Theoretical and Data-driven Study for New Perspectives on Material Chemistry

Dong Yeon Kim Ulsan National Institute of Science and Technology 2021 국내박사

With the rapid advances in experimental techniques and continued expansion of material spaces, millions of super-functional materials have been created and developed in the field of material science. These newly created super-functional materials exhibit totally different catalytic, optical, electrical, and thermal properties recording a high-value to be utilized in a wide variety of applications. Especially, the multi-composed (more than tertiary systems) and extremely downscaled (e.g. single atom catalysts, and strongly correlated systems) materials show dramatic and distinct properties under the influence of their complexity and quantum effect. However, the interpretation of these particular materials is really hard to understand by human-intuitions and the experimental observations because their properties are different from the conventional materials. Therefore, special techniques should be required to gain a more fundamental understanding of the materials than is observed in the experiments. Theoretical chemistry has emerged with the development of quantum theory and high-end supercomputers to interpret and explain the roles of electronic structures on material properties. In this regard, the physicochemical phenomena of super-functional materials could be understood with an aid of a theoretical approach using the first-principles calculations (e.g. density functional theory, coupled cluster, and configuration interaction). In fact, until now, theoretical chemistry is one of the powerful tools to elucidate and investigate the electronic structure of organic compounds, catalytic activity of energy materials, optical properties of solids, and electrical properties of perovskites. Indeed, the theoretical studies are now allowed us to obtain new insight into the material. Moreover, with the advent of machine learning, which is opened a golden period of artificial intelligence with numerous applications in visual recognition, healthcare, natural language processing, and even first-principles calculations, the data-driven studies combined with theoretical chemistry and machine learning have become very attractive in the field of material chemistry. Here, I depict the theoretical and data-driven researches showing the finding of new perspectives on material chemistry. In Section 1, general introduction and key concepts for theoretical and data-driven researches are introduced for a better understanding of this dissertation. Next, detailed examples related to the subject are described as following contents; the theoretical approach to materials, finding chemical trends with massive case-study, accelerated computational screening strategy to find promising catalysts, computational-aided material design, and derivation of the empirical equation with machine learning. In Section 2, theoretical studies for band alignment with dimensional reduction and defect control of material are investigated using the combinations of theory and experiment. The new-type of sheet-like zinc orthogermanate (Zn2GeO4, denoted as S-ZGO representing dimensional reduction) is synthesized and further modified using heat treatment to prepare the defected sample. A comparison of photocatalytic activity for water splilting are reported to investigate the effects of dimensional reduction and defects. For proving effects of them on photocatalytic activity, the band alignment is demonstrated with density functional theory showing the increased density of states at the edge of conduction band (CB) and valence band (VB), and a new defect level between CB and VB. In Section 3, A large-scale case study identifies chemical trends in carbene chemistry. From the models of diverse carbenes including CX2, C(YHn)2, and cyclic systems of C(ZHm)2, we elucidate the relationships among electron configurations, electron accepting/donating strength of atoms attached to carben center(:C), π conjugations, singlet/triplet energy gap, anisotropic hard wall radii, anisotropic electrostatic potentials, and amphotericity in carbenes, which are vital to carbene chemistry. The three specific electronic configurations (σ2, π2 or σπ) associated with :C on the :CA2 plane (where A is an adjacent atom) in singlet and triplet carbenes largely governs the amphoteric behavior along the :C tip and :C face-on directions. The :C tip and :C face-on sites of σ2 singlet carbenes tend to show negative and positive EPs favoring nucleophiles and electrophiles, respectively, whereas those of π2 singlet carbenes such as very highly π-conjugated 5-membered cyclic C(NCH)2 tend to show the opposite behavior. The open-shell σπ singlet (such as highly π-conjugated 5-membered cyclic C(CHCH)2) and triplet carbenes show less anisotropic and amphoteric behaviors. In Section 4, we introduce universal computational screening strategy that can accelerate the prediction of theoretical overpotential (ηDFT) for Oxygen Evolution/Reduction Reaction (OER/ORR) using only reaction free energy of O*. Our accelerated screening strategy can effectively reduce the computing time by skipping the costly calculations of reaction free energies of OH* and OOH*. Besides, the efficiency of accelerated screening strategy was verified using 1,008 combinations of single-atom-anchored transition metal dichalcogenides. The given candidate materials are rapidly screened using our strategy and finally 23 promising catalysts are found out of 1,008 candidates. In Section 5, a new oxygen-ligand steered SAC (M-O-C) is synthesized with a computation-aided approach. Based on theoretical calculations, the stability of various oxygen-ligand steered SACs is tested and the theoretical model proves that single metals can be stable with acetylacetonate ligands found in unzipped carbon materials. Besides, the newly designed M-O-C catalysts are experimentally realized and show a distinct electrocatalytic activity for oxygen evolution reaction (OER). The Ni-O-C shows excellent activity, followed by Co/Zn-O-C and their theoretical predictions for OER agree well with the experimental results. In Section 6, the analytic equations between band gap and properties of constituent elements (valence-electron numbers, electron affinities, melting points, van der Waals radii, group numbers, heat of vaporization and nonmetallic character, etc.) are derived using machine learning techniques suitable for small datasets: alternating conditional expectation (ACE) and projection pursuit regression (PPR). We present several models that predict the band gap with the coefficient of determination, R2 ≈ 0.9. These equations are a convenient tool in obtaining further insights into the nature of band gap and will pave the way for finding new light-active materials for optoelectronic devices.

Development of demonstration-enhanced courses throughout the chemistry curriculum and a comparative study of student responses

허진휴 Drexel Univ. 1996 해외박사

강의를 주로하는 수업형태에서 화학의 개념학습을 위한 일련의 데몬스트레 이션들이 일반 화학 교수학습 교재로 개발되었다. 1960년 이후의 학술 잡지 에 발표된 데몬스트레이션들을 재시험하고, 화학 개념별로 범주화 시킨 뒤, 투시물 환등기(overhead projector)를 이용하는 수업형태에 맞도록 시약의 종 류나, 농도, 용량등을 조절한 뒤 가시적 특수 기구의 조립등을 이용하여 실제 수업을 통해 재조정되었다. 일반 화학 교과 과정에 따른 각각의 데몬스트레 이션들에 관한 시약, 기구 및 방법들을 가르쳐야할 필수 개념의 설명과 함께 컴퓨터 데이타 베이스로 제작되었다. 이러한 데몬스트레이션들은 2년간 이공계 학생들을 위한 일반 화학 강좌에 실제 이용되어졌으며, 이를 이용한 교수 방법에 대한 평가 및 연구가 계속적 인 학생들의 태도 및 성취도 비교 등을 통하여 실시되었다. 주된 평가 방법 은 누적적인 설문 조사 방법과 수업 종료 직전의 형성평가, 강의실 관찰법, 개인별 면접법등이다. 학생들의 응답 결과는 데몬스트레이션의 형태별, 추상 적인 화학 개념의 난이도 별로 비교 되었으며, 각 개념과 데몬스트레이션의 방법에 따른 특성이 고찰되었다. 학생들의 태도에 관한 설문 조사 결과를 바 탕으로 개념학습을 위한 교수자료로서의 데몬스트레이션에 관한 추가적인 개 발과 유기화학, 물리화학 및 분석화학등의 교수 자료로서의 확대 이용이 요구 됨을 보였다. A set of demonstration materials was designed to teach chemistry concepts in the lecture setting. A database of overhead demonstrations was created based upon papers published in the Journal of Chemical Education from 1960 to current. All existing demonstrations were examined and categorized as being ready for overhead projection, adaptable for overhead projection or unsuitable for use on the overhead. New overhead projector demonstrations were developed along with new devices and methods to adapt standard experiments and bench-top demonstration to the overhead projector. All demonstrations were tested and organized according to concepts covered in the typical general chemistry curriculum. Each demonstration was designed with special attention paid to simplicity of equipment, ease of performing, and ready availability of chemicals, as well as organization according to topics presented in general chemistry texts A manual of all overhead demonstrations was created including short descriptions, list of chemicals and equipment, instructions for performing, and useful information such as formulas, data, and equations. Evaluation of the lecture demonstration enhanced course was studied by obtaining information on students attitude toward selected lecture demonstrations. This experiment involved a single large lecture section of general chemistry with mostly science and engineering majors. Evaluations were performed over a period of two years with two independent groups of students. Survey questions were designed as one means of obtaining information about students's attitude toward each demonstration. In addition, in-class writing assignments, classroom observation, and personal interviews were conducted. Results of the surveys indicated that in general, students found demonstrations to be interesting. In most cases they also found them to be informative, as long as the demonstrations were clearly connected to a single concept. The survey results were used to improve each demonstration, sometimes to remove a demonstration from the course, and to guide development of new demonstrations. Students felt that chemical demonstrations in lecture enhanced leaming and should be expanded and should cover more topics. Overall, there was a strong recommendation for increasing the use of demonstrations in chemistry lectures, creating new demonstrations to cover under represented topics, and including material covered in advanced courses such as organic chemistry, physical chemistry and analytical chemistry.

Integration of Computational Approaches, Machine Learning, Synthesis, and In Vitro Evaluation for Designing Carbonic Anhydrase, DHODH, and EGFR Inhibitors

Hossam Hammouda Nada Hammouda 동국대학교 일반대학원 2023 국내박사

1990년대 초만 해도 의약화학은 경험주의와 합성에 기반을 두고 있었기 때문에 계산화학의 중요성이 크지 않았다. 그럼에도 불구하고 다양한 연구와 투자로 점진적인 발전이 이루어져 현재는 의약화학분야내에서 계산화학의 역할이 커졌다. 이는 단백질 데이터베이스나 화합물 라이브러리 같은 구조적으로 사용가능한 표적 데이터의 급격한 증가, 지속적인 무어 법칙의 영향, 구조기반 약물개발에 집중하는 회사 설립으로 뒷받침되었다. 현재 신약개발 과정에서 계산을 통한 예측과 실제 실험적 테스트의 조합은 주목받고 있으며, 세계 유수의 신약개발 회사 일부에서도 다양한 계산 기법을 사용하고 있다. 이처럼 계산 기술에 대한 의존도가 높아진 것은 신약개발 과정에서 전임상 시험과 임상 시험 등 시간이 많이 소모되는 과정이라는 것에서 기인되었다. 신약개발에는 약 12억 달러의 비용이 사용되며, 신약개발 단계에서 실패율이 높기 때문에 계산 기법을 사용한 개발과정에서 비용을 줄일 필요성이 있다. 컴퓨터 보조 약물 디자인(Computer-aided drug design, CADD)은 유사한 생화학적 특성을 가진 약물 및 활성물질 발굴, 개발 및 분석을 가능하게 하는 일련의 계산 기법이다. 이런 기법에는 초고속 가상 스크리닝(virtual high-throughput screening, vHTS), 분자 도킹, 정량적 구조-활성 상관관계(quantitative structure-activity relationship, QSAR), 삼차원 약리활성단 맵핑(3D pharmacophore mapping), 분자동역학 시뮬레이션(molecular dynamics simulation), 자유에너지 계산 그리고 ADME 예측이 있다. 이런 기법은 신약개발의 첫번째 단계인 선도 화합물의 발견과 개선을 빠르게 하기 위해 사용된다. CADD에 사용되는 다양한 기법 중 가상 스크리닝은 가장 널리 활용되는 방법이다. 가상 스크리닝은 컴퓨터 알고리즘을 사용하여 특정 단백질 표적에 화합물을 가상으로 스크리닝하여 활성물질을 식별하고 최적화하는데 사용하는 계산기법이다. 스크리닝을 통해 화합물이 단백질 표적과의 상호작용하는 정도를 계산하고, 그 순위를 매겨 연구자가 비용을 절감하며 빠르게 선도화합물을 선정할 수 있도록 도움을 준다. 가상 스크리닝은 크게 구조 기반 가상 스크리닝과 리간드 기반 가상 스크리닝으로 나뉜다. 구조 기반 가상 스크리닝에서는 수용체나 단백질과 같은 생물학적 표적의 3D 데이터와 리간드/약물 후보물질을 도킹하고 결합 친화도에 따라 점수를 매겨 후보물질의 순위를 결정한다. 생물학적 표적의 3D 구조를 활용할 수 없는 경우 리간드 기반 가상 스크리닝을 사용한다. 리간드 기반 가상 스크리닝은 기존에 활성이 확인된 물질의 구조-활성 상관관계 정보를 활용한다. 이 가상 스크리닝 기법은 3D 형상 매칭, 약리활성단 기반 검색, QSAR, 유사성 검색, 하위구조 검색과 같은 다양한 기술을 포함한다. 가상 스크리닝은 많은 양의 화합물 라이브러리를 빠르게 스크리닝할 수 있지만, 기본적으로 표적단백질 분자의 유동성은 분자 도킹을 기반으로 하고 있다. 실제 단백질은 고정 되어있지 않고 여러 자극에 의하여 다양한 모양과 형태로 변할 수 있는 동적인 상태로 존재하며, 이러한 단백질 구조의 변형은 리간드의 결합형태와 신약 후보물질의 효능을 변화시킬 수 있다. 따라서 고정된 단백질을 가상 스크리닝에 사용하는 방법은 주요 결합부위를 간과하여 위음성을 나타내거나 부정확한 예측을 초래할 수 있다. 일반적으로 이런 한계점을 피하기 위해 분자동역학 시뮬레이션을 통한 가상 스크리닝 결과와 통합하여 정확성을 향상시킨다. 계산 기법의 예측가능성을 향상시키기 위해 자유 에너지 섭동(free energy perturbation, FEP)이라고도 알려진 자유 에너지 계산방법을 분자 동역학 시뮬레이션과 통합시킨다. FEP 계산은 두 리간드의 결합 친화도와 자유에너지를 비교하는 정밀한 방법을 제공한다. FEP 계산방법의 정확성과 신뢰성은 컴퓨터 기술의 발전으로 인해 전향적, 후향적 연구 모두에서 광범위하게 테스트되었다. 수많은 화합물 라이브러리에서 소수의 물질만이 연구 및 개발되기 때문에 FEP 계산 값은 신약 개발 과정에서 가장 큰 영향을 미친다. 기존의 약물후보물질 발굴 과정에서는 합성과정에서 많은 비용을 들이지 않고는 최적의 물질을 찾기 어렵다. 이런 상황은 표적 단백질과 다른 단백질의 구조가 서로 유사하여 높은 수준의 약물 선택성이 필요한 경우 부각된다. 약물의 선택성 뿐만 아니라 효능, 용해도, 대사 안정성, 막 투과도 등 약물로서 필요한 주요 특성 또한 성공적으로 고려하기 위해서는 더욱 많은 비용이 들어간다. 표적 단백질의 유형도 약물 개발 난이도에 상당한 영향을 미치며, 일부 표적 단백질은 리간드 결합부위가 굉장히 까다로워 효과적인 약물 후보물질을 개발하는데 어려움이 있다. 이 연구에서는 약물 개발과정을 향상시키기 위해 합리적인 약물 디자인과 합성, 몇몇 계산기법을 결합하였다. 앞서 언급한 다양한 계산기법은 신규 억제제의 결합 메커니즘을 설명하고, 새로운 약물 후보물질을 식별하며, 이전에 알려지지 않은 단백질-단백질 및 리간드-단백질 상호작용 메커니즘을 설명하는데 사용된다. 이러한 계산기법을 활용하여 약물 상호작용의 분자적 메커니즘을 밝히고 신규 약물 후보물질 디자인에 대한 통찰을 제공하고자 한다. At the start of the 1990s, the significance of computational chemistry in the field was debatable, with the majority of medicinal chemistry based on empiricism and synthesis. Nonetheless, a combination of discoveries, investments, and incremental advances has resulted in an increase in the role of computation in the field. This has been supported by a surge of structurally enabled targets, the continued impact of Moore's Law, and the establishment of companies completely dedicated to structure-based medication creation. The combination of computer prediction and experimental testing has given the area its present traction in the drug discovery process with some of the Worlds’ leading pharmaceutical companies relying heavily on the various computational tools for their day-to-day operations. This increased reliance on computational techniques stems from the fact that the Drug development is a difficult, time-consuming process that includes preclinical testing followed by clinical trials in human subjects. Drug development costs around $ 1.2 billion and has a high failure rate at any stage of drug development which has necessitated the use of computational techniques to decrease the cost of this process. Computer-aided drug design (CADD) refers to a set of computational techniques that enable the discovery, development, and analysis of drugs and active molecules with similar biochemical properties. These techniques include virtual high-throughput screening (vHTS), molecular docking, quantitative structure-activity relationship (QSAR), three-dimensional (3D) pharmacophore mapping, molecular dynamic simulations, free energy calculations and ADME prediction. These techniques are used in the first stages of drug development to quicken the discovery and improvement of lead compounds. Among the various strategies used in CADD, virtual screening is the most widely utilized one. Virtual screening has been established as a reliable and widely accepted computational technique for hit identification and optimization that supports experimental high-throughput screening. It involves the use of computer algorithms to screen a large variety of chemicals against a specific protein target. The program ranks the compounds based on their ability to attach to the target, allowing researchers to discover viable leads for future refining in a fast and cost-effective manner. Virtual screening can be divided into two main categories: ligand-based virtual screening and structure-based virtual screening (sometimes referred to as receptor-based or target-based virtual screening). A docking strategy is employed in structure-based virtual screening, which depends on the availability of 3D data on the biological target, to dock the ligand/drug candidate molecules to the receptor or protein target. The molecules are then ranked according to their docking score, which is determined by their expected binding affinity. When the 3D structure of the protein target is unavailable, ligand-based virtual screening is used. It makes use of structure-activity information gathered from a set of known active compounds. This virtual screening technique encompasses a variety of techniques such as 3D shape matching, pharmacophore-based search, QSAR, similarity search, and substructure search. Although virtual screening allows for the rapid screening of a large library, it is fundamentally based on molecular docking, which disregard the protein target's flexibility. Proteins, in reality, are not static, but rather exist in a dynamic state in which their shape and conformation can vary in response to various stimuli. These changes in protein shape can affect ligand binding and alter the potency and efficacy of the drug candidate. As a result, the rigid docking method utilized in virtual screening may overlook key binding sites, resulting in false negatives or inaccurate predictions. To circumvent this limitation, molecular dynamics simulations are typically incorporated into virtual screening to improve the accuracy of the screening results. In order to improve the predictability of the calculations, free energy calculations, also known as free energy perturbation (FEP), are one of the technologies that have been integrated with molecular dynamics. FEP calculations provide a precise method to compare the free energy of the binding affinities of two ligands. The accuracy and dependability of FEP methods have been extensively tested in both retrospective and prospective research thanks to advancements in computer technology as well as FEP methodology. Since only a small number of compounds from a large library of candidates can best develop the research, FEP estimates have the biggest impact on drug discovery projects. The best compounds could be difficult to find using conventional methods without spending a lot of money on synthetic chemistry. Such circumstances are frequently encountered in drug development efforts, especially when a high level of selectivity is required against numerous members of a family who are closely related to one another. It is quite difficult to achieve this selectivity, as well as other crucial qualities including potency, solubility, metabolic stability, and membrane permeability. The type of the target also substantially affects the degree of difficulty; some targets have extremely difficult binding sites, which makes the development of a drug-like yet effective molecule a big challenge. This study combines several computational techniques, as well as rational drug design and synthesis, to enhance the process of drug discovery. The various computational techniques mentioned earlier are used to elucidate the binding mechanism of novel inhibitors, identify new drug candidates, and explain the mechanism of previously unknown protein-protein and ligand-protein interactions. By utilizing these techniques, the study successfully sheds light on the molecular mechanisms behind drug interactions and provides valuable insights into the design of new drug candidates.

Polymer chemistry based on ring-opening reaction of aziridine

장현재 Korea University 2016 국내석사

During my two year stay at Korea University, I wished to demonstrate the potential utility of aziridine chemistry in polymer chemistry. Epoxide derivatives have been extensively studied in polymer chemistry, and a wide and number of applications using these materials have been demonstrated in academia and industry. However, aziridines, which are structurally similar to epoxides, have been rarely investigated in polymer chemistry. Thus, I have focused on developing methodologies to prepare polymers having aziridine moieties, and to polymerize aziridine monomers. In Chapter 2, I describe the synthesis of clickable polymers based on ring-opening reaction of aziridines. Copolymerization of aziridine-terminated methacrylate and methyl methacrylate is demonstrated. Lewis acid-assisted ring-opening reactions of the aziridine moieties incorporated in the polymer side-chain allow for the post-modification of polymer with alcohol derivatives. In Chapter 3, I describe a polymerization methodology based on the ring opening reaction of aziridine monomers. Ring opening polymerization of unactivated aziridines having different N-substituents is demonstrated. The polymerization process is highly efficient and rapid; it progresses at room temperature under a solvent-free condition, and is almost completed in ~30 min. The method I developed is applicable to the construction of homopolymers as well as random and block copolymers.

Design and fabrication of mesoporous heterogeneous catalysts for C1 chemistry

Li, Chengbin Sungkyunkwan university 2018 국내박사

Nowadays, increasing environment concerns related to chemical manufacturing and carbon resource utilization have led to the development of environmentally friendly catalysis and green chemistry. These new applications strongly require the catalysts to promote the reaction towards the desired product, minimize the generation of potentially polluting by-products, and eliminate any otherwise unavoidable emissions while maintaining their catalytic activity. Heterogeneous catalyst has provided an opportunity to solve these problems, at least partially. Heterogeneous catalysis has long been a topic of substantial interest for fundamental studies of chemistry and for practical applications in chemical industries; more than 90% of chemical manufacturing processes use catalysts. Heterogeneous catalysis is also a major technology for the energy and environmental field, involving the production of fuels/chemicals and in the clean-up of hazardous or polluting wasters. Heterogeneous catalysis essentially refers to chemical reactions on the surface of a solid catalyst, where the reactions containing a series of elementary steps: the adsorption of reactants, the diffusion of intermediate species, the transformation of chemical bonds, and the eventual desorption of products. In general, catalysts are thought to accelerate chemical reaction rates by lowering the activation energy, particularly that of the rate-determining step of the reaction network. However, the structural and morphology changes also can accelerate chemical reaction. First, compared with the bulk material the mesoporous structure material has large specific surface area, which could give more active site and even act as a support. Then, the uniformed crystalline framework and the controllable mesopore size system will benefit for the reactants and products diffusion fast during the reaction process. Lastly, the mesoporous material also exhibits well thermal stability even in the high temperature range. Based upon information, both of the structure morphology and highly active site are played a key role in design and development of heterogeneous catalytic materials. In this work, we focus on the catalysts application in C1 chemistry of ordered crystalline mesoporous ternary metal oxide. Based on our research results, by choosing the different kinds of third metal let the ternary metal oxide nano-framework more multiple and functional compare with the single or binary metal oxide catalysts. This kind of ternary system metal oxides which the main body CeO2 was modified by dopants ions and the small copper oxides particles were supported on surface. The strong metal support interaction (SMSI) between the metal oxide (mainly CuOx) and the modified CeO2 will help to provide the CuOx sintering and deactivation compare with the single and even binary metal oxide catalysts.

Fundamental characterization of host-guest chemistry in the gas phase and its applications in carbohydrate analysis

이현희 Korea University 2019 국내박사

Mass spectrometry (MS) is an analytical technique with advantages such as low sample consumption, high sensitivity, and compatibility with chromatographic techniques. Hence, MS is nowadays widely utilized in various fields of science such as proteomics, environmental science, and pharmaceutical science. Recently, MS also contributed to the advancement of glycomics. Investigation of carbohydrates using MS and tandem mass spectrometry (MSn) facilitates their structure determination and precise quantification. Nevertheless, the carbohydrate analysis by MS generally requires several sample preparation steps such as pre-derivatization, which can lead to incorrect determination of carbohydrates, because of their high structural complexities. In this thesis, a combination of host-guest chemistry and MS was utilized to develop new methods for the efficient analysis of diverse carbohydrates. Host–guest interactions of carbohydrates with a host receptor in the gas phase allowed us to distinguish subtle structural differences among carbohydrates by MS, and achieve high–accuracy quantification. In Chapter 1, a background on carbohydrate analysis using MS and host–guest chemistry of hydrophilic guests is introduced. Previous studies on the host–guest chemistry in the gas phase are also reviewed. In Chapter 2, distinct host–guest interactions of neutral hexose isomers with a host receptor, cucurbit[7]uril (CB[7]), in the gas phase are studied using two MS techniques, collision-induced dissociation (CID) and ion mobility spectrometry (IMS), and other analytical techniques. It is observed that host–guest interactions generate different fragmentation patterns upon collisional activation, facilitating effective identification and quantification of the isomers. In addition, these unique host–guest phenomena occur because of distinct host–guest interactions between CB[7] and neutral hexose isomers in the gas phase. In Chapter 3, the gas-phase host–guest chemistry of 12 monosaccharide derivatives including hexosamines, N-acetylhexosamines, deoxyhexoses, and uronic acids was investigated by using MSn and IM-MS. The results of the study served as the basis to extend the applicability of gas-phase host–guest chemistry and establish a comprehensive system for qualifying and quantifying diverse types of constituent monosaccharide isomers in a simple manner. In Chapter 4, the developed system was further extended to a practical application of the gas-phase host–guest chemistry. This study revealed that the host–guest system can be effectively utilized for accurate quantification of N-glycolylneuraminic acid and N-acetylneuraminic acid in therapeutic glycoproteins, which were difficult to analyze without additional sample preparation steps.

Metallosupramolecular chemistry of mixed-donor macrocycles : from self-assembly of mono-and multinuclear complexes to molecular recognition

서주범 Gyeongsang National Univ. 2007 국내박사

Structural study of host-guest assembly using ion mobility spectrometry-mass spectrometry

이지연 Pohang University of Science and Technology 2024 국내박사

Host–guest chemistry defines the formation of complexes involving two or more molecules or ions held together in unique structural relationships by non-covalent bonds. This versatility extends its applicability across diverse fields, including biomedical and catalysis. Complexes formed through the interactions between host and guest molecules can manifest varied structures, a crucial aspect for studying the foundations of host-guest chemistry. Mass spectrometry coupled with electrospray ionization and ion mobility spectrometry (ESI-IMS-MS) offers a highly suitable analytical approach capable of observing the structure and behavior of complexes from solution to the gas phase. Within this thesis, the focus centers on exploring structures and mechanistic properties derived from host-guest complexes, employing IMS-MS, with a particular emphasis on cucurbituril and cyclodextrin. In Chapter 1, the focus is on providing an overview of host-guest chemistry, centered around host molecules such as cucurbituril and cyclodextrin. The chapter delves into the properties of host-guest chemistry and explores various examples of host-guest complex structures depending on the guest molecule using various methods. In addition to conventional analytical methods, the chapter describes the analysis of complex structures derived from the gas or solution phase using IMS-MS, highlighting the advantages of this analytical approach. In Chapter 2, the investigation of protonation sites in small molecules within host molecules using IMS-MS is elaborated. It is known that small molecules with multiple proton-accessible sites play a significant role in biological systems and host-guest chemistry. The protonation states of these molecules influence specific host-guest interactions, but determining the protonation site is challenging. To address this, we employ electrospray ionization IMS-MS to investigate imipramine, a molecule with two protonation sites, in the presence of cucurbit[7]uril as a host molecule. This approach distinguishes the two protomers of protonated imipramine as host-guest complex ions, offering insight into the energetically less preferable protomer. In Chapter 3, the observation of the unique host-guest chemistry between alkali metal halides and cucurbit[7]uril (CB[7]) during the electrospray process is described. Investigating how guest molecules are trapped in the nano-sized cavity is crucial for exploring new derivatives and applications in host-guest chemistry involving cavity-containing host molecules. In the present work, we observed CB[7] complexed with various alkali chloride cluster cations or anions generated during the electrospray ionization. Interestingly, trends in the collision cross section (CCS) values indicate that the small clusters smaller than a specific critical size are readily trapped inside the CB[7] cavity in the gas phase, although the trapping alkali halide clusters in the solution at the given concentration are supposed to be unfavorable. The critical size shows a strong dependence on the ionic size of alkali metal species. The density functional theory calculations predicted several stable inclusion complexes. Molecular dynamics simulations were also performed to gain insights into the driving force for forming and trapping alkali halide clusters inside the CB[7] cavity. We suggest that the rapid solvent evaporation, which leads to the abrupt increase of ion concentrations and subsequent formation of alkali-chloride contact ion pair, may provide the specific molecular environment enabling the formation of the inclusion complexes. In Chapter 4, the exploration of unique cyclodextrin aggregation arising from the interaction with alkali metal halide clusters is detailed. Cyclodextrins (CDs) exhibit versatile self-assembly properties due to their hydrophilic and hydrophobic components. While extensive research has focused on CD self-assembly, limited studies have explored their aggregation behavior, particularly in interaction with small molecule guests due to their complex structures. In this study, we investigated the tetramer structure of CDs formed in the presence of alkali metal chloride clusters (MCl). Compact isomers, defined as a tetrahedral structure, emerged only when a specific number (n) of alkali halide clusters were included. Furthermore, the specific value of n varied depending on the size of the alkali metal, leading to the determination of the critical volume condition for creating the tetrahedral isomer. The present work demonstrates that alkali metal clusters serve as a template for the formation of a new tetramer, unlike cases where alkali metals standalone to construct complexes.

Supramolecular anion recognition properties of MESO-substituted, non-planar tetrapyrrolic macrocycles

Mulugeta, Beza Endale Kangwon National University 2018 국내박사

The anion recognition chemistry of calix[4]pyrroles and their derivatives have attracted considerable attentions in the supramolecular anion binding chemistry due to the ubiquitous role of the anion in biological processes. Among various model systems, meso-substituted calix[4]pyrrole derivatives have been utilized for the selective recognition of anions either direct binding or through the so-called ‘Indicator Displacement Assay (IDA)’. Along with this line of research, we have designed and synthesized meso-substituted calix[4]pyrroles bearing benzimidazole or benzimidazolium group at the two diametrical meso-positions. The synthesized receptors have been fully characterized by spectroscopic means. Then, the anion recognition properties were studied using Fluorescence Dye Displacement Assay protocol. The studies indicate that the receptors show analyte selectivity and analyte-dependent fluorescence changes. The solution state anion binding studies of the meso-benzimidazolium-functionalized calix[4]pyrrole exhibit highly selective binding with bicarbonate anion (HCO3–). The single crystal X-ray diffraction analysis clearly confirms that this dicationic receptors form a stable complex with bicarbonate anion. The bound bicarbonate anion resides on the cavity in face to face (FTF) fashion. Surprisingly, the receptor-bound bicarbonate anion is converted to a mono-carbonate methyl ester when methanol is present in acetonitrile. These results indicate that the receptor catalyze the transformation of bicarbonate to mono-methyl carbonate. These results also suggest that chemical trapping of CO2 and its hydrated form HCO3– to mono-alkyl carbonate are possible by this dicationic receptor. Further study indicates that this receptor acts as a sensitive ‘turn-on’ chemosensor for the dissolved bicarbonate anion. The detection limit is as low as 4.2 nM. To demonstrate the practicality of the receptor, various carbonated drinks were tested. The results clearly revealed that its ability to function as an easy-to-use sensor for dissolved CO2 in aqueous media. On the other hand, the neutral meso-benzimidazole functionalized calix[4]pyrrole displays the higher binding affinity for fluoride anion over chloride anion with high discrimination factor. However, the binding studies using 1H NMR spectroscopic and isothermal titration calorimetry (ITC) indicates the significant differences in the solid state geometries between fluoride and chloride complexes. Meso-Alkylidenyl porphyrins are non-aromatic porphyrinoids which are most recently joined to the porphyrinoid family. Chemistry of several porphyrin derivatives have been explored to study their unique prototropy, protonation selectivity and spectroscopic properties. In order to obtain further insight into the prototropy properties of meso-alkylidenyl porphyrins, different derivatives of dimethoxybenziporphyrins have been synthesized and characterized. An attempted was made to demethylate the methyl-groups to generate a meso-quinonoidal porphyrins bearing p-quinoidal moiety at meso-positions. 생물학적 과정에서 음이온이 중요한 역할을 하기 때문에 칼릭스[4]피롤과 그 유도체의 음이온 인식에 관한 연구는 초분자를 이용한 음이온 인식 분야에서 상당한 관심을 받고 있다.다양한 모델 시스템 중에서 메소 치환된 칼릭스[4]피롤 유도체는 직접 결합 또는 이른바 '지시약 치환 분석 (Indicator Displacement Assay, IDA)'을 통한 음이온의 선택적인 인식에 이용되었다. 이러한 연구 결과로 우리는 마주 보는 두 메소 위치에 benzimidazole 또는 benzimidazolium 그룹을 갖는 메소 치환된 칼릭스[4]피롤을 합성하였다. 합성된 수용체는 분광학적 방법으로 구조를 분석하였다. 그런 다음 음이온 인식 특성을 형광 염료 치환 분석 방법을 사용하여 연구하였다. 연구 결과 수용체는 분석물 선택성 및 분석물 의존적 형광 변화를 나타냈다.메소 위치에 benzimidazolium기가 도입된 칼릭스[4]피롤은 용액 상태에서 중탄산 음이온 (HCO3-)과의 높은 선택적 결합을 나타냈다. 단결정 X-선 회절 분석으로 양이온 수용체가 중탄산 음이온과 안정한 착물을 형성함을 확인하였다. 결합된 중탄산 음이온은 FTF (face to face) 방식으로 공동에 존재하였다. 놀랍게도, 수용체와 결합된 중탄산 음이온은 아세토나이트릴에 메탄올이 존재할 때 모노-카보네이트 메틸 에스테르로 전환되었다. 수용체가 중탄산염을 모노 메틸 탄산염으로 전환하는 촉매 역할을 한다는 것을 알 수 있었다. 이러한 결과로 양이온 수용체에 의해 CO2와 수화 된 형태인 HCO3-를 모노-알킬 카보네이트 형태로 화학적 포획이 가능하다는 것을 알 수 있다. 또한 수용체가 용해된 중탄산 음이온에 대해 '켜짐 (turn-on)' 화학 센서로 작용한다는 것을 보여준다. 검출 한계가 4.2 nM 정도로 낮아 수용체의 실용성을 입증하기 위해 다양한 탄산 음료수로 실험하였다. 실험 결과 수용체는 수용액에서 용존 CO2 센서로써 사용 가능함을 확인하였다. 반면에 메소 위치에 benzimidazole 기가 도입된 칼릭스[4]피롤은 염소 음이온보다 불소 음이온에 대한 높은 결합력을 보였다. 그러나 1H NMR 분광법 및 등온 적정 열량계 (ITC)를 사용하여 결합 연구를 한 결과 고체 상태에서는 불소와 염소 음이온에 대한 착물 형성에 상당한 차이가 있었다. 메소-Alkylidenyl 포르피린은 비 방향족 porphyrinoids이며 가장 최근에 porphyrinoid 계통이 되었다. 몇 가지 포르피린 유도체에 관한 연구는 독특한 양성자 이동, 양성자 선택성 및 분광학적 특성에 관한 것이다. 메소-alkylidenyl 포르피린의 양성자 이동에 관해 좀 더 자세히 알아보기 위해 dimethoxybenziporphyrins의 유도체를 합성하고 분석하였다. 메소 위치에 메소-퀴논형 포르피린을 만들기 위해 탈 메틸화 반응을 수행하였다.

Design of Novel Networked Polymer Architectures via Side-Chain Chemistry

조민영 울산과학기술원 Ulsan National Institute of Science and Te 2026 국내박사