Hui-Hsu Gavin Tsai

National Central University, Taoyuan City, Taiwan, Taiwan

Are you Hui-Hsu Gavin Tsai?

Claim your profile

Publications (31)130.64 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The trans isomers of fatty acids are found in human adipose tissue. These isomers have been linked with deleterious health effects (e.g., coronary artery disease). In this study, we performed molecular dynamics simulations to investigate the structures and dynamic properties of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) and 1-palmitoyl-2-elaidoyl sn-glycero-3-phosphatidylcholine (PEPC) lipid bilayers. Our simulations revealed that the geometry of the olefinic bond and membrane packing effects significantly influenced the conformations and dynamics of the two CC single bonds adjacent to the olefinic bond. For the PEPC lipid, the two CC single bonds adjacent to the olefinic bond adopted mainly nonplanar skew-trans and planar cis-trans motifs; although the cis conformation featured relatively strong steric repulsion, it was stabilized through membrane packing because its planar structure is more suitable for membrane packing. Moreover, membrane packing effects stabilized the planar transition state for conformational conversion to a greater extent than they did with the nonplanar transition state, thereby affecting the dynamics of conformational conversion. The rotational motions of the first neighboring CC single bonds were much faster than those of typical saturated CC single bonds; in contrast, the rotational motions of the second neighboring CC single bonds were significantly slower than those of typical saturated torsion angles. The packing of PEPC lipids is superior to that of POPC lipids, leading to a smaller area per lipid, a higher order parameter and a smaller diffusion coefficient. The distinct properties of POPC and PEPC lipids result in PEPC lipids forming microdomains within a POPC matrix. Copyright © 2015 Elsevier B.V. All rights reserved.
    Biochimica et Biophysica Acta (BBA) - Biomembranes 02/2015; 1848(5). DOI:10.1016/j.bbamem.2015.02.016 · 3.43 Impact Factor
  • Source
    Hui-Hsu Gavin Tsai · Chun-Jui Tan · Wen-Hsin Tseng
    [Show abstract] [Hide abstract]
    ABSTRACT: Because the intense absorptions of squaraine (SQ) dyes in the red/near-infrared spectral regions closely match the spectral response of sunlight, SQ dyes have great potential for use in dye-sensitized solar cells (DSCs). In this study, we employed density functional theory (DFT) and time-dependent DFT to investigate the structural, optical, and electron transfer properties of seven recently reported SQ-derived dyes adsorbed on a (TiO2)38 cluster having an anatase (101) surface, as a model for corresponding DSCs. In particular, we calculated the proportions of the electron densities in the dye-(TiO2)38 systems that were transferred to the TiO2 moieties upon excitation, allowing us to investigate their electron injection mechanisms. We found that the dye-(TiO2)38 systems followed different direct and indirect mechanisms of electron injection to TiO2 depending on the localization of the excited state electron density and the driving force for excited-state electron injection. JD10 and YR6 owning two intense absorption bands, which have significant proportions of electron density delocalized into the TiO2 moiety upon excitation and have driving forces for excited-state electron injection, followed direct electron injection mechanisms to TiO2. These results are compatible with their higher experimentally observed short-circuit currents (Jsc) than those of the SQ dyes. In contrast, SQ12, SQ2, and SQ4 followed the indirect electron injection mechanism due to their negligible proportion of electron density injected into TiO2; in addition, SQ2 and SQ4 do not provide driving force for electron injection. SQ12, SQ2, and SQ4 dyes had lower experimentally observed Jsc values than those of the other SQ dyes. The calculated probabilities of electron density being delocalized into TiO2 and driving force for excited-state electron injection from these studied SQ dyes are compatible with their experimentally observed Jsc values. This study provides insight into the electron injection mechanisms of SQ-derived dyes adsorbed on TiO2 upon photo-excitation. Furthermore, our calculations and findings give clues for designing new SQ-derived sensitizers for DSC applications.
    The Journal of Physical Chemistry C 02/2015; 119(9):150206161025005. DOI:10.1021/jp508034f · 4.77 Impact Factor
  • Source
    Hui-Hsu Gavin Tsai · Che-Ming Chang · Jian-Bin Lee
    [Show abstract] [Hide abstract]
    ABSTRACT: Membrane fusion is essential for intracellular trafficking and virus infection, but the molecular mechanisms underlying the fusion process remain poorly understood. In this study, we employed all-atom molecular dynamics simulations to investigate the membrane fusion mechanism using vesicle models which were pre-bound by inter-vesicle Ca(2+)-lipids clusters to approximate Ca(2+)-catalyzed fusion. Our results show that the formation of the hemifusion diaphragm for vesicle fusion is a multi-step event. This result contrasts with the assumptions made in most continuum models. The neighboring hemifused states are separated by an energy barrier on the energy landscape. The hemifusion diaphragm is much thinner than the planar lipid bilayers. The thinning of the hemifusion diaphragm during its formation results in the opening of a fusion pore for vesicle fusion. This work provides new insights into the formation of the hemifusion diaphragm and thus increases understanding of the molecular mechanism of membrane fusion.
    Biochimica et Biophysica Acta 01/2014; 1838(6). DOI:10.1016/j.bbamem.2014.01.018 · 4.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Four donor–conjugated spacer–acceptor (D–π–A) organic dyes containing cyclopentadithiophene unit as a part of the conjugated spacer are prepared and studied to investigate the effects of the conjugated spacer and donor on the short-circuit current and conversion efficiency of the corresponding DSSCs. Theoretical calculations reveal that a shorter conjugated spacer or a stronger donor leads to more effective electron injection upon photo excitation. Therefore, D–π–A typed dye with longer conjugated spacer may have higher absorption coefficient and longer λmax. Nevertheless, it may also have lower effective electron injection upon photo excitation. Calculation data also show that cyclopentadithiophene although is a good moiety for extending the conjugation length of the organic dyes, it also acts as an electron sink, decreasing the effective electron injection. The transition probability calculated with the electron density difference analyses combining with the experimental absorption and photovoltaic performance data provides a useful protocol for designing organic photosensitizers for DSSCs at the electronic and structural levels.
    Dyes and Pigments 12/2013; 99(3):1091-1100. DOI:10.1016/j.dyepig.2013.08.016 · 3.97 Impact Factor
  • Hui-Hsu Gavin Tsai · Wei-Fu Juang · Che-Ming Chang · Tsai-Yi Hou · Jian-Bin Lee
    [Show abstract] [Hide abstract]
    ABSTRACT: Although membrane fusion plays key roles in intracellular trafficking, neurotransmitter release, and viral infection, its underlying molecular mechanism and its energy landscape are not well understood. In this study, we employed all-atom molecular dynamics simulations to investigate the fusion mechanism, catalyzed by Ca(2+) ions, of two highly hydrated 1-palmitoyl-2-oleoyl-sn-3-phosphoethanolamine (POPE) micelles. This simulation system mimics the small contact zone between two large vesicles at which the fusion is initiated. Our simulations revealed that Ca(2+) ions are capable of catalyzing the fusion of POPE micelles; in contrast, we did not observe close contact of the two micelles in the presence of only Na(+) or Mg(2+) ions. Determining the free energy landscape of fusion allowed us characterize the underlying molecular mechanism. The Ca(2+) ions play a key role in catalyzing the micelle fusion in three aspects: creating a more-hydrophobic surface on the micelles, binding two micelles together, and enhancing the formation of the pre-stalk state. In contrast, Na(+) or Mg(2+) ions have relatively limited effects. Effective fusion proceeds through sequential formation of pre-stalk, stalk, hemifused-like, and fused states. The pre-stalk state is a state featuring lipid tails exposed to the inter-micellar space; its formation is the rate-limiting step. The stalk state is a state where a localized hydrophobic core is formed connecting two micelles; its formation occurs in conjunction with water expulsion from the inter-micellar space. This study provides insight into the molecular mechanism of fusion from the points of view of energetics, structure, and dynamics.
    Biochimica et Biophysica Acta 08/2013; 1828(11). DOI:10.1016/j.bbamem.2013.07.022 · 4.66 Impact Factor
  • Mani Ramanathan · Chun-Jui Tan · Wen-Jung Chang · Hui-Hsu Gavin Tsai · Duen-Ren Hou
    [Show abstract] [Hide abstract]
    ABSTRACT: We describe the synthesis of the decalin core of codinaeopsin (), a tryptophan-polyketide hybrid natural product with promising antimalarial activity (IC50 4.7 μM, against Plasmodium falciparum), via an intramolecular Diels-Alder (IMDA) reaction. A convergent synthesis was developed to prepare the precursors for the IMDA reaction in 10 steps. The exo cycloadducts were derived from thermal, IMDA reactions of the substrates containing a Weinreb amide or ester conjugated dienophile, and the endo adducts were from Lewis acid promoted reactions of the substrates with a formyl group. Both exo and endo products of the IMDA were exclusively isolated and characterized by NMR spectroscopy. One endo cycloadduct was further confirmed with X-ray crystallography. Theoretical calculations reveal the influence of the substituents of the decalin core on the IMDA process.
    Organic & Biomolecular Chemistry 05/2013; 11. DOI:10.1039/c3ob40480c · 3.49 Impact Factor
  • Source
    Hui-Hsu Gavin Tsai · Jian-Bin Lee · Jian-Ming Huang · Ratna Juwita
    [Show abstract] [Hide abstract]
    ABSTRACT: Cell membranes are composed mainly of phospholipids which are in turn, composed of five major chemical elements: carbon, hydrogen, nitrogen, oxygen, and phosphorus. Recent studies have suggested the possibility of sustaining life if the phosphorus is substituted by arsenic. Although this issue is still controversial, it is of interest to investigate the properties of arsenated-lipid bilayers to evaluate this possibility. In this study, we simulated arsenated-lipid, 1-palmitoyl-2-oleoyl-sn-glycero-3-arsenocholine (POAC), lipid bilayers using all-atom molecular dynamics to understand basic structural and dynamical properties, in particular, the differences from analogous 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, (POPC) lipid bilayers. Our simulations showed that POAC lipid bilayers have distinct structural and dynamical properties from those of native POPC lipid bilayers. Relative to POPC lipid bilayers, POAC lipid bilayers have a more compact structure with smaller lateral areas and greater order. The compact structure of POAC lipid bilayers is due to the fact that more inter-lipid salt bridges are formed with arsenate-choline compared to the phosphate-choline of POPC lipid bilayers. These inter-lipid salt bridges bind POAC lipids together and also slow down the head group rotation and lateral diffusion of POAC lipids. Thus, it would be anticipated that POAC and POPC lipid bilayers would have different biological implications.
    International Journal of Molecular Sciences 04/2013; 14(4):7702-15. DOI:10.3390/ijms14047702 · 2.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we performed all-atom long-timescale molecular dynamics simulations of phospholipid bilayers incorporating three different proportions of negatively charged lipids in the presence of K(+), Mg(2+), and Ca(2+) ions to systemically determine how membrane properties are affected by cations and lipid compositions. Our simulations revealed that the binding affinity of Ca(2+) ions with lipids is significantly stronger than that of K(+) and Mg(2+) ions, regardless of the composition of the lipid bilayer. The binding of Ca(2+) ions to the lipids resulted in bilayers having smaller lateral areas, greater thicknesses, greater order, and slower rotation of their lipid head groups, relative to those of corresponding K(+)- and Mg(2+)-containing systems. The Ca(2+) ions bind preferentially to the phosphate groups of the lipids. The complexes formed between the cations and the lipids further assembled to form various multiple-cation-centered clusters in the presence of anionic lipids and at higher ionic strength-most notably for Ca(2+). The formation of cation-lipid complexes and clusters dehydrated and neutralized the anionic lipids, creating a more-hydrophobic environment suitable for membrane aggregation. We propose that the formation of Ca(2+)-phospholipid clusters across apposed lipid bilayers can work as a "cation glue" to adhere apposed membranes together, providing an adequate configuration for stalk formation during membrane fusion.
    Biochimica et Biophysica Acta 06/2012; 1818(11):2742-55. DOI:10.1016/j.bbamem.2012.05.029 · 4.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A sequence of ring-closing metathesis and palladium-catalyzed formate reduction was developed for preparing O-heterocycles with an exocyclic olefin and applied to the asymmetric synthesis of zoapatanol. The key vicinal stereocenters in zoapatanol were constructed from the l-malic acid-derived lactone by successive chelation-controlled addition of alkyl groups. The O-allylations to prepare the dienes for RCM were achieved with the tertiary alcohols bearing internal olefins. The ring opening of oxepane, a new reaction pathway for the Pd-formate reduction, is also reported.
    Tetrahedron 01/2012; 68(2). DOI:10.1016/j.tet.2011.10.023 · 2.82 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Well-ordered mesoporous silicas SBA-15 functionalized with variable contents of phosphonic acid groups (up to 25 mol % based on silica) have successfully synthesized via cocondensation of tetraethoxysilane (TEOS) and diethylphosphatoethyltriethoxysilane (PETES) using triblock copolymer Pluronic P123 as the structure-directing agent under acidic conditions. The status and local structures of the phosphonic functional groups are investigated by extensive multinuclear solid-state NMR studies. Solid-state 13C and 31P NMR results reveal that phosphonic ester moieties are obtained for the as-synthesized samples and for the samples subjected to template removal by concentratedH2SO4. The generation of phosphonic acid groups can be accomplished by dealkylation reaction via treating the templateextracted samples with concentrated HCl. Two distinct local environments for the phosphorus sites of phosphonic acid groups have been observed at 32 and 22 ppm in the 31P magic angle spinning (MAS) NMR spectra. The relative ratio between these two species is not sensitive to the loading of phosphonic acid groups incorporated, but it strongly depends on the moisture present in the materials. The PO3H2 groups forming the hydrogen bonds with the nearby Q3 Si�OH are the major species responsible for the 22 ppm peak based on the results of 1Hf31P f29Si double cross-polarization NMR experiments and density functional theory calculations (DFT). Of particular interest is that 29Si{31P} rotational echo double resonance (REDOR) NMRexperiments are utilized to measure 31P�29Si distances between the phosphorus site in the functional groups and the silicon sites in the silica framework. A 29Si�31P distance of 5.0 Å is obtained for the phosphorus site in the functional groups to the silicon site of the Q3 species for the as-synthesized sample. A reasonable fitting to the REDOR data for the acidified sample can also be achievable by assuming the presence of different structural units, whose 31P�29Si distance information is referred from the DFT results. The combination of REDOR and 1Hf31P f 29Si double cross-polarization NMR measurements and the DFT calculations allow one to gain deeper insights into the local environments of the organic groups functionalized in mesoporous silica materials.
    The Journal of Physical Chemistry C 12/2011; 116(2):1658-1669. DOI:10.1021/jp206017j · 4.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Well-ordered cubic mesoporous silicas SBA-1 functionalized with sulfonic acid groups have been synthesized through in situ oxidation of mercaptopropyl groups with H(2)O(2) via co-condensation of tetraethoxysilane (TEOS) and 3-mercaptopropyltrimethoxysilane (MPTMS) templated by cetyltriethylammonium bromide (CTEABr) under strong acidic conditions. Various synthesis parameters such as the amounts of H(2)O(2) and MPTMS on the structural ordering of the resultant materials were systematically investigated. The materials thus obtained were characterized by a variety of techniques including powder X-ray diffraction (XRD), multinuclear solid-state Nuclear Magnetic Resonance (NMR) spectroscopy, (29)Si{(1)H} 2D HETCOR (heteronuclear correlation) NMR spectroscopy, thermogravimetric analysis (TGA), and nitrogen sorption measurements. By using (13)C CPMAS NMR technique, the status of the incorporated thiol groups and their transformation to sulfonic acid groups can be monitored and, as an extension, to define the optimum conditions to be used for the oxidation reaction to be quantitative. In particular, (29)Si{(1)H} 2D HETCOR NMR revealed that the protons in sulfonic acid groups are in close proximity to the silanol Q(3) species, but not close enough to form a hydrogen bond.
    Journal of Colloid and Interface Science 07/2011; 359(1):86-94. DOI:10.1016/j.jcis.2011.03.072 · 3.55 Impact Factor
  • Source
    Hui-Hsu Gavin Tsai · Jian-Bin Lee · Sheng-Shiuan Tseng · Xiao-An Pan · Yuan-Ci Shih
    [Show abstract] [Hide abstract]
    ABSTRACT: The mechanisms of interfacial folding and membrane insertion of the Alzheimer's amyloid-beta fragment Abeta(25-35) and its less toxic mutant, N27A-Abeta(25-35) and more toxic mutant, M35A-Abeta(25-35), are investigated using replica-exchange molecular dynamics in an implicit water-membrane environment. This study simulates the processes of interfacial folding and membrane insertion in a spontaneous fashion to identify their general mechanisms. Abeta(25-35) and N27A-Abeta(25-35) peptides share similar mechanisms: the peptides are first located in the membrane hydrophilic region where their C-terminal residues form helical structures. The peptides attempt to insert themselves into the membrane hydrophobic region using the C-terminal or central hydrophobic residues. A small portion of peptides can successfully enter the membrane's hydrophobic core, led by their C-terminal residues, through the formation of continuous helical structures. No detectable amount of M35A-Abeta(25-35) peptides appeared to enter the membrane's hydrophobic core. The three studied peptides share a similar helical structure for their C-terminal five residues, and these residues mainly buried within the membrane's hydrophobic region. In contrast, their N-terminal properties are markedly different. With respect to the Abeta(25-35), the N27A-Abeta(25-35) forms a more structured helix and is buried deeper within the membrane, which may result in a lower degree of aggregation and a lower neurotoxicity; in contrast, the less structured and more water-exposed M35A-Abeta(25-35) is prone to aggregation and has a higher neurotoxicity. Understanding the mechanisms of Abeta peptide interfacial folding and membrane insertion will provide new insights into the mechanisms of neurodegradation and may give structure-based clues for rational drug design preventing amyloid associated diseases.
    Proteins Structure Function and Bioinformatics 06/2010; 78(8):1909-25. DOI:10.1002/prot.22705 · 2.92 Impact Factor
  • Source
    Hui-Hsu Gavin Tsai · Hui-Lun Sara Sun · Chun-Jui Tan
    [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we used TD-PBE0 calculations to investigate the first singlet excited state (S(1)) behavior of 2-(2'-hydroxyphenyl)benzimidazole (HBI) and its amino derivatives. We employed the potential energy surfaces (PESs) at the S(1) state covering the normal syn, tautomeric (S(1)-T(syn)), and intramolecular charge-transfer (S(1)-T(ICT)) states in ethanol and cyclohexane to investigate the reaction mechanisms, including excited-state intramolecular proton transfer (ESIPT) and intramolecular charge-transfer (ICT) processes. Two new S(1)-T(ICT) states, stable in ethanol and cyclohexane, were found for HBI and its amino derivatives; they are twisted and pyramidalized. The flat PES of the ICT process makes the S(1)-T(ICT) states accessible. The S(1)-T(ICT) state is effective for radiationless relaxation, which is responsible for quenching the fluorescence of the S(1)-T(syn) state. In contrast to the situation encountered conventionally, the S(1)-T(ICT) state does not possess a critically larger dipole moment than its precursor, S(1)-T(syn) state; hence, it is not particularly stable in polar solvents. On the basis of the detailed PESs, we rationalize various experimental observations complementing previous studies and provide insight to understand the excited-state reaction mechanisms of HBI and its amino derivatives.
    The Journal of Physical Chemistry A 02/2010; 114(12):4065-79. DOI:10.1021/jp100022y · 2.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ordered periodic mesoporous organosilicas containing different fractions of benzene groups in the silica framework, based on the cubic SBA-1 mesostructure (Pm3̅n mesophase), were synthesized with the direct-synthesis route via co-condensation of tetraethoxysilane (TEOS) and 1,4-bis(triethoxysilyl)benzene (BTEB) under acidic conditions using cetyltriethylammonium bromide as a structure-directing agent. A significantly large amount of TEOS, up to 70 mol % based on silica, can be incorporated into the silica wall without degrading the structural integrity of the materials. By optimization of the synthesis compositions, the resulting materials exhibited much higher surface areas (up to 1210 m2/g) and larger pore volumes (up to 0.64 cm3/g) as compared to the previous analogue, which only exhibited a surface area of 381 m2/g and a pore volume of 0.11 cm3/g. Two-dimensional (2D) 29Si{1H} heteronuclear correlation (HETCOR) NMR spectra, acquired as a function of contact time, provided direct spectroscopic evidence that a single mesophase with various Q (from TEOS) and T silicon species (from BTEB) located randomly within the pore walls via co-condensation of BTEB and TEOS at a molecular level. Such information is often not achievable by other characterization techniques. The 1H−29Si distance information between phenylene protons and nearby T3 silicon atoms obtained from density functional theory calculations is also in good agreement with the observations of 2D 29Si{1H} HETCOR NMR experiments.
    The Journal of Physical Chemistry C 10/2009; 113(42). DOI:10.1021/jp905626g · 4.77 Impact Factor
  • Source
    Jye-Shane Yang · Jyu-Lun Yan · Kang-Ling Liau · Hui-Hsu Gavin Tsai · Chung-Yu Hwang
    [Show abstract] [Hide abstract]
    ABSTRACT: The electronic absorption and emission spectra and fluorescence lifetimes of four pentiptycene-derived 1,4-bis(phenylethynyl)benzenes 2–5 and three segments of 2 (i.e., compounds 6–8) in MTHF at a variety of temperature between 80 and 300K are reported. Compound 2 is an ethynylene-bridged pentiptycene trimer with octyloxy substituents at the two terminals. Compounds 3–5 differ from 2 only in the middle ring, which is a triptycene (3), a tetramethylphenylene (4), or the parent phenylene group (5). Despite the different ground-state conformer distribution in solutions, there is only a small difference in fluorescence properties for 2–5 at room temperature due to fast excited-state planarization reaction. However, in the solvent glass at low temperatures the planarization reaction is restricted with an extent depending on the middle-ring substituents. The well-resolved spectra and decay times for the planar and the twisted conformers of 2 allow one to deduce the excited-state planarization barrier (3.0kcal/mol) and the overall phenylene torsional barrier (8.5kcal/mol). These values are larger than those (0.47 and 3.54kcal/mol, respectively) predicted by the AM1 and ZINDO/S calculations. The similarities in photophysical behavior between the twisted form of 2 and the model compounds 7 and 8 suggest that the former possesses large dihedral angles between the central and either one or both of the neighboring phenylene rings. Our results provide the first experimental approach toward the evaluation of the excited-state torsional barrier for the p-phenyleneethynylene systems.
    Journal of Photochemistry and Photobiology A Chemistry 09/2009; 207(1):38-46. DOI:10.1016/j.jphotochem.2009.01.002 · 2.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Antimicrobial peptides (AMPs) have attracted much interest in recent years because of their potential use as new-generation antibiotics. Indolicidin (IL) is a 13-residue cationic AMP that is effective against a broad spectrum of bacteria, fungi, and even viruses. Unfortunately, its high hemolytic activity retards its clinical applications. In this study, we adopted molecular dynamics (MD) simulations as an aid toward the rational design of IL analogues exhibiting high antimicrobial activity but low hemolysis. We employed long-timescale, multi-trajectory all-atom MD simulations to investigate the interactions of the peptide IL with model membranes. The lipid bilayer formed by the zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) was chosen as the model erythrocyte membrane; lipid bilayers formed from a mixture of POPC and the negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol were chosen to model bacterial membranes. MD simulations with a total simulation time of up to 4 micros revealed the mechanisms of the processes of IL adsorption onto and insertion into the membranes. The packing order of these lipid bilayers presumably correlated to the membrane stability upon IL adsorption and insertion. We used the degree of local membrane thinning and the reduction in the order parameter of the acyl chains of the lipids to characterize the membrane stability. The order of the mixed 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol/POPC lipid bilayer reduced significantly upon the adsorption of IL. On the other hand, although the order of the pure-POPC lipid bilayer was perturbed slightly during the adsorption stage, the value was reduced more dramatically upon the insertion of IL into the membrane's hydrophobic region. The results imply that enhancing IL adsorption on the microbial membrane may amplify its antimicrobial activity, while the degree of hemolysis may be reduced through inhibition of IL insertion into the hydrophobic region of the erythrocyte membrane. In addition, through simulations, we identified the amino acids that are most responsible for the adsorption onto or insertion into the two model membranes. Positive charges are critical to the peptide's adsorption, whereas the presence of hydrophobic Trp8 and Trp9 leads to its deeper insertion. Combining the hypothetical relationships between the membrane disordering and the antimicrobial and hemolytical activities with the simulated results, we designed three new IL-analogous peptides: IL-K7 (Pro7-->Lys), IL-F89 (Trp8 and Trp9-->Phe), and IL-K7F89 (Pro7-->Lys; Trp8 and Trp9-->Phe). The hemolytic activity of IL-F89 is considerably lower than that of IL, whereas the antimicrobial activity of IL-K7 is greatly enhanced. In particular, the de novo peptide IL-K7F89 exhibits higher antimicrobial activity against Escherichia coli; its hemolytic activity decreased to only 10% of that of IL. Our simulated and experimental results correlated well. This approach-coupling MD simulations with experimental design-is a useful strategy toward the rational design of AMPs for potential therapeutic use.
    Journal of Molecular Biology 08/2009; 392(3):837-54. DOI:10.1016/j.jmb.2009.06.071 · 4.33 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Three new series of hexacatenar liquid crystals derived from heterocyclic bisthiazoles and bisoxazoles exhibiting columnar phases were reported, and the formation of columnar phases was strongly sensitive to central heteroatoms and/or their positions incorporated.
    Tetrahedron Letters 04/2009; 50(17):1906-1910. DOI:10.1016/j.tetlet.2009.02.078 · 2.39 Impact Factor
  • Yu-Chi Pan · Hao-Yiang Wu · Guang-Liang Jheng · Hui-Hsu Gavin Tsai · Hsien-Ming Kao
    [Show abstract] [Hide abstract]
    ABSTRACT: Periodic mesoporous organosilicas (PMOs) based on the cubic SBA-1 mesostructure (Pm3n mesophase) were synthesized by co-condensation of tetraethoxysilane (TEOS) and 1,2-bis(triethoxysilyl)ethane (BTEE) under acidic conditions using cetyltriethylammonium bromide (CTEABr) as a structure-directing agent. The ethane-bridged PMO materials thus obtained were characterized by powder X-ray diffraction (XRD), solid-state 13C and 29Si NMR spectroscopy, thermogravimetric analysis (TGA), and nitrogen sorption measurements. The maximum BTEE contents that can be incorporated into the pore wall without degrading the Pm3n mesostructure were up to 60% (based on silica). The resulting materials were hydrothermally stable up to 120 h in boiling water with only a slight decrease in their structural properties, whereas the structure of the pure silica counterpart SBA-1 material was completely collapsed after such treatment. The presence of the ethane groups in the mesoporous wall led to a more hydrophobic environment and thus enhancement of hydrothermal stability, as revealed by water adsorption. The combined results of 2D 29Si{1H} heteronuclear correlation (HETCOR) NMR and density functional theory calculations suggested that the T3−T2−Q4−Q3 motif could be the favorable framework building unit in PMOs.
    The Journal of Physical Chemistry C 02/2009; 113(7). DOI:10.1021/jp807534m · 4.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A novel reaction route for the oxidation of thiol groups to disulfide bonds in mesoporous silicas with the aid of Cu2+ adsorption is reported for the first time, and most importantly it can serve as a diagnostic reaction for probing the spatial proximity and distribution of organic functional groups.
    New Journal of Chemistry 01/2009; 33(11). DOI:10.1039/b9nj00389d · 3.16 Impact Factor
  • Hui-Hsu Gavin Tsai · Guang-Liang Jheng · Hsien-Ming Kao
    [Show abstract] [Hide abstract]
    ABSTRACT: A facile one-pot synthesis route for preparation of a well-ordered cubic mesoporous silica SBA-1 functionalized with -COOH functional groups is reported for the first time. The results of 29Si{1H} HETCOR NMR provide direct evidence for the interactions between the carboxylic acid and silanol groups in carboxylic acid functionalized SBA-1. Density functional theory calculations indicate that the T3-Q4-Q3 motif is the favorable framework composition in the material and the carboxylic protons in the T3 species can form hydrogen bonds with the spatially proximate oxygen atom in the Q3 Si-OH species.
    Journal of the American Chemical Society 10/2008; 130(35):11566-7. DOI:10.1021/ja802051a · 11.44 Impact Factor