高性能聚集诱导发光分子的精确设计（2020-10-22）

Xu S, Duan Y, Liu B. Precise Molecular Design for High-Performance Luminogens with Aggregation-Induced Emission. Adv Mater. 2020;32(1):e1903530. doi:10.1002/adma.201903530这篇发表在“Advanced Materials”的文章系统的总结了AIE分子的设计，具体内容包括以下七个方面：· 1）如何为有效的生物医学应用设计具有长波长吸收/发射的AIE分子；· 2）如何获得高固体量子产率，以提供更好的器件性能和成像质量；· 3）如何在太阳能电池和光疗应用中实现高的摩尔吸收；· 4）如何提高光子吸收（2PA）横截面，以进行精确的成像和治疗；· 5）如何微调单重态-三重态的能隙，以实现较高的系统间穿越（ISC）率，生成高效的三重态材料，例如光敏剂，延迟的荧光和磷光材料；· 6）如何利用AIE现象设计高对比度的机械致变色和摩擦发光材料；· 7）如何微调固态的分子堆积，以提高光声（PA）成像和光热疗法（PTT）的效果。这篇综述中内容很多，我提取了一些和医学关系比较密切的内容：一、长波长AIEgens的设计在基础研究和实际应用中，具有长波长吸收/发射的材料都至关重要。 例如，对于生物医学应用，与短波长光相比，长波长光对健康组织和细胞的危害较小。 此外，更长的激发波长可实现更深的穿透力以及与自发荧光的更好光谱分离，这有利于以更高的信噪比进行体内和体外成像。分子的光学范围取决于最高能级分子轨道（HOMO）与最低能级分子轨道（LUMO）之间的能量差。 因此，提高HOMO或降低LUMO是设计长波长材料的本质。根据分子光化学的量子理论，扩展π共轭体系（或π范围）会增加耦合分子轨道的数量，并增强π离域的程度。 结果，提高HOMO能级通常会导致能量带隙减小，从而发生红移。 将电子供体（D）和受体（A）基团引入π-共轭体系是减少带隙的另一种方法。 通常，D驱动HOMO，A驱动LUMO。为了阐述使AIEgen的光学范围红移的方法，可以将AIE芯结构可以分为三类：“中性” AIE核团，“供体”和“受体” AIE核团，它们反映了电子的“吸/给”核心结构的能力。 吸/给核的电子的性质决定了HOMO / LUMO工程中要采用的相应方法。例如，基于经典的红色发射D–A荧光团（例如4-（二氰基亚甲基）-2-甲基-6-（4-二甲基氨基苯乙烯基）-4H-吡喃，DCM），将中性AIE核连接至D或A分子的一部分可以产生新的红色发射AIEgen。 同样与母体结构相比，将D和A或仅将A添加到中性AIE核基团可能会导致光学范围发生红移。二、高光热转换效率的AIEgens设计尽管可以将AIEgens设计为在聚集体状态下显示明亮的荧光，但最近的研究表明AIE转子在促进纳米聚集体中有机分子的非辐射衰减方面具有潜力。 具有高光热转换效率的有机纳米材料不仅已用于光热疗法（PTT），而且还用作光声成像（PA）的造影剂。对于后者，它依赖于捕获由于造影剂的光吸收而产生的声波信号，这会引起组织的热膨胀。 据报道，各种分子设计策略有利于PTT和PA应用的非辐射衰变。4,9-二-（5-溴-噻吩-2-基）噻二唑并喹喔啉（TTQ）是一种良好的电子受体，在635 nm处具有最大吸收。 通过将两种TPE单元的螺旋桨结构作为TTQ的电子供体，形成了在724 nm处具有最大吸收的高效PTT剂（114号NPs）。 尽管在NP中分子运动受到一定程度的限制，但114号NP的PA信号生成比TTQ NP高15％。 114NPs显示出40％的PCE，优于广泛使用的金纳米棒（29％）。 该结果证明了具有螺旋桨结构的化合物在PA成像和光热疗法应用中的巨大潜力。 重要的是要注意，尽管114号NPs在NP中显示出良好的PA信号，但与溶液相比，处于聚集状态的整体PA性能较弱，这间接证明了分子运动在PA信号生成中起着重要作用。


图1: 114号纳米颗粒

唐等人还发现，含有转子结构的有机分子的松散堆积是高PCE的关键。115号化合物具有转子状的扭曲结构，并且在远红/近红外区域具有强吸收性。根据分子动力学模拟，115号聚集体为无定形形式，由处于松散堆积状态的无序分子组成，产生有效的分子内运动，从而提高了热失活途径的能量耗散。这些固有功能使115号NP表现出51.2％的出色光热转换效率。最近，Tang等人介绍了一种新的工作原理，即激发态分子内运动诱导的光热敏（iMIPT），用于开发有效的光热/光声成像纳米剂。与广泛使用的亚甲基蓝和半导体聚合物纳米粒子相比，纳米粒子内部具有iMIPT的一类近红外吸收有机分子（116和117）分别显示54.9％和43.0％的高PCE，并具有出色的光声成像效果。在此设计中，添加了TPE单元作为分子转子，长烷基链充当了间隔基，使处于聚集状态的分子能够进行分子间空间隔离，从而产生了一些必要的空间来促进分子内的自由运动。固态分子运动已通过NMR和寿命测量得到证实图2:115号分子
图3:116/117号分子
英文版：This article published in "Advanced Materials" systematically summarizes the design of AIE molecules, including the following seven aspects:· 1) How to design AIEgens with long wavelength absorption/emission for effective biomedical applications;· 2) How to yield high photo luminescence quantum yields in solid state for better device performance and enhanced imaging quality;· 3) How to realize enhanced molar absorption of AIEgens for solar cells and phototherapy applications;· 4) How to achieve improved two-photon absorption (2PA) cross sections for precise imaging and therapy;· 5) How to fine-tune singlet-triplet energy gap for high inter system crossing (ISC)rate, generating efficient triplet materials such as photosensitizers, delayed fluorescent, and phosphorescent materials;· 6) How to design high contrast mechanochromism and triboluminescent materials by taking advantages of the AIE phenomenon;· 7) How to fine-tune the molecular packing in the solid state for photoacoustic (PA) imaging and photothermal therapy (PTT).There is a lot of content in this review, and I extracted some content that is closely related to medicine:1. Design of AIEgens with Long Wavelength EmissionIn both fundamental research and practical applications, materials with long-wavelength absorption/emission are of  crucial importance. For example,  for biomedical applications, long-wavelength light is less harmful to healthy tissues and  cells in comparison with short-wavelength light. Moreover, longer wavelength of excitation allows for deeper penetration and better spectral separation from autofluorescence, which favors both in vivo and in vitro imaging with higher signal-to-background ratios.The optical range of a molecule is determined by energy difference between the highest occupied molecular orbital  (HOMO) and the lowest unoccupied molecular orbital (LUMO). Thereby, rising HOMO or lowering LUMO is the essence of designing long-wavelength materials.According to the quantum theories of molecular photochemistry, extending the π-conjugation system (or π range) increases the number of coupled molecular orbitals and strengthens the degree of π-delocalization. As a result, elevating the HOMO energy level often leads to reduced bandgap and thus red-shifted optical range. Introducing electron donor (D) and acceptor (A) groups into a π-conjugation system is another approach to reduce bandgap. In general, D drives up the HOMO and A pulls down the LUMO.To illustrate the strategies for red-shifting the optical range of AIEgens, the AIE core structures can be divided into three categories: “neutral ’’ AIE core, “donor’’ and “acceptor’’ AIE cores, which reflect the electron withdrawing/donating abilities of the core structures . The nature of electron withdrawing/donating of the cores determines the respective methodologies to be applied in the HOMO/LUMO engineering.For example, based on a classic red emissive D–A fluorophore (e.g., 4-(dicyanomethylene)-2-methyl-6-(4-dimethylaminostyryl)-4H-pyran, DCM), attaching a neutral AIE core to the D or A part of the molecule can yield new red emissive AIEgens. Likewise, adding D and A, or simply A to a neutral AIE core can result in red-shifted optical range as compared to the parent structure.2. Design of AIEgens with High Photothermal Conversion EfficiencyAlthough AIEgens could be designed to show bright fluorescence in the aggregate state, recent studies have revealed the potential of AIE rotors in promoting nonradiative decay of organic molecules in the nanoaggregates. Organic nanomaterials with high photothermal conversion efficiency have not only been used for photothermal therapy (PTT), but also served as the contrast agents for photoacoustic imaging (PA).For the latter, it relies on capturing the acoustic wave signals generated due to the light absorption of the contrast agents, which induces thermal expansion of tissue. Various molecular design strategies have been reported to favor nonradiative decays for PTT and PA applications.4,9-Di-(5-bromo-thiophen-2-yl)thiadiazolo-quinoxaline (TTQ) is a good electron acceptor with an absorption maximum at 635 nm. By introducing two propeller structures of TPE units as the electron donor to TTQ, a highly efficient PTT agent with absorption maximum at 724 nm was formed（114） . Despite the fact that the molecular motion is restricted to a certain degree in the NPs, 114 NPs show 15% higher PA signal generation than that for TTQ NPs. The 114 NPs also showed a PCE of 40%, which is superior to that of the widely used gold nanorods (29%). This result demonstrated the great potential of compounds with propeller structures for PA imaging and photothermal therapy applications. It is important to note that although 114 showed good PA signal in NPs, the overall PA performance in the aggregate state is weaker as compared to that in solution, which indirectly proved that molecular motions played an important role in PA signal generation.T ang et al. also found that loose packing of organic molecules containing rotor structures was the key to high PCE.Compound 115 possesses a rotor-like twisted structure and strong absorption in the far red/near-infrared region. According to molecular dynamics simulations, the 115 aggregate is in an amorphous form consisting of disordered molecules in a loose packing state, which allows efficient intramolecular motions, and consequently elevates energy dissipation from the pathway of thermal deactivation. These intrinsic features enabled 115 NPs to display an excellent photothermal conversion efficiency of 51.2%.More recently, T ang et al. introduced a new working principle, excited state intramolecular motion-induced photothermy (iMIPT), for developing efficient photothermal/photoacoustic imaging nanoagents. A class of near infrared-absorbing organic molecules (116 and 117) with iMIPT inside nanoparticle show high PCEs of 54.9% and 43.0%, respectively, and superior photoacoustic imaging compared to the widely used methylene blue and semiconducting polymer nanoparticles.In this design, TPE units were added as molecular rotors and long alkyl chains acted as spacer to enable the intermolecular spatial isolation of the molecules in the aggregate state to produce some necessary rooms to promote free intramolecular motion. The solid-state molecular motion has been  confirmed by NMR and lifetime measurements.