The aim of this work is to improve physical properties and biological activities of the two flava... more The aim of this work is to improve physical properties and biological activities of the two flavanones hesperetin and naringenin by complexation with β-cyclodextrin (β-CD) and its methylated derivatives (2,6-di-O-methyl-β-cyclodextrin, DM-β-CD and randomly methylated-β-CD, RAMEB). The free energies of inclusion complexes between hesperetin with cyclodextrins (β-CD and DM-β-CD) were theoretically investigated by molecular dynamics simulation. The free energy values obtained suggested a more stable inclusion complex with DM-β-CD. The vdW force is the main guest-host interaction when hesperetin binds with CDs. The phase solubility diagram showed the formation of a soluble complex of AL type, with higher increase in solubility and stability when hesperetin and naringenin were complexed with RAMEB. Solid complexes were prepared by freeze-drying, and the data from differential scanning calorimetry (DSC) confirmed the formation of inclusion complexes. The data obtained by the dissolution method showed that complexation with RAMEB resulted in a better release of both flavanones to aqueous solution. The flavanones-β-CD/DM-β-CD complexes demonstrated a similar or a slight increase in anti-inflammatory activity and cytotoxicity towards three different cancer cell lines. The overall results suggested that solubilities and bioactivities of both flavanones were increased by complexation with methylated β-CDs.
Combined experimental-theoretical method is an effective tool to study dye–zeolite system.The con... more Combined experimental-theoretical method is an effective tool to study dye–zeolite system.The confinement of LTL zeolite affects isomerization of trans- to cis- azobenzene.Our model can accurately predict the optical properties of t-azobenzene in zeolite.The t-azobenzene adsorbed in H-LTL channel is protonated by Brønsted acid site of H-LTL.The t-azobenzene can be converted back to the cis-form with exposure to UV-light.The spectroscopic methods and molecular modeling were employed to study the photophysical properties of t-azobenzene in solution and in the channel of zeolite LTL. The effects of the interactions between the dye molecules and zeolite framework on the electronic states were examined experimentally by diffuse reflectance UV–visible absorption and fluorescence emission. The changes observed in the spectra were dependent on the forms of zeolite LTL (H-LTL and K-LTL). In addition the structural properties of the dye in the different environments were also intensively investigated by density functional theory (DFT) calculations with B3LYP/6-31G(d,p) level of theory. The 324T cluster model and the ONIOM (B3LYP/6-31G(d,p):UFF) methods were employed for the calculating the orientations of the dye in the zeolite system. The experimental data are consistent with the calculation results. The dye in solution can be relaxed into the planar structure, however, when the dye is in LTL zeolite it is constrained by the framework and is therefore twisted due to the confinement effects of zeolite. Moreover, emission spectra were detected only from protonated t-azobenzene incorporated into H-LTL while no emission was detected from t-azobenzene confined in K-LTL framework. The results of the study lead to the conclusion that the zeolite framework affects both the structural and photophysical properties of t-azobenzene.The spectroscopic methods and molecular modeling were employed to study the photophysical properties of t-azobenzene in the channel of zeolite LTL. The trans-isomer can be isomerized to the cis-isomer with the confinement effect in zeolite channel.
Pinostrobin (PNS) is one of the important flavonoids and can be abundantly found in the rhizomes ... more Pinostrobin (PNS) is one of the important flavonoids and can be abundantly found in the rhizomes of fingerroot (Boesenbergia rotrunda) and galangal (Alpinia galangal and Alpinia officinarum), the herbal basis of Southeast Asian cooking. Similar to other flavonoids, PNS exhibits anti-oxidative, anti-inflammatory and anti-cancer properties. However, this compound has an extremely low water solubility that limits its use in pharmaceutical applications. Beta-cyclodextrin (βCD) and its derivatives, 2,6-dimethyl-βCD (2,6-DMβCD) and the three hydroxypropyl-βCDs (2-HPβCD, 6-HPβCD and 2,6-DHPβCD), have unique properties that enhance the stability and solubility of such low-soluble guest molecules. In the present study, molecular dynamics simulations were applied to investigate the dynamics and stability of PNS inclusion complexes with βCD and its derivatives (2,6-DMβCD, 2,6-DHPβCD, 2-HPβCD and 6-HPβCD). PNS was able to form complexes with βCD and all four of its derivatives by either the chromone (C-PNS) or phenyl (P-PNS) ring dipping toward the cavity. According to the molecular mechanics-generalized Born surface area binding free energy values, the stability of the different PNS/βCD complexes was ranked as 2,6-DHPβCD>2,6-DMβCD>2-HPβCD>6-HPβCD>βCD. These theoretical results were in good agreement with the stability constants that had been determined by the solubility method.
There is growing interest in large-ring cyclodextrins (LR-CDs) which are known to be good host mo... more There is growing interest in large-ring cyclodextrins (LR-CDs) which are known to be good host molecules for larger ligands. The isolation of a defined size LR-CD is an essential prerequisite for studying their structural properties. Unfortunately the purification procedure of these substances turned out to be very laborious. Finally the problem could be circumvented by a theoretical consideration: the highly advantageous replica exchange molecular dynamics (REMD) simulation (particularly suitable for studies of conformational changes) offers an ideal approach for studying the conformational change of ɛ-cyclodextrin (CD10), a smaller representative of LR-CDs. Three carbohydrate force fields and three solvent models were tested. The conformational behavior of CD10 was analyzed in terms of the flip (turn) of the glucose subunits within the macrocyclic ring. In addition a ranking of conformations with various numbers of turns was preformed. Our findings might be also helpful in the temperature controlled synthesis of LR-CDs as well as other experimental conditions, in particular for the host-guest reaction.
Journal of Biomolecular Structure and Dynamics, 2015
Epidermal growth factor (EGF) was used as the targeting ligand to enhance the specificity of a ca... more 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 (MDSs) 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.
ABSTRACT The effect of electron donating and withdrawing substituents on the enol absorption and ... more ABSTRACT The effect of electron donating and withdrawing substituents on the enol absorption and keto emission spectra of 2-(2′-hydroxyphenyl)benzoxazole (HBO) and its derivatives has been systematically investigated by means of density functional theory (DFT) and time-dependent DFT (TD-DFT) methods. The enol absorption spectra of HBO were simulated by using five different DFTs with various exchange-correlation functions to validate a suitable functional prior to being further used as a method of choice to study the effect of substituents on the spectral characteristics of HBO derivatives. The popular B3LYP (Becke, three-parameter, Lee–Yang–Parr) exchange-correlation functional is found to provide the best desirable result in predicting the absorption spectrum close to experimental data. In the ground state, enol forms of HBO and its derivatives are more stable than those of keto forms, while in the first lowest excited state, keto forms are found to be more stable than their enol forms. Overall, simulated absorption and emission spectra of HBO and its derivatives from TD-B3LYP calculations are in good agreement with the experimental data. For enol, absorption maxima of HBO derivatives having electron-withdrawing groups are red-shift corresponding to their lower HOMO–LUMO energy gaps compared to that of HBO. For keto emission, HBO having electron donating groups (m-MeHBO and MHBO) and withdrawing group (CNHBO) at 4′-position on the phenol fragment as well as electron donating groups (HBOMe and HBOM) at 6-position on the benzoxazole fragment make the position of keto emission peak shift to shorter wavelength (blue-shift). However, HBO derivatives with electron withdrawing groups (HBOF, HBOCl, HBOA and HBOE) at 6-position give redshifted emission compared to the parent compound (HBO). The type of substituent on both 4′- and 6-positions certainly has a pronounced effect on the absorption and emission spectra of HBO derivatives.
ABSTRACT ABSTRACT We performed a theoretical investigation on a series of organic dyes incorporat... more ABSTRACT ABSTRACT We performed a theoretical investigation on a series of organic dyes incorporating an anthracene moiety between a carbazole donor group and a cyanoacrylic acid acceptor, in which a triple bond (TB)-modified moiety acts as a Π-conjugated linker. Density functional theory (DFT) and time-dependent DFT (TD-DFT) were applied to understand the electronic, photophysical, and electron injection properties of the dyes. We found that optimized anthracene structures lay almost perpendicular to the plane of the adjacent substituents. The introduction of a modified TB moiety significantly decreases the dihedral angle and results in a planar structure, which extends the length of -conjugated system to provide a broader absorption spectrum, the An4 dye exhibited the greatest red shift in maximum absorption wavelength. Introduction of a TB moiety into the dye structure facilitates electron transfer from the donor and acceptor. The TB-modified dye structure has a significant effect on electron injection from the dye sensitizer to the TiO2 surface. Our results demonstrate that use of computational design can to help the experimentalist for out looking future developments to identify TB modified anthracene sensitizers for highly efficient solar cells.
The aim of this work is to improve physical properties and biological activities of the two flava... more The aim of this work is to improve physical properties and biological activities of the two flavanones hesperetin and naringenin by complexation with β-cyclodextrin (β-CD) and its methylated derivatives (2,6-di-O-methyl-β-cyclodextrin, DM-β-CD and randomly methylated-β-CD, RAMEB). The free energies of inclusion complexes between hesperetin with cyclodextrins (β-CD and DM-β-CD) were theoretically investigated by molecular dynamics simulation. The free energy values obtained suggested a more stable inclusion complex with DM-β-CD. The vdW force is the main guest-host interaction when hesperetin binds with CDs. The phase solubility diagram showed the formation of a soluble complex of AL type, with higher increase in solubility and stability when hesperetin and naringenin were complexed with RAMEB. Solid complexes were prepared by freeze-drying, and the data from differential scanning calorimetry (DSC) confirmed the formation of inclusion complexes. The data obtained by the dissolution method showed that complexation with RAMEB resulted in a better release of both flavanones to aqueous solution. The flavanones-β-CD/DM-β-CD complexes demonstrated a similar or a slight increase in anti-inflammatory activity and cytotoxicity towards three different cancer cell lines. The overall results suggested that solubilities and bioactivities of both flavanones were increased by complexation with methylated β-CDs.
Combined experimental-theoretical method is an effective tool to study dye–zeolite system.The con... more Combined experimental-theoretical method is an effective tool to study dye–zeolite system.The confinement of LTL zeolite affects isomerization of trans- to cis- azobenzene.Our model can accurately predict the optical properties of t-azobenzene in zeolite.The t-azobenzene adsorbed in H-LTL channel is protonated by Brønsted acid site of H-LTL.The t-azobenzene can be converted back to the cis-form with exposure to UV-light.The spectroscopic methods and molecular modeling were employed to study the photophysical properties of t-azobenzene in solution and in the channel of zeolite LTL. The effects of the interactions between the dye molecules and zeolite framework on the electronic states were examined experimentally by diffuse reflectance UV–visible absorption and fluorescence emission. The changes observed in the spectra were dependent on the forms of zeolite LTL (H-LTL and K-LTL). In addition the structural properties of the dye in the different environments were also intensively investigated by density functional theory (DFT) calculations with B3LYP/6-31G(d,p) level of theory. The 324T cluster model and the ONIOM (B3LYP/6-31G(d,p):UFF) methods were employed for the calculating the orientations of the dye in the zeolite system. The experimental data are consistent with the calculation results. The dye in solution can be relaxed into the planar structure, however, when the dye is in LTL zeolite it is constrained by the framework and is therefore twisted due to the confinement effects of zeolite. Moreover, emission spectra were detected only from protonated t-azobenzene incorporated into H-LTL while no emission was detected from t-azobenzene confined in K-LTL framework. The results of the study lead to the conclusion that the zeolite framework affects both the structural and photophysical properties of t-azobenzene.The spectroscopic methods and molecular modeling were employed to study the photophysical properties of t-azobenzene in the channel of zeolite LTL. The trans-isomer can be isomerized to the cis-isomer with the confinement effect in zeolite channel.
Pinostrobin (PNS) is one of the important flavonoids and can be abundantly found in the rhizomes ... more Pinostrobin (PNS) is one of the important flavonoids and can be abundantly found in the rhizomes of fingerroot (Boesenbergia rotrunda) and galangal (Alpinia galangal and Alpinia officinarum), the herbal basis of Southeast Asian cooking. Similar to other flavonoids, PNS exhibits anti-oxidative, anti-inflammatory and anti-cancer properties. However, this compound has an extremely low water solubility that limits its use in pharmaceutical applications. Beta-cyclodextrin (βCD) and its derivatives, 2,6-dimethyl-βCD (2,6-DMβCD) and the three hydroxypropyl-βCDs (2-HPβCD, 6-HPβCD and 2,6-DHPβCD), have unique properties that enhance the stability and solubility of such low-soluble guest molecules. In the present study, molecular dynamics simulations were applied to investigate the dynamics and stability of PNS inclusion complexes with βCD and its derivatives (2,6-DMβCD, 2,6-DHPβCD, 2-HPβCD and 6-HPβCD). PNS was able to form complexes with βCD and all four of its derivatives by either the chromone (C-PNS) or phenyl (P-PNS) ring dipping toward the cavity. According to the molecular mechanics-generalized Born surface area binding free energy values, the stability of the different PNS/βCD complexes was ranked as 2,6-DHPβCD>2,6-DMβCD>2-HPβCD>6-HPβCD>βCD. These theoretical results were in good agreement with the stability constants that had been determined by the solubility method.
There is growing interest in large-ring cyclodextrins (LR-CDs) which are known to be good host mo... more There is growing interest in large-ring cyclodextrins (LR-CDs) which are known to be good host molecules for larger ligands. The isolation of a defined size LR-CD is an essential prerequisite for studying their structural properties. Unfortunately the purification procedure of these substances turned out to be very laborious. Finally the problem could be circumvented by a theoretical consideration: the highly advantageous replica exchange molecular dynamics (REMD) simulation (particularly suitable for studies of conformational changes) offers an ideal approach for studying the conformational change of ɛ-cyclodextrin (CD10), a smaller representative of LR-CDs. Three carbohydrate force fields and three solvent models were tested. The conformational behavior of CD10 was analyzed in terms of the flip (turn) of the glucose subunits within the macrocyclic ring. In addition a ranking of conformations with various numbers of turns was preformed. Our findings might be also helpful in the temperature controlled synthesis of LR-CDs as well as other experimental conditions, in particular for the host-guest reaction.
Journal of Biomolecular Structure and Dynamics, 2015
Epidermal growth factor (EGF) was used as the targeting ligand to enhance the specificity of a ca... more 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 (MDSs) 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.
ABSTRACT The effect of electron donating and withdrawing substituents on the enol absorption and ... more ABSTRACT The effect of electron donating and withdrawing substituents on the enol absorption and keto emission spectra of 2-(2′-hydroxyphenyl)benzoxazole (HBO) and its derivatives has been systematically investigated by means of density functional theory (DFT) and time-dependent DFT (TD-DFT) methods. The enol absorption spectra of HBO were simulated by using five different DFTs with various exchange-correlation functions to validate a suitable functional prior to being further used as a method of choice to study the effect of substituents on the spectral characteristics of HBO derivatives. The popular B3LYP (Becke, three-parameter, Lee–Yang–Parr) exchange-correlation functional is found to provide the best desirable result in predicting the absorption spectrum close to experimental data. In the ground state, enol forms of HBO and its derivatives are more stable than those of keto forms, while in the first lowest excited state, keto forms are found to be more stable than their enol forms. Overall, simulated absorption and emission spectra of HBO and its derivatives from TD-B3LYP calculations are in good agreement with the experimental data. For enol, absorption maxima of HBO derivatives having electron-withdrawing groups are red-shift corresponding to their lower HOMO–LUMO energy gaps compared to that of HBO. For keto emission, HBO having electron donating groups (m-MeHBO and MHBO) and withdrawing group (CNHBO) at 4′-position on the phenol fragment as well as electron donating groups (HBOMe and HBOM) at 6-position on the benzoxazole fragment make the position of keto emission peak shift to shorter wavelength (blue-shift). However, HBO derivatives with electron withdrawing groups (HBOF, HBOCl, HBOA and HBOE) at 6-position give redshifted emission compared to the parent compound (HBO). The type of substituent on both 4′- and 6-positions certainly has a pronounced effect on the absorption and emission spectra of HBO derivatives.
ABSTRACT ABSTRACT We performed a theoretical investigation on a series of organic dyes incorporat... more ABSTRACT ABSTRACT We performed a theoretical investigation on a series of organic dyes incorporating an anthracene moiety between a carbazole donor group and a cyanoacrylic acid acceptor, in which a triple bond (TB)-modified moiety acts as a Π-conjugated linker. Density functional theory (DFT) and time-dependent DFT (TD-DFT) were applied to understand the electronic, photophysical, and electron injection properties of the dyes. We found that optimized anthracene structures lay almost perpendicular to the plane of the adjacent substituents. The introduction of a modified TB moiety significantly decreases the dihedral angle and results in a planar structure, which extends the length of -conjugated system to provide a broader absorption spectrum, the An4 dye exhibited the greatest red shift in maximum absorption wavelength. Introduction of a TB moiety into the dye structure facilitates electron transfer from the donor and acceptor. The TB-modified dye structure has a significant effect on electron injection from the dye sensitizer to the TiO2 surface. Our results demonstrate that use of computational design can to help the experimentalist for out looking future developments to identify TB modified anthracene sensitizers for highly efficient solar cells.
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Papers by Nawee Kungwan