팔라듐 촉매에 의한 탈이산화탄소-양성자화 반응의 활용

김세희 전남대학교 대학원 2010 국내석사

본 논문에서는 Pd-catalyzed decarboxylative protonation protocol을 이용하여 cycloalkenone의 β-위치에 새로운 C-C bond를 도입하는 방법과 Baylis- Hillman adducts로부터 chromanone 유도체와 chromone 유도체를 합성하는 방법에 대해 연구하였다. 첫 번째로, 2-cycloalken-1-one 유도체에 allyl arylacetate의 conjugate addition을 통해 합성한 출발물질로부터 Pd-catalyzed decarboxylative protonation protocol을 이용하여 β-aralkyl cycloalkanone 유도체를 합성하였다. 전자가 부족한 aryl group이 생성된 π-allylpalladium complex를 안정화시킬 수 있는 electron-sink로 작용하여 Pd-catalyzed decarboxylative protonation이 효과적으로 일어날 수 있었다. 두 번째로, Pd-catalyzed decarboxylative protonation strategy를 통해 2-cycloalken-1-one의 β-위치에 -CH2EWG moiety를 도입하는데 성공하였다. 이 과정에서 Pd-catalyzed intramolecular redox step을 거친 것으로 추정되는 흥미로운 α,β-unsaturated carbonyl compound가 관찰되기도 하였다. 세 번째로, Baylis-Hillman adducts의 primary 위치에 SN2' type의 반응으로 페놀 유도체를 도입한 후, 이의 ester group을 가수분해 하였다. 이렇게 얻어진 출발 물질로부터 TFAA-assisted intramolecular Friedel-Crafts type cyclization을 통해 3-benzylideneflavanone 유도체를 합성하였다. 또한 이 화합물로부터 PCC를 이용한 oxidation을 통해 3-benzoylflavone 유도체의 합성이 가능하였다. 이와 같이, 본 논문에서는 Pd-catalyzed decarboxylative protonation의 개념을 응용하여 cycloalkenone으로부터 β-위치가 치환된 다양한 cycloalkanone 유도체들을 효과적으로 합성하는 방법에 대해 연구하였다. 또한 intramolecular Friedel-Crafts type cyclization을 이용하여 Baylis-Hillman adducts로부터 flavanone 유도체를 합성하였고, 이 화합물로부터 PCC에 의한 oxidation을 통해 flavone 유도체를 합성하였다. In this thesis, an expedient protocol for the synthesis of β-aralkyl cycloalkanones was developed via the conjugate addition of allyl arylacetate to cycloalkenones and the following Pd-catalyzed decarboxylative protonation strategy. Aryl moiety with an electron-withdrawing group such as 4-NO2 can accommodate electron efficiently and could be used in the Pd-catalyzed protonation reaction effectively. Also, we demonstrated some interesting applications of this protocol including the synthesis of vinyl compound and spiro compound. Similarly, an expedient method for the introduction of CH2EWG moiety at the β-position of 2-cycloalken-1-ones was developed via the conjugate addition of allyl esters having -CH2EWG moiety to cycloalkenones and the Pd-catalyzed decarboxylative protonation protocol. Interestingly, good to moderate yields of α,β-unsaturated compounds were obtained. Some cases cycloalkene derivatives were produced in low yields via the Pd(0)-catalyzed intramolecular redox process. A facile synthesis protocol of 3-benzylideneflavanones and 3-benzoylflavones from Baylis-Hillman adducts was developed. The synthesis was carried out by following the sequential processes: (i) preparation of cinnamyl bromide from Baylis-Hillman adduct and HBr, (ii) introduction of phenol at the primary position, (iii) hydrolysis of ester moiety, (iv) TFAA-mediated intramolecular Friedel-Crafts type cyclization to 3-benzylideneflavanone, and (v) PCC oxidation to 3-benzoylflavone. In summary, we developed an efficient protocol for the synthesis of various β-substituted cycloalkanones via the conjugate addition of various allyl ester to cycloalkenones followed by Pd-catalyzed decarboxylative protona tion strategy. In addition, we synthesized various chromanone derivatives from the Baylis-Hillman adducts using intramolecular Friedel-Crafts type cyclization protocol.

Chiral oxazaborolidinium ion activated carboxylic acids and aldimines : catalytic enantioselective protonation/nucleophilic addition, strecker and povarov reactions

Kang, Kitae Sungkyunkwan university 2020 국내박사

Chiral boron Lewis acid catalyst has a long history and the enantioselective synthetic method. It is a useful and versatile synthetic method for the stereoselective generation of chiral centers. Since it was first reported by Corey et al., chiral oxazaborolidinium ions (COBI), active forms of oxazaborolidine derived from proline, have been used as powerful Lewis acid catalysts. Initially, enantioselective Diels-Alder reaction catalyzed by COBI was reported, followed by nucleophilic 1,2- or 1,4-additions and cycloaddition reactions of various carbonyl compounds. Then corresponding tandem reactions were mainly developed. In this thesis, catalytic enantioselective protonation/nucleophilic addition with carboxylic acids was studied. Catalytic tandem reactions involving an enantioselective protonation step provide a powerful tool for the construction of structurally complex chiral molecules. A new chiral Brønsted acid derived from carboxylic acid and a chiral oxazaborolidinium ion (COBI), as an activator, is introduced. This acid was successfully applied as a catalyst for the highly enantioselective protonation/nucleophilic addition of diazoesters with carboxylic acids. This mild and chemoselective transition-metal-free coupling reaction provides access to a variety of α- or β-acyloxy esters in good yields and high to excellent enantioselectivities. The resulting α- or β-acyloxy esters can easily be converted into enantioenriched (S)-tropic acid methyl ester without loss of optical purity. Next, chiral oxazaborolidinium ion (COBI)-catalyzed enantioselective nucleophilic addition reactions of aldimines using tributyltin cyanide and have been developed. Various α-aminonitriles was synthesized in high yield (up to 98%) with high to excellent enantioselectivity (up to 99% ee). A rational mechanistic model for the complex of COBI and aldimine is provided to account for these enantioselective reaction. Finally, a new catalytic enantioselective Povarov reaction of imine was successfully developed. Chiral tetrahydroquinoline cores are characteristic structural motifs in many biologically active natural products and pharmacologically relevant therapeutics. A synthesis of chiral functionalized tetrahydroquinolines has been developed by means of catalytic enantioselective Povarov reaction of aldimines with various alkenes in the presence of a chiral COBI catalyst. The reaction gave the corresponding highly functionalized tetrahydroquinolines in good yields, excellent diastereoselectivities (>20:1 dr), and high enantioselectivities (up to 98% ee). This thesis summarizes recent research of catalytic enantioselective protonation/nucleophilic addition, Strecker and Povarov reactions catalyzed by COBI catalysts.

Enantioselective protonation of silyl enol ethers using a cation-binding catalyst

Jung, Minjung Sungkyunkwan university 2018 국내석사

본 석사학위 논문에서는 새로운 양이온 바인딩 촉매를 이용한 수소첨가반응의 연구에 대하여 보고하려 한다. 유기합성분야에서 proton은 가장 작은 작용기이며, 이를 조절하여 화합물의 입체선택성을 조절하는 일은 매우 도전적인 분야로 여겨진다. 이 연구에서는 chiral anion generator로 양이온 바인딩 촉매를 이용하여 입체선택적인 수소첨가반응을 통한 alpha-카보닐 3차탄소중심을 갖는 chiral 화합물의 합성반응에 도전하였다. 새로운 양이온 바인딩 촉매는 potassium fluoride와 coordination을 통해 fluoride anion을 활성화하게 되고 이는 반응물인 silyl enol ether의 silyl 그룹을 deprotection 하여 enolate를 형성하고 촉매의 proton과 반응하여 원하는 입체선택적인 생성물을 얻게 된다. 개발한 반응을 다양한 치환그룹을 가진 tetralone type의 반응물에 적용해 보았고, 높은 수율과 입체선택성을 보이는 것을 확인하였다. 또한 tetralone 뿐만 아니라 chromanone, thiochromanone까지도 반응 영역을 넓히는데 성공하였다. 그 이외에 alpha 위치에 훨씬 더 acidic한 proton을 가지는 alpha-fluorotetralone type의 반응물에서도 좋은 반응성과 높은 입체선택성으로 생성물을 얻을 수 있었다. The development of asymmetric transformations using in-situ generated chiral fluoride ions is a long-standing goal of chemical research. In this regard, the potential of the 3,3’-diiodine-substituted BINOL (1,1’-bi-2,2’-naphthol)-based bis(hydroxyl) polyether was explored in the highly enantioselective protonation of trimethyl silyl enol ethers by using CsF as the source for the in situ generation of chiral fluoride anion. Various silyl enol ethers of α-substituted tetralones have been successfully converted to the enantiomerically enriched α-chiral tetralones derivatives. Moreover, the established protocol was also successfully extended to the synthesis of chiral α-substituted chromanone and thiochromanone derivatives. Even highly enantioselective protonation of silyl enol ethers of α-fluoro cyclic ketones, extremely challenging substrates, could be successfully achieved for the first time, producing chiral α-fluoro cyclic ketones in good yields and ees.

Factors controlling pH in coastal groundwater and seawater of a volcanic island

이정현 서울대학교 대학원 2015 국내박사

The oceans are being acidified as a result of oceanic uptake of anthropogenic CO2, and global surface pH levels have already decreased by more than 0.1 units since preindustrial times. This ocean acidification may have critical consequences for marine ecosystems and biogeochemical cycles. In addition to ocean acidification driven by rising atmospheric CO2 levels, some coastal regions have experienced more rapid declines in their seawater pH than that in the open ocean as a result of anthropogenic nutrient inputs through river water and groundwater discharge. Although a number of studies have dealt with coastal pH changes related to river water discharge, studies on the effects of coastal groundwater discharge, which has recently been recognized as an important pathway for nutrients, organic matter, and other trace elements, are limited. Therefore, in this study, I aimed to investigate the pH changes in coastal groundwater itself and evaluate the effects of this groundwater discharge on coastal seawater pH. In order to evaluate pH changes in coastal groundwater, pH (NBS scale), dissolved inorganic carbon (DIC), total alkalinity (TAlk), and δ13C-DIC were measured in groundwater of a subterranean estuary (STE) in Hwasun Bay, which is located in the southwestern part of Jeju Island that lies off the coast of South Korea. This site was chosen because the amount of submarine groundwater discharge (SGD), which includes a substantial amount of submarine fresh groundwater discharge (SFGD), is large in this area and thus water is exchanged actively between the land and ocean through a sandy sediment layer. In the STE of Hwasun, the pH values (7.4±0.2) of fresh groundwater increased sharply to ~10 and then behaved conservatively in the mixing zone between alkalified fresh groundwater and seawater. Similar patterns were observed for pH at Samyang on the northern coast and at Iho on the northwestern coast of the island. The distributions of DIC, TAlk, δ13C-DIC, Ca2+, and Mg2+ in coastal groundwater of Hwasun, along with the results from laboratory experiments on sediment columns, suggest that the increase of pH in this STE is associated with the adsorption of protons (protonation) onto sandy sediments, rather than other geochemical processes. The laboratory experiments that used sediment samples from five different sites (Hwasun, Samyang, Hyeobjae, Hamdeok, and Pyoseon) on Jeju Island showed that the protonation (1) is a common occurrence for various sediments, (2) increases pH effectively for low salinity (salinity <10) groundwater, and (3) depends on the relative amount of transition metal (i.e., Fe, Ti, and Mn) oxides. The chamber experiments at the interface of seawater and groundwater of Hwasun Bay indicate that there is direct seepage of high pH water into the ocean. This increase in pH leads to the corresponding uptake of CO2 from the atmosphere. Thus, these results suggest that the reaction between groundwater and coastal sediments should be considered as an important driver of pH change that regulates the magnitude of chemical species in coastal groundwater seeping into the ocean at the volcanic island of Jeju. The effect of protonation of sediments occurs throughout the entire coast of Jeju beach sediments. However, in some STEs where the loading of organic matter is substantial and the residence time of SGD is long enough to allow organic matter to decompose, the decreases in pH down to 7.7 and the increases in DIC up to 2.5 mmol kg-1 were observed. Therefore, the pH in coastal groundwater of this volcanic island is controlled mainly by two factors, namely, protonation and organic matter oxidation. In order to evaluate the effect of SGD on the coastal ocean, variations in pH of coastal seawaters in Hwasun Bay off the volcanic island of Jeju were measured. This bay is situated in the oligotrophic open ocean. In this region, salinities of all coastal waters depend primarily on SGD because of the lack of any contributions from the river or stream waters. A significant increase in pH along the lower-salinity plume zone was observed, and this zone was extended 0.5 km horizontally where it encompassed the waters from the bottom to the surface (<15m water depth). The observed data for the entire bay-water column showed a significant negative correlation (r2 = 0.82) between salinity and pH. A simple two-endmember (submarine groundwater and offshore seawater) mixing model showed that this pH increase was caused by enhanced biological production, which resulted from the SGD-driven nutrient inputs rather than from the groundwater dilution itself. Since a number of local and regional studies have shown that SGD-driven fluxes of nutrients are comparable to or higher than riverine fluxes, these results from an SGD-dominated environment suggest that SGD may have a significant influence on coastal biogeochemical changes such as acidification, deoxygenation, and eutrophication. The change in pH of coastal groundwater discharge and the associated transport of substances (i.e., nutrients, organic matter, and inorganic carbon) may have a great impact on the coastal ecosystem and biogeochemistry of volcanic islands standing in oligotrophic ocean, which is very vulnerable to ongoing acidification. Therefore, the results presented here provides a good starting point for investigating the various effect of SGD on coastal ocean acidification over different temporal and spatial scales.

Asymmetric Organocatalytic Reactions in Confined Water Cages

박시준 성균관대학교 일반대학원 2022 국내박사

본 박사학위 논문에서는 물이 만들어내는 한정된 공간 안에서, 소수성 수화 효과에 의해, 비대칭 유기촉매를 이용한 유기반응들이 반응속도가 가속되거나, 광학선택성이 증폭되는 결과와, 이러한 반응속도와 광학선택성의 증폭의 물리적 근원에 대한 연구를 보고하려 한다. 첫 번째 부분에서, 비대칭 유기촉매를 이용한 생체 효소 모방형 시스템을 개발하여, 물을 용매로 이용하였을 때 반응속도가 비약적으로 증가하면서도 입체선택성이 저하되지 않는 헤미싸이오아세탈의 비대칭 양성자 도입 반응을 진행하였다. 물 안에서 양성자는 물 분자간 이동시간이 수 피코초밖에 되지 않을 정도로 통제하기 힘들고, 이로 인하여 비대칭 양성자 도입 반응에서 물 분자와 양성자가 반응 입체선택 전이상태를 방해하게 된다. 소수성 용매 첨가물의 도입과 이중상 미세유체흐름 시스템에서의 정적 반응 조건을 통하여 물 분자와 양성자가 전이상태를 방해하여 라세미화를 일으키는 것을 통제해내면서도 반응속도의 저하 없이 높은 광학선택성을 갖는 베타하이드록시싸이오에스터 화합물을 합성해냈으며, 해당 비대칭 양성자 도입 반응이 물에서 가속되는 실험적 근거와 그 물리적 근원을 찾기 위해 역학실험과 적외선 분광법 실험을 진행하였고, 이를 통하여 수화 쉘에 갖힌 소수성 반응물 방울에 가장 근접한 물 분자간 수소결합이 강화됨을 발견하였다. 두번째 부분에서, 물에 의해 한정된 공간 내에서 비대칭 유기촉매를 이용한 만니히 반응의 입체선택성 증폭에 대한 연구내용에 대해 다루었다. 촉매의 소수성과 교반 속도 조절을 통해 소수성 수화 효과를 극대화 시킬 때 입체선택성이 증폭된다는 것을 발견하였고, 이 증폭 현상의 정량적 분석을 위하여 이중상 미세유체흐름 시스템을 적용시켰다. 이중상 미세유체흐름 시스템 하에서, 물에 의해 한정되는 유기 반응물의 부피를 조절할 수 있었고, 더 작은 부피의 유기 반응물 방울을 형성할수록 입체선택성 증폭이 더 크게 일어남을 정량적인 결과로 얻어낼 수 있었다. 이러한 소수성 수화 효과에 의한 입체선택성의 증폭의 근원을 밝혀내기 위해 고압실험을 진행하여, 시작 반응물의 부피에서부터 반응이 진행되어 R-이성질체와 S-이성질체를 각각 형성하는 전이상태가 되며 감소하는 부피가 차이가 있으며, 소수성 수화 효과를 통한 가압 효과로 인하여 부피가 더 작은 전이상태로의 진행이 가속되어 입체선택성이 증폭되는 것임을 제시하였다. 마지막 부분에서 물을 용매로 이용한 한정 공간에서의 비대칭 자가촉매 마니히 반응이 마찬가지로 물에 둘러싸인 한정 공간 내에서 입체선택성이 증폭될 뿐만 아니라, 한정 공간에 의해 형성된 유기 반응물의 길이에도 영향을 받는 것을 발견하였다. This dissertation describes rate acceleration and chirality amplification of asymmetric organocatalytic reactions by hydrophobic hydration effect under “on-water” conditions and studies to reveal their physical origin. In the first part, the water-enabled biomimetic organocatalytic enantioselective protonation of hemithioacetals under the “on-water” condition is presented. I successfully controlled the interference of water molecules or protons on an enantio-determining transition state to give β-hydroxy thioester compounds with excellent enantioselectivity. Further improvement of enantioselectivity without a slowdown of the reaction rate was achieved by biphasic microfluidic system. The physical origin of the rate acceleration under “on-water” condition was explored by an IR spectroscopy and kinetic experiment. The second part presents the chirality amplification of organocatalytic asymmetric Mannich reaction in confined water cage. It was discovered that under the “on-water” condition, the enantioselectivity can be amplified by enhanced hydrophobic hydration effect by controlling hydrophobicity of catalysts or droplet sizes via stirring rate. Quantitative analysis of the amplification effect “on-water” was achieved by the biphasic microfluidic system which can precisely control the droplet size of organic reaction mixture surrounded by water plugs in confined space. The quantitative relationship between the decreasing size of organic reaction mixture droplet and increasing enantioselectivity could be obtained. To access to the origin of chirality amplification by the “on-water” effect, a high-pressure experiment was carried out. In the last part, chirality amplification of autocatalytic asymmetric Mannich reaction in confined water cage is presented. It was revealed that not only the size of the droplet, length of organic plugs also affected to the enantioselectivity.

Conformational changes of [30] and [32]heptaphyrins upon protonation : effects on the photophysical properties and aromaticity

신재윤 Graduate School, Yonsei University 2009 국내석사

meso-Hexakis(pentafluorophenyl) [30]heptaphyrin(1.1.1.1.1.1.0) and mseo-heptakis(2,6-dichlorophenyl) [32]heptaphyrin(1.1.1.1.1.1.1) have been investigated with a particular focus on their photophysical properties affected by protonation with acids using steady-state and time-resolved spectroscopic measurements along with femtosecond Z-scan method. It was found that the smaller Stokes shift and longer excited singlet/triplet state lifetimes of protonated [30] and [32]heptaphyrin compared to their distorted neutral counterparts are strongly associated with the rigid molecular structures. Much larger two photon absorption cross-section values of protonated [30] and [32] heptaphyrin than those of their neutral forms also reflect the enhanced rigidity as well as aromaticity. In parallel with this, the nucleus-independent chemical shift (NICS) values of protonated forms exhibit large negative values. Thus we have demonstrated the structure-property relationships between molecular planarity, photophysical properties, and aromaticity of expanded porphyrins upon protonation based on our experimental and theoretical investigations. This study also promises a possibility of structural control of expanded porphyrins through protonation in which the molecular flexibilities of expanded porphyrins lead to distorted structures especially as the number of pyrrole rings increases. 산첨가를 통한 양성자화에 의해 영향을 받아 변화하는 meso-hexakis(pentafluorophenyl) [30]헵타피린과 meso-heptakis(2,6-dichlorophenyl) [32]헵타피린의 광물리적 성질을 정류상태 및 시분해 분광학과 펨토초 지스캔 (Z-scan)법을 이용하여 연구하였다. 그 결과, 뒤틀린 구조를 가지고 있는 중성상태의 헵타피린과 비교해 보았을 때, 양성자화된 [30], [32]헵타피린에서 관측된 더 작은 스톡스 이동 (Stokes shift)과 더 긴 단일항/삼중항 들뜬 준위의 수명시간은 보다 더 단단해진 분자 구조 때문인 것으로 확인되었다. 또한 양성자화된 [30],[32]헵타피린에서 관측된 중성상태에 비해 훨씬 큰 이광자 흡수 횡단면 값은 이 분자의 구조적 단단함 뿐만 아니라 방향성 (aromaticity)도 크게 향상되었음을 말해준다. 이러한 실험결과와 동일한 결과로 양자계산을 통해 얻어진 양성자화된 [30], [32]헵타피린의NICS (nucleus-independent chemical shift) 값이 음의 값을 보였다. 따라서, 우리는 실험적, 이론적 연구를 바탕으로 산첨가에 의해 나타나는 확장 포피린의 분자의 평면성과 광물리적 특성 그리고 방향성 사이에서 나타나는 구조-성질 관계를 밝혔다. 이 연구는 또한 피롤의 개수가 증가함에 따라 구조적 유연성에 의해 뒤틀린 구조가 나타나게 되는 확장 포피린의 구조를 양성자화를 통해 제어할 수 있는 가능성을 보여주는 연구이다.

Li+/H+ 교환 반응이 Li6.25Ga0.25La3Zr2O12의 비정상 입성장에 미치는 영향

최성진 충북대학교 2022 국내석사

The garnet-type Li7La3Zr2O12(LLZO) has been considered a promising oxide-based solid electrolyte (SEs) for All-Solid-State batteries (ASSBs) with improved energy density and superior safety. In particular, the LLZO solid-state electrolyte gives benefits such as wide potential window, lithium dendrite growth inhibition, and non-toxicity compared to other solid-state electrolytes, i.e. polymer, sulfide state, etc. However, the nature of the Li+/H+ exchange reaction (protonation) of LLZO with protic solvents such as water, EtOH, acetone, etc. makes LLZO difficult to handle. The protonation of LLZO is well known which makes a Li2CO3 layer that is considered a lithium-ion resistor on the LLZO surface. Furthermore, in this study, we proved that protonation affects the sintering behavior of Ga-LLZO. The solid electrolytes sintered from Ga-LLZO powder with different protonation times had different microstructure and electrochemical properties. The electrolyte sintered with protonated powder has Abnormal Grain Growth (AGG) compared to that sintered with bare powder. The lithium-ion conductivity of Ga-LLZO solid electrolyte increased with increasing protonation time by AGG from 0.49 mS∙cm-1 to 0.89 mS∙cm-1. But, the lithium dendric growth was promoted in the AGG ceramics sintered from the powder protonated for 1 hour.

Quinizarin-based simple and convenient colorimetric sensor for carbon dioxide

성민석 서울대학교 대학원 2017 국내석사

Abstract Quinizarin-based Simple and Convenient Colorimetric Sensor for Carbon Dioxide MinSeok Seong Department of Materials Science and Engineering The Graduate School Seoul National University In search of simple and fast method to estimate the concentration of atmospheric carbon dioxide, the quinizarin and TBD system was discovered and its mechanism was studied and the applications were tried. From UV-VIS spectrum, the reason behind the change in color of the solution was found to be the different electronic forms of quinizarin. In other words, the color of the quinizarin solution was orange yellow when quinizarin was neutral while its color changed to purple once mixed with TBD as a result of deprotonation. Also, the molar ratio of quinizarin to TBD was 1 to 1 because there was no increase in the strength of the absorption band when TBD was excessive whilst there was a decrease when TBD was deficit. Also, the shift of the absorption band was observed as a result of TBD binding with carbon dioxide and giving back protons to quinizarin. From 1H-NMR spectrum, the hydroxyl proton of quinizarin was observed initially but it was soon given to TBD. Also, the fact that TBD bound itself with carbon dioxide was verified by the 13C-NMR spectrum as a new peak was observed at 161 ppm. In assistance with FT-IR spectrums, the proposed mechanism was supported once more. Quinizarin loses a proton to TBD and the protonated TBD loses the proton as it binds with carbon dioxide. As a result, the color of the solution changed from purple to yellow. The intensity of the vibrational modes for the corresponding functional groups changed accordingly; N-H bond decreased and O-H bond increased. For the experimental parts, the saturation volume of carbon dioxide was studied; the total volumetric capacity of the detecting system at different concentrations were measured and it was used to estimate the approximate response time and detectable concentration of carbon dioxide for each concentration of the system. The response time of the system at given concentration of carbon dioxide was figured out in the next step. As predicted, the system with lower concentrations of the chemicals had a shorter response time. However, the systems with the other organic bases such as DBU and piperidine were found to be not fast enough to detect the concentration of carbon dioxide fast compared to the system with TBD at the same concentration. Most importantly, the system could be recycled for at least 3 to 5 times and the performance was maintained relatively well. The system could actually be re-used upto 10 times but it became harder and harder to notice the color change when re-used too many times. Known the properties of the system as sensor, new applications were tried.. For solidification, TBD was physically fixed onto silica and it was successfully done. Nextly, the solid TBD was dipped in the quinizarin solution to become blue. Although the system was seemingly ready, it was not be able to interact with the atmospheric carbon dioxide and did not undergo any color change. Obviously, the solid system failed to interact with carbon dioxide because of too high thermodynamic barrier between solid and gas. The other option was an Agarose gel technique. The quinizarin and TBD solution was made and mixed with hot agarose solution and cooled down. However, the gel had too much viscosity so the response time was significantly increased. Keywords: Carbon dioxide, Chemical dye, Organic base, Protonation, Deprotonation, Adduct, Colorimetric sensor, Student Number: 2015-20829

Atomic insights into the stability of the electrostatic network and hydrophobic core in the prion protein

Juhwan Lee DGIST 2020 국내박사

Destabilization of a prion protein (PrP) induces a conformational change that alters a normal prion protein (PrPC) to an abnormal prion protein (PrPSC). The structural stability of PrP is dramatically destabilized by unfavorable external environmental conditions and mutations in the protein. Environmental pH is a critical determinant of misfolding and aggregation of PrP, which leads to fatal neurodegenerative diseases. Because protonation of H187 and mutation of the hydrophobic core on the H2-H3 bundle are strongly linked to a change in PrP stability, I examined its charged residues R156, E196, and D202 around H187 and hydrophobic residues V176, V180, T183, V210, I215, and Y218. Interestingly, there are reports on mutants, such as V176G, T183A, H187R, E196A, D202N, I215V, and Y218N, which cause genetic prion diseases. First, I focused on the mechanism by which an acidic pH and mutants disrupt this electrostatic network and how this broken network destabilizes the PrP structure. Towards this objective, I performed a temperature-based replica-exchange molecular dynamics (T-REMD) simulation using a cumulative 252μs simulation time. I measured the distance between amino acids comprising four salt bridges (R156–E196/D202 and H187–E196/D202). Our results showed that the spatial configuration of the electrostatic network was significantly altered by an acidic pH and mutations. The structural alteration in the electrostatic network increased the RMSF value around the first helix (H1). Thus, the structural stability of H1 anchored to the H2–H3 bundle was decreased, which induced separation of R156 from the electrostatic network. Analysis of the anchoring energy also showed that the two salt-bridges (R156-E196/D202) are critical for PrP stability. Second, I focused on the hydrophobic interaction. Not only electrostatic interaction but also hydrophobic interaction is the main driving force for protein folding, critically affecting the stability and solubility of the protein. To examine the importance of the hydrophobic core in the PrP, I chose six amino acids (V176, V180, T183, V210, I215, and Y218) that form the hydrophobic core at the middle of the H2-H3 bundle. A few pathological mutants of these amino acids have been reported, such as V176G, V180I, T183A, V210I, I215V, and Y218N. I revealed how these mutations affect the hydrophobic core and thermostability of PrP. Towards this, I used a temperature-based replica-exchange molecular dynamics (T-REMD) simulation for extensive ensemble sampling. From the T-REMD ensemble, I calculated the protein folding free energy difference between wild-type and mutant PrP using the thermodynamic integration (TI) method. Our results showed that the mutants V176G, T183A, I215V, and Y218N decreased PrP stability. At the atomic level, I examined the change [valine-valine to valine-isoleucine (and vice versa)] in pair-wise hydrophobic interactions, which is induced by mutation V180I, V210I (I215V) at the 180th–210th (176th–215th) pair. Additionally, I investigated the importance of the π-stacking between Y218 and F175. 프리온 단백질(PrP)의 불안정화는 정상 프리온 단백질(PrPC)에서 비정상 프리온 단백질 (PrPSC)로 구조적 적 변화를 유도합니다. PrP의 구조적 안정성은 불리한 외부적 환경 및 단백질 상의 돌연변이에 의해 극적으로 불안정화됩니다. 특히, pH는 프리온 단백질의 잘못된 접힘 및 응집을 결정하는 중요한 결정 인자이며, 이는 치명적인 신경 퇴행성 질환을 초래합니다. H187의 양자화가(protonation) PrP 안정성의 변화와 강하게 연관되어 있기 때문에, H187 주위의 전하를 띄는 아미노산 R156, E196 및 D202를 조사하였습니다. 흥미롭게도 H187R, E196A 및 D202N의 경우 병리학적 돌연변이에 관한 보고가 있었습니다. H187의 양성자화와(protonation) H2-H3 번들의 소수성 코어의(hydrophobic core) 돌연변이가 PrP 안정성의 변화와 강하게 연관되어 있기 때문에, H187 주위의 전하를 띄는 아미노산 R156, E196 및 D202 및 소수성 아미노산 V176, V180, T183, V210, I215 및 Y218을 조사하였습니다. 흥미롭게도 이 아미노산들은 V176G, T183A, H187R, E196A, D202N, I215V 및 Y218N과 같은 병리학적 돌연변이체에 대한보고가 있었습니다. 첫째로, 산성 pH 및 병리학적 돌연변이가 어떻게 전기적 네트워크를(electrostatic network) 방해하는지, 그리고 손상된 네트워크가 PrP 구조를 어떻게 불안정하게 만드는지에 관해 초점을 맞췄습니다. 이를 위해 온도기반 레플리카-교환 분자 동역학 시뮬레이션 (temperature-based replica-exchange mo-lecular dynamics, T-REMD)을 총 252μs 수행했습니다. 본 연구에서 4개의 염다리 (R156–E196 / D202 및 H187–E196 / D202)의 사이의 거리를 측정했고, 전기적 네트워크의 공간적 배열은 산성 pH와 돌연변이에 의해 크게 차이를 보였습니다. 전기적 네트워크의 구조적 변화는 첫 번째 나선 (H1) 주위의 RMSF(root mean square fluctuation of specified residues) 값을 증가 시켜 H2–H3 번들에 고정된 H1의 구조적 안정성이 감소시키고, 전기적 네트워크에서 R156의 분리를 유도합니다. 또한 앵커링 에너지의 분석을 통해 2개의 염다리 (R156-E196 / D202)가 PrP 안정성에 중요하다는 것을 보였습니다. 둘째로, 소수성 상호 작용에 중점을 두었습니다. 전기적 상호 작용뿐만 아니라 소수성 상호 작용도 단백질 폴딩의 주요 원동력이며 안정성과 용해도에 결정적으로 영향을 미칩니다. PrP에서 소수성 코어의 중요성을 조사하기 위해, H2-H3 번들의 중간에 소수성 코어를 구성하는 6개의 아미노산 (V176, V180, T183A, V210, I215 및 Y218)을 선택했습니다. 이들 아미노산의 병리학적 돌연변이 체가(V176G, V180I, T183A, V210I, I215V 및 Y218N) 이미 보고된 바 있습니다. 본 연구에서는 이러한 병리학적인 돌연변이가 소수성 코어 및 PrP의 열역학적 안정성에 어떻게 영향을 미치는지에 관해 연구하였습니다. 이를 위해 광범위한 앙상블 샘플링을 위해 온도기반 레플리카-교환 분자 동역학 시뮬레이션 (temperature-based replica-exchange molecular dynamics, T-REMD) 시뮬레이션을 수행했습니다. T-REMD 앙상블로부터, 열역학적 통합 방법 (thermodynamic integration, TI) 을 사용하여 야생형과 돌연변이체 PrP 사이의 단백질 접힘 자유 에너지의 차이를 계산하였습니다. 이를 통해 병리학적 돌연변이체인 V176G, T183A, I215V 및 Y218N PrP의 안정성 감소를 확인하였습니다. 또한 180th-210th (176th-215th) 아미노산의 돌연변이 V180I, V210I (I215V)에 의해 유도되는 “발린-발린”에서 “발린-아이소류신” (또는 그 반대, “발린-아이소류신”에서 “발린-발린”)으로 상호작용 파트너가 바뀌는 상황에서 소수성 에너지의 변화를 원자 수준에서 조사하였습니다. 마지막으로, Y218과 F175 사이의 π-겹침의(π-stacking) 중요성을 조사했습니다.

Ultrafast dynamics in various porphyrioids from triphyrin to decaphyrin

성영모 Graduate School, Yonsei University 2015 국내박사

There have been continuous attempts to develop functional π-electronic systems considered as being one of the most important research of core technology such as renewable energy, nano scale molecular device and low-cost photovoltaic technologies. Porphyrinoids, one of the most famous functional π-electronic systems, have attracted the interest of scientists due to their facile tunability of the molecular structures and the number of π-electrons which can determine the photophysical properties (e.g. ground-state electronic feature, excited-state dynamics, and nonlinear optical properties). In this reagard, much research has been conducted to control the chemical properties of porphyrinoids, which is important as not only the basic research, but also application in industry due to their potential applications in photovoltaic devices, photodynamic therapy, and photosensitizers. To control the chemical features of porphyrinoids, there are strenuous efforts by the modification of porphyrins such as subtracting and adding pyrrole subunit in porphyrins, substituting the pyrrole to pyrrole-related ring, and metal insertion. Although there are numerous study to synthesize various porphyrinoids, the photophysical and theoretical study on porphyrinoids have not yet been fully conducted. In this regard, I have prepared porphyrinoids (trihyrins, vacataporphyrins, etheneporphyrin, rhodium hexaphyrins, larger expanded porphyrins to explain the chemical and physical features of porphyrinoids and reveal the photophysical properties depending on the number of π-electrons, the molecular structures, π-conjugation and aromaticity. First of all, I have investigated the photophysical properties of two type of triphyrins with a focus on the fused-moiety effects by performing various spectroscopic measurements and theoretical calculations. Secondly, I have investigated the photophysical properties of vacataporphyrins possessing systematically controlled butadiene linkers on their π-electron pathways by conducting various spectroscopic analysis along with quantum mechanical calculations. Thirdly, I have revealed the the electronic structure and photophysical properties of (C=C)TTP2+ by using quantum mechanical calculations and transient absorption spectroscopic measurements. Fourthly, by investigating the photophysical properties of a series of thiaaceneporphyrinoids in a various condition such as high viscosity and low temperature, I could confirm that a series of thiaaceneporphyrinoids show structural diversity giving rise to conformers with either aromatic or nonaromatic π-conjugation depending on their structures. Fifthly, I have demonstrated the reversal of Huckel (anti)aromaticity in the lowest triplet states, suggested by Baird in 1972, by revealing the difference between the ground and excited state properties of two closely-related bis-rhodium hexaphyrins containing [26]- and [28] π-electron peripheries. Finally, through the spectroscopic measurements of larger expanded porphyrins, I have revealed that the protonation effect which can retrieve the aromaticity in either planar Huckel or distorted Mobius structures of larger expanded porphyrins with all meso-carbon bridged pyrroles is achieved up to [42] Nonaphyrins. I expected that the researches in this thesis would provide fruitful insight into the relationship between the molecular structures and photophysical properties, and as a consequence, development of innovative nano-materials.