형광 세포-이미징과 광역학치료를 위한 수용성 BODIPY 염료의 합성
- Issued Date
- 2022
- Abstract
- 의학 분야에서 바이오이미징은 발달되었고 중요하게 여겨져왔다. 형광 탐침은 실시간으로 표적종과 바이오프로세스를 모니터하는 유용한 도구이다. BODIPY 염료 또한 형광물질이고, 감광제로서 생물학적으로 응용하여 형광 세포-이미징과 광역학 치료에 사용할 수 있다. 수용성이 낮은 감광제는 응집체를 형성하고, 광역학 효율을 감소시킨다. 따라서 본 연구에서는 수용성의 BODIPY 염료를 합성하였다. 광역학 효율을 최적화시키고 수용성을 향상시키기 위해 친수성의 PEG(Polyethylene glycol)가 화학적으로 결합되었다. PEG의 결합으로 인해, BODIPY 염료는 높은 세포 투과성과 생체적합성을 가졌다. 그리고 BODIPY 염료의 2,6-위치에 할로젠 원자를 치환시킨 결과, 중원자 효과에 의해 단일항 산소 생성 효율이 증가하였다. 그리고 Knoevenagel 반응을 통해 styryl기가 치환되었고 근적외선에서 빛 흡수가 유도되었다. Methylation 후에 생성된 4차 암모늄 염 화합물은 미토콘드리아 표적화 능력을 가졌고 수용성이 증가하였다.|Bio-imaging has been developed and considered importantly in medical field. Fluorescent probe is a useful tool for monitoring targets and bioprocess in real-time. BODIPY dye is also fluorescent, and used in biological application for fluorescence cell-imaging and photodynamic therapy as a photosensitizer. Photosensitizers with low water solubility form aggregation, and decrease photodynamic efficiency. Therefore, we synthesized water-soluble BODIPY dyes. In order to optimize photodynamic efficiency and improve water solubility, hydrophilic polyethylene glycol(PEG) was chemically bonded. Because of the binding with PEG, the BODIPY dye have high cell permeability and bio-stability. We substituted halogen atom at the 2,6-position of the BODIPY dye and consequently, the singlet oxygen generation efficiency was increased by the heavy atom effect. And the styryl substituent was substituted via Knoevenagel reaction and the light absorption in near-infrared was induced. After methylation, the quaternary ammonium salt compounds had mitochondrial targeting capability and increased water solubility.
- Alternative Title
- Synthesis of water-soluble BODIPY dyes for fluorescence cell-imaging and photodynamic therapy
- Alternative Author(s)
- Lim HeeJung
- Affiliation
- 조선대학교 일반대학원
- Department
- 일반대학원 화학과
- Advisor
- 김호중
- Awarded Date
- 2022-02
- Table Of Contents
- Chapter Ⅰ 1
1. Introduction 1
1.1 Application of BODIPY dye and PDT mechanism 1
1.2 Synthesis of BODIPY core and characterizations 4
1.3 Halogenated BODIPY dye 5
2. Experiment 6
2.1 Materials 6
2.2 Synthesis 7
2.3 Experiment and characterization of compound 1~11 9
2.3.1 Synthesis of compound 1 9
2.3.2 Synyhesis of compound 2 10
2.3.3 Synthesis of compound 3 10
2.3.4 Synthesis of compound 4 11
2.3.5 Synthesis of compound 5 11
2.3.6 Synthesis of compound 6 12
2.3.7 Synthesis of compound 7 12
2.3.8 Synthesis of compound 8 13
2.3.9 Synthesis of compound 9 13
2.3.10 Synthesis of compound 10 14
2.3.11 Synthesis of compound 11 14
3. Results and discussion 15
3.1 Theoretical characterizations and analysis 15
3.1.1 PEG(polyethylene glycol) 15
3.1.2 Halogenated BODIPYs 16
3.1.3 Knoevenagel reaction 17
3.1.4 Methylation 18
3.2 Spectroscopic measurements 18
3.2.1 UV-Vis absorption and fluorescence emission spectra 19
3.2.2 Quantum yield measurements 24
3.3 Photos of compound 9, compound 10, compound 11 under 365nm in different solvents 24
4. Conclusions 25
5. Spectrum 26
6. References 40
Chapter Ⅱ43
1. Introduction 43
2. Experiment 44
2.1 Materials 44
2.2 Synthesis 45
2.3 Experimental process of compound 12~19 49
2.3.1 Synthesis of compound 12 49
2.3.2 Synthesis of compound 13 49
2.3.3 Synthesis of compound 14 50
2.3.4 Synthesis of compound 15 50
2.3.5 Synthesis of compound 16 51
2.3.6 Synthesis of compound 17 51
2.3.7 Synthesis of compound 18 52
2.3.8 Synthesis of compound 19 52
3. Results and discussion 53
3.1 Theoretical characterizations and analysis 53
3.1.1 Electronic properties of the compounds 53
3.1.2 Suzuki coupling reaction 54
3.1.3 Methylation 55
3.2 Spectroscopic measurements 56
3.2.1 UV-Vis absorption and fluorescence emission spectra 56
3.2.2 Quantum yield measurements 59
3.3 Photos of compound 15, compound 19 under 365nm in different solvents 60
4. Conclusions 61
5. Spectrum 62
6. References 72
- Degree
- Master
- Publisher
- 조선대학교 대학원
- Citation
- 임희정. (2022). 형광 세포-이미징과 광역학치료를 위한 수용성 BODIPY 염료의 합성.
- Type
- Dissertation
- URI
- https://oak.chosun.ac.kr/handle/2020.oak/17346
http://chosun.dcollection.net/common/orgView/200000588843
- Appears in Collections:
- General Graduate School > 3. Theses(Master)
- Files in This Item:
-
-
Download
형광 세포-이미징과 광역학치료를 위한 수용성 BODIPY 염료의 합성.pdf
기타 데이터 / 1.51 MB / Adobe PDF
-
Items in Repository are protected by copyright, with all rights reserved, unless otherwise indicated.