• Title/Summary/Keyword: $S_N1$ mechanism

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Investigation of the effect of Erythrosine B on a β-amyloid (1-40) peptide using molecular modeling method

  • Lee, Juho;Kwon, Inchan;Cho, Art E.;Jang, Seung Soon
    • Proceeding of EDISON Challenge
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    • 2015.03a
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    • pp.14-23
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    • 2015
  • Alzheimer's disease is one of the most common types of degenerative dementia. As a considerable cause of Alzheimer's disease, neurotoxic plaques composed of 39 to 42 residue-long amyloid beta($A{\beta}$) fibrils have been found in the patient's brain in large quantity. A previous study found that erythrosine B (ER), a red color food dye approved by FDA, inhibits the formation of amyloid beta fibril structures. Here, in an attempt to elucidate the inhibition mechanism, we performed molecular dynamics simulations to demonstrate the conformational change of $A{\beta}40$ induced by 2 ERs in atomistic detail. During the simulation, the ERs bound to the surfaces of both N-terminus and C-terminus regions of $A{\beta}40$ rapidly. The observed stacking of the ERs and the aromatic side chains near the N-terminus region suggests a possible inhibition mechanism in which disturbing the inter-chain stacking of PHEs destabilizes beta-sheet enriched in amyloid beta fibrils. The bound ERs block water molecules and thereby help stabilizing alpha helical structure at the main chain of C-terminus and interrupt the formation of the salt-bridge ASP23-LYS28 at the same time. Our findings can help better understanding of the current and upcoming treatment studies for Alzheimer's disease by suggesting inhibition mechanism of ER on the conformational transition of $A{\beta}40$ at the molecular level.

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Kinetics and mechanism of hydrolysis of insecticidal buprofezin (살충제 buprofezin의 가수분해 반응 메카니즘)

  • Sung, Nack-Do;Yu, Seong-Jae;Choi, Kyung-Sub;Kwon, Ki-Sung
    • The Korean Journal of Pesticide Science
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    • v.2 no.1
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    • pp.46-52
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    • 1998
  • The hydrolysis rate of insecticidal buprofezin(IUPAC : tert-butylimino-3-isopropyl-5-phenylperhydro-1,3,5-thiadiazin-4-one) in the range of pH 2.0 and 12.0 have been examined in 15%(v/v) aqueous dioxane at $45^{\circ}C$. The hydrolysis mechanism of buprofezin is proposed from the pH-effect, solvent effect(${\ell}{\gg}m$), thermodynamic parameter(${\Delta}H^{\neq}$=11.12 $Kcal{\cdot}mol^{-1}$ &, ${\Delta}S^{\neq}=5.0e.u.$), rate equation and hydrolysis product, l-isopropyl-3-phenyl urea. General acid catalyzed hydrolysis and specific acid catalyzed($k_{H3O+}$) hydrolysis through $A-S_{E}2$ and A-2(or $A_{AC}2$) reaction mechanism with orbital-control reaction proceed below pH 8.0 and above pH 9.0, the nucleophilic addition-elimination, $Ad_{N}-E$ mechanism via tetrahedral($sp^{3}$) intermediate is initiation by general base catalyzed($k_{H2O}$) reaction. Buprofezin was more stable in alkaline ($k=10^{-8}sec.^{-1}$) than acid solutions from the sigmoid pH-rate profile. And the half-life($t=\frac{1}{2}$) of hydrolysis reaction in neutral aqueous solution(pH 7.0) at $45^{\circ}C$ was about 3 months.

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Diastereoselective Synthesis of Unsaturated 1,4-Amino Alcohols as a Biologically Important Moiety

  • Jung Young Hoon;Kim Ji Duck
    • Archives of Pharmacal Research
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    • v.28 no.4
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    • pp.382-390
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    • 2005
  • chial allylic ethers with a hydroxyl group attached to the $\pi-system$ and chlorosulfonyl isocyanate. The enantioselectivity of the CSI reaction with the chiral allylic and benzylic ethers was examined in various solvents and temperatures. Based on these results, it was proposed that the CSI reaction is a competitive reaction of a $S_{N}i$ (retention) and a $S_{N}1$ mechanism (racemization) according to the stability of the carbocation intermediate. This means that there is a greater proportion of retention with the less stable the carbocation intermediate and vise versa.

Smile Rearrangement of Herbicidal Flazasulfuron (제초성 Flazasulfuron의 Smile 자리옮김 반응)

  • Lee, Gwnag-Jae;Kim, Yong-Jip;Kim, Dae-Whang;Sung, Nack-Do
    • Applied Biological Chemistry
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    • v.39 no.1
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    • pp.70-76
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    • 1996
  • A series of the herbicidal pyridylsulfonyl areas, none substitutent, 1-(4,6-dimethoxypyrimidine-2-yl)-3-(2-pyridylsulfonyl) urea, 3 and 3-trifluoromethyl substitutent, 1-(4,6-dimethoxypyrimidine-2-yl)-3-(3-trifluoromethyl-2-pyridylsulfonyl) urea, 5(Flazasulfuron) were synthesizied and the rate of hydrolysis of their has been studied in 25%(v/v) aqueous dioxane at $45^{\circ}C$. From the results of solvent effect($m{\ll}1,\;n{\ll}3\;&\;{\mid}m{\mid}{\ll}{\mid}{\ell}{\mid}$), thermodynamic parameter (${\Delta}S^{\neq}=0.54{\sim}\;-2.19\;e.u.\;&\;{\Delta}H^{\neq}=0.025\;Kcal.mol.^{-1}$), hydrolysis product analysis, $pK_a$ constant(3: 4.9 & 5: lit.4.6) and the rate equation, a marked difference in the kinetics of the reaction of 3 and 5(Flazasulfuron) was observed. It may be concluded that the hydrolysis of 5 proceeds through the $A-S_N2Ar$ reaction via conjugate acid$(5H^+)$ below pH 7.0, whereas, above pH 9.0, the hydrolysis proceeds through irreversibly $(E_1)_{anion}$ and reversibly $(E_1CB)_R$ mechanism via conjugate base(CB), respectively. But in case of 5, $A-S_N2Ar,\;(E_1)anion\;and\;(E_1CB)_R$ mechanism involved Smile rearrangement. The mate of rearrangement of 5 to a 3-trifluoromethyl-2-pyridylpyrimidinyl urea(PPU) in acid and 3-trifluoromethyl-2-pyridyl-4.6-dimethoxypyridinyl amine (PPA) in base was increased about 3.5 times by the introduction of trifluoromethyl group in the 3-position on the 2-pyridyl ring. From the basis of these findings, a possible mechanism for the hydrolysis of 5 was proposed and discussed.

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Development of piston contact mechanism for radial piston pump (레이디얼 피스톤 펌프의 피스톤 접촉 메커니즘 개발)

  • Ham, Y.B.;Cha, J.G.;Kim, D.M.;Kong, T.W.;Yun, S.N.;Ahn, K.Y.;Kweon, B.S.
    • Transactions of The Korea Fluid Power Systems Society
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    • v.7 no.1
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    • pp.1-5
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    • 2010
  • This paper presents the experimental results of the radial piston type oil pump with new mechanism for a metal diaphragm hydrogen compressor. Generally, metal diaphragm type hydrogen compressor systems are operated by oil hydraulic power. In this system an oil compensating pump has been demanded to compensate for a leakage oil head chamber. The metal diaphragm type hydrogen compressor consists of an oil compensating pump, commonly used hydraulic piston pump and driven by main crank shaft. The radial piston type oil compensating pump with new rolling contacted piston mechanism is developed and experimented. The developed piston element of the radial piston pump consists of piston, steel ball, return spring, two check valves, eccentric cam and ball racer. In this study, designed 4 type pistons as and orifice hole. Operating characteristics and pressure ripple characteristics are tested under no load to 60bar loaded with every 20bar increasing step and pressure ripple and flow rate are experimentally investigated.

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Development of BiPbSrCaCuO Superconductor by Diffusion of Dual-Layer Sample (이중층 시료에서 확산에 의한 BiPbSrCaCuO 초전도체 개발)

  • 최성환;박성진;유현수;강형곤;한병성
    • The Transactions of the Korean Institute of Electrical Engineers
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    • v.43 no.5
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    • pp.795-801
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    • 1994
  • The BiPbSrCaCuO superconductor was fabricated by diffusion of The dual layer composed of SrS12TCaS11TCuS12TOS1xT in upper layer and BiS12TPbSI0.3TCuS12TOS1yT in lower layer, and varified growh-mechanism of BiPbSrCaCuO superconducting phase. And, we produced optimum conditions of spread volume and each stage of sintering time were upper layer:Lower layer=1:0.2, 1:0.4, 1:0.6 and 24hr., 120hr., 210hr. From the result, the optimum conditions are spread volume(Upper layer:Lower layer=1:0.6), sintering time(210hrs.) at 820$^{\circ}C$.The BiPbSrCaCuO superconductor, fabricated optimum condition, showed zero resistance at critical temperature of 70k.

Pressure Effect on the Solvolysis of o-Methylbenzyl Chloride in Ethanol-Water Mixtures (o-메틸염화벤질의 가용매분해반응에 대한 압력의 영향)

  • Oh Cheun Kwun;Jin Burm Kyong;Yong Kyun Shin
    • Journal of the Korean Chemical Society
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    • v.30 no.1
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    • pp.40-46
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    • 1986
  • Rate constants for the solvolysis of o-methylbenzyl chloride were determined at 30$^{\circ}$ and 40$^{\circ}$C in aqueous ethanol mixtures under various pressures up to 1600 bar. From the rate constants, the activation parameters ${\Delta}V^{\neq}$, ${\Delta}{\beta}^{\neq}$, ${\Delta}H^{\neq}$, ${\Delta}S^{\neq}$ and${\Delta}G^{\neq}$ were evaluated. The values exhibit the extremum behavior at about 0.30 mole fraction of ethanol. This behavior is discussed in terms of electrostriction. To examine the reaction mechanism by Laidler and Eyring equation, we compared the rate constants with the dielectric constants of aqueous ethanol and the number of water molecule participated in the transition state. It was concluded that solvolytic reaction proceeds via $S_N$1 mechanism.

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Pseudomonas sp. strain DJ77에 존재하는 Glutathione S-Transferase 아미노 말단잔기의 Site-directed Mutagenesis

  • Woo, Hee-Jong;Park, Yong-Chjun;Kim, Sungje;Chung, Yong-Je;Chung, An-Sik;Kim, Young-Chang
    • Microbiology and Biotechnology Letters
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    • v.25 no.4
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    • pp.374-378
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    • 1997
  • Glutathione S-transferase (GST) was purified from Pseudomonas sp. DJ77, and its N-terminal sequence was determined to be MKLFISPGACSL. A specific tyrosyl residue in the vicinity of the N terminus is conserved in all the known cytosolic GSTs and has been shown to function as a catalytic residue in $\alpha$, $\mu$, $\pi$ class GSTs from mammals. However, Pseudomonas sp. DJ77 GST has the Phe-4 and Ile-5 instead of Tyr in N-terminus. Its replacement with tyrosine did not significantly affect the enzyme activity. Results from in vitro biochemical analyses were confirmed by the in vivo activity-based CDNB growth inhibition analyses. Our results clearly indicate that GST of Pseudomonas sp. DJ77 has a novel reaction mechanism different from that of mammalian GSTs.

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Study on Dynamic Crawling of The Five-bar Planar Mechanism (5절 평면형 메커니즘의 동적 포복에 관한 연구)

  • Lee J.H.;Lim N.S.;Kim W.K.;Yi B.J.
    • Proceedings of the Korean Society of Precision Engineering Conference
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    • 2005.06a
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    • pp.1045-1049
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    • 2005
  • In this paper, the dynamic crawling of a five-bar planar mechanism is investigated. One complete cycle of the crawling selected in this study consists of four different steps, i) sliding at one contact point between the mechanism and the ground, ii) changing its configuration without sliding at two contact points, iii) sliding at the other contact point, and iv) again changing its configuration without sliding at two contact points. In this type of crawling, the crawling mechanism maintains the shape of the parallel structure throughout a complete crawling cycle. The modeling algorithm for serial manipulators proposed by M. Thomas and et al.[1] is employed by introducing imaginary joints and links which represent the contact interfaces between the one end of the mechanism and the ground, while the other end of the mechanism is regarded as an end-effector of the imaginary serial manipulator which treats the reaction force and torque at the contact point as external forces. Then, a complete cycle of dynamic crawling of the mechanism is investigated through various computer simulations. The simulation result show that the stable crawling characteristics of the mechanism could be secured when the proper configurations depending on specified frictional constraints are met.

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Optimal Synthesis of Steering Mechanisms Considering Transmission Angles (전달각을 고려한 조향기구의 최적합성)

  • Park, Jong-Keun
    • Journal of the Korean Society of Manufacturing Process Engineers
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    • v.11 no.1
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    • pp.68-75
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    • 2012
  • In this study, the optimal synthesis of planar steering mechanisms for vehicles is studied. The author minimized the steering error between two front wheels subject to the constraints of transmission angles. Nonlinear programming methods such as BFGS method and golden section search method are used for this optimization. As numerical examples, Ackermann's steering mechanism, 6-link and 10-link planar mechanism are adopted to check the usefulness of this method. Consequently, among the three optimized mechanisms, 10-link planar one conducts far more accurate performance subject to tight constraints of transmission angles.