revealed that the binding stability decreases in the sequence thioguanine > mercaptopurine > fluorouracil. We found that adsorption near the middle of the sheet is more favorable than adsorption near the edge due to the edge effect. This edge effect is stronger for the adsorption of thioguanine or mercaptopurine than for fluorouracil adsorption. However, the edge effect reduces the binding energy of the drug to the flake by only a small amount, <5 kcal/mol, depending on the adsorption site and the alignment of the drug at this site.

Complete reaction mechanisms of mercury oxidation on halogenated activated carbon.

The reaction mechanisms of mercury (Hg) adsorption and oxidation on halogenated activated carbon (AC) have been completely studied for the first time using density functional theory (DFT) method. Two different halogenated AC models, namely X-AC and X-AC-X (X=Cl, Br, I), were adopted. The results revealed that HgX is found to be stable-state on the AC edge since its further desorption from the AC as HgX, or further oxidation to HgX2, are energetically unfavorable. Remarkably, the halide type does not significantly affect the Hg adsorption energy but it strongly affects the activation energy barrier of HgX formation, which obviously increases in the order HgIBr-AC>Cl-AC. Thus, the study of the complete reaction mechanism is essential because the adsorption energy can not be used as a guideline for the rational material design in the halide impregnated AC systems. The activation energy is an important descriptor for the predictions of sorbent reactivity to the Hg oxidation process.

Protein-protein interactions between SWCNT/chitosan/EGF and EGF receptor: a model of drug delivery system.

Epidermal growth factor (EGF) was used as the targeting ligand to enhance the specificity of a cancer drug delivery system (DDS) via its specific interaction with the EGF receptor (EGFR) that is overexpressed on the surface of some cancer cells. To investigate the intermolecular interaction and binding affinity between the EGF-conjugated DDS and the EGFR, 50 ns molecular dynamics simulations were performed on the complex of tethered EGFR and EGF linked to single-wall carbon nanotube (SWCNT) through a biopolymer chitosan wrapping the tube outer surface (EGFR·EGF-CS-SWCNT-Drug complex), and compared to the EGFR·EGF complex and free EGFR. The binding pattern of the EGF-CS-SWCNT-Drug complex to the EGFR was broadly comparable to that for EGF, but the binding affinity of the EGF-CS-SWCNT-Drug complex was predicted to be somewhat better than that for EGF alone. Additionally, the chitosan chain could prevent undesired interactions of SWCNT at the binding pocket region. Therefore, EGF connected to SWCNT via a chitosan linker is a seemingly good formulation for developing a smart DDS served as part of an alternative cancer therapy.

Co-solvation effect on the binding mode of the α-mangostin/ß-cyclodextrin inclusion complex.

Cyclodextrins (CDs) have been extensively utilized as host molecules to enhance the solubility, stability and bioavailability of hydrophobic drug molecules through the formation of inclusion complexes. It was previously reported that the use of co-solvents in such studies may result in ternary (host:guest:co-solvent) complex formation. The objective of this work was to investigate the effect of ethanol as a co-solvent on the inclusion complex formation between α-mangostin (α-MGS) and ß-CD, using both experimental and theoretical studies. Experimental phase-solubility studies were carried out in order to assess complex formation, with the mechanism of association being probed using a mathematical model. It was found that α-MGS was poorly soluble at low ethanol concentrations (0-10% v/v), but higher concentrations (10-40% v/v) resulted in better α-MGS solubility at all ß-CD concentrations studied (0-10 mM). From the equilibrium constant calculation, the inclusion complex is still a binary complex (1:1), even in the presence of ethanol. The results from our theoretical study confirm that the binding mode is binary complex and the presence of ethanol as co-solvent enhances the solubility of α-MGS with some effects on the binding affinity with ß-CD, depending on the concentration employed.

Binding mode and free energy prediction of fisetin/ß-cyclodextrin inclusion complexes.

In the present study, our aim is to investigate the preferential binding mode and encapsulation of the flavonoid fisetin in the nano-pore of ß-cyclodextrin (ß-CD) at the molecular level using various theoretical approaches: molecular docking, molecular dynamics (MD) simulations and binding free energy calculations. The molecular docking suggested four possible fisetin orientations in the cavity through its chromone or phenyl ring with two different geometries of fisetin due to the rotatable bond between the two rings. From the multiple MD results, the phenyl ring of fisetin favours its inclusion into the ß-CD cavity, whilst less binding or even unbinding preference was observed in the complexes where the larger chromone ring is located in the cavity. All MM- and QM-PBSA/GBSA free energy predictions supported the more stable fisetin/ß-CD complex of the bound phenyl ring. Van der Waals interaction is the key force in forming the complexes. In addition, the quantum mechanics calculations with M06-2X/6-31G(d,p) clearly showed that both solvation effect and BSSE correction cannot be neglected for the energy determination of the chosen system.