Photodynamic therapy based on organic small molecular fluorescent dyes

Photodynamic therapy (PDT) has shown promise as an effective treatment modality for cancer and other localized diseases due to its noninvasive properties and spatiotemporal selectivity. Near-infrared (NIR) fluorescent dyes based on organic small molecules are characterized with low cytotoxicity, good biocompatibility and excellent phototoxicity, which are widely used in PDT. In this review, we attempt to summarize the development of imaging-induced PDT based on organic small molecules and classify it according to the structures of dyes including cyanines, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) analogues, phthalocyanine and other agents such as rhodamine analogues.     

Near-infrared small molecular fluorescent dyes for photothermal therapy

This review aims to provide a summary of the progress in fluorescent dyes for photothermal therapy in recent years and it is classified according to the structure of organic molecules including cyanines, phthalocyanines, rhodamine analogues and BODIPYs.     

以芳胺为电子给体的D-π-A有机光敏染料———— 染料敏化太阳电池中的应用

不含金属的有机染料在染料敏化太阳电池（DSC）中的应用愈加广泛,以芳胺为电子给体的D-π-A分子是其中重要的一类。本文依据芳香胺的结构,将近5年来应用于DSC中一百多个D-π-A分子分成四类,包括：基于N-烷基-苯胺的D-π-A光敏染料,基于三苯胺的D-π-A光敏染料,由包含芴基团的三芳胺构建的D-π-A光敏染料,包含芳胺基团的其它结构类型的D-π-A光敏染料。评述了它们的光电转换性能。     

Strategy for Tuning the Photophysical Properties of Photosensitizers for Use in Photodynamic Therapy

A novel approach for tuning spectral properties, as well as minimizing aggregation, in zinc porphyrin and zinc phthalocyanine‐based compounds is presented. Particular emphasis is placed on use of these compounds as photosensitizers in photodynamic therapy (PDT). To accomplish this aim, a bulky hydrophobic cation, trihexyltetradecylphosphonium, is paired with anionic porphyrin and phthalocyanine dyes to produce a group of uniform materials based on organic salts (GUMBOS) that absorb at longer wavelengths with high molar absorptivity and high photostability. Nanoparticles derived from these GUMBOS possess positively charged surfaces with high zeta potential values, which are highly desirable for PDT. Upon irradiation at longer wavelengths, these GUMBOS produced singlet oxygen with greater efficiency as compared to the respective parent dyes.     

Rational design of small indolic squaraine dyes with large two-photon absorption cross section

Small organic dyes with large two-photon absorption (TPA) cross sections (δ) are more desirable in many applications compared with large molecules. Herein, we proposed a facile theoretical method for the fast screening of small organic molecules as potential TPA dyes. This method is based on a theoretical analysis to the natural transition orbitals (NTOs) directly associated with the TPA transition. Experimental results on the small indolic squaraine dyes (ISD) confirmed that their TPA cross sections is strongly correlated to the delocalization degree of the NTOs of the S₂ excited states. Aided by this simple and intuitive method, we have successfully designed and synthesized a small indolic squaraine dye (ISD) with a remarkable δ value above 8000 GM at 780 nm. The ISD dye also exhibits a high singlet oxygen generation quantum yield about 0.90. The rationally designed TPA dye was successfully applied in both two-photon excited fluorescence cell imaging and in vivo cerebrovascular blood fluid tracing.     

Dithiolodithiole as a Building Block for Conjugated Materials

The development of new conjugated organic materials for dyes, sensors, imaging, and flexible light emitting diodes, field‐effect transistors, and photovoltaics has largely relied upon assembling π‐conjugated molecules and polymers from a limited number of building blocks. The use of the dithiolodithiole heterocycle as a conjugated building block for organic materials is described. The resulting materials exhibit complimentary properties to widely used thiophene analogues, such as stronger donor characteristics, high crystallinity, and a decreased HOMO–LUMO gap. The dithiolodithiole (C₄S₄) motif is readily synthetically accessible using catalytic processes, and both the molecular and bulk properties of materials based on this building block can be tuned by judicious choice of substituents.     

Synthesis and Application of Rylene Imide Dyes as Organic Semiconducting Materials

Rylene imide dyes have been among the most promising organic semiconducting materials for several years due to their remarkable optoelectronic properties and high chemical/thermal stability. In the past decades, various excellent rylene imide dyes have been developed for optoelectronic devices, such as organic solar cells (OSCs) and organic field‐effect transistors (OFETs). Recently, tremendous progress of perylene diimides (PDIs) and their analogues for use in OSCs has been achieved, which can be attributed to their ease of functionalization. In this review, we will mainly focus on the synthetic strategies toward to latest PDI dyes and higher rylene imide analogues. A variety of compounds synthesized from different building blocks are summarized, and some properties and applications are discussed.     

Triptycene-derived calixarenes,heterocalixarenes and analogues

With unique three-dimensional triptycene derivatives as the building blocks, several kinds of novel macrocyclic compounds including triptycene-derived calixarenes, heterocalixarenes, N(H)-bridged azacalixarenes, homooxacalixarene analogues, and tetralactam macrocycles could be conveniently synthesized with satisfactory yields by one-pot method or two-step fragment coupling reactions. With rigid triptycene moiety, these macrocyclic hosts not only have large enough cavities, but also show specific fixed conformations. These structural features made them exhibit well molecular recognition toward small organic molecules, fullerenes and organic dyes. Moreover, these macrocycles could also show interest self-assembly abilities in both solution and solid state, which will make them be broad application prospects.     

Diketopyrrolopyrrole-derived organic small molecular dyes for tumor phototheranostics

Cancer is one of the leading causes of human death around the world. Phototherapy, including photodynamic therapy(PDT) and photothermal therapy(PTT), is an emerging light-triggered cancer treatment and shows the advantages of non-invasiveness and low side effects. The design and preparation of efficient phototherapeutic agents are of great significance for phototherapy. Diketopyrrolopyrrole(DPP) is a small molecular organic dye featuring outstanding photophysical properties, facile tuning of str...     

有机小分子纳米粒子的光学诊疗应用

癌症严重威胁着人类健康, 因此, 急需开发高效的诊断和治疗方法. 基于光敏剂和近红外激光的光学诊疗将诊断和治疗集于一体, 与传统的手术治疗和化学治疗相比, 光学诊疗显示出无创性和高空间选择性的优点. 有机小分子染料具有确定且易于修饰的化学结构、 良好的重现性和优异的生物相容性, 与无机和聚合物材料相比, 它是一类具有前景的可用于光学诊疗的光敏剂. 本文总结了基于传统小分子染料、 给体-受体(D-A)共轭小分子和聚集诱导发光(AIE)分子等有机小分子的纳米粒子在光学诊疗中的应用. 此外, 对于光学诊疗用有机小分子染料纳米粒子未来的挑战和前景也进行了展望.     

Enantioselective Organocatalysis

The last few years have witnessed a spectacular advancement in new catalytic methods based on metal-free organic molecules. In many cases, these small compounds give rise to extremely high enantioselectivities. Preparative advantages are notable: usually the reactions can be performed under an aerobic atmosphere with wet solvents. The catalysts are inexpensive and they are often more stable than enzymes or other bioorganic catalysts. Also, these small organic molecules can be anchored to a solid support and reused more conveniently than organometallic/bioorganic analogues, and show promising adaptability to high-throughput screening and process chemistry. Herein we focus on four different domains in which organocatalysis has made major advances: 1) The activation of the reaction based on the nucleophilic/electrophilic properties of the catalysts. This type of catalysis has much in common with conventional Lewis acid/base activation by metal complexes. 2) Transformations in which the organic catalyst forms a reactive intermediate: the chiral catalyst is consumed in the reaction and requires regeneration in a parallel catalytic cycle. 3) Phase-transfer reactions: The chiral catalyst forms a host-guest complex with the substrate and shuttles between the standard organic solvent and the second phase (i.e. a solid, aqueous, or fluorous phase in which the organic transformation takes place). 4) Molecular-cavity-accelerated asymmetric transformations: the catalyst can select between competing substrates, depending on size and structure criteria. The rate acceleration of a given reaction is similar to the Lewis acid/base activation and is the consequence of the simultaneous action of different polar functions. Herein it is shown that organocatalysis complements rather than competes with current methods. It offers something conceptually novel and opens new horizons in synthesis.     

Highly efficient organic indolocarbazole dye in different acceptor units for optoelectronic applications—a first principle study

A series of novel organic dyes (ICZA1, ICZA2, ICZA3, ICZA4) with D-π-A structural configuration incorporating indolo[3,2,1-jk]carbazole moiety as donor (D) unit, thiophene as π-linker and 2-cyanoacrylic acid as acceptor unit were investigated using density functional theory (DFT) and time-dependent DFT (TD-DFT) methods. Indolo[3,2,1-jk]carbazole-based D-π-A dyes composed of different acceptor groups were designed. By modulating acceptor unit, the efficiency of D-π-A dye-based dye-sensitized solar cells (DSSCs) can be further improved. In the present work, four novel push-pull organic dyes only differing in electron acceptor, have been designed based on the experimental literature value of IC-2. In order to further improve the light harvesting capability of indolo[3,2,1-jk]carbazole dyes, the acceptor influence on the dye performance were examined. The NLO property of the designed dye molecules can be derived as polarizability and hyperpolarizability. The calculated value of ICZA2 dye is the best candidate for NLO properties. Furthermore, the designed organic dyes exhibit good photovoltaic performance of charge transfer characteristics, driving force of electron injection, dye regeneration, global reactivity, and light harvesting efficiency (LHE). From the calculated value of ICZA4 dye, it has been identified as a good candidate for DSSCs applications. Finally, it is concluded that the both ICZA2 and ICZA4 dyes theoretically agrees well with the experimental value of IC-2 dye. Hence, the dyes ICZA2 and ICZA4 can serve as an excellent electron withdrawing groups for NLO and DSSCs applications.     

An azo dye for photodynamic therapy that is activated selectively by two-photon excitation

Two-photon photodynamic therapy (TP-PDT) is a promising approach for the treatment of cancer because of its better penetration depth and superior spatial selectivity. Here, we describe an azo group containing cyclized-cyanine derivatives (ACC1 and ACC2) as a two-photon activated, type I based photosensitizer (PS). These small-molecule and heavy atom-free organic dyes showed marked reactive oxygen species (ROS)-generating ability under physiological conditions, as well as fast loading ability into the cells and negligible dark toxicity. Live cell analyses with one- and two-photon microscopy revealed that these dyes showed higher ROS generation ability upon two-photon excitation than upon one-photon excitation via the type I process. The PSs have superior PDT properties compared to conventional Visudyne and 5-ALA under mild conditions. These characteristics allowed for precise PDT at the target region in mimic tumor spheroids, demonstrating that the developed TP PS could be useful in efficient PDT applications and in designing various PSs.

Azo containing dyes as a two-photon selective and type I based photosensitizers (PSs) were developed that exhibit excellent photodynamic therapy properties under mild condition.     

Observation and Photophysical Characterization of Silicon Phthalocyanine J‐Aggregate Dimers in Aqueous Solutions

The use of macrocyclic molecules for both imaging and photodynamic therapy (PDT) has proven to be a powerful method for assessing and treating diseases, respectively. However, many potential candidates for these applications rely on rigid organic structures which are hydrophobic and thus lead to possible aggregation in aqueous solutions such as blood. Here, we describe the discovery of noncovalent J‐aggregate dimers of the asymmetrically, axially modified silicon phthalocyanine 4 (Pc 4) in aqueous solutions through steady‐state and time‐resolved spectroscopy. Remarkably, the monomer–dimer equilibrium is dictated by water content and pH, with free monomers resulting in favorable solvation conditions even after formation of the dimer complex. This work sheds light on previous observations of Pc 4 behavior in cells during PDT, and can further elucidate the structure–activity relationship of these important molecules.     

DNA Photocleavage by a Cationic BODIPY Dye through Both Singlet Oxygen and Hydroxyl Radical: New Insight into the Photodynamic Mechanism of BODIPYs

Two new NIR‐absorbing BODIPY dyes, each bearing two pyridinium groups, are synthesized and their DNA‐binding affinities and DNA photocleavage abilities examined in depth. While one BODIPY dye photocleaves DNA mainly through singlet oxygen, the other photocleaves DNA through both singlet oxygen and hydroxyl radical. To the best of our knowledge, this is the first example of a hydroxyl radical being involved in the photodynamic behavior of BODIPY‐type dyes. EPR experiments confirm the ability of these and several related BODIPYs to generate superoxide anion radical and hydroxyl radical. This finding may shed light on the mechanism of BODIPY‐based photodynamic therapy (PDT) and open a new avenue for development of more efficient BODIPY‐type PDT agents.     

Conformation of p-dimethylamino aza styryl dyes

Conformational studies on some p-dimethylamino β-aza and β-aza (with respect to the dimethylamino phenyl ring) styryl dyes derived from quinoline-4, quinoline-2, pyridine-4, pyridine-2, and benzothiazole-2 have been carried out using the quantum mechanical PCILO (perturbative configuration interaction using localized orbitals) method. These molecules may be considered as heterocyclic analogues of benzylidene anilines whose conformations have been studied extensively by both theoretical and experimental methods to explain the difference of their spectra from the isoelectronic benzylidene compounds. The results of the present studies show that the β-aza styryl dyes are nearly planar. In case of β-aza styryl dyes, although the phenyl ring is coplanar with the central atoms, there is a substantial twist of the heterocyclic ring. These results are explained in terms of CT -1 and CT -2 effects and are used as a possible explanation for the observed spectral and sensitization properties.     

Thermally activated delayed fluorescence molecules and their new applications aside from OLEDs

Thermally activated delayed fluorescence molecules (TADF) molecules have been found to undergo efficient intersystem crossing (ISC) and reverse intersystem crossing (RISC) processes, which benefit their successful applications in organic light emitting diodes (OLEDs). Due to their long-lived delayed fluorescence, TADF molecules can also be applied in time-resolved luminescence imaging. Besides their special singlet properties, their excited triplet characteristics provide their potential applications in triplet-triplet annihilation upconversion (TTA-UC), photodynamic therapy (PDT) and organic photocatalytic synthesis by used as a triplet photosensitizer.     

Thermally activated delayed fluorescence molecules and their new applications aside from OLEDs

Thermally activated delayed fluorescence (TADF) organic molecules feature with long-lived delayed fluorescence, because they can undergo not only efficient intersystem crossing (ISC), but also efficient reverse intersystem crossing (RISC) at room temperature. As a new type of luminescent molecules, they have exhibited successful applications in organic light emitting diodes (OLEDs). Aside from OLEDs, they are also found to have potential applications in time-resolved luminescence imaging based on long-lived fluorescence property. Meanwhile, due to their excited triplet characteristic originated from efficient ISC, they were found to be applied in triplet-triplet annihilation upconversion (TTA-UC), photodynamic therapy (PDT) and organic photocatalytic synthesis. This review briefly summarizes the characteristics and excellent photophysical properties of TADF organic compounds, then covers their applications to date aside from OLEDs based on their highly efficient ISC ability and RISC ability at room temperature.     

Exploring BODIPY Derivatives as Singlet Oxygen Photosensitizers for PDT

This minireview is devoted to honoring the memory of Dr. Thomas Dougherty, a pioneer of modern photodynamic therapy (PDT). It compiles the most important inputs made by our research group since 2012 in the development of new photosensitizers based on BODIPY chromophore which, thanks to the rich BODIPY chemistry, allows a finely tuned design of the photophysical properties of this family of dyes to serve as efficient photosensitizers for the generation of singlet oxygen. These two factors, photophysical tuning and workable chemistry, have turned BODIPY chromophore as one of the most promising dyes for the development of improved photosensitizers for PDT. In this line, this minireview is mainly related to the establishment of chemical methods and structural designs for enabling efficient singlet oxygen generation in BODIPYs. The approaches include the incorporation of heavy atoms, such as halogens (iodine or bromine) in different number and positions on the BODIPY scaffold, and also transition metal atoms, by their complexation with Ir(III) center, for instance. On the other hand, low-toxicity approaches, without involving heavy metals, have been developed by preparing several orthogonal BODIPY dimers with different substitution patterns. The advantages and drawbacks of all these diverse molecular designs based on BODIPY structural framework are described.     

两个新的苯并噻唑衍生物的合成与光物理性质

以苯并噻唑、苯乙酰基和吡啶阳离子为电子受体,二乙烯基苯为共轭桥,合成了两个新的A-π-A′型苯并噻唑衍生物:4-(2-苯并噻唑)-乙烯基查尔酮(1)和4-{4-[2-(苯并噻唑)乙烯基]苯乙烯基}-N-甲基吡啶碘盐(2).研究了它们在溶液和固体基质中的光物理性质.研究发现:染料2由于具有较强的极性和较好的平面性,从而具有较长的吸收、发射峰和较强的荧光发射.有机染料在聚甲基丙烯酸甲酯/溶胶-凝胶复合玻璃中的发光行为与聚甲基丙烯酸甲酯和溶胶-凝胶玻璃二者的基质性质有关,同时由于固体基质中分子发生聚集的可能性降低,荧光强度相对于同浓度溶液增强,稳定性提高.