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Herein, we present a comprehensive total synthesis of cannabidiol integrating both batch and continuous flow conditions. Our approach is planned to streamline the synthesis of olivetolic acid derivatives and utilize an enantiomerically pure monoterpene moiety obtained from naturally occurring (R)-(+)-limonene by photocatalysis. Key reactions, including the synthesis of olivetolic ester and a Friedel-Crafts alkylation, are successfully adapted to continuous flow, resulting in improved yields and selectivities. This study not only offers a scalable and efficient route for cannabidiol synthesis but also contributes to the synthetic approaches to access cannabinoids (diversity synthesis), with potential applications in medicinal and industrial contexts., (© 2024 Wiley-VCH GmbH.)

The integration of multicomponent reactions (MCRs), which offer a rapid and efficient approach to synthesize complex molecular scaffolds, with continuous flow platforms is an increasingly recognized strategy in green synthesis. This association enables precise control over reaction parameters, including improved kinetics and selectivity, reduced reaction times, enhanced yields and scalabilities, while aligning with sustainable and green chemistry principles through resource utilization, minimized waste, and reduced environmental impact. This review presents a critical analysis of recent studies covering the MCR-continuous flow association, with a focus on achieving greener and more sustainable synthesis practices., (© 2024 Wiley-VCH GmbH.)

Background: The combination of photodynamic therapy (PDT) and LL-37 has never been tested in an animal study and our research team background suggests this strategy might be a promising alternative to intensify periodontitis resolution. This study aimed to assess the effects of multiple sessions of PDT with chlorin-e6 conjugated to the antimicrobial peptide LL-37 loaded nanoemulsion, as adjunctive therapy in experimental periodontitis in rats., Methods: Experimental periodontitis was induced in 81 rats. After disease establishment, animals were assigned to three groups: SRP (scaling and root planning); SRP + 1PDT, SRP followed by a single PDT session; SRP + 4PDT (n = 27), SRP followed by four PDT sessions at 0, 24, 48 and 72 h after SRP. Animals were subjected to euthanasia at 7, 14 and 28 days, and samples were submitted to osteoclast quantification, immunological and microtomography analysis., Results: All treatments resulted in significant periodontal improvements and there was no significant difference between the groups in both local inflammatory response and healing process. Minimal adjunctive effects could be found for the combined therapy in terms of cytokine levels (IL-1β and IL-10), with no statistical significance. However, the number of TRAP-positive osteoclasts per mm of alveolar bone linear surface for the group treated with PDT sessions was significantly lower than those treated with SRP only., Conclusions: Multiple PDT sessions with chlorin-e6 and LL-37 nanoemulsion as an adjunct to scaling and root planning reduced the presence of osteoclast in the local site but did not contribute towards bone regeneration and IL-1β and IL-10 levels., Competing Interests: Declaration of competing interest This manuscript has been read and approved in final form by all authors and the authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Curcumin serves as a photosensitizer (PS) in the context of microbial inactivation when subjected to light exposure, to produce reactive oxygen species, which exhibit efficacy in eradicating microorganisms. This remarkable property underscores the growing potential of antimicrobial photodynamic therapy (aPDT) in the ongoing fight against bacterial infections. Considering this, we investigate the efficacy of various in vitro curcumin formulations within a PDT protocol designed to target Staphylococcus aureus. Specifically, we conduct a comparative analysis involving synthetic curcumin (Cur-Syn) and curcumin derivatives modified with chlorine (Cl), selenium (Se), and iodine (I) (Cur-Cl, Cur-Se, Cur-I). To assess the impact of aPDT, we subject S. aureus to incubation with curcumin, followed by irradiation at 450 nm with energy doses of 3.75, 7.5, and 15 J/cm 2 . Our investigation encompasses an evaluation of PS uptake and photobleaching across the various curcumin variants. Notably, all three modifications (Cur-Cl, Cur-Se, Cur-I) induce a significant reduction in bacterial viability, approximately achieving a 3-log reduction. Interestingly, the uptake kinetics of Cur-Syn and Cur-Se exhibit similarities, reaching saturation after 20 min. Our findings suggest that modifications to curcumin have a discernible impact on the photodynamic properties of the PS molecule., (© 2024 American Society for Photobiology.)

Palladium(II) complexes have stimulated research interest mainly due to their in vitro cytotoxicity against various cancer cell lines and their low cytotoxicity in healthy cells. Thus, in this work, we combined Pd(II)/phosphine systems with the natural product curcumin as a ligand, obtaining a series of complexes, [Pd(cur)(PPh 3 ) 2 ]PF 6 (A1), [Pd(cur)(dppe)]PF 6 (A2), [Pd(cur)(dppp)]PF 6 (A3), [Pd(cur)(dppb)]PF 6 (A4) and [Pd(cur)(dppf)]PF 6 (A5), where dppe = 1,2-bis(diphenylphosphino)ethane, dppp = 1,3-bis(diphenylphosphino)propane, dppb = 1,4-bis(diphenylphosphino)butane, and dppf = 1,1'-bis(diphenylphosphino)ferrocene (P-P), which were characterized by elemental analysis, molar conductivity analysis, and mass, NMR ( 1 H, 13 C, 31 P{ 1 H}), UV-vis, and IR spectroscopies, and four of them (A1, A2, A4, and A5) by X-ray crystallography. The in vitro cell viability of the complexes A1-A5, cisplatin, and the free ligand curcumin against MDA-MB-231 (human triple-negative breast tumor cells), SK-BR-3 (human breast tumor cells), A549 (human lung tumor cells), MRC-5 (non-tumor human lung cells), A2780 (human ovarian carcinoma cells), and A2780cis (cisplatin-resistant human ovarian carcinoma cells), was evaluated by the MTT colorimetric assay. For the tumor cell lines tested, the complexes showed good anticancer activities. The results showed that in general the complexes had lower IC 50 values than free curcumin and the precursors [PdCl 2 (P-P)]. IC 50 results obtained for the A1-A5 complexes, in the MCF-7 cell line, are similar to those that had already been observed for some Pd/bipy/curcumin complexes. In the MDA-MB-231 cell line, complexes A1 and A5 stood out, with their lowest IC 50 values, around 5 μmol L -1 , and the complexes appeared to be more active (lower IC 50 values) against the ovarian cell lines. Complex A1 was 23 and 22-fold more cytotoxic than cisplatin, against the A2780 and A2780cis cells, respectively. The complex A1 was studied on A2780cis cells and it was found that this complex inhibits colony formation and induces cell cycle arrest in the sub-G1 phase in a concentration-dependent manner and leads to cell death by apoptosis. The DCFDA assay revealed a potent ROS induction for complex A1.

Herein, we present an overview of continuous flow chemistry, including photoflow and electroflow technologies in the preparation of active pharmaceutical ingredients (APIs) and fine chemical intermediates. Examples highlighting the benefits and challenges associated with continuous flow processes, mainly involving continuous thermal, photo- and electrochemical transformations, are drawn from the relevant literature, especially our experience and collaborations in this area, with emphasis on the synthesis and prospective scale-up.

In our previous studies, Chlorin-e6 (Ce6) demonstrated a significant reduction of microorganisms' viability against multi-species biofilm related to periodontitis while irradiated with blue light. However, the conjugation of Ce6 and antimicrobial peptides, and the incorporation of this photosensitizer in a nanocarrier, is still poorly explored. We hypothesized that chlorin-e6 conjugated to the antimicrobial peptide LL-37 loaded nanoemulsion could inhibit a multi-species biofilm related to periodontitis during photodynamic therapy (PDT), the pre-treatment with hydrogen peroxide was also tested. The nanoemulsion (NE) incorporated with Ce6 was characterized regarding the physiochemical parameters. Images were obtained by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Later, the Ce6 and LL-37 incorporated in NE was submitted to UV-Vis analysis and Reactive Oxygen Species (ROS) assay. Finally, the combined formulation (Ce6+LL-37 in nanoemulsion) was tested against multi-species biofilm related to periodontitis. The formed nanoformulation was kinetically stable, optically transparent with a relatively small droplet diameter (134.2 unloaded and 146.9 loaded), and weak light scattering. The NE system did not impact the standard UV-VIS spectra of Ce6, and the ROS production was improved while Ce6 was incorporated in the NE. The combination of Ce6 and LL-37 in NE was effective to reduce the viability of all bacteria tested. The treatment with hydrogen peroxide previous to PDT significantly impacted bacterial viability. The current aPDT regimen was the best already tested against periodontal biofilm by our research team. Our results suggest that this combined protocol must be exploited for clinical applications in localized infections such as periodontal disease. - Nanoemulsion demonstrated to be an excellent nanocarrier for photodynamic application. - Chlorin-e6 incorporated in nanoemulsion showed great physicochemical and biophotonic parameters. - The combination of chlorin-e6 and LL-37 peptide in nanoemulsion is effective to eliminate periodontal pathogenic bacteria. - The treatment with hydrogen peroxide previous to PDT significantly impacted bacterial viability., Competing Interests: Declaration of Competing Interest This manuscript has been read and approved in final form by all authors and the authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

A transition-metal free methodology for the chemoselective reduction of benzylidene thiazolidine-2,4-diones and similar heterocycles is described, allowing the preparation of a broad scope of the corresponding reduced derivatives in up to 90% yield. The protocol has a simple and safe experimental setup, in which water was employed as the hydrogen source. To further demonstrate the synthetic utility of this transformation, the antidiabetic API Pioglitazone was prepared in 81% yield. To the best of our knowledge, this is the first hydride and transition-metal free protocol for the synthesis of Pioglitazone, highlighting its potential utility as a greener alternative in both academic and industrial synthesis.

Biallelic loss of function of IMPA1 causes autosomal recessive intellectual developmental disorder 59 (MRT59, OMIM #617323). MRT59 has been reported to present with significant intellectual disability and disruptive behavior, but little is known about the neurocognitive pattern of those patients. Thus, the aims of this study were: (1) to assess the cognitive profile of these patients, and (2) to evaluate their functional dependence levels. Eighteen adults, aged 37 to 89 years, participated in this study: nine MRT59 patients, five heterozygous carriers and four non-carrier family members. All of them were from a consanguineous family living in Northeast Brazil. All IMPA1 patients had the (c.489_493dupGGGCT) pathogenic variant in homozygosis. For cognitive assessment, the WASI battery was applied in nine MRT59 patients and compared to heterozygous carriers and non-carrier family members. Functional dependence was evaluated using the functional independence measure (FIM). Patients showed moderate to severe intellectual disability and severe functional disabilities. Heterozygous carriers did not differ from non-carriers. MRT59 patients should be followed up by health professionals in an interdisciplinary way to understand their cognitive disabilities and functional needs properly.

We report the DNA-binding properties of three porphyrins with peripheral thienyl substituents ( TThPor , PdTThPor and PtTThPor ). The binding capacity of each porphyrin with DNA was determined by UV-Vis and steady-state fluorescence emission spectroscopy combined with molecular docking calculations. The results suggest that the interaction of these compounds probably occurs via secondary interactions via external grooves (minor grooves) around the DNA macromolecule. Moreover, porphyrins containing peripheral Pd(II) or Pt(II) complexes ( PdTThPor and PtTThPor ) were able to promote photo-damage in the DNA.

An original total synthesis of the antiepileptic drug brivaracetam (BRV) is reported. The key step in the synthesis consists of an enantioselective photochemical Giese addition, promoted by visible-light and the chiral bifunctional photocatalyst Δ- RhS . Continuous flow conditions were employed to improve the efficiency and allow an easy scale-up of the enantioselective photochemical reaction step. The intermediate obtained from the photochemical step was converted into BRV by two different pathways, followed by one alkylation and amidation, thus giving the desired active pharmaceutical ingredients (API) in 44% overall yield, 9:1 diastereoisomeric ratio (dr) and >99:1 enantiomeric ratio (er)., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Context: Curcumin is a popular food additive around the world whose medicinal properties have been known since ancient times. The literature has recently highlighted several biological properties, but besides the health-related usages, its natural yellowish color may also be helpful for light-harvesting applications. This research aims to close a knowledge gap regarding the photophysical description of curcumin and its metallic complexes., Methods: We conducted benchmark experiments comparing NEVPT calculations with several DFT functionals (B3LYP, M06-L, M06-2X, CAM-B3LYP, and ωB97X-D) for describing the UV spectra of curcumin and its metallo-derivative, curcumin-copper(II). Once we determined the most suitable functional, we performed tests with different basis sets and conditions, such as solvation and redox state, to identify their impact on excited state properties. These results are also reported for the curcumin-zinc(II) derivative. We found that the accuracy of DFT functionals depends strongly on the nature of curcumin's excitations. Intra-ligand transitions dominate the absorption spectra of the complexes. Curcumin absorption is marginally affected by solvation and chelation, but when combined with redox processes, they may result in significant modifications. This is because copper cation changes its coordination geometry in response to redox conditions, changing the spectrum. We found that, compared to a NEVPT reference, B3LYP is the best functional for a general description of the compounds, despite not being appropriate for charge transfer transitions. M06-L was the best for LMCT transitions. However, compared with NEVPT2 and PNO-LCCSD(T)-F12 results, no functional achieved acceptable accuracy for MLCT transitions., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In our previous study, Chlorin-e6 (Ce6) demonstrated a significant reduction of microorganisms' viability against single-species biofilm related to periodontitis once irradiated by red light (660 nm). Also, higher bacteria elimination was observed under blue light (450 nm) irradiation. However, the use of blue light irradiation of Ce6 for antimicrobial administration is poorly explored. This study evaluated the effect of chlorin-e6-mediated antimicrobial photodynamic therapy (aPDT) using different wavelengths (450 or 660 nm) against multi-species biofilms related to periodontitis. Streptococcus oralis, Fusobacterium nucleatum, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans composed the mature biofilm developed under proper conditions for five days. aPDT was performed using different concentrations of Ce6 (100 and 200 μM), wavelengths (450 or 660 nm), and comparisons were made after qPCR assay and confocal laser scanning microscopy (CLSM) analysis. The greatest bacterial elimination was observed in the groups where Ce6 was used with blue light, for S. orallis (2.05 Log 10 GeQ mL-1, p < 0.0001) and P. gingivalis (1.4 Log 10 GeQ mL-1, p < 0.0001), aPDT with red light showed significant bacteria reduction only for S. orallis. aPDT with blue light demonstrated statistically higher elimination in comparison with aPDT with red light. The aPDT did not show a statistically significant effect when tested against A. actinomycetemcomitans and F. nucleatum (p=0.776 and 0.988, respectively). The aPDT using blue light showed a promising higher photobiological effect, encouraging researchers to consider it in the irradiation of Ce6 for further investigations., Competing Interests: Declaration of Competing Interest None of the authors has any conflict of interest to be disclosed. This manuscript has been read and approved in final form by all authors and the authors declare no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

Over the last two decades, with the advent of continuous flow technologies, continuous processes have emerged as a major area in organic synthesis. In this context, continuous flow processes have been increasing in the preparation of Active Pharmaceutical Ingredients (APIs) and fine chemicals, such as complex synthetic intermediates, agrochemicals, and fragrances. Thus, the development of multi-step protocols has attracted special interest from the academic and industrial chemistry communities. In addition to the beneficial aspects intrinsically associated with continuous processes (e.g., waste reduction, optimal heat transfer, improved safety, and the possibility to work under harsh reaction conditions and with more dangerous reagents), these protocols also allow a rapid increase in molecular complexity. Moreover, in telescoped multi-step processes, isolation and purification steps are generally avoided or, if necessary, carried out in-line, presenting an important economy of time, solvents, reagents, and labor. Last, important synthetic strategies such as photochemical and electrochemical reactions are compatible with flow processes and are delivering relevant advances to the synthetic approaches. In this review, a general overview of the fundamentals of continuous flow processes is presented. Recent examples of multi-step continuous processes for the preparation of fine chemicals, including telescoped and end-to-end processes, are discussed, pointing out the possible advantages and/or limitations of each of these methodologies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Multicomponent reactions (MCRs) are processes in which three or more starting materials are combined in the same reaction vessel, forming an adduct that contains all or most of the atoms of the starting materials. MCRs are one-pot processes that provide attractive advantages for the total synthesis of target molecules. These reactions allow rapid access to structurally complex adducts from particularly simple starting materials. Moreover, MCRs are generally intrinsically associated with principles of green syntheses, such as atom economy, minimization of isolation, and purification of synthetic intermediates, leading to large solvent economies and avoiding the production of large amounts of reaction waste. Thus, synthetic routes employing multicomponent reactions are generally more convergent, economical and often allow higher overall yields. In total synthesis, the use of MCRs has been mainly applied in the preparation of key advanced intermediates. Progress in the use of MCRs in total synthesis has been described over the last decades, including not only classical MCRs reactions (e.g. isocyanide-based transformations), but also non-traditional multicomponent reactions. Furthermore, reports concerning stereoselective multicomponent transformations are still scarce and present further development opportunities. This review aims to provide a general overview of the application of MCRs as key steps in the rapid preparation of structurally complex derivatives and fine chemicals. In special, some selected examples have been successfully applied for medicinal purposes. Finally, in some representative cases, either key intermediates formed during the reaction vessel or corresponding transition states have been disclosed in order to provide insights into the reaction mechanisms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In this study, the action of antimicrobial peptide (AMP) P5 and antimicrobial photodynamic therapy (aPDT) mediated by bixin and chlorin-e6 (Ce6) on Cutibacterium acnes (C. acnes) in planktonic phase and biofilm were evaluated both as monotherapies and combined therapies. Microbial viability after treatments were quantified by colony-forming units per milliliter of the sample (CFU/mL) and have demonstrated that all treatments employed exerted bactericidal activity, reducing the microbial load by more than 3 log 10 CFU/mL, also demonstrating for the first time in the literature the antimicrobial photodynamic effect of bixin that occurs mostly through type I mechanism which was proved by the quantification of superoxide anion production. Bacterial biofilm was completely eliminated only after its exposure to aPDT mediated by this PS, however, Ce6 proved to be a more efficient PS, considering that most of the photodynamic effect of bixin- aPDT was exerted by excitation of the endogenous C porphyrins of C. acnes with blue light. The combination of P5 with Ce6-aPDT showed a synergistic effect on the bacterial biofilm with a reduction in microbial load by more than 10 log 10 CFU/mL, in which the ability of P5 to permeabilize the polymeric extracellular matrix of the biofilm explains the obtained results, with greater internalization of the PS as shown by the Confocal Laser Scanning Microscopy. One-way ANOVA (Analysis of Variance) with Tukey's post-test and two-way ANOVA with Bonferroni's post-test were used to compare the values of continuous variables between the control group and the treatment groups., Competing Interests: Disclosure of author of conflicts of interest The authors declare that there are no conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

An advantageous and original synthesis of fentanyl is described. This new approach includes two efficient continuous flow reductive aminations achieved via photoredox catalysis and a final batch acylation. A telescoped protocol for the two photocatalyzed steps is also presented, and overall, this protocol provides improved sustainability, significant efficiency, reduced temperatures and reaction times, and is functional for scaling up this relevant active pharmaceutical ingredient (API).

A concise synthesis of molnupiravir in a one-pot two-step approach starting from uridine is described. Formally, herein, two sets of one-pot two-reaction steps introducing simplicity for purifications and using chemically available reagents are presented. In this context, molnupiravir was obtained in up to 68% overall yield and multigram-scale. In addition, HPLC analysis showed the molnupiravir purity above 99%., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The efficient C-4 selective modification of pyridines is a major challenge for the synthetic community. Current strategies are plagued with at least one drawback regarding functional group-tolerant electronic activation of the heteroarene, mild generation of the required alkyl radicals, regioselectivity, safety and/or scalability. Herein, we describe a fast, safe and scalable flow process which allows preparation of said C-4 alkylated pyridines. The process involves a photochemical hydrogen atom transfer (HAT) event to generate the carbon-centered radicals needed to alkylate the C-2 blocked pyridine. In a two-step streamlined flow process, this light-mediated alkylation step is combined with a nearly instantaneous inline removal of the blocking group. Notably, cheap benzophenone plays a dual role in the pyridine alkylation mechanism by activating the hydrocarbon feedstock reagents via a HAT mechanism, and by acting as a benign, terminal oxidant. The key role of benzophenone in the operative reaction mechanism has also been revealed through a combination of experimental and computational studies., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A novel visible-light-promoted coupling of diazoketones with sulfoxonium ylides, employing a violet light-emitting diode, is described under both batch and continuous flow conditions. This transformation permits the direct synthesis of synthetically useful 1,3-dicarbonyl sulfoxonium ylides (33 examples, 21-85% yields), by means of an acylation from the in situ and selective generation of ketenes. The reaction performed under flow conditions proved to be very efficient, providing the 1,3-dicarbonyl sulfoxonium ylides with higher yields and shorter reaction times.

In this study, we describe the semisynthesis of cost-effective photosensitizers (PSs) derived from chlorophyll a containing different substituents and using previously described methods from the literature. We compared their structures when used in photodynamic inactivation (PDI) against Staphylococcus aureus , Escherichia coli , and Candida albicans under different conditions. The PSs containing carboxylic acids and butyl groups were highly effective against S. aureus and C. albicans following our PDI protocol. Overall, our results indicate that these nature-inspired PSs are a promising alternative to selectively inactivate microorganisms using PDI.

This study reports curcumin as an efficient photolarvicide against Aedes aegypti larvae under natural light illumination. Larval mortality and pupal formation were monitored daily for 21 days under simulated field conditions. In a sucrose-containing formulation, a lethal time 50 (LT50) of 3 days was found using curcumin at 4.6 mg L -1 . This formulation promoted no larval toxicity in the absence of illumination, and sucrose alone did not induce larval phototoxicity. The photodegradation byproducts (intermediates) of curcumin were determined and the photodegradation mechanisms proposed. Intermediates with m/z 194, 278, and 370 were found and characterized using LC-MS. The ecotoxicity of the byproducts on non-target organisms ( Daphnia , fish, and green algae) indicates that the intermediates do not exhibit any destructive potential for aquatic organisms. The results of photodegradation and ecotoxicity suggest that curcumin is environmentally safe for non-target organisms and, therefore, can be considered for population control of Ae . aegypti .

Onychomycosis is the most common disease caused by fungal nail infections, and often caused by dermatophytes. This infection is very resistant to antifungal treatments, and promising Photodynamic Therapy (PDT) mediated treatments has been presented as a multitarget tracking. Optimization of PDT guide for uptake time, concentration of photosensitizers (PS) and the light dose to inactivate Trichophyton mentagrophytes. Curcumin derivatives, porphyrin Chlorin e6 (CHL-E6) and Chlorin-P6-6-N-butylamide-7-methyl-ester (CHL-butyl) were evaluated. PS photobleaching was observed on the hyphae photosensitized over the time, correlating the PS concentration and light dose of antifungal PDT. Porphyrin, Curcumin, Chl-e6 and Chl-butyl concentrations of 2.5 µg/mL, 0.025 µg/mL, 10 µg/mL and 5 µg/mL respectively, under illumination of 10.5 J/cm 2 were the best antifungal conditions found in the study. Curcumin, in low concentrations, and chlorin were the PSs with higher activity anti-T. mentagrophytes., (© 2022. The Author(s), under exclusive licence to European Photochemistry Association, European Society for Photobiology.)

Dengue, Zika, chikungunya, and yellow fever are arboviruses transmitted by Aedes aegypti mosquito. In this regard, a number of techniques have emerged aiming to combat its proliferation. Elimination of Aedes aegypti larvae by photodynamic action has been reported as an efficient approach. In this regard, this study was aimed at synthetize and characterize formulations with different proportions (w/w) of the plant-based photolarvicidal curcumin and d-mannitol (CCD 1-4) and their evaluation on sublethal photolarvicidal efficiency, photodegradation profile,solubility, internalization, elimination time, persistence in simulated field, growth of microorganisms in water and the toxicity using an animal models (Zebrafish). CCD 3 (curcumin:d-mannitol 50:50 w/w) showed the best efficacy (LC 50-24h  = 0.01 mg/L), and also presented the shortest internalization and longest elimination time, 60 min and 8 days, respectively. This formulation caused an extrusion into the intestine and peritrophic membrane. Moreover, CCD 3 showed a photodegradation of 50% (in 24 h) under white fluorescent lamps. In a small-scale field trial, CCD 3 had a residual time of 14 days and abnormal microbial growth was not observed. Finally, CCD 3 did not present any toxicity in Zebrafish, after exposition for 24 h at 100 mg/L. Overall, these results raise the possibility of reducing virus transmission through the controlled photoinactivation of Aedes aegypti larvae using a non-toxic plant-based formulated photolarvicide., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We investigated the electrochemical sulfenylation reaction in both batch and continuous flow regimes, involving thiophenols/thiols and enol-acetates to yield α-sulfenylated ketones, without using additional oxidants or catalysts. Studies with different electrolytes were also performed, revealing that quaternary ammonium salts are the best mediators for this reaction. Notably, during the study of the reaction scope, a Boc-cysteine proved to be extremely tolerant to our protocol, thus increasing its relevance. The methodology also proved to be scalable in both batch and continuous flow conditions, opening up possibilities for further studies since these relevant functional groups are important moieties in organic synthesis.

While photochemical transformations with sunlight almost exclusively utilize the UV-vis part of the solar spectrum, the majority of the photons emitted by the sun have frequencies in the near-infrared region. Phthalocyanines show high structural similarity to the naturally occurring light-harvesting porphyrins, chlorins, and mainly bacteriochlorins and are also known for being efficient and affordable near-infrared light absorbers as well as triplet sensitizers for the production of singlet oxygen. Although having been neglected for a long time in synthetic organic chemistry due to their low solubility and high tendency toward aggregation, their unique photophysical properties and chemical robustness make phthalocyanines attractive photocatalysts for the application in near-infrared-light-driven synthesis strategies. Herein, we report a cheap, simple, and efficient photocatalytic protocol, which is easily scalable under continuous-flow conditions. Various phthalocyanines were studied as near-infrared photosensitizers in oxidative cyanations of tertiary amines to generate α-aminonitriles, a synthetically versatile compound class.

We report the synthesis and characterization of two novel tetra-cationic porphyrins, containing Pt(II) or Pd(II) polypyridyl complexes attached at the peripheral position of N 4 -macrocycle. Compounds were characterized through elemental analysis, molar conductivity, cyclic voltammetry, and spectroscopy analysis. Photophysical and photobiological parameters were also evaluated. Also, the binding capacity of each porphyrin with human serum albumin (HSA) was determined by UV-Vis, steady-state, and time-resolved fluorescence spectroscopy, combined with molecular docking calculations. The results suggest that the interaction of these compounds is spontaneous, weak to moderate, and probably occurs at site III (subdomain IB) by non-covalent forces, including van der Waals and H-bonding. Moreover, porphyrins containing peripheral complexes improve their interactions with biomolecules, show good photostability, generate reactive oxygen species under white light studied by electron paramagnetic resonance (EPR) analysis, and promote photo-damage of HSA.

Herein we report a machine-assisted and scaled-up synthesis of propofol, a short-acting drug used in procedural sedation, which is extensively in demand during this COVID-19 pandemic. The continuous-flow protocol proved to be efficient, with great potential for industrial translation, reaching a production up to 71.6 g per day with process intensification (24 h-continuous experiments). We have successfully telescoped a continuous flow approach obtaining 5.74 g of propofol with productivity of 23.0 g/day (6 h-continuous experiment), proving the robustness of the method in both separated and telescoped modes. Substantial progress was also achieved for the in-line workup, which provides greater safety and less waste, also relevant for industrial application. Overall, the synthetic strategy is based on the Friedel-Crafts di-isopropylation of low-cost p -hydroxybenzoic acid, followed by a decarboxylation reaction, giving propofol in up to 84% overall yield and very low by-product formation. The continuous flow synthesis of propofol 3 is presented as a two-step protocol. The isopropylated intermediate 2 was obtained from 4-hydroxybenzoic acid ( 1 ) in up 43.8 g, 85% yield and 30 min residence time. Propofol 3 was then obtained in 71.6 g, 87% yield, and 16 min residence time. A safe and cost-competitive machine-assisted protocol is described with a process intensification demonstration (24 h experiments) and a telescoped process intensification (6 h)., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© Akadémiai Kiadó 2022.)

Antimicrobial photodynamic therapy (aPDT) has been considered as a potential alternative to antibiotics for the treatment of biofilm infections. There is evidence that an additional H 2 O 2 enhances the antimicrobial efficacy of aPDT. However, the minimum H 2 O 2 concentration to achieve this synergistic effect is unclear. A saliva-derived multi-species biofilm was treated with the photosensitizer chlorin e6 (Ce6, 50 µM), H 2 O 2 (0.3, 3.3, 33.3 mM), or their combination for 5 min, followed by no irradiation or irradiation at 15 J (cm 2 ) -1 (λ = 450 nm or 660 nm), with or without oxygen. Biofilm viability and metabolic activity were evaluated. The combination of 33.3 mM H 2 O 2 and Ce6-aPDT strongly enhanced antimicrobial efficacy compared with either component alone, irrespective of oxygen availability and irradiation wavelength. In particular, the combination resulted in a 6.6-log colony forming unit (CFU) reduction anaerobically under blue irradiation. This combination is a promising treatment for biofilm infections, especially those thriving in an anaerobic microenvironment.

Photodynamic therapy presents a therapeutic choice that can be utilized to treat diverse neoplasms. In this technique, the critical element is a photosensitive molecule that absorbs light energy and transfers it to molecular oxygen or biological molecules to form reactive oxygen species, thus inducing irreversible damage to target cells and ultimately leading to cell death. Bacteriochlorin derivatives are employed as photosensitizers (PSs), possessing light-absorbing capacity in the near-infrared region. The objective of this study was to prepare a semi-synthetic bacteriochlorin from Rhodopseudomonas faecalis and adding Trizma® to improve solubility. Cell viability tests, flow cytometry (apoptotic and necrotic cells were identified by Annexin V and propidium iodide), and confocal microscopy were used to evaluate the photoactivity of bacteriochlorin-Trizma (Bchl-T) in fibroblast (HFF-1-control cells) and breast cancer (MCF-7 cells-target cells) cells. At concentrations above 0.5 μM, Bchl-T demonstrated 80 % cell death, presenting the highest PS interaction (via fluorescence microscopy) with lysosomes, mitochondria, and the endoplasmic reticulum; the cell death type was revealed as apoptosis (via cytometry). Our findings indicated the suitability of Bchl-T for future application in photodynamic therapy against cancer cells by inducing apoptosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Resistant populations of Ae. aegypti have been a major problem in arboviruses epidemic areas, generating a strong demand for novel methods of vector control. In this regard, our group has demonstrated the use of curcumin as an efficient photoactive larvicide to eliminate Ae. aegypti larvae. This work was aimed to evaluate the Ae. aegypti (Rockefeller) development under sublethal conditions, using a curcumin/d-mannitol (DMC) formulation. The photolarvicidal efficacy under semi-field and field conditions (wild populations) was also analyzed, as well as the photobleaching and residual activity of DMC., Results: A delay in development time when larvae were exposed to sublethal concentrations of DMC was observed, followed by significant changes in sex ratio and reduction in longevity. DMC also presented a low residual activity when compared to usual larvicides, and had a substantial photolarvicidal activity against wild populations in field trials, achieving 71.3% mortality after 48 h., Conclusions: Overall, these findings are of great biological importance for the process of enabling the implementation of DMC as a new product in the control of Ae. aegypti larvae, and contributes to the improvement of new plant-based larvicides. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Numerous methodologies to obtain pyridines from ylidenemalononitriles are described in the literature. Nevertheless, they are limited to the use of microwave or conventional heat and few lead to 2,3,4 or 2,3,4,5-substituted pyridines as multi-proposal molecular scaffolds or even universal pyridines. Herein, we present a mild and facile solvent-free methodology to obtain a scope of multi-substituted pyridines at room temperature. We also report an example where one of the resulting amino-nicotinonitriles exhibits a preliminary evidence of aggregation-induced emission (AIE).

In the present study, the photophysical properties and preliminary time-dependent density functional theory (TD-DFT) data of new rhenium(i) polypyridyl compounds, fac-[Re(L)(Am2phen)(CO)3]0/+, where Am2phen = 4,7-diamine-1,10-phenanthroline and L = Cl and ethyl isonicotinate (et-isonic), provided new insights into excited-state deactivation through an unusual inversion between two metal-to-ligand charge-transfer excited states. In addition, their cellular uptake using breast cancer (MCF-7) and melanoma (SkMel-147 and SkMel-29) cell lines and bioactivity were investigated and their cell-killing mechanism and protein expression were also studied. Preliminary TD-DFT results showed that both compounds exhibited a strong and broad absorption band around 300-400 nm which corresponds to a combination of ILAm2phen and MLCTRe→Am2phen transitions, and a strong contribution of charge transfer transition MLCTRe→et-isonic for fac-[Re(et-isonic)(Am2phen)(CO)3]+ is also observed. In contrast to typical Re(i) polypyridyl complexes, the substitution of Cl with the et-isonic ligand showed a bathochromic shift of the emission maxima, relatively low emission quantum yield and fast lifetime. Photophysical investigation of the fac-[ReCl(et-isonic)2(CO)3] compound provided meaningful information on the excited state manifold of the fac-[Re(L)(Am2phen)(CO)3]0/+ complexes. As shown in the absorption profile, a remarkable inversion of the lowest-lying excited state takes place from the usually observed MLCTRe→Am2phen to the unusual MLCTRe→et-isonic. The lipophilicity of the positive-complex was higher than that of the non-charge compound and the same trend for the activity against cells was observed, in the absence of light. In addition, flow cytometry and Western Blot analyses showed an overexpression of pro-caspase-9, suggesting a caspase proteolytic cascade through an intrinsic-pathway apoptosis mechanism. The photophysical properties of these compounds reported herein provide new fundamental insights into the understanding of substituent groups on polypyridyl ligands which are relevant to practical development.

A novel electron-donor-acceptor (EDA) complex-enabled flow photochemical hydrotrifluoromethylation of unsaturated β-keto esters is described. The developed protocol has an easy experimental procedure and does not require the use of transition-metal-based photocatalysts, allowing the isolation of 14 new compounds in up to 86% yield. Control experiments and computational studies revealed that the reaction proceeds through a Michael-type 1,4-addition of a trifluoromethyl radical, followed by a proton transfer step. Furthermore, the reaction could be scaled up to 1 mmol, and the final product could be employed in the preparation of an isoxazolone and a pyrazolone as trifluoro-substituted heterocycles.

Recently, we demonstrated that ylidenemalononitriles (YMs) react with amines to form cyclic amidines and that the starting linear YMs are nonemissive in solution and the cyclic amidines are fluorescent. These turn-on systems were of interest to us because of their potential as biosensors and synthons for accessing functionalized pyridines. While our original method was promising, several limitations persisted, including access to more functionalized and polar-solvent-soluble structures as well as increased control over the rate of cyclization. Herein, we report a new approach that allows the electrophilic substitution of YMs. These substituted YMs exhibit faster turn-on rates, color tunability, access to polar-solvent-soluble species, and increased control over cyclization rate. This allowed us to significantly expand the fluorophore's chemical space.

Combating the Aedes aegypti vector is still the key to control the transmission of many arboviruses, such as Dengue, Zika, and Chikungunya. As few products are efficient for Aedes aegypti control, the search for new strategies have become pivotal., t Substances with photodynamic activity, such as curcumin and their formulations, are strongly encouraged, due to their multi-target mechanism of action. In this study, we evaluated the photolarvicidal and ovicidal activity of curcumin in the presence of sucrose (named SC) and d-mannitol (named DMC). To support the understanding of the larvicidal action of these formulations, Raman micro-spectroscopy was employed. We also studied the morphological changes in Danio rerio (Zebrafish) gills, a non-target organism, and demonstrate that this is an environmentally friendly approach. Both SC and DMC presented a high photo-larvicidal potential. DMC showed the highest larval mortality, with LC 50-24h values between 0.01 and 0.02 mg.L -1 . DMC also significantly decreased egg hatchability, reaching a hatching rate of 10 % at 100 mg.L -1 . The analysis of molecular mechanisms via Raman micro-spectroscopy showed that DMC is highly permeable to the peritrophic membrane of the larva, causing irreversible damage to the simple columnar epithelium of the digestive tube. Histological changes found in the D. rerio gills were of minimal or moderate pathological importance, indicating an adaptive trait rather than detrimental characteristics. These findings indicate that curcumin in sugar formulations is highly efficient, especially DMC, proving it to be a promising and safe alternative to control Aedes mosquitoes. Moreover, Raman micro-spectroscopy demonstrated high potential as an analytical technique to understand the mechanism of action of larvicides., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Chlorin-e6 (Ce6), as a photosensitizer (PS), has demonstrated significant reduction of microorganisms' viability when irradiated by red light. However, the main absorption peak of this PS is located at blue light spectrum, which is less investigated. This study aimed to evaluate the effect of pure-chlorin-e6-mediated photodynamic inactivation (PDI) using different light sources (450 or 660 nm) against biofilms related to periodontitis. Streptococcus oralis, Fusobacterium nucleatum, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans single-species biofilms were developed under proper conditions for five days. PDI was performed using different concentrations of Ce6 (100 and 200 mM), wavelengths (450 and 660 nm) and comparisons were made after colony forming unit and confocal laser scanning microscopy (CLSM) analysis. The use of light and PS were also individually tested. The greatest bacterial elimination was observed in the group where PDI was employed with blue light and concentration of 200 mM for all bacterial strains tested (4.01 log 10 for A. actinomycetemcomitans, and total elimination for P. gingivalis and S. oralis), except for F. nucleatum, where 3.46 log 10 reduction was observed when red light and 200 mM Ce6 were applied (p < 0.05). The antimicrobial effects of PDI mediated by Ce6 for all single pathogenic biofilms were confirmed by live/dead staining under CLSM analysis. For all single-species biofilms, the use of PDI mediated by chlorin-e6 photosensitizer under blue or red-light irradiation (450 and 660 nm) demonstrated a significant reduction in bacterial viability, but blue light showed a promising higher photobiological effect, encouraging its adjuvant use to basic periodontitis treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Leishmaniasis is a serious and neglected disease that affects 14 million people around the World. The currently available drugs for treatment present several drawbacks such as low efficacy and severe side effects, contributing to patients' low compliance. Photodynamic therapy (PDT) is rising as a promising treatment of cutaneous leishmaniasis, mainly considering its topical administration that circumvents any potential adverse effects commonly related to oral/parenteral administration. PDT depends on the interaction between a light-sensitive compound (photosensitizer - PS), light and molecular oxygen. The reaction generates reactive oxygen species (ROS) which induce cell death by oxidative stress. The main goal of this study is to demonstrate the antileishmanial effect of three chlorin derivatives (CHL-OH-A, CHL-OH-B, CHL-TRISMA) using PDT, as well as to investigate their cell death pathway on Leishmania amazonensis promastigote forms after chlorin-PDT application. The chlorin derivatives herein studied did not exhibit aggregates in aqueous medium and showed fast accumulation in Leishmania acidic compartments. CHL-OH-A exhibited the highest antiparasitic activity at 24 h (0.33 μmol L -1 ) and 48 h (0.14 μmol L -1 ) after irradiation at 660 nm (6.0 Jcm -2 ). CHL-OH-A, CHL-OH-B and CHL-TRISMA molecules induced the cell death of parasites mainly by an apoptotic-like process in the presence of light. These chlorin derivatives are 80-fold more active against Leishmania when compared to other PSs reported in the literature. In this study, we have shown that these amphiphilic chlorins, and in particular, CHL-OH-A, exert an interesting leishmanicidal activity suggesting that the use of these PSs associated with PDT could be a promising strategy for treatment of cutaneous leishmaniasis., (Copyright © 2020. Published by Elsevier B.V.)

Background: An appropriate photosensitizer (PS) for photodynamic inactivation should have a pronounced antimicrobial efficacy but low dark toxicity. The aim of this study is to investigate the concentration-dependent antimicrobial efficacies of methylene blue (MB) and chlorin e6 (Ce6), against Streptococcus mutans biofilms and to compare the efficacies of these two PSs., Methods: The 48-h S. mutans UA159 biofilms, grown on glass coverslips, were subjected to MB or Ce6 at 25, 50, 100 and 200 μM with or without irradiation by 660 nM LED light (L). Control groups (-PS-L and -PS + L) were also included. Viability of the biofilm was analyzed by CFU/biofilm and biofilm lactic acid production was quantified by an enzymatic assay., Results: With irradiation, MB under 25 μM resulted in 2-log reduction in biofilm viability and 30-fold reduction in biofilm lactic acid production. However, this biofilm killing efficacy did not change with increasing MB concentration. The biofilm killing efficacy of Ce6 increased with increasing Ce6 concentrations and resulted in 5-log reduction in biofilm viability. The lactic acid inhibitory effect of Ce6 was significantly lower than MB at 25 μM (p<0.01) but higher than MB at 200 μM (p=0.05), although the difference at 200 μM did not reach statistical significance. No dark toxicity could be observed for MB whereas low dark toxicity could be seen for Ce6 when the concentration is above 50 μM., Conclusion: Ce6 under 200 μM showed to be a more powerful PS for photodynamic inactivation than MB. Both Ce6- and MB-based photodynamic inactivation are useful methods for biofilm control in caries prevention., (Copyright © 2020 Elsevier B.V. All rights reserved.)

This study aimed to evaluate the effect of the continuous irradiation with low intensity (continuous mode) and fractioned irradiation with high intensity (fractionated mode), keeping the same dose of light by using Light Emitting Diode (LEDs) with wavelength emission centered at 450 and at 660 nm, using methylene blue (MB), chlorin-e6 (Ce 6 ) and curcumin (CUR) as photosensitizers (PSs) against planktonic phase of E. faecalis. Cell viability was assessed by counting colonies forming per mL (CFU/mL), and the quantification of reactive species was performed by fluorescence with the photodegradation rate evaluated by measurements of absorbance of PSs at different times. The results revealed that MB-mediated PDT was efficient to achieve total microbial load reduction in both irradiation modes, but in fractional mode it was possible to use a lower light dose. Using Ce 6 , a total bacterial reduction was observed when fractional light was used, but at the same light dose, there was no reduction in the continuous irradiation mode. CUR-mediated PDT under continuous irradiation mode promoted the total microbial load reduction. However, for fractional mode, a higher concentration of CUR was required to completely reduce E. faecalis cell viability. Our results suggest that the biological response to PDT is variable depending on the irradiation mode and on the photosensitizer. Therefore, these studies indicate that the irradiation mode, intensity and the specific PSs should be taken into account for the development of clinical protocols for PDT., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this study, direct C-H photoarylation of pyrazine with aryldiazonium salts under visible-light irradiation (blue-LEDs) is described, and additional examples including photoarylations of pyrimidine and pyridazine are also covered. The corresponding aryl-diazines were prepared in yields up to 84% only by mixing and irradiating the reaction with no need for an additional photocatalyst. We demonstrate the efficacy of this protocol by the scope with electron-donor, -neutral, and -withdrawing groups attached at the ortho , meta , and para positions of the aryldiazonium salts; the results are better than those reported for ruthenium-complex mediated photoarylations. Additionally, we demonstrate the robustness of this methodology with a 5 mmol scaled-up experiment. Mechanistic studies were carried out giving support to the proposal of a photocatalyzed approach by an electron donor-acceptor (EDA) complex, also highlighting the crucial role that solvents play in the formation of the EDA complex., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Aedes aegypti is the vector of important diseases like dengue, zika, chikungunya, and yellow fever. Vector control is pivotal in combating the spread of these mosquito-borne illnesses. Photoactivable larvicide curcumin obtained from Curcuma longa Linnaeus has shown high potential for Ae. aegypti larvae control. However, the toxicity of this photosensitizer (PS) might jeopardize non-target aquatic organisms. The aim of this study was to evaluate the toxicity of this PS to Daphnia magna and Danio rerio, besides assessing its mode of action through larvae biochemical and histological studies. Three PS formulations were tested: PS in ethanol+DMSO, PS in sucrose, and PS in D-mannitol. The LC 50 of PS in ethanol+DMSO to D. rerio was 5.9 mg L -1 , while in D. magna the solvents were extremely toxic, and LC 50 was not estimated. The PS formulations in sugars were not toxic to neither of the organisms. Reactive oxygen species (ROS) were generated in D. magna exposed to 50 mg L -1 of PS in D-mannitol, and D. rerio did not elicit this kind of response. D. magna feeding rates were not affected by the PS in D-mannitol. Concerning Ae. aegypti larvae, there were changes in reduced glutathione and protein levels, while catalase activity remained stable after exposure to PS in D-mannitol and sunlight. Histological changes were observed in larvae exposed to PS in sucrose and D-mannitol, most of them irreversible and deleterious. Our results show the feasibility of this photolarvicide use in Ae. aegypti larvae control and its safety to non-target organisms. These data are crucial to this original vector control approach implementation in public health policies.

The antimicrobial photodynamic therapy (aPDT) has stood out as an alternative and promising method of disinfection and has been exploited for the treatment of oral bacteria. In this study, we evaluate in vitro the action of aPDT, mediated by methylene blue, chlorin-e6, and curcumin against clinical subgingival plaques that were resistant to metronidazole. The sensitivity profile of the samples to metronidazole was analyzed by the agar dilution method. Cell viability in the planktonic and biofilm phase was assessed by CFU / mL. The composition of the biofilm was evaluated by the checkboard DNA-DNA Hibrydization technique. Photosensitizers internalization was qualitatively assessed by confocal fluorescence microscopy (CLSM). The aPDT mediated by the three photosensitizers tested was able to reduce the totality of the planktonic microbial load and partially reduce the biofilm samples. The analysis performed by CLSM showed that the photosensitizers used in the application of aPDT were able to permeate the interior of the biofilm. The aPDT has been shown to be useful in a supportive and effective approach to the treatment of periodontal disease., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this review we present relevant and recent applications of porphyrin derivatives as photocatalysts in organic synthesis, involving both single electron transfer (SET) and energy transfer (ET) mechanistic approaches. We demonstrate that these highly conjugated photosensitizers show increasing potential in photocatalysis since they combine both photo- and electrochemical properties which can substitute available metalloorganic photocatalysts. Batch and continuous-flow approaches are presented highlighting the relevance of enabling technologies for the renewal of porphyrin applications in photocatalysis. Finally, the reaction scale in which the methodologies were developed are highlighted since this is an important parameter in the authors' opinion., (Copyright © 2020, Costa e Silva et al.; licensee Beilstein-Institut.)

Breast cancer is a serious public health problem that causes thousands of deaths annually. Chemotherapy continues to play a central role in the management of breast cancer but is associated with extreme off-target toxicity. Therefore, treatments that directly target the tumor and display reduced susceptibility to resistance could improve the outcome and quality of life for patients suffering from this disease. Photodynamic therapy is a targeted treatment based on the use of light to activate a photosensitizer (PS) that then interacts with molecular oxygen and other biochemical substrates to generate cytotoxic levels of Reactive Oxygen Species. Currently approved PS also tends to have poor aqueous solubility that can cause problems when delivered intravenously. In order to circumvent this limitation, in this manuscript, we evaluate the potential of a phthalocyanine-loaded nanostructured lipid carrier (NLC) functionalized with folic acid (FA). To prepare the FA labelled NLC, the polymer PF127 was first esterified with FA and emulsified with an oil phase containing polyoxyethylene 40 stearate, capric/caprylic acid triglycerides, ethoxylated hydrogenated castor oil 40 and the PS zinc phthalocyanine. The resulting PS loaded FA-NLC had a hydrodynamic diameter of 180 nm and were stable in suspension for >90 days. Interestingly, the amount of singlet oxygen generated upon light activation for the PS loaded FA-NLC was substantially higher than the free PS, yet at a lower PS concentration. The PS was released from the NLC in a sustained manner with 4.13 ± 0.58% and 27.7 ± 3.16% after 30 min and 7 days, respectively. Finally, cytotoxicity assays showed that NLC in the concentrations of 09.1 μM of PS present non-toxic with >80 ± 6.8% viable and after 90 s of the light-exposed the results show a statistically significant decrease in cell viability (57 ± 4%). The results obtained allow us to conclude that the functionalized NLC incorporated with PS associated with the PDT technique have characteristics that make them potential candidates for the alternative treatment of breast cancer., (Published by Elsevier B.V.)

A series of cis -[Ru(LL)(dcbH 2 )(NCS) 2 ] compounds, where dcbH 2 = 2,2'-bipyridine-4,4'-dicarboxylic acid and LL = 1,10-phenanthroline (Ru(phen)), 4,7-dipyrrole-1,10-phenanthroline (Ru(pyr)), 4,7-diindole-1,10-phenanthroline (Ru(ind)), or 4,7-dicarbazole-1,10-phenanthroline (Ru(cbz)), was investigated for application as sensitizers in mesoporous TiO 2 dye-sensitized solar cells (DSSCs). A systematic increase in the number of rings of the aromatic substituents at the 4,7-positions of the 1,10-phenanthroline allowed tuning of the molecular size of the sensitizers and the energy stored in the excited state while maintaining the same ground-state Ru 3+/2+ reduction potentials. These small structural changes had a significant influence on the rates and/or efficiencies of electron injection, back-electron transfer, recombination to oxidized mediators, lateral self-exchange electron transfer, and regeneration through iodide oxidation that were reflected in distinct photoelectrochemical performance of full operating DSSCs. The global efficiencies, open-circuit voltages, and short-circuit current densities of the DSSCs consistently followed the trend Ru(pyr) < Ru(ind) < Ru(phen) < Ru(cbz), and the most optimal performance of Ru(cbz) was ascribed to dramatically slower recombination to the oxidized redox mediators. Transient photovoltage and transient absorption experiments both revealed significantly slower recombination as the size of the aromatic substituents increased with Ru(cbz) providing the most promising behavior for application in dye sensitization.

A metal-free methodology for the photoarylation of pyridines, in water, is described giving 2 and 4-arylated-pyridines in yields up to 96%. The scope of the aryldiazonium salts is presented showing important results depending on the nature and position of the substituent group in the diazonium salt, that is, electron-donating or electron-withdrawing in the ortho , meta , or para positions. Further heteroaromatics were also successfully photoarylated. Mechanistic studies and comparison between our methodology and similar metal-catalyzed procedures are presented, suggesting the occurrence of a visible-light EDA complex which generates the aryl radical with no need for an additional photocatalyst.

The self-produced extracellular polymeric matrix of biofilms renders them difficult to eliminate once they are established. This makes the inhibition of biofilm formation key to successful treatment of biofilm infection. Antimicrobial photodynamic therapy (aPDT) and antimicrobial peptides offer a new approach as antibiofilm strategies. In this study sub-lethal doses of aPDT (with chlorin-e6 (Ce6-PDT) or methylene blue (MB-PDT)) and the peptides AU (aurein 1.2 monomer) or (AU) 2 K (aurein 1.2 C-terminal dimer) were combined to evaluate their ability to prevent biofilm development by Enterococcus faecalis . Biofilm formation was assessed by resazurin reduction, confocal microscopy, and infrared spectroscopy. All treatments successfully prevented biofilm development. The (AU) 2 K dimer had a stronger effect, both alone and combined with aPDT, while the monomer AU had significant activity when combined with Ce6-PDT. Additionally, it is shown that the peptides bind to the lipoteichoic acid of the E. faecalis cell wall, pointing to a possible key mechanism of biofilm inhibition.

Sulfonyl fluorides are valuable synthetic motifs for a variety of applications, among which sulfur(VI) fluoride exchange-based "click chemistry" is currently the most prominent. Consequently, the development of novel and efficient synthetic methods to access these functional groups is of great interest. Herein, we report a mild and environmentally benign electrochemical approach to prepare sulfonyl fluorides using thiols or disulfides, as widely available starting materials, in combination with KF, as an inexpensive, abundant and safe fluoride source. No additional oxidants nor additional catalysts are required and, due to mild reaction conditions, the reaction displays a broad substrate scope, including a variety of alkyl, benzyl, aryl and heteroaryl thiols or disulfides.

1H and 13C NMR spectroscopy is used to investigate the organic constituents of metal complexes, MOFs and coordination compounds synthesised under solvothermal and precipitation conditions. The elucidation of the ligands in paramagnetic compounds bearing Cu2+ (d9), Gd3+ (f7), Eu3+ (f6), Fe3+ (d5), ions after treatment with a cationic exchange resin is possible. We prove the efficiency of two post-synthesis linker modifications on diamagnetic IRMOF-3 Zn2+ (d10) with ethyl isocyanate and benzyl bromide.