Sichuan University to Transfer Near-Infrared Fluorescent Probe Patent Based on Purine Scaffold for RMB 1 Million

Recently, Sichuan University released a public notice on the transformation of scientific and technological achievements, proposing to transfer a“A Purine Skeleton-Based Near-Infrared Emissive Fluorescent Molecule, Its Preparation Method, and Applications”Invention Patent, with the agreed price being1 million yuanRMB.

This achievement was jointly accomplished by researchers from Sichuan University, including Yu Kangkang, Li Kun, Yu Xiaoqi, and Wang Haoyuan. It is reported that Professor Yu Xiaoqi, a core member of the team, is a professor at the College of Chemistry, Sichuan University. He has long been dedicated to research in frontier interdisciplinary fields such as bioorganic chemistry and functional molecule design. His research interests broadly cover bioorganic chemistry, supramolecular chemistry, drug delivery systems, and other cutting-edge interdisciplinary areas. The identity of the transferee in this transaction has not yet been disclosed.

Purine is a nitrogen-containing heterocyclic compound composed of pyrimidine and imidazole rings. Purine derivatives are widely distributed in nature, with certain derivatives serving as signaling molecules within organisms and participating in various biological processes. Consequently, research on purines and their derivatives has consistently attracted significant attention from the scientific community.

Inspired by the unique structure and function of purine molecules, early efforts were primarily focused on designing purine-based drugs for the treatment of various diseases, including antiviral and antitumor therapies. However, further research has revealed thatPurine molecules also feature a planar conjugated structure and multiple sites amenable to functional modification.these characteristics, it is therefore considered to have the potential as a novel fluorescent molecular scaffold.

Meanwhile, some experimental structures have confirmed that purine molecules possess certain photoluminescent properties. However, it should not be overlooked that their fluorescence emission wavelengths are mainly concentrated inBlue-Violet Light Region. This characteristic makes purine molecules susceptible to interference from background fluorescence in their surrounding environment when applied in fields such as fluorescence imaging, thereby compromising their imaging performance.

To address the limitations of purine molecules in terms of fluorescence wavelength, researchers have attempted toFrom the Perspective of Molecular Designstarting point, to modulate the optical properties of purine molecules. Current research findings indicate that, on one hand, the emission wavelengths of most purine-based fluorescent derivatives are concentrated in the blue-to-green region, while purine derivatives exhibiting near-infrared fluorescence emission are scarce and possess relatively complex molecular structures; on the other hand, compared with classic fluorophore scaffolds such as rhodamine and coumarin, there are relatively few types of purine-based fluorescent derivatives suitable for bioimaging, and their imaging potential remains to be further explored.

Thus, it is evident that there is an urgent need to design and developNovel Purine Fluorescent Derivatives, to compensate for the deficiencies of purines in terms of optical properties and application capabilities. One of the research team's objectives is to provideA Near-Infrared Emitting Fluorescent Molecule Based on a Purine Scaffold, aiming to address the issues of existing purine fluorescent derivatives in optical properties and application capabilities.To this end, the team invented a class ofNovel Fluorescent Molecules with a Purine Core Scaffold. Through ingenious molecular design, electron-donating dimethylamino groups and electron-withdrawing organic cationic salt-type substituents were introduced, successfully constructing an intramolecular“Push-Pull” Electronic System, and expanded the conjugated structure of the molecule by utilizing an olefin bridge.

This design successfully red-shifted the fluorescence emission wavelength of purine to>650 nmin the near-infrared region, effectively reducing interference from biological background fluorescence and significantly enhancing its performance in imaging applications. Furthermore, this series of molecules features a simple structure, a straightforward synthetic route, and mild reaction conditions. It exhibits excellent cell membrane permeability, enabling specific staining of intracellular mitochondria or cell membranes for clear fluorescent imaging. It demonstrates broad application prospects in fields such as biomedical detection, in vivo imaging, and drug development.

This patent is not directed at a single specific disease, but rather aims to address common technical challenges encountered in the precise diagnosis and treatment of a range of major diseases (such as cancer, neurological disorders, and metabolic diseases): how to achieve high-contrast, low-background deep-tissue fluorescence imaging at the in vivo, cellular, and even subcellular levels.

Existing clinical and research protocols rely heavily on fluorescent probes with short emission wavelengths (such as dyes based on classic scaffolds like rhodamine and coumarin), whose emission light mostly falls within the blue-green spectrum. This characteristic leads to critical limitations in clinical applications:

On one hand, short-wavelength light exhibits extremely weak penetration in biological tissues, making it ineffective for imaging deep-seated lesions. On the other hand, biological tissues themselves generate intense autofluorescence in this wavelength range, creating background noise that is difficult to eliminate. This severely obscures target signals, hindering the clear delineation of tumor boundaries during surgical navigation and preventing the precise tracking of subtle physiological processes in cell dynamics research. Although the purine scaffold is regarded as a highly promising fluorescent platform due to its excellent biocompatibility, its inherent short-wavelength emission characteristics have long limited its practical applications.

The team successfully red-shifted the luminescence of purine dyes toNear-Infrared Window, providing a novel material-based solution to overcome the fundamental limitations of existing clinical imaging technologies in terms of sensitivity, penetration depth, and signal-to-noise ratio. This approach effectively addresses the long-standing technical bottleneck associated with purine-based fluorescent molecules, namely their inherent drawback of excessively short emission wavelengths, which has precluded their effective application in bioimaging.

Through ingenious molecular structure design, the research team on the purine scaffoldConstructed a unique “push-pull” electronic system, and effectively extended the conjugated structure of the molecule through olefin bridging, thereby successfully achieving for the first timeStabilizing the red-shifted emission wavelength of purine-based fluorophores to the near-infrared region (>650 nm)。

This breakthrough brings multiple significant advantages: its near-infrared emission characteristics and the “"Optical Window"This high degree of compatibility endows the probe with enhanced tissue penetration and minimal background fluorescence interference, enabling the acquisition of clear images with a signal-to-noise ratio significantly higher than that of conventional blue-green light probes.

Furthermore, this series of molecules not only inherits the inherent excellent biocompatibility of the purine scaffold, enabling efficient cell membrane penetration and achieving specific staining and high-precision imaging of key organelles such as mitochondria and cell membranes, but also demonstrates comprehensive advantages including a concise and flexible molecular structure, a straightforward and efficient synthetic route, mild reaction conditions, and ease of scale-up. These attributes lay a solid technical foundation for the development of next-generation high-performance biomedical imaging agents.

Compared with infrared fluorescence imaging, near-infrared emissive molecular imaging represents a significant technological leap. By utilizing longer-wavelength light in the second near-infrared window (NIR-II), it fundamentally addressesTraditional optical imaging suffers from shallow penetration depth and low resolution.Overcoming two core bottlenecks has pushed the sensitivity and clarity of in vivo fluorescence imaging to new heights. Although challenges remain in probe development and clinical translation, it is undoubtedly a revolutionary tool driving future precision medicine and life sciences research.

Oncology ResearchThis is the most widely applied field of near-infrared emitting fluorescent molecular imaging technology. Through tumor-targeting probes, even very smallTumor Metastases (as small as 0.5 mm), and can also be clearly identified in deep tissues. Furthermore, this technology assists physicians in distinguishing blood vessels and nerves enveloped by tumors within the complex environment of the central nervous system. In future oncological surgeries, this technique is poised to become a vital tool for assisting surgeons in differentiating cancerous tissue from normal tissue, thereby enabling complete resection.

During the course of pharmacological treatment for tumors,Near-Infrared Emission Fluorescent Molecular Imaging TechnologyIt can also dynamically monitor changes in tumor size and its internal vascular network, accurately reflecting the apoptotic status of cancer cells, which may provide a crucial basis for the early assessment of drug efficacy.

Not only that, thanks to the technology's superiorSpatial Resolution, researchers are able to conduct unprecedentedly detailed observations of the vascular system, thereby enabling breakthroughs in fields such as in vivo brain imaging, stroke monitoring, and research on peripheral vascular and metabolic diseases.

Currently, several large companies specializing in near-infrared fluorescence technology have emerged abroad. For instance, LI-COR Biosciences’ classic Pearl series of small-animal in vivo imaging systems is regarded as the industry gold standard. MediLux, founded by Chinese scientist Academician Hong Minghui, and the Dutch tech company SurgVision focus on intraoperative navigation. In contrast, most domestic enterprises in China are primarily engaged in research services and small-animal imaging, although innovative companies with university affiliations, such as Caipu Technology, have also emerged.

In contrast, near-infrared emissive fluorescent molecular imaging technology in China is still in an emerging market stage, urgently requiring more optimized design pathways, engineering structures, and probe technologies. Professor Yu Xiaoqi’s team has adopted a small-molecule-based technical approach, demonstrating significant advantages in manufacturing cost, process complexity, and cell penetrability, thereby laying a novel material foundation for the development of next-generation, cost-effective, and highly specific imaging diagnostic tools.