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Simple Summary: Carbon dots (CDs) are carbon-based nanomaterials with versatile applications, including fluorescence imaging, drug and gene transport, drug delivery, medical diagnosis, and biosensing. In this study, we successfully synthesized various CDs without significantly impacting the cell viability of cancer cells, which suggests the potential for future bioimaging and drug delivery applications. These findings contribute to advancing the potential of CDs in various biomedical research contexts. Backgroung: The rising complexity and associated side effects of cancer treatments highlight the need for safer and more effective therapeutic agents. Carbon-based nanomaterials such as CDs have been gaining prominence for their unique characteristics, opening avenues for diverse applications such as fluorescence imaging, drug and gene transport, controlled drug delivery, medical diagnosis, and biosensing. Despite promising advancements in research, it remains imperative to scrutinize the properties and potential cytotoxicity of newly developed CDs, ensuring their viability for these applications. Methods: We synthesized four N-doped CDs through a hydrothermal method. Cell viability assays were conducted on A549 and UM-UC-5 cancer cells at a range of concentrations and incubation times, both individually and with the chemotherapeutic agent 5-fluorouracil (5-FU). Results: The obtained results suggest that the newly developed CDs exhibit suitability for applications such as bioimaging, as no significant impact on cell viability was observed for CDs alone. [ABSTRACT FROM AUTHOR]

Bioluminescence (BL) and chemiluminescence (CL) are remarkable processes in which light is emitted due to (bio)chemical reactions. These reactions have attracted significant attention for various applications, such as biosensing, bioimaging, and biomedicine. Some of the most relevant and well-studied BL/CL systems are that of marine imidazopyrazine-based compounds, among which Coelenterazine is a prime example. Understanding the mechanisms behind efficient chemiexcitation is essential for the optimization and development of practical applications for these systems. Here, the CL of a fluorinated Coelenterazine analog was studied using experimental and theoretical approaches to obtain insight into these processes. Experimental analysis revealed that CL is more efficient under basic conditions than under acidic ones, which could be attributed to the higher relative chemiexcitation efficiency of an anionic dioxetanone intermediate over a corresponding neutral species. However, theoretical calculations indicated that the reactions of both species are similarly associated with both electron and charge transfer processes, which are typically used to explain efficiency chemiexcitation. So, neither process appears to be able to explain the relative chemiexcitation efficiencies observed. In conclusion, this study provides further insight into the mechanisms behind the chemiexcitation of imidazopyrazinone-based systems. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) of cancer possesses advantageous features, such as a minimally invasive nature and few side-effect [1]. However, its use can be restricted to more surface tumors, due to its dependance on light-irradiation. To overcome this problem, we propose the development of single-molecule photosensitizers (PSs), based on chemiluminescent (CL) marine Coelenterazine (Clz) [2-6], which can be self-activated in the absence of light. Clz analogs were synthesized via routes optimized by our team [2-6], and their structure was characterized by HR-MS, NMR and FTIR spectroscopy. They were subjected to a through luminometric and photophysical characterization, to determine their CL features and singlet oxygen sensitization [2-6]. Their toxicity was investigated in vitro toward different cancer (breast, prostate, neuroblastoma, lung and gastric) and noncancer (breast and keratinocytes) cell lines, via the MTT assay in the absence of light [2-6]. The obtained Clz analogs were designed so their CL reaction generate mainly triplet states, instead of singlet excited ones [2-6]. They were shown to indeed be able to sensitize the highly cytotoxic singlet oxygen, without light-irradiation, due to a CL reaction triggered solely by molecule overexpressed in cancer cells (superoxide anion) [2-6]. In vitro assays showed that these analogs present cytotoxicity toward all the different studied cancer cell lines [2-6]. Moreover, some of them even showed comparable or even better activity than a reference chemotherapeutic drug [3,4]. Finally, a promising profile of safety was observed in testing with noncancer cells [3]. Different single-molecule PSs were developed, which are capable of intracellular self-activation without light-irradiation [2-6]. Namely, they are directly chemiexcited to triplet excited states via a CL reaction triggered by a molecule overexpressed in cancer cells, which generates singlet oxygen without light-irradiation. This new approach was found to induce toxicity toward different cancer cell lines, while possessing a promising profile of safety for noncancer cells. Thus, these PSs can provide a pathway for eliminating the light-related restrictions of PDT, while maintaining its advantages. [ABSTRACT FROM AUTHOR]

Despite decades of research, it is still not clear what is the mechanism behind the efficient chemiexcitation of dioxetanones in chemiluminescent and bioluminescent reactions. In fact, long‐standing theories (charge transfer‐initiated luminescence and chemically induced electron‐exchange luminescence) have been demonstrated to not be able to explain this phenomenon. Herein, a theoretical approach using reliable and up‐to‐date methodology was used to address this problem, by focusing on model dioxetanones. Time‐dependent (TD)‐Density functional theory (DFT) and multireference complete‐active‐space second‐order perturbation theory (CASPT2) calculations provided evidence that points to efficient intramolecular chemiexcitation being the result of the reacting molecules having access to a long zone of the Potential energy surface (PES), within the biradicalar region, where S0 and S1 are degenerate. Molecules with inefficient chemiexcitation are unable to reach this zone of degeneracy. Our main finding is that access to the region of degeneracy appears to be given due to increased interaction between the keto and CO2 moieties, as supported by the use of the activation strain model and Born‐Oppenheimer molecular dynamics, which extends the biradical region by delaying the rupture of the peroxide ring. Increased interaction derives from attractive electrostatic interactions between the moieties of dioxetanone. Thus, we hypothesize that efficient chemiexcitation results not only from electron/charge transfer and subsequent charge annihilation but is instead based on the degree of interaction between the keto and CO2 moieties, which controls the access to a region of degeneracy between the ground and excited states. Efficient chemiexcitation results from attractive interaction between the keto and CO2 moieties of dioxetanone, which delays the detachment of CO2. This allows the reacting molecule to access a zone of degeneracy between the ground and excited states, within the biradical region of the thermolysis reaction. [ABSTRACT FROM AUTHOR]