Small molecule donors (SMDs) play subtle roles in the signaling mechanism and disease treatments. While many excellent SMDs have been developed, dosage control, targeted delivery, spatiotemporal feedback, as well as the efficiency evaluation of small molecules are still key challenges. Accordingly, fluorescent small molecule donors (FSMDs) have emerged to meet these challenges. FSMDs enable controllable release and non-invasive real-time monitoring, providing significant advantages for drug development and clinical diagnosis. Integration of FSMDs with chemotherapeutic, photodynamic or photothermal properties can take full advantage of each mode to enhance therapeutic efficacy. Given the remarkable properties and the thriving development of FSMDs, we believe a review is needed to summarize the design, triggering strategies and tracking mechanisms of FSMDs. With this review, we compiled FSMDs for most small molecules (nitric oxide, carbon monoxide, hydrogen sulfide, sulfur dioxide, reactive oxygen species and formaldehyde), and discuss recent progress concerning their molecular design, structural classification, mechanisms of generation, triggered release, structure–activity relationships, and the fluorescence response mechanism. Firstly, from the large number of fluorescent small molecular donors available, we have organized the common structures for producing different types of small molecules, providing a general strategy for the development of FSMDs. Secondly, we have classified FSMDs in terms of the respective donor types and fluorophore structures. Thirdly, we discuss the mechanisms and factors associated with the controlled release of small molecules and the regulation of the fluorescence responses, from which universal guidelines for optical properties and structure rearrangement were established, mainly involving light-controlled, enzyme-activated, reactive oxygen species-triggered, biothiol-triggered, single-electron reduction, click chemistry, and other triggering mechanisms. Fourthly, representative applications of FSMDs for trackable release, and evaluation monitoring, as well as for visible in vivo treatment are outlined, to illustrate the potential of FSMDs in drug screening and precision medicine. Finally, we discuss the opportunities and remaining challenges for the development of FSMDs for practical and clinical applications, which we anticipate will stimulate the attention of researchers in the diverse fields of chemistry, pharmacology, chemical biology and clinical chemistry. With this review, we hope to impart new understanding thereby enabling the rapid development of the next generation of FSMDs.

中文翻译：

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荧光小分子供体

小分子供体（SMD）在信号传导机制和疾病治疗中发挥着微妙的作用。尽管已经开发出许多优秀的SMD，但剂量控制、靶向递送、时空反馈以及小分子的效率评估仍然是关键挑战。因此，荧光小分子供体（FSMD）的出现来应对这些挑战。 FSMD可实现可控释放和无创实时监测，为药物开发和临床诊断提供显着优势。将 FSMD 与化疗、光动力或光热特性相结合，可以充分利用每种模式来增强治疗效果。鉴于 FSMD 的显着特性和蓬勃发展，我们认为需要对 FSMD 的设计、触发策略和跟踪机制进行综述。通过这篇综述，我们编制了大多数小分子（一氧化氮、一氧化碳、硫化氢、二氧化硫、活性氧和甲醛）的 FSMD，并讨论了它们的分子设计、结构分类、生成机制、触发释放、结构-活性关系，以及荧光响应机制。首先，从大量可用的荧光小分子供体中，我们组织了生产不同类型小分子的通用结构，为FSMD的开发提供了总体策略。其次，我们根据各自的供体类型和荧光团结构对 FSMD 进行了分类。第三，我们讨论了与小分子受控释放和荧光响应调节相关的机制和因素，由此建立了光学性质和结构重排的通用指南，主要涉及光控、酶激活、活性氧等。 -触发、生物硫醇触发、单电子还原、点击化学和其他触发机制。第四，概述了 FSMD 在可追踪释放、评估监测以及可见体内治疗方面的代表性应用，以说明 FSMD 在药物筛选和精准医疗方面的潜力。最后，我们讨论了 FSMD 开发用于实际和临床应用的机遇和挑战，我们预计这将引起化学、药理学、化学生物学和临床化学等不同领域研究人员的关注。通过这次审查，我们希望传达新的理解，从而促进下一代 FSMD 的快速发展。