Chompoonut Rungnim

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

Summary In the present study, our aim is to investigate the preferential binding mode and encapsulation of the flavonoid fisetin in the nano-pore of β-cyclodextrin (β-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 β-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/β-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.

Replica exchange molecular dynamics simulation of chitosan for drug delivery system based on carbon nanotube

Chitosan is an important biopolymer in the medical applications because of its excellent biocompatibility. It has been recently highlighted in the targeted drug delivery system (DDS) by improvement of the carbon nanotube (CNT) solubility. To investigate the effect of chitosan length, the two targeted DDSs with 30 and 60 chitosan monomers were performed by replica-exchange molecular dynamics simulations at temperatures in the range of 300-455K with three different combinations of force fields and implicit solvation models. Each DDS model contains the epidermal growth factor (EGF), chitosan (CS) of 30 (30CS) and 60 (60CS) monomers, single-wall CNT (SWCNT) and gemcitabine (Gemzar) as the model payload anticancer drug, called EGF/30CS/SWCNT/Gemzar and EGF/60CS/SWCNT/Gemzar, respectively. The SWCNT confines gemcitabine inside its cavity, while the outer surface is wrapped by chitosan in which one end is linked to the EGF. Even though the REMD results from different force fields and implicit solvation models are not exactly identical, all of them are in the same trend confirming that in the EGF/30CS/SWCNT/Gemzar DDS the 30CS chain was not long enough to wrap around the SWCNT, and consequently the EGF was located so close to the tube as to potentially cause steric inhibition of the binding of EGF to its receptor (EGFR), which is highly expressed on the surface of cancer cells. On the other hand, this phenomenon is not observed in the EGF/60CS/SWCNT/Gemzar DDS in which the 60CS was found to completely wrap over the CNT outer surface using only 50 chitosan units. The evidence suggested that a ratio of chitosan molecular weight per SWCNT surface area larger than 9.9×10(-7)kg/m(2) is suitable for application in targeted DDSs. Although an increase in the temperature is likely to influence the overall DDS structure, and especially the orbit of helical chitosan on the SWCNT and the EGF conformation, gemcitabine is still encapsulated inside the tube.

A density functional study of propylene glycol conversion to propanal and propanone of various acid-catalyzed reaction models : A water-addition effect

The acid‐catalyzed models on reaction mechanisms of pinacol rearrangement of propylene glycol conversion to propanal and propanone have been investigated using the density functional method at 298.15 K. Thermodynamic quantities of activation steps of four water‐addition models were obtained. The number of added water interacting with the transition states of three concerted pathways has obviously affected the product ratio. The relative energetic profiles of the conversion reactions of all solvation models have been comparatively displayed. Estimation of the percent ratio of product composition computed from activation free energies of each acid‐catalyzed reaction model was carried out. The percent ratios of propanal and propanone were decreased as the number of added water increased.

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 HgI<HgBr<HgCl. This trend coincides with the experimental observations which reported the efficiency of halogen impregnated AC for Hg elimination significantly decreases as I-AC>Br-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/β-cyclodextrin inclusion complex

Summary 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 β-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 β-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 β-CD, depending on the concentration employed.

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 thioguanineu2009>u2009mercaptopurineu2009>u2009fluorouracil. 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, <5xa0kcal/mol, depending on the adsorption site and the alignment of the drug at this site.

Metal cluster-deposited graphene as an adsorptive material for m-xylene

Tetramer clusters of platinum (Pt), palladium (Pd), gold (Au) and silver (Ag) deposited on pristine and defective graphenes were studied as potential adsorptive materials for m-xylene using density functional theory (DFT) calculations including van der Waals contributions to the Hamiltonian. Structural, energetic and electronic (i.e. d-band center, partial density of state and explicit charge) properties have been investigated for understanding the m-xylene adsorption process. The m-xylene adsorption capability of these materials has been compared. The calculation results revealed that Pt4- and Pd4–DG adsorb m-xylene via a chemisorption process, while Au4- and Ag4–DG adsorb m-xylene via physisorption. These insights are valuable for applying and developing carbon-based materials for volatile organic compound (VOC) removal applications, since physisorption-driven materials are suitable as sorbents while their chemisorption counterparts are suitable as catalysts in an oxidation reaction. Those properties in turn can be tuned by modulating metal adsorption on the carbon-based materials.

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.

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

In this study, the inclusion complex formation between α-mangostin and water-soluble quaternized β-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 β-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%u202f>u202f15%u202f>u202f75%). 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.