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This study explores the potential of natural bioactive peptides from animal venoms as targeted anti-cancer agents with reduced toxicity. Initially, we screened a broad collection of animal venoms for their antiproliferative activity against cancer cell lines. From this collection, we selected venoms from Naja anchietae and Naja senegalensis due to their promising activity. Utilizing reverse- phase high-performance liquid chromatography (RP HPLC), mass spectrometry (MALDI-TOF MS and MALDI-TOF TOF MSMS), and Edman degradation sequencing, we isolated and characterized three peptides named CTNanc1, CTNanc2, and CTNanc3 from Naja anchietae, and three others named CTNsen1, CTNsen2, and CTNsen3 from Naja senegalensis, each with a molecular weight of around 7 kDa. These purified peptides demonstrated inhibition of U87 glioblastoma cell proliferation, but not of U251 and T98G cells, in cell viability assays. To assess the impact of these treatments on cell viability, apoptosis, and necrosis, flow cytometry assays were conducted on U87 cells at 72 h. The results showed a decrease in cell viability and an increase in dead cells, suggesting that the treatments not only promote apoptosis, but may also lead to increased necrosis or late-stage apoptosis as the exposure time increases. These findings suggest that these peptides could be developed as leads for cancer therapy.

Animal venoms are intricate and teem with potential for groundbreaking medical advancements. Although traditional methods for purifying venom proteins are effective, they usually require complicated, multi-step processes that lead to lower yields. Our study introduces an efficient, one-step technique for extracting venom-derived proteins through reverse-phase high-performance liquid chromatography (RP-HPLC). We carefully optimized the RP-HPLC process, focusing on the gradient elution conditions and the strategic use of our columns’ stationary phase characteristics, to enhance the effectiveness of our separations. This enabled us to efficiently isolate six venom proteins: melittin (2.846 kDa) from Apis mellifera with a yield of 4.5% and homogeneity of 99%; α-cobratoxin (7.821 kDa) from Naja kaouthia with a yield of 15% and homogeneity of 99%; α-bungarotoxin (7.983 kDa) from Bungarus multicinctus with a yield of 7% and purity of 99%; calciseptine (7.035 kDa) from Dendroaspis polylepis with a yield of 6% and homogeneity of 95%; notexin (13.593 kDa) from Notechis scutatus with a yield of 10% and homogeneity of 95%; and CVFm (150 kDa) from Naja melanoleuca with a yield of 0.8% and homogeneity of 94%. These were all accomplished in one step. This breakthrough simplifies the purification of venom peptides and proteins, making the process more feasible and economical. It paves the way for developing new drugs and promising treatments that are both more effective and precisely targeted.

The use of cheap and safe near-infrared (NIR) light is still the subject of intense research efforts but remains a huge challenge due to the associated low photon energy (wavelength from 0.78 to 2.5 µm). In this study, a series of 17 NIR dyes mainly based on a well-established cyanine scaffold is proposed. Remarkably, 11 of them were never synthesized before. Markedly, noncharged structures, negatively charged cyanine bearing Na+ as counter cation, and positively charged cyanines bearing (B(Ph)4−) or (I−) as counter anions were examined as promising NIR light photoinitiating systems. Excellent photoinitiating abilities were found for some reported dyes when used in combination with iodonium salt and amine. Markedly, photothermal effects with a huge heater behavior were also observed for different NIR dye structures. Interestingly, the synthesis of interpenetrating polymer networks (IPNs, e.g., for the polymerization of acrylate/epoxy monomer blends) can also be carried out upon NIR light with the proposed systems.

Microtubule targeting agents (MTA) are anti-cancer molecules that bind tubulin and interfere with the microtubule functions, eventually leading to cell death. In the present study, we used an in vitro microtubule polymerization assay to screen several venom families for the presence of anti-microtubule activity. We isolated myotoxin-3, a peptide of the crotamine family, and three isoforms from the venom of the Northern Pacific rattlesnake Crotalus oreganus oreganus, which was able to increase tubulin polymerization. Myotoxin-3 turned out to be a cell-penetrating peptide that slightly diminished the viability of U87 glioblastoma and MCF7 breast carcinoma cells. Myotoxin 3 also induced remodeling of the U87 microtubule network and decreased MCF-7 microtubule dynamic instability. These effects are likely due to direct interaction with tubulin. Indeed, we showed that myotoxin-3 binds to tubulin heterodimer with a Kd of 5.3 µM and stoichiometry of two molecules of peptide per tubulin dimer. Our results demonstrate that exogenous peptides are good candidates for developing new MTA and highlight the richness of venoms as a source of pharmacologically active molecules.

Calixarenes are cyclic oligomers obtained by condensation reactions between phenols and formaldehyde and usually include up to eight phenolic subunits. Here the authors demonstrate the synthesis of calixarenes with up to 90 phenolic subunits with up to 65% yield via a scalable process.

Objectives: Coenzyme Q10, incorporated in DOPC lyposomes or naturally present in liver bovine mitochondria or in human blood plasma, was reacted with nitrogen dioxide •NO2 or with a •NO/•NO2 mixture. Methods and Results: The reaction course was monitored by Electron Paramagnetic Resonance (EPR) spectroscopy and in all cases the formation of a di-tert-alkyl nitroxide was observed, deriving from the addition of •NO2 to one of the double bonds, most likely the terminal one, of the isoprenic chain. The rate constant for nitroxide formation was also determined by EPR spectroscopy and an initial rate of ca. 7 × 10−8 M s−1 was obtained.

Recent progresses achieved in terms of synthetic procedures allow now the access to polymers of well-defined composition, molecular weight and architecture. Thanks to these recent progresses in polymer engineering, the scope of applications of polymers is far wider than that of any other class of material, ranging from adhesives, coatings, packaging materials, inks, paints, optics, 3D printing, microelectronics or textiles. From a synthetic viewpoint, photoredox catalysis, originally developed for organic chemistry, has recently been applied to the polymer synthesis, constituting a major breakthrough in polymer chemistry. Thanks to the development of photoredox catalysts of polymerization, a drastic reduction of the amount of photoinitiators could be achieved, addressing the toxicity and the extractability issues; high performance initiating abilities are still obtained due to the catalytic approach which regenerates the catalyst. As it is a fast-growing field, this review will be mainly focused on an overview of the recent advances concerning the development of organic and organometallic photoredox catalysts for the photoreticulation of multifunctional monomers for a rapid and efficient access to 3D polymer networks.

Glioblastoma is the most aggressive and invasive form of central nervous system tumors due to the complexity of the intracellular mechanisms and molecular alterations involved in its progression. Unfortunately, current therapies are unable to stop its neoplastic development. In this context, we previously identified and characterized AaTs-1, a tetrapeptide (IWKS) from Androctonus autralis scorpion venom, which displayed an anti-proliferative effect against U87 cells with an IC50 value of 0.57 mM. This peptide affects the MAPK pathway, enhancing the expression of p53 and altering the cytosolic calcium concentration balance, likely via FPRL-1 receptor modulation. In this work, we designed and synthesized new dendrimers multi-branched molecules based on the sequence of AaTs-1 and showed that the di-branched (AaTs-1-2B), tetra-branched (AaTs-1-4B) and octo-branched (AaTs-1-8B) dendrimers displayed 10- to 25-fold higher effects on the proliferation of U87 cells than AaTs-1. We also found that the effects of the newly designed molecules are mediated by the enhancement of the ERK1/2 and AKT phosphorylated forms and by the increase in p53 expression. Unlike AaTs-1, AaTs-1-8B and especially AaTs-1-4B affected the migration of the U87 cells. Thus, the multi-branched peptide synthesis strategy allowed us to make molecules more active than the linear peptide against the proliferation of U87 glioblastoma cells.

The design of highly emissive and stable blue emitters for organic light emitting diodes (OLEDs) is still a challenge, justifying the intense research activity of the scientific community in this field. Recently, a great deal of interest has been devoted to the elaboration of emitters exhibiting a thermally activated delayed fluorescence (TADF). By a specific molecular design consisting into a minimal overlap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) due to a spatial separation of the electron-donating and the electron-releasing parts, luminescent materials exhibiting small S1–T1 energy splitting could be obtained, enabling to thermally upconvert the electrons from the triplet to the singlet excited states by reverse intersystem crossing (RISC). By harvesting both singlet and triplet excitons for light emission, OLEDs competing and sometimes overcoming the performance of phosphorescence-based OLEDs could be fabricated, justifying the interest for this new family of materials massively popularized by Chihaya Adachi since 2012. In this review, we proposed to focus on the recent advances in the molecular design of blue TADF emitters for OLEDs during the last few years.

On-surface synthesis, in which molecular units assemble and couple on a defined surface, can access rare reaction pathways and products. Here, the authors synthesize functionalized organic nanoribbons on the Ag(110) surface, and monitor the evolution of the covalent reactions by an unorthodox vibrational spectroscopy approach.

In this paper, nine organic compounds based on the coumarin scaffold and different substituents were synthesized and used as high-performance photoinitiators for free radical photopolymerization (FRP) of meth(acrylate) functions under visible light irradiation using LED at 405 nm. In fact, these compounds showed a very high initiation capacity and very good polymerization profiles (both high rate of polymerization (Rp) and final conversion (FC)) using two and three-component photoinitiating systems based on coum/iodonium salt (0.1%/1% w/w) and coum/iodonium salt/amine (0.1%/1%/1% w/w/w), respectively. To demonstrate the efficiency of the initiation of photopolymerization, several techniques were used to study the photophysical and photochemical properties of coumarins, such as: UV-visible absorption spectroscopy, steady-state photolysis, real-time FTIR, and cyclic voltammetry. On the other hand, these compounds were also tested in direct laser write experiments (3D printing). The synthesis of photocomposites based on glass fiber or carbon fiber using an LED conveyor at 385 nm (0.7 W/cm2) was also examined.

In order to improve the electrochemical properties of poly(ethylene oxide), a well-known-solid polymer electrolyte, by adding zwitterion molecules, the synthesis of a new zwitterion (ZN) having imidazolium cation and sulfonyl(trifluoromethane sulfonyl)imide anion is investigated. The addition of different amounts of ZN to the mixture of lithium bis(trifluoromethane sulfonyl)imide (LiTFSI) and poly(ethylene glycol)dimethyl ether (PEGDM) of 1000 g mol−1 does not significantly affect the transition temperature of PEGDM but causes a slight decrease in ionic conductivity of the electrolyte mixtures. However, even with the presence of only 0.05 mole fraction of ZN, the anodic stability of LiTFSI/PEGDM based electrolytes is improved to over 4.5 V vs. Li+/Li at 25 °C. This makes the new synthesized zwitterion a promising electrolyte’s additive for high voltage batteries.

Polymerization photoinitiators that can be activated under low light intensity and in the visible range are being pursued by both the academic and industrial communities. To efficiently harvest light and initiate a polymerization process, dyes with high molar extinction coefficients in the visible range are ideal candidates. In this field, Donor-acceptor Stenhouse Adducts (DASA) which belong to a class of recently discovered organic photochromic molecules still lack practical applications. In this work, a series of DASA-based dyes are proposed as photoinitiators for the free radical polymerization of (meth)acrylates upon exposure to a near infrared light (laser diode at 785 nm).

In the soft treatment of cancer tumours, consequent downregulation of the malignant tissue angiogenesis constitutes an efficient way to stifle tumour development and metastasis spreading. As angiogenesis requires integrin−promoting endothelial cell adhesion, migration, and vessel tube formation, integrins represent potential targets of new therapeutic anti−angiogenic agents. Our work is a contribution to the research of such therapeutic disintegrins in animal venoms. We report isolation of one peptide, named Dabmaurin−1, from the hemotoxic venom of snake Daboia mauritanica, and we evaluate its potential anti−tumour activity through in vitro inhibition of the human vascular endothelial cell HMECs functions involved in tumour angiogenesis. Dabmaurin−1 altered, in a dose−dependent manner, without any significant cytotoxicity, HMEC proliferation, adhesion, and their mesenchymal migration onto various extracellular matrix proteins, as well as formation of capillary−tube mimics on MatrigelTM. Via experiments involving HMEC or specific cancers cells integrins, we demonstrated that the above Dabmaurin−1 effects are possibly due to some anti−integrin properties. Dabmaurin−1 was demonstrated to recognize a broad panel of prooncogenic integrins (αvβ6, αvβ3 or αvβ5) and/or particularly involved in control of angiogenesis (α5β1, α6β4, αvβ3 or αvβ5). Furthermore, mass spectrometry and partial N−terminal sequencing of this peptide revealed, it is close to Lebein−1, a known anti−β1 disintegrin from Macrovipera lebetina venom. Therefore, our results show that if Dabmaurin−1 exhibits in vitro apparent anti−angiogenic effects at concentrations lower than 30 nM, it is likely because it acts as an anti−tumour disintegrin.

Iodonium salts are well established photoacid generators, cationic photoinitiators, as well as additives commonly used in photoredox catalytic cycles. However, as a strong limitation, iodonium salts are characterized by low light absorption properties for λ > 300 nm so that these latter cannot be activated with cheap, safe, and eco-friendly near UV or even visible light emitting diodes (LEDs). To overcome this drawback, the covalent linkage of an iodonium salt to a chromophore absorbing at longer wavelength is actively researched. With aim at red-shifting the absorption spectrum of the iodonium salt, the synthesis of new compounds combining within a unique chemical structure both the chromophore (here the naphthalimide scaffold) and the iodonium salt is presented. By mean of this strategy, a polymerization could be initiated at 365 nm with the modified iodonium salts whereas no polymerization could be induced with the benchmark iodonium salt i.e., Speedcure 938 at this specific wavelength. To examine the effect of the counter-anion on the photoinitiating ability of these different salts, five different counter-anions were used. Comparison between the different anions revealed the bis(trifluoromethane)sulfonimide salt to exhibit the best photoinitiating ability in both the free radical polymerization of acrylates and the cationic polymerization of epoxides. To support the experimental results, molecular orbital calculations have been carried out. By theoretical calculations, the initiating species resulting from the photocleavage of the iodonium salts could be determined. The cleavage selectivity and the photochemical reactivity of the new iodoniums are also discussed.

Milk and dairy products harbor a wide variety of bacterial species that compete for both limited resources and space. Under these competitive conditions, bacteria develop specialized mechanisms to protect themselves during niche colonization and nutrient acquisition processes. The bacterial antagonism mechanisms include the production of antimicrobial agents or molecules that facilitate competitor dispersal. In the present work, a bacterial strain designated RC6 was isolated from Ricotta and identified as Bacillus cereus. It generates antimicrobial peptide (AMP) when grown in the presence of casein. The AMP was active against several species of Bacillus and Listeria monocytogenes. MALDI-TOF analysis of the RP-HPLC purified fractions and amino acid sequencing revealed a molecular mass of 751 Da comprised of a 6-residue sequence, YPVEPF. BLAST analysis showed that the AMP corresponds to the fractions 114–119 of bovine β-casein and represents the product of a specific proteolysis. Analysis of the purified proteolytic fractions from the B. cereus RC6 culture supernatant indicated that the presence of at least two different endoproteases is crucial for the generation of the AMP. Indeed, we were able to identify two new candidate endoproteases by means of genome sequencing and functional assignment using a 3D structural model and molecular docking of misannotated hypothetical proteins. In this light, the capacity of B. cereus RC6 to generate antimicrobial peptides from casein, through the production of extracellular enzymes, presents a new model of antagonistic competition leading to niche colonization. Hence, as a dairy product contaminant, this strategy may enable proteolytic B. cereus RC6 niche specialization in milk matrices.

In the present paper, the photoredox catalysis is presented as a unique approach in the field of photoinitiators of polymerization. The principal photocatalysts already reported as well as the typical oxidation and reduction agents used in both reductive or oxidative cycles are gathered. The chemical mechanisms associated with various systems are also given. As compared to classical iridium-based photocatalysts which are mainly active upon blue light irradiation, a new photocatalyst Ir(piq)2(tmd) (also known as bis(1-phenylisoquinolinato-N,C2’)iridium(2,2,6,6-tetramethyl-3,5-heptanedionate) is also proposed as an example of green light photocatalyst (toward the long wavelength irradiation). The chemical mechanisms associated with Ir(piq)2(tmd) are investigated by ESR spin-trapping, laser flash photolysis, steady state photolysis, cyclic voltammetry and luminescence experiments.

The range of applications of cellulose, a glucose-based polysaccharide, is limited by its inherently poor mechanical properties. The grafting of synthetic polymer chains by, for example, a “grafting from” process may provide the means to broaden the range of applications. The nitroxide-mediated polymerization (NMP) method is a technique of choice to control the length, the composition and the architecture of the grafted copolymers. Nevertheless, cellulose is difficult to solubilize in organic media because of inter- and intramolecular hydrogen bonds. One possibility to circumvent this limitation is to solubilize cellulose in N,N-dimethylformamide (DMF) or N,N-dimethylacetamide (DMA) with 5 to 10 wt % of lithium salts (LiCl or LiBr), and carry out grafted polymerization in this medium. The stability of nitroxides such as SG1 has not been studied under these conditions yet, even though these parameters are of crucial importance to perform the graft modification of polysaccharide by NMP. The aim of this work is to offer a model study of the stability of the SG1 nitroxide in organic media in the presence of unprotected glucose or cellobiose (used as a model of cellulose) and in the presence of lithium salts (LiBr or LiCl) in DMF or DMA.Contrary to TEMPO, SG1 proved to be stable in the presence of unprotected sugar, even with an excess of 100 molar equivalents of glucose. On the other hand, lithium salts in DMF or DMA clearly degrade SG1 nitroxide as proven by electron-spin resonance measurements. The instability of SG1 in these lithium-containing solvents may be explained by the acidification of the medium by the hydrolysis of DMA in the presence of LiCl. This, in turn, enables the disproportionation of the SG1 nitroxide into an unstable hydroxylamine and an oxoammonium ion.Once the conditions to perform an SG1-based nitroxide-mediated graft polymerization from cellobiose have been established, the next stage of this work will be the modification of cellulose and cellulose derivatives by NMP.

Eleven di- and trifunctional compounds based on a core-pyrene π structure (Co_Py) were synthesized and investigated for the formation of free radicals. The application of two- and three-component photoinitiating systems (different Co_Pys with the addition of iodonium or sulfonium salts, alkyl halide or amine) was investigated in detail for cationic and radical photopolymerization reactions under near-UV–vis light. The proposed compounds can behave as new photocatalysts. Successful results in terms of rates of polymerization and final conversions were obtained. The strong MO coupling between the six different cores and the pyrene moiety was studied by DFT calculations. The different chemical intermediates are characterized by ESR and laser flash photolysis experiments. The mechanisms involved in the initiation step are discussed, and relationships between the core structure, the Co_Py absorption property, and the polymerization ability are tentatively proposed.

Organic light-emitting diodes offer attractive perspectives for the next generation display and lighting technologies. The potential is huge and the list of potential applications is almost endless. So far, blue emitters still suffer from noticeably inferior electroluminescence performances in terms of efficiency, lifespan, color quality, and charge injection/transport when compared to that of the other colors. Emitting materials matching the NTSC standard blue of coordinates (0.14, 0.08) are extremely rare and still constitutes the focus of numerous academic and industrial researches. In this context, we review herein the recent developments on highly emissive deep-blue thermally activated delayed fluorescence emitters that constitute the third-generation electroluminescent materials.

In this study, a phthalimide-based fluorescent material has been examined as a green emitter for multilayered organic light-emitting diodes (OLEDs). By optimizing the device stacking, a maximum brightness of 28,450 cd/m2 at 11.0 V and a maximum external quantum efficiency of 3.11% could be obtained. Interestingly, OLEDs fabricated with Fluo-2 presented a 20-fold current efficiency improvement compared to the previous results reported in the literature, evidencing the crucial role of the device stacking in the electroluminescence (EL) performance of a selected emitter. Device lifetime was also examined and an operational stability comparable to that reported for a standard triplet emitter i.e., bis(4-methyl-2,5-diphenyl-pyridine)iridium(III) acetylacetonate [(mdppy)2Iracac] was evidenced.

Radical chemistry is a very convenient way to produce polymer materials. Here, an application of a particular photoinduced radical chemistry is illustrated. Seven new carbazole derivatives Cd1–Cd7 are incorporated and proposed as high performance near-UV photoinitiators for both the free radical polymerization (FRP) of (meth)acrylates and the cationic polymerization (CP) of epoxides utilizing Light Emitting Diodes LEDs @405 nm. Excellent polymerization-initiating abilities are found and high final reactive function conversions are obtained. Interestingly, these new derivatives display much better near-UV polymerization-initiating abilities compared to a reference UV absorbing carbazole (CARET 9H-carbazole-9-ethanol) demonstrating that the new substituents have good ability to red shift the absorption of the proposed photoinitiators. All the more strikingly, in combination with iodonium salt, Cd1–Cd7 are likewise preferred as cationic photoinitiators over the notable photoinitiator bis(2,4,6-trimethylbenzoyl)phenylphosphine oxide (BAPO) for mild irradiation conditions featuring their remarkable reactivity. In particular their utilization in the preparation of new cationic resins for LED projector 3D printing is envisioned. A full picture of the included photochemical mechanisms is given.

Adult olfactory ectomesenchymal stem cells (OE-MSCs) and olfactory ensheathing cells (OECs), both from the nasal olfactory lamina propria, display robust regenerative properties when transplanted into the nervous system, but the mechanisms supporting such therapeutic effects remain unknown. Matrix metalloproteinases (MMPs) are an important family of proteinases contributing to cell motility and axonal outgrowth across the extracellular matrix (ECM) in physiological and pathological conditions. In this study, we have characterized for the first time in nasal human OE-MSCs the expression profile of some MMPs currently associated with cell migration and invasiveness. We demonstrate different patterns of expression for MMP-1, MMP-2, MMP-9, and MT1-MMP upon cell migration when compared with nonmigrating cells. Our results establish a correspondence between the localization of these proteinases in the migration front with the ability of cells to migrate. Using various modulators of MMP activity, we also show that at least MMP-2, MMP-9, and MT1-MMP contribute to OE-MSC migration in an in vitro 3D test. Furthermore, we demonstrate under the same conditions of culture used for in vivo transplantation that OE-MSCs and OECs secrete neurotrophic factors that promote neurite outgrowth of cortical and dorsal root ganglia (DRG) neurons, as well as axo-dendritic differentiation of cortical neurons. These effects were abolished by the depletion of MMP-2 and MMP-9 from the culture conditioned media. Altogether, our results provide the first evidence that MMPs may contribute to the therapeutic features of OE-MSCs and OECs through the control of their motility and/or their neurotrophic properties. Our data provide new insight into the mechanisms of neuroregeneration and will contribute to optimization of cell therapy strategies.

There have been considerable interests in attempting to reverse the deficit because of an SCI (spinal cord injury) by restoring neural pathways through the lesion and by rebuilding the tissue network. In order to provide an appropriate micro-environment for regrowing axotomized neurons and proliferating and migrating cells, we have implanted a small block of pHPMA [poly N-(2-hydroxypropyl)-methacrylamide] hydrogel into the hemisected T10 rat spinal cord. Locomotor activity was evaluated once a week during 14 weeks with the BBB rating scale in an open field. At the 14th week after SCI, the reflexivity of the sub-lesional region was measured. We also monitored the ventilatory frequency during an electrically induced muscle fatigue known to elicit the muscle metaboreflex and increase the respiratory rate. Spinal cords were then collected, fixed and stained with anti-ED-1 and anti-NF-H antibodies and FluoroMyelin. We show in this study that hydrogel-implanted animals exhibit: (i) an improved locomotor BBB score, (ii) an improved breathing adjustment to electrically evoked isometric contractions and (iii) an H-reflex recovery close to control animals. Qualitative histological results put in evidence higher accumulation of ED-1 positive cells (macrophages/monocytes) at the lesion border, a large number of NF-H positive axons penetrating the applied matrix, and myelin preservation both rostrally and caudally to the lesion. Our data confirm that pHPMA hydrogel is a potent biomaterial that can be used for improving neuromuscular adaptive mechanisms and H-reflex responses after SCI.

Photoredox catalysis is now well-known in organic synthesis for the formation of free radicals under very soft irradiations conditions (e.g. sunlight, household fluorescence or LED bulbs, Xe lamp). This method has been introduced here to the polymer chemistry area to initiate ring opening polymerizations (ROP) or free radical polymerizations (FRP). The present paper will give an up-to date situation of the photocatalyst achievements in FRP and ROP.