Investigation of the Chemiluminescent Reaction of a Fluorinated Analog of Marine Coelenterazine.

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.

Application of Fluorescent Carbon Dots as Catalysts for the Ring-Opening Reaction of Epoxides.

Considering the increased anthropogenic emissions of CO2 into the atmosphere, it is important to develop economic incentives for the use of CO2 capture methodologies. The conversion of CO2 into heterocyclic carbonates shows significant potential. However, there is a need for suitable organocatalysts to reach the required efficiency for these reactions. Given this, there has been an increasing focus on the development of organocatalytic systems consisting of a nucleophile and a hydrogen bond donor (HBD) so that CO2 conversion can occur in ambient conditions. In this work, we evaluated the potential of fluorescent carbon dots (CDs) as catalytic HBDs in the ring-opening reaction of epoxides, which is typically the rate-limiting step of CO2 conversion reactions into heterocyclic carbonates. The obtained results demonstrated that the CDs had a relevant catalytic effect on the studied model reaction, with a rate constant of 0.2361 ± 0.008 h-1, a percentage of reactant conversion of 70.8%, and a rate constant enhancement of 32.2%. These results were better than the studied alternative molecular HBDs. Thus, this study demonstrated that CDs have the potential to be used as HBDs and employed in organocatalyzed CO2 conversion into value-added products.

Synchrotron-based FTIR evaluation of biochemical changes in cancer and noncancer cells induced by brominated marine coelenteramine.

The mode of action toward gastric cancer cells of brominated Coelenteramine, an analogue of a metabolic product of a marine bioluminescent reaction, was investigated by synchrotron radiation-based Fourier Transform Infrared spectrocopy (FTIR). This method revealed that the anticancer activity of brominated Coelenteramine is closely connected with cellular lipids, by affecting their organization and composition. More specifically, there is an increasing extent of oxidative stress, which results in changes in membrane polarity, lipid chain packing and lipid composition. However, this effect was not observed in a noncancer cell line, helping to explain its selectivity profile. Thus, synchrotron radiation-based FTIR helped to identify the potential of this Coelenteramine analogue in targeting membrane lipids, while proving to be a powerful technique to probe the mechanism of anticancer drugs.

Chemical Characterization and Evaluation of Antimicrobial Properties of the Wild Medicinal Mushroom Ganoderma lucidum Growing in Northern Moroccan Forests.

Ganoderma lucidum is an extensively famous medicinal mushroom distributed worldwide. Despite being widely grown in Moroccan forests, there are no studies on its nutritional, nutraceutical and pharmaceutical values. Herein, the objective of this study was to investigate the chemical characterization and antimicrobial properties of G. lucidum methanolic extract. Total phenolic, flavonoid, tannin, ascorbic acid and carotenoid contents were determined by spectrophotometry. The results revealed that the most prevalent bioactive compounds were phenolics and flavonoids, with total values of 154.60 mg GAE/g of dry methanolic extract (dme) and 60.55 mg CE/mg of dme, respectively. A GC-MS analysis identified 80 biologically active molecules, which were mainly divided into the following major groups: sugars (49.49%), organic acids (8.89%), fatty acids (7.75%), amino acids (7.44%), steroids (7.32%), polyphenols (5.92%), and others (13.16%). Additionally, 22 individual phenolic compounds were identified and quantified using HPLC-MS, with emphasis on kaempferol (1714 µg/g of dry weight (dw)), apigenin (1955 µg/g dw) and quercetin (947.2 µg/g dw). The methanolic extract of G. lucidum indicated strong antioxidant capacity by means of the following: DPPH radical-scavenging activity (53.7 µg/mL), ß-carotene/linoleate assay (43.75 µg/mL), and reducing power assay (76.62 µg/mL). Furthermore, the extract exhibited potent antimicrobial properties against seven human pathogenic microorganisms, including two bacteria and five fungal strains, at concentrations ranging from 1 to 16 mg/mL. The most sensitive pathogen was Epidermophyton floccosum (MIC = MFC = 1 mg/mL), while Aspergillus fumigatus was the most resistant one (MIC = 16 mg/mL and MFC ≥ 16 mg/mL). Overall, our findings demonstrated valuable nutritional and bioactive compound attributes, and potent antioxidant and antimicrobial properties, of G. lucidum growing in Moroccan forests. Moreover, these findings suggest that the Moroccan mushroom can be extremely useful for the food and medicinal industries to positively affect socioeconomic status.

Nanomaterial-Based Advanced Oxidation/Reduction Processes for the Degradation of PFAS.

This review focuses on a critical analysis of nanocatalysts for advanced reductive processes (ARPs) and oxidation processes (AOPs) designed for the degradation of poly/perfluoroalkyl substances (PFAS) in water. Ozone, ultraviolet and photocatalyzed ARPs and/or AOPs are the basic treatment technologies. Besides the review of the nanomaterials with greater potential as catalysts for advanced processes of PFAS in water, the perspectives for their future development, considering sustainability, are discussed. Moreover, a brief analysis of the current state of the art of ARPs and AOPs for the treatment of PFAS in water is presented.

Antioxidant Properties, Bioactive Compounds Contents, and Chemical Characterization of Two Wild Edible Mushroom Species from Morocco: Paralepista flaccida (Sowerby) Vizzini and Lepista nuda (Bull.) Cooke.

Mushrooms have been consumed for centuries and have recently gained more popularity as an important source of nutritional and pharmaceutical compounds. As part of the valorization of mushroom species in northern Morocco, the current study aimed to investigate the chemical compositions and antioxidant properties of two wild edible mushrooms, Paralepista flaccida and Lepista nuda. Herein, the bioactive compounds were determined using spectrophotometer methods, and results showed that the value of total phenolic content (TPC) was found to be higher in P. flaccida (32.86 ± 0.52 mg) than in L. nuda (25.52 ± 0.56 mg of gallic acid equivalents (GAEs)/mg of dry methanolic extract (dme)). On the other hand, the value of total flavonoid content (TFC) was greater in L. nuda than in P. flaccida, with values of 19.02 ± 0.80 and 10.34 ± 0.60 mg of (+)-catechin equivalents (CEs)/g dme, respectively. Moreover, the ascorbic acid, tannin, and carotenoids content was moderate, with a non-significant difference between the two samples. High-performance liquid chromatography-mass spectrometry (HPLC-MS) analysis allowed the identification and quantification of thirteen individual phenolic compounds in both P. flaccida and L. nuda, whereas p-Hydroxybenzoic acid was recognized as the major compound detected, with values of 138.50 ± 1.58 and 587.90 ± 4.89 µg/g of dry weight (dw), respectively. The gas chromatography-mass spectrometry (GC-MS) analysis of methanolic extracts of P. flaccida and L. nuda revealed the presence of sixty-one and sixty-six biomolecules, respectively. These biomolecules can mainly be divided into four main groups, namely sugars, amino acids, fatty acids, and organic acids. Moreover, glycerol (12.42%) and mannitol (10.39%) were observed to be the main chemical compositions of P. flaccida, while L. nuda was predominated by linolelaidic acid (21.13%) and leucine (9.05%). L. nuda showed a strong antioxidant property, evaluated by DPPH (half maximal effective concentration (EC50) 1.18-0.98 mg/mL); ß-carotene bleaching (EC50 0.22-0.39 mg/mL); and reducing power methods (EC50 0.63-0.48 mg/mL), respectively. These findings suggested that both mushrooms are potential sources of various biomolecules, many of which possess important biological activities which are interesting for the foods and pharmaceuticals industry.

Investigation of the role of pH and the stoichiometry of the N-dopant in the luminescence, composition and synthesis yield of carbon dots.

Carbon dots (CDs) are carbon-based nanoparticles with very attractive luminescence features, which simplicity and flexibility of their fabrication can lead to an endless number of CDs with distinct properties and applications. High fluorescence quantum yields (QYFL) are generally a necessary feature for various applications of CDs. One commonly employed strategy to improve the fluorescence properties of CDs is heteroatom-doping using precursors containing desired heteroatoms (with focus on N-doping). In this work, we report the synthesis and systematic investigation of an array of N-doped CDs, obtained from the dry heating of solid mixtures of glucose and urea in different molar ratios with two main objectives: to study the role of stoichiometry in the optical properties and composition of CDs and to investigate the formation of possible alkaline-responsive nanoparticles and the potential of this procedure for obtaining CDs with higher synthesis yields. We have characterized the optical properties of this diverse array of glucose and urea-based CDs using both UV-Vis and fluorescence spectroscopies. In addition, we have also examined the CDs by using high-resolution transmission electron microscopy (HR-TEM) and X-Ray photoelectron (XPS) spectroscopy, as well as by assessing the thermal stability of the nanoparticles. We have found that this fabrication process generates two types of CDs, one readily soluble in water and other only soluble at basic pH. The latter was characterized by higher synthesis yields, and lower QYFL and thermal stability, when compared with those of the former. Furthermore, the stoichiometry of the N-dopant does not appear to be correlated with the QYFL of the obtained CDs. This study provides novel information that should be useful for the future rational development of CDs with higher QYFL and synthesis yields.

Dental and health aspects in the co-occurrence of Treacher Collins and Down syndromes: Case report.

The goal of this case report is to identify the dental care of a patient who has co-occurrence of Treacher Collins and Down syndromes. It is the third case reported in the literature and the first relating dental treatment under general anesthesia and multidisciplinary importance. It was necessary the child's nutritional assessment in this case. This case highlights the importance of individualizing therapeutic protocols, due to the behavioral aspects of patients with special needs, optimizing treatment results in a single session under general anesthesia. Oral health is closely related to overall health, and it is important for awareness that the whole influences the success of medical treatment.

Combined Experimental and Theoretical Investigation into the Photophysical Properties of Halogenated Coelenteramide Analogs.

Marine Coelenterazine is one of the most well-known chemi-/bioluminescent systems, and in which reaction the chemi-/bioluminophore (Coelenteramide) is generated and chemiexcited to singlet excited states (leading to light emission). Recent studies have shown that the bromination of compounds associated with the marine Coelenterazine system can provide them with new properties, such as anticancer activity and enhanced emission. Given this, our objective is to characterize the photophysical properties of a previously reported brominated Coelenteramide analog, by employing a combined experimental and theoretical approach. To better analyze the potential halogen effect, we have also synthesized and characterized, for the first time, two new fluorinated and chlorinated Coelenteramide analogs. These compounds show similar emission spectra in aqueous solution, but with different fluorescence quantum yields, in a trend that can be correlated with the heavy-atom effect (F > Cl > Br). A blue shift in emission in other solvents is also verified with the F−Cl−Br trend. More relevantly, the fluorescence quantum yield of the brominated analog is particularly sensitive to changes in solvent, which indicates that this compound has potential use as a microenvironment fluorescence probe. Theoretical calculations indicate that the observed excited state transitions result from local excitations involving the pyrazine ring. The obtained information should be useful for the further exploration of halogenated Coelenteramides and their luminescent properties.

Investigation of the Anticancer and Drug Combination Potential of Brominated Coelenteramines toward Breast and Prostate Cancer.

Cancer is a very challenging disease to treat, both in terms of therapeutic efficiency and harmful side effects, which continues to motivate the pursuit for novel molecules with potential anticancer activity. Herein, we have designed, synthesized, and evaluated the cytotoxicity of different brominated coelenteramines, which are metabolic products and synthesis precursors of the chemi-/bioluminescent system of marine coelenterazine. The evaluation of the anticancer potential of these molecules was carried out for both prostate and breast cancer, while also exploring their potential for use in combination therapy. Our results provided further insight into the structure-activity relationship of this type of molecule, such as their high structural specificity, as well highlighting the 4-bromophenyl moiety as essential for the anticancer activity. The obtained data also indicated that, despite their similarity, the anticancer activity displayed by both brominated coelenteramines and coelenterazines should arise from independent mechanisms of action. Finally, one of the studied coelenteramines was able to improve the profile of a known chemotherapeutic agent, even at concentrations in which its anticancer activity was not relevant. Thus, our work showed the potential of different components of marine chemi-/bioluminescent systems as novel anticancer molecules, while providing useful information for future optimizations.

Discovery of the Anticancer Activity for Lung and Gastric Cancer of a Brominated Coelenteramine Analog.

Cancer is still a challenging disease to treat, both in terms of harmful side effects and therapeutic efficiency of the available treatments. Herein, to develop new therapeutic molecules, we have investigated the anticancer activity of halogenated derivatives of different components of the bioluminescent system of marine Coelenterazine: Coelenterazine (Clz) itself, Coelenteramide (Clmd), and Coelenteramine (Clm). We have found that Clz derivatives possess variable anticancer activity toward gastric and lung cancer. Interestingly, we also found that both brominated Clmd (Br-Clmd) and Clm (Br-Clm) were the most potent anticancer compounds toward these cell lines, with this being the first report of the anticancer potential of these types of molecules. Interestingly, Br-Clm possessed some safety profile towards noncancer cells. Further evaluation revealed that the latter compound induced cell death via apoptosis, with evidence for crosstalk between intrinsic and extrinsic pathways. Finally, a thorough exploration of the chemical space of the studied Br-Clm helped identify the structural features responsible for its observed anticancer activity. In conclusion, a new type of compounds with anticancer activity toward gastric and lung cancer was reported and characterized, which showed interesting properties to be considered as a starting point for future optimizations towards obtaining suitable chemotherapeutic agents.

Comparative Investigation of the Chemiluminescent Properties of a Dibrominated Coelenterazine Analog.

Chemi- and bioluminescence are remarkable light-emitting phenomena, in which thermal energy is converted into excitation energy due to a (bio)chemical reaction. Among a wide variety of chemi-/bioluminescent systems, one of the most well-known and studied systems is that of marine imidazopyrazinones, such as Coelenterazine and Cypridina luciferin. Due to the increasing usefulness of their chemi-/bioluminescent reactions in terms of imaging and sensing applications, among others, significant effort has been made over the years by researchers to develop new derivatives with enhanced properties. Herein, we report the synthesis and chemiluminescent characterization of a novel dibrominated Coelenterazine analog. This novel compound consistently showed superior luminescence, in terms of total light output and emission lifetime, to natural imidazopyrazinones and commercially available analogs in aprotic media, while being capable of yellow light emission. Finally, this new compound showed enhanced chemiluminescence in an aqueous solution when triggered by superoxide anion, showing potential to be used as a basis for optimized probes for reactive oxygen species. In conclusion, bromination of the imidazopyrazinone scaffold appears to be a suitable strategy for obtaining Coelenterazines with enhanced properties.

Tuning the Intramolecular Chemiexcitation of Neutral Dioxetanones by Interaction with Ionic Species.

The intramolecular chemiexcitation of high-energy peroxide intermediates, such as dioxetanones, is an essential step in different chemi- and bioluminescent reactions. Here, we employed the Time-Dependent Density Functional Theory (TD-DFT) methodology to evaluate if and how external stimuli tune the intramolecular chemiexcitation of model dioxetanones. More specifically, we evaluated whether the strategic placement of ionic species near a neutral dioxetanone model could tune its thermolysis and chemiexcitation profile. We found that these ionic species allow for the "dark" catalysis of the thermolysis reaction by reducing the activation barrier to values low enough to be compatible with efficient chemi- and bioluminescent reactions. Furthermore, while the inclusion of these species negatively affected the chemiexcitation profile compared with neutral dioxetanones, these profiles appear to be at least as efficient as anionic dioxetanones. Thus, our results demonstrated that the intramolecular chemiexcitation of neutral dioxetanones can be tuned by external stimuli in such a way that their activation barriers are decreased. Thus, these results could help to reconcile findings that neutral dioxetanones could be responsible for efficient chemi-/bioluminescence, while being typically associated with high activation parameters.

UV-Based Advanced Oxidation Processes of Remazol Brilliant Blue R Dye Catalyzed by Carbon Dots.

UV-based advanced oxidation processes (AOPs) (UV/H2O2 and UV/S2O82-) with a titanium(IV)-doped carbon dot, TiP-CD, as a catalyst were developed for the decomposition of Remazol Brilliant Blue R (Reactive Blue 19), an anthraquinone textile dye (at T = 25 °C and pH = 7). The Ti-CD, with marked catalytic UV properties, was successfully synthesized by the one-pot hydrothermal procedure, using L-cysteine as carbon precursor, ethylenediamine as nitrogen source, PEG (polyethylene glycol) as a capping agent, and titanium(IV) isopropoxide (precursor of TiO2 doping). Contrary to azo dyes (methyl orange, orange II sodium salt, and reactive black 5), which achieved complete degradation in a time interval less than 30 min in the developed AOP systems (UV/H2O2, UV/S2O82-, and UV/TiO2), the RBB-R showed relatively low degradation rates and low discoloration rate constants. In the presence of the catalyzer, the reaction rate significantly increased, and the pseudo-first-order rate constants for the RBB-R discoloration were UV/3.0 mM H2O2/TIP-CD-0.0330 min-1 and UV/1.02 mM S2O82-/TIP-CD-0.0345 min-1.

Life Cycle Assessment-Based Comparative Study between High-Yield and "Standard" Bottom-Up Procedures for the Fabrication of Carbon Dots.

Carbon dots (CDs) are carbon-based nanomaterials with remarkable properties that can be produced from a wide variety of synthesis routes. Given that "standard" bottom-up procedures are typically associated with low synthesis yields, different authors have been trying to devise alternative high-yield fabrication strategies. However, there is a doubt if sustainability-wise, the latter should be really preferred to the former. Herein, we employed a Life Cycle Assessment (LCA) approach to compare and understand the environmental impacts of high-yield and "standard" bottom-up strategies, by applying different life cycle impact assessment (LCIA) methods. These routes were: (1) production of hydrochar, via the hydrothermal treatment of carbon precursors, and its alkaline peroxide treatment into high-yield CDs; (2) microwave treatment of carbon precursors doped with ethylenediamine; (3) and (6) thermal treatment of carbon precursor and urea; (4) hydrothermal treatment of carbon precursor and urea; (5) microwave treatment of carbon precursor and urea. For this LCA, four LCIA methods were used: ReCiPe, Greenhouse Gas Protocol, AWARE, and USEtox. Results identified CD-5 as the most sustainable synthesis in ReCiPe, Greenhouse Gas Protocol, and USEtox. On the other hand, in AWARE, the most sustainable synthesis was CD-1. It was possible to conclude that, in general, high-yield synthesis (CD-1) was not more sustainable than "standard" bottom-up synthesis, such as CD-5 and CD-6 (also with relatively high-yield). More importantly, high-yield synthesis (CD-1) did not generate much lower environmental impacts than "standard" approaches with low yields, which indicates that higher yields come with relevant environmental costs.

Theoretical Study of the Thermolysis Reaction and Chemiexcitation of Coelenterazine Dioxetanes.

Coelenterazine and other imidazopyrazinones are important bioluminescent substrates widespread in marine species and can be found in eight phyla of luminescent organisms. Light emission from these systems is caused by the formation and subsequent thermolysis of a dioxetanone intermediate, whose decomposition allows for efficient chemiexcitation to singlet excited states. Interestingly, some studies have also reported the involvement of unexpected dioxetane intermediates in the chemi- and bioluminescent reactions of Coelenterazine, albeit with little information on the underlying mechanisms of these new species. Herein, we have employed a theoretical approach based on density functional theory to study for the first time the thermolysis reaction and chemiexcitation profile of two Coelenterazine dioxetanes. We have found that the thermolysis reactions of these species are feasible but with relevant energetic differences. More importantly, we found that the singlet chemiexcitation profiles of these dioxetanes are significantly less efficient than the corresponding dioxetanones. Furthermore, we identified triplet chemiexcitation pathways for the Coelenterazine dioxetanes. Given this, the chemiexcitation of these dioxetanes should lead only to minimal luminescence. Thus, our theoretical investigation of these systems indicates that the thermolysis of these dioxetanes should only provide "dark" pathways for the formation of nonluminescent degradation products of the chemi- and bioluminescent reactions of Coelenterazine and other imidazopyrazinones.

Photocatalytic removal of pharmaceutical water pollutants by TiO2 - Carbon dots nanocomposites: A review.

Pharmaceuticals are becoming increasingly more relevant water contaminants, with photocatalysts (such as TiO2) being a promising approach to remove these compounds from water. However, TiO2 has poor sunlight-harvesting capacity, low photonic efficiency, and poor adsorption towards organic pollutants. One of the emerging strategies to enhance the photocatalytic performance of TiO2 is by conjugating it with fluorescent carbon dots. Herein, we performed a critical review of the development of TiO2 - carbon dots nanocomposites for the photocatalytic removal of pharmaceuticals. We found that carbon dots can improve the photocatalytic efficiency of the resulting nanocomposites, mostly due to increasing the adsorption of organic pollutants and enhancing the absorption in the visible range. However, while this approach shows significant promise, we also identified and discussed several aspects that need to be addressed before this strategy could be more widely used. We hope that this review can guide future studies aiming to the development of enhanced photocatalytic TiO2 - carbon dots nanocomposites.

Target-Oriented Synthesis of Marine Coelenterazine Derivatives with Anticancer Activity by Applying the Heavy-Atom Effect.

Photodynamic therapy (PDT) is an anticancer therapeutic modality with remarkable advantages over more conventional approaches. However, PDT is greatly limited by its dependence on external light sources. Given this, PDT would benefit from new systems capable of a light-free and intracellular photodynamic effect. Herein, we evaluated the heavy-atom effect as a strategy to provide anticancer activity to derivatives of coelenterazine, a chemiluminescent single-molecule widespread in marine organisms. Our results indicate that the use of the heavy-atom effect allows these molecules to generate readily available triplet states in a chemiluminescent reaction triggered by a cancer marker. Cytotoxicity assays in different cancer cell lines showed a heavy-atom-dependent anticancer activity, which increased in the substituent order of hydroxyl < chlorine < bromine. Furthermore, it was found that the magnitude of this anticancer activity is also dependent on the tumor type, being more relevant toward breast and prostate cancer. The compounds also showed moderate activity toward neuroblastoma, while showing limited activity toward colon cancer. In conclusion, the present results indicate that the application of the heavy-atom effect to marine coelenterazine could be a promising approach for the future development of new and optimized self-activating and tumor-selective sensitizers for light-free PDT.

Editorial Materials: Special Issue on Advances in Luminescent Engineered Nanomaterials.

Engineered nanomaterials are purposely manufactured particles with sizes typically between 1 and 100 nm, which can be either organic, inorganic, or organometallic in nature [...].

Normal breast epithelial MCF-10A cells to evaluate the safety of carbon dots.

The human normal breast cell line MCF-10A is being widely used as a model in toxicity studies due to its structural similarity to the normal human mammary epithelium. Over the years, application of carbon dots (C-dots) in biomedicine has been increasing due to their photoluminescence properties, biocompatibility, biosafety and possible applications in bioimaging and as drug carriers. In this work we prepared three different C-dots from the same set of carbon and nitrogen precursors (citric acid and urea, respectively) via three distinct bottom-up synthetic routes and their safety was tested against the normal breast cell line MCF-10A. The characterization results demonstrated a similar size range and composition for all the C-dots. The MCF-10A cells were treated with different concentrations of C-dots for 24, 48 and 72 h to evaluate the cell viability over time. For the 24 h incubation, there were no significant decreases in the viability of the MCF-10A cells. For the 48 h treatment, there was a significant decrease in the viability of the cells treated with calcination-based C-dots, but without significant cellular viability changes for microwave and hydrothermal-based C-dots. For 72 h, cells treated with hydrothermal-based C-dots have the most promising viability profile. Also, compared with paclitaxel, these C-dots have a safety profile very close to that of an antineoplastic in non-tumor cells. Our results suggest that these new C-dots have potential as imaging candidates or biosensing tools as well as drug carriers, and further investigation in animal models is needed for future application in medicine.