Detail Synthetic Study of Infrared Fluorescent Dyes: Design, Synthesis and Chemical Properties of their Photodynamic Therapy Probes

Dipyrromethene boron difluoride (BODIPY) derivatives can be used as effective photosensitizers (PS’s) to eradicate a broad spectrum of microbes that threaten the global population health. Moreover, these compounds could be used in diagnostic or therapy, controlling the balance between the fluorescence emission and the photodynamic activity. There is still much work to be done in the search for ideal PS’s with applications in photodynamic therapy (PDT). To effectively use near infrared region BODIPY dyes for labelling during biological analyses, or as biomarkers in biomedical applications such as imaging diagnosis, a hydrophilic character is usually required. It was found that the introduction of the strong electron-withdrawing group at the meso position in the BODIPY skeleton was responsible for the drastic bathochromic shift in the absorption spectrum. Several studies on the development of small molecule fluorescent probes have been performed with short wavelengths and with poor water solubility. There should be new investigations to obtain more information on the mechanisms of photodynamic action relating to cell damage and experiments in vivo infection models. In order to understand the effect of the substituents, a predictive quantitative structure-activity relationship (QSAR) regression model, based on theoretical holistic molecular descriptors as developed. An even better fluorescent probe would combine the photostability of the BODIPY group with a chromophore that absorbs at longer wavelength that makes for better light penetration in cells and tissues. In this review, we will summarize ideas on different wavelengths and hydroelectric abilities through modifications of molecular structures of the biological probe molecule. BODIPY’s materials and chemical modification methods for modulating the optical properties presented here could be versatile for developing efficient photo-responsive bio-related materials to control the biological activities and efficient quenchers on the biotechnological assays with labelled biomolecules

Photophysics of BODIPY Dyes: Recent Advances

BODIPY dyes are unique fluorophores that can be used in numerous application areas because of their interesting photophysical properties such as high molar absorptivity, tunable absorption and emission energies, and high fluorescence quantum yields. They show impressive photophysical property changes upon substitution of functional groups on the main core structure. Exchange of the meso-carbon on dipyrrin core with nitrogen produces an analog class of BODIPY called aza-BODIPY. Up to now, various kinds of BODIPY and aza-BODIPY derivatives have been developed and applied in science and industry. In this chapter, recent studies on photophysical properties of BODIPY derivatives are summarized

Exclusive Feature Papers in Colorants

“Exclusive Feature Papers in Colorants” is a collection of important high-quality papers (original research articles or comprehensive review papers) published in open access. This Special Issue aims to discuss new knowledge or new cutting-edge developments in the colorants research field through selected works, in the hope of making a great contribution to the community. We intend for this issue to be the best forum for disseminating excellent research findings as well as sharing innovative ideas in the field

BODIPYs in PDT: A Journey through the Most Interesting Molecules Produced in the Last 10 Years

Over the past 30 years, photodynamic therapy (PDT) has shown great development. In the clinical setting the few approved molecules belong almost exclusively to the porphyrin family; but in the scientific field, in recent years many researchers have been interested in other families of photosensitizers, among which BODIPY has shown particular interest. BODIPY is the acronym for 4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene, and is a family of molecules well-known for their properties in the field of imaging. In order for these molecules to be used in PDT, a structural modification is necessary which involves the introduction of heavy atoms, such as bromine and iodine, in the beta positions of the pyrrole ring; this change favors the intersystem crossing, and increases the O-1(2) yield. This mini review focused on a series of structural changes made to BODIPYs to further increase O-1(2) production and bioavailability by improving cell targeting or photoactivity efficiency

Photophysics of multicomponent molecules under dynamic control

PhD ThesisThis work focusses on seeking to gain a deep understanding of the photophysical processes inherent to multi-functional and/or multi-component supermolecules in the condensed phase. To do this, a variety of molecular systems have been subjected to spectroscopic examination, most commonly using steady-state and time-resolved emission spectroscopy to interrogate the samples. A common feature of all the molecular architectures examined herein relates to the possibility for structural motion on timescales of concern to the photophysical event. Furthermore, to provide a spectroscopic signature, most of the target dynamic systems comprise a donor covalently attached to a complementary acceptor. These systems possess the potential to be used as solar-energy concentrators or for specific sensing applications. However, attention is given only to the fundamental properties. Chapter 1 provides a general introduction to the field of molecular rotors and to the concepts of energy and electron transfer in molecular systems. Key literature examples are used to illustrate the current state-of-the-art and to set the tone for later discussions. Each chapter includes a brief introduction to the specific topic under discussion while avoiding the generic details covered in the main introduction. The essential experimental details and underlying analytical protocols for all the studies described are provided in the final chapter. Chapter 2 describes a new series of molecular rotors based on the boron dipyrromethene (BODIPY) structure. This series includes structurally-similar compounds that exhibit surprisingly disparate behaviours as putative probes for solvent viscosity. In fact, the results tend to challenge the conventional understanding of BODIPY-based molecular probes. In this chapter, we highlight the importance of asymmetry, question how it might be used to one’s advantage in the design of next generation probes, and raise ideas about porosity of the excited-state potential energy surface

Molecular design for efficient triplet photosensitizers

학위논문(박사) -- 서울대학교대학원 : 공과대학 재료공학부, 2021.8. 김재필.유기 도너 억셉터 기반 광감응제는 유가 감응형 태양전지, 열활성 지연 형광재료, 광역동치료, 삼중항-삼중항 소멸에 의한 광에너지 향상 등 다양한 분야에서 많은 관심을 받아왔다. 광감응제의 도너와 억셉터는 각각 전자를 밀어내고 당기는 능력을 갖고 있기 때문에 빛을 조사하였을 때 흡수된 전자가 도너에서 억셉터로 이동하게 되고 이는 전하분리 준위를 만들어낸다. 생성된 전하분리 준위는 높은 쌍극자 모멘트를 나타내기 때문에, 주변의 환경에 따라 형광 특성이 큰 폭으로 변화하고 이는 온도 센서, 극성 센서 등으로의 적용을 가능하게 한다. 또한 도너에서 억셉터로의 일 방향성 전하 전달 (Charge transfer)은 염료감응형 태양전지의 구성성분인 염료로 적용을 가능하게 한다. 염료감응형 태양전지 내 염료는 빛을 흡수하여 도너에서 억셉터로 전자를 전달시키고 이러한 일방향성 에너지는 전자가 염료로부터 TiO2로 이동할 수 있게 만든다. 도너와 억셉터의 두 단위체를 단일 결합으로 연결하면 두 단위체 사이의 회전 변화를 가능하게 한다. 이는 주변 압력에 따라 분자내 회전의 정도가 달라지도록 만들기 때문에 압력 센서로 사용할 수 있으며, 이러한 특성을 활용하여 지문 센서 등의 분야에 적용이 가능하다. 또한 이 도너-억셉터 광감응제는 유기발광 다이오드의 핵심기술인 열활성지연 형광을 구현할 수 있다. 도너-억셉터 기반 광감응제의 구조는 도너와 억셉터가 서로 수직하게 꺾이게 되어있으며 이는 전하분리를 유도한다. 이 전하 분리는 두 에너지 스테이트의 축퇴를 야기하고 결과적으로 일중항과 삼중항 준위 사이의 계간 전이를 가능하게 만든다. 도너-억셉터 분자는 광여기 과정 중에 계간전이에 의하여 삼중항 준위에 전자가 이동이 된다. 이 T1 준위의 전자 (또는 에너지)는 삼중항 산소를 일중항 산소로 변환시킬 수 있는 능력을 가지고 있기 때문에 일중항 산소발생을 활용하는 광역동치료에 적용할 수 있으며, 발생한 일중항 산소를 중간 촉매로 사용할 수 있어 유기합성의 광촉매로도 활용가능하다. 이렇듯 도너-억셉터 기반 광감응제는 다양한 분야로의 가능성을 가지고 있음에도 불구하고 여전히 그 메커니즘이 완전히 밝혀지지 않았다. 뿐만 아니라, 최근 도너-억셉터 기반 광감응제를 삼중항 광감응제로 적용하는 많은 연구들이 진행되고 있으며, 기존의 삼중항 광감응제의 특성을 상회하는 도너-억셉터 기반 삼중항 광감응제들이 지속적으로 보고되고 있다. 본 연구에서는 보디피를 기반으로 한 도너-억셉터 광감응제를 디자인 및 개발하였으며, 이들의 구조와 형광 및 삼중항 특성 등의 광물리적 특성 간의 상관관계에 대하여 조사하였다. 먼저 도너-억셉터 광감응제를 형광재료 특히 압력에 따른 형광색의 변화가 가능한 Mechanofluorochromism의 분야에 적용가능성을 확인하였으며, 그 메커니즘에 대한 체계적인 조사를 진행하였다. 다음으로 도입되는 염소 원자의 개수를 조절하여 전자 받개 능력을 달리한 보디피 기반 도너-억셉터 광감응제를 개발하였다. 그리고 전자 받개 능력이 삼중항 특성에 미치는 영향에 대한 연구를 진행하였고 페르미 골든룰을 통하여 이들의 동역학을 분석하였다. 삼중항 특성을 강화하기 위하여, 도너와 억셉터의 구조에 중원자를 도입한 도너-억셉터-중원자 기반 삼중항 광감응제를 고안 및 개발하였으며, 이는 기존의 도너-억셉터, 순수한 중원자 기반 재료보다 삼중항 양자수율과 삼중항 수명이 모두 개선됨을 확인할 수 있었다. 도너-억셉터-중원자 기반의 삼중항 광감응제의 삼중항 수명을 더욱 증가시키기 위하여 도너와 억셉터 사이의 회전을 억제할 수 있는 구조를 도입하였으며, 결과적으로 회전이 억제되지 않은 광감응제와 비교하여 5배 이상 높은 1,503μs의 긴 삼중항 수명을 달성할 수 있었다. 이는 보고된 보디피 계열 삼중항 광감응제 중에서 가장 긴 삼중항 수명을 나타냈고, 기존의 삼중항 광감응제와 비교하여도 상당히 높은 편이다. 긴 삼중항 수명은 삼중항 삼중항 소멸 양자수율(TTA-UC quantum yield)의 증가를 야기하였고 문턱 세기 (Threshold intensity)도 개선시킬 수 있었다. 따라서 도너-억셉터-중원자에 회전 억제 전략을 도입하여 삼중항 특성이 상당히 향상될 수 있음을 증명하였고 이러한 결과는 삼중항 광감응제를 활용하는 다양한 산업분야에 큰 기여를 할 수 있을 것이다.Organic donor-acceptor based photosensitizers have received a lot of attention in various fields such as dye sensitizers solar cells (DSSC), OLED using thermally activated delayed fluorescence (TADF), photodynamic therapy (PDT), and triplet-triplet annihilation upconversion (TTA-UC). The electron donor and the electron acceptor of donor-acceptor photosensitizers pushes and pulls the electrons, respectively, during photoexcitation, resulting in charge separation state. This charge separation states, due to its high dipole moment, are sensitively affected by the surrounding environment, which can cause the drastic change of the fluorescence properties. The donor-acceptor photosensitizers can thus be used for a variety of sensors such as a temperature sensor and a polarity sensor. In addition, the one-directional charge transfer property from donor to acceptor enables application as a dye, a component of dye-sensitized solar cells (DSSC). The dye in DSSC absorbs light and transfers electrons from the donor to the acceptor, and this one-directional energy allows electrons to move from the dye to TiO2. Moreover, the donor and acceptor moieties are commonly connected with single bond, which allows various rotational change between the donor and acceptor. Because the degree of conformation between donor and acceptor varies depending on the surrounding pressure, donor-acceptor photosensitizers can be used as a pressure sensor, applicable to the fingerprint sensors. In addition, it can be implemented to the thermally activated delayed fluorescence (TADF) in the research field of OLED. The orthogonal coordination of donor and acceptor increases the charge separation between donor and acceptor, which reduces in the energy gap between the singlet and triplet excited states. The completely separated charge of donor-acceptor induces the degeneration of the both energy states, resulting in the intersystemcrossing (ISC) between singlet and triplet states. Thus, D-A photosensitizers may populate electrons in the triplet state through ISC during the photoexcitation process. Since the electrons of the triplet state have the potential to convert triplet oxygen into singlet oxygen, D-A photosensitizers can be applied to photodynamic therapy (PDT) using singlet oxygen. Although D-A photosensitizers have potential in various fields, their photophysical kinetics are still not fully revealed. Recently, a number of researches were performed that applying the D-A photosensitizers as a triplet sensitizer, and D-A-based triplet sensitizers that even exceed the characteristics of conventional triplet sensitizers have been continuously reported. In this study, we designed and developed D-A photosensitizers based on boron dipyrromethane (BODIPY), and studied the correlation between the molecular structure and photophysical properties such as fluorescence and triplet characteristics. First, we examined the applicability of D-A photosensitizers to the field of fluorescent materials, especially mechanofluorochromism (MFC), where the fluorescent color changes according to pressure, and the mechanism for the MFC systematically investigated based on the theory of the twisted intramolecular charge transfer (TICT) and the aggregation induced emission enhancement (AIEE). Second, we developed BODIPY-based D-A photosensitizers with different accepting power by controlling the number of chlorines, studied the effect of accepting power on triplet characteristics. And the ISC kinetics were analyzed through the theory of fermi's golden rule. Third, we suggested the donor-acceptor-heavy atom (D-A-H) triplet photosensitizers where heavy atoms were introduced into the D-A photosensitizers to enhance the triplet characteristics. D-A-H photosensitizers showed higher triplet quantum yield and shorter triplet lifetime compared to donor-acceptor and pure heavy atom-based photosensitizers. Fourth, to further increase the triplet lifetime, methyl moieties suppressing rotation between D and A were introduced to the D-A-H-based triplet photosensitizers. As a result, a rotational restricted triplet photosensitizer showed an ultra-long triplet lifetime (1,503μs), which is more than 5 times higher than that of a rotational free photosensitizer. As far as we know, this is the longest triplet lifetime among the reported BODIPY based triplet photosensitizers, and is even considerably higher than that of conventional triplet photosensitizers. Ultra-long triplet lifetime caused an increase in TTA-UC properties such as TTA-UC quantum yield and threshold intensity. Therefore, we proved that the triplet characteristics can be improved considerably by rotational restriction strategy to D-A-H photosensitizers, and this result may contribute to various industrial fields using triplet photosensitizers.Chapter 1 Introduction 1 1.1 Aggregation induced emission (AIE) 1 1.2 The basic principle of photoinduced electron transfer (PET) 3 1.3 Marcus theory of photoinduced electron transfer 6 1.4 Intersystemcrossing mechanism of donor-acceptor photosensitizers 9 1.5 Triplet-triplet annihilation upconversion (TTA-UC) 10 1.6 References 12 Chapter 2 Mechanofluorochromism of Triphenylamine-BODIPY: Effect of twisted intramolecular charge transfer and restriction in rotation on fluorescence 17 2.1 Introduction 17 2.2 Experimentals 19 2.3 Results and discussion 24 2.4 Conclusions 44 2.5 References 46 Chapter 3 A study on photophysical and photodynamic properties of donor–acceptor BODIPY complexes: correlation between sin-glet oxygen quantum yield and singlet-triplet energy gap Theoretical Formulation 56 3.1 Introduction 56 3.2 Experimentals 59 3.3 Results and discussion 72 3.4 Conclusions 94 3.5 References 95 Chapter 4 Synergistic effects of photoinduced electron transfer and heavy atom effect based on BODIPY for efficient triplet photosensitizers 102 4.1 Introduction 102 4.2 Experimentals 104 4.3 Results and discussion 111 4.4 Conclusions 146 4.5 References 147 Chapter 5 Enhanced triplet-triplet annihilation upconversion luminesncece through the conformational restriction based on donor - acceptor - heavy atom molecules 155 5.1 Introduction 155 5.2 Experimentals 158 5.3 Results and discussion 165 5.4 Conclusions 191 5.5 References 192 Summary 199 Korean Abstract 201박

Fluorescent probes for lipid droplet and lipid membrane imaging in cells and models

Cell membranes are believed to be laterally ordered into micro and nano-domains comprising of more fluid liquid-disordered (Ld) and more viscous liquid-ordered (Lo) phases. The latter subphases contain high concentrations of cholesterol and glycosphingolipids. These so call lipid rafts are experimentally distinguishable on the basis of their resistance to detergent solubilisation and are believed to play important roles in membrane function including in protein trafficking and signalling as they can drive protein-protein interactions through sequestering of proteins to these domains. Membrane domains in living cells are difficult to interrogate as they are dynamic and at sub-microscopic length scales they are outside the range of most conventional microscopies. However, they can potentially be imaged using recently developed super-resolution methods and as they are dynamic structures their diffusion can be measured using correlation methods. Therefore, new fluorescent probes are needed that can (a) partition selectively to membranous regions, (b) target the Lo and Ld phases selectively (c) that have appropriate photophysical properties compatible with the above techniques. These include large Stokes shift, high selectivity, excellent photostability, high molecular brightness, low cytotoxicity and high quantum yields. A key aim of this thesis was to design and synthesize new fluorescent probes that sequester specifically to lipid rich regions of cells or models and can distinguish Lo/Ld regions or lipid droplets, using confocal microscopy, fluorescence correlation spectroscopy (FCS), fluorescent lifetime imaging (FLIM) and the relatively new technique of super resolution microscopy, specifically, STimulated Emission Depletion (STED) microscopy

Thiophene-Based Trimers and Their Bioapplications: An Overview

Certainly, the success of polythiophenes is due in the first place to their outstanding electronic properties and superior processability. Nevertheless, there are additional reasons that contribute to arouse the scientific interest around these materials. Among these, the large variety of chemical modifications that is possible to perform on the thiophene ring is a precious aspect. In particular, a turning point was marked by the diffusion of synthetic strategies for the preparation of terthiophenes: the vast richness of approaches today available for the easy customization of these structures allows the finetuning of their chemical, physical, and optical properties. Therefore, terthiophene derivatives have become an extremely versatile class of compounds both for direct application or for the preparation of electronic functional polymers. Moreover, their biocompatibility and ease of functionalization make them appealing for biology and medical research, as it testifies to the blossoming of studies in these fields in which they are involved. It is thus with the willingness to guide the reader through all the possibilities offered by these structures that this review elucidates the synthetic methods and describes the full chemical variety of terthiophenes and their derivatives. In the final part, an in-depth presentation of their numerous bioapplications intends to provide a complete picture of the state of the art.Operational Program Research, Development, and Education Project “MSCAfellow4@MUNI” (No. CZ.02.2.69/0.0/0.0/20_079/0017045) is acknowledged. The European Union is acknowledged for funding this research through Horizon 2020 MSCA-IF-2018 No 838171 (TEXTHIOL)