Degradation of Pesticides Using Semiconducting and Tetrapyrrolic Macrocyclic Photocatalysts-A Concise Review.

Exposure to pesticides is inevitable in modern times, and their environmental presence is strongly associated to the development of various malignancies. This challenge has prompted an increased interest in finding more sustainable ways of degrading pesticides. Advanced oxidation processes in particular appear as highly advantageous, due to their ability of selectively removing chemical entities form wastewaters. This review provides a concise introduction to the mechanisms of photochemical advanced oxidation processes with an objective perspective, followed by a succinct literature review on the photodegradation of pesticides utilizing metal oxide-based semiconductors as photosensitizing catalysts. The selection of reports discussed here is based on relevance and impact, which are recognized globally, ensuring rigorous scrutiny. Finally, this literature review explores the use of tetrapyrrolic macrocyclic photosensitizers in pesticide photodegradation, analyzing their benefits and limitations and providing insights into future directions.

Photoantimicrobial chitosan-gelatin-pomegranate peel extract films for strawberries preservation: From microbiological analysis to in vivo safety assessment.

This study aimed to investigate the application of biopolymeric materials (chitosan, gelatin, and pomegranate peel extract as photosensitizer) and antimicrobial photodynamic therapy (aPDT) on the physicochemical and microbial safety of strawberries. The photosensitizer potential of the materials was confirmed by a light-dose-dependent photobleaching profile. The application of light (525 nm; 50 J cm-2) decreased by >2 log CFU mL-1 the survival of Staphylococcus aureus on the surface of the photoactive-biopolymeric films. Moreover, the materials did not present in vivo cytotoxicity using Danio rerio (Zebrafish) as well as cytophytotoxic, genotoxic, or mutagenic potentials against Allium cepa plant model, which points out their safety to be used as films without posing a risk to the humans and the environment. The photoactive-polymeric coatings were able to maintain the strawberries weight, and the association with green light was 100 % effective in delaying fungal contamination. These coated-strawberries presented a significant reduction in S. aureus survival after light application (5.47-4.34 log CFU mL-1). The molecular level analysis of the photoactive compound cyanidin-3-glucoside indicates absorption on UV-Vis consistent with aPDT action. Therefore, this study showed that the antimicrobial effects of aPDT combined with photoactive-biopolymeric coatings were enhanced, while the quality of the strawberries was maintained.

Molecular basis of two pyrimidine-sulfonylurea herbicides: from supramolecular arrangement to acetolactate synthase inhibition.

CONTEXT: The design and synthesis of safe and highly active sulfonylurea herbicides is still a challenge. Therefore, following some principles of structure-activity relationship (SAR) of sulfonylurea herbicides, this work focuses on evaluating two sulfonylurea derivatives bearing electron-withdrawing substituents, namely, -(CO)OCH3 and -NO2 on the aryl group, on herbicidal activity. To understand the effects caused by the substituent groups, the molecular and electronic structures of the sulfonylureas were evaluated by density functional theory. Likewise, the crystalline supramolecular arrangements of both compounds were analyzed by Hirshfeld surface, QTAIM, and NBO, with the aim of verifying changes in intermolecular interactions caused by substituent groups. Finally, through a toxicophoric analysis, we were able to predict the interacting groups in their biological target, acetolactate synthase, and verify the interactions with the binding site. METHODS: All theoretical calculations were conducted using the highly parameterized empirical exchange-correlation functional M06-2X accompanied by the diffuse and polarized basis set 6-311++G(d,p). The atomic coordinates were obtained directly from the crystalline structures, and from the energies of the frontier molecular orbitals (HOMO and LUMO), chemical descriptors were obtained that indicated the influence of the functional groups in the sulfonylureas on the reactivity of the molecules. The intermolecular interactions in the crystals were analyzed using the Hirshfeld, QTAIM, and NBO surfaces. Toxicophoric modeling was performed by the PharmaGist webserver and molecular docking calculations were performed by the GOLD 2022.1.0 software package so that the ligand was fitted to the binding site in a 10 Å sphere. For this, genetic algorithm parameters were used using the ChemPLP scoring function for docking and ASP for redocking.

Structural basis of antibacterial photodynamic action of curcumin against S. aureus.

Antimicrobial photodynamic therapy (aPDT) is an alternative tool to commercial antibiotics for the inactivation of pathogenic bacteria (e.g., S. aureus). However, there is still a lack of understanding of the molecular modeling of the photosensitizers and their mechanism of action through oxidative pathways. Herein, a combined experimental and computational evaluation of curcumin as a photosensitizer against S. aureus was performed. The radical forms of keto-enol tautomers and the energies of curcumin's frontier molecular orbitals were evaluated by density functional theory (DFT) to point out the photodynamic action as well as the photobleaching process. Furthermore, the electronic transitions of curcumin keto-enol tautomers were undertaken to predict the transitions as a photosensitizer during the antibacterial photodynamic process. Moreover, molecular docking was used to evaluate the binding affinity with the S. aureus tyrosyl-tRNA synthetase as the proposed a target for curcumin. In this regard, the molecular orbital energies show that the curcumin enol form has a character of 4.5% more basic than the keto form - the enol form is a more promising electron donor than its tautomer. Curcumin is a strong electrophile, with the enol form being 4.6% more electrophilic than its keto form. In addition, the regions susceptible to nucleophilic attack and photobleaching were evaluated by the Fukui function. Regarding the docking analysis, the model suggested that four hydrogen bonds contribute to the binding energy of curcumin's interaction with the ligand binding site of S. aureus tyrosyl-tRNA synthetase. Finally, residues Tyr36, Asp40, and Asp177 contact curcumin and may contribute to orienting the curcumin in the active area. Moreover, curcumin presented a photoinactivation of 4.5 log unit corroborating the necessity of the combined action of curcumin, light, and O2 to promote the photooxidation damage of S. aureus. These computational and experimental data suggest insights regarding the mechanism of action of curcumin as a photosensitizer to inactivate S. aureus bacteria.

Photoantibacterial Poly(vinyl)chloride Films Applying Curcumin Derivatives as Bio-Based Plasticizers and Photosensitizers.

Herein we describe the design of natural curcumin ester and ether derivatives and their application as potential bioplasticizers, to prepare photosensitive phthalate-free PVC-based materials. The preparation of PVC-based films incorporating several loadings of newly synthesized curcumin derivatives along with their standard solid-state characterization is also described. Remarkably, the plasticizing effect of the curcumin derivatives in the PVC material was found to be similar to that observed in previous PVC-phthalate materials. Finally, studies applying these new materials in the photoinactivation of S. aureus planktonic cultures revealed a strong structure/activity correlation, with the photosensitive materials reaching up to 6 log CFU reduction at low irradiation intensities.

Natural versus synthetic curcuminoids as photosensitizers: Photobleaching and antimicrobial photodynamic therapy evaluation.

Antimicrobial photodynamic therapy (aPDT) has been studied as an alternative to combat bacterial resistance to the commonly used antibiotics. aPDT requires the use of a photosensitizer and curcumin is one of the more promising, though the usage of natural curcumin can be inconsistent in certain biomedical uses due to differences in soil condition and turmeric age, besides a large quantity of the plant is necessary to obtain useful amounts of the actual molecule. As such, a synthetic analogue is preferred as it is pure, and its components are better characterized. The present work studied photophysical differences in both natural and synthetic curcumin using photobleaching experiments and searched for whether differences existed in aPDT studies against Staphylococcus aureus. The results showed a faster O2 consumption and a singlet oxygen's generation rate lower by the synthetic curcumin, in comparison with the natural derivative. However, no statistical difference was observed when inactivating S. aureus and these results were following a concentration-based pattern. Thus, the use of synthetic curcumin is indicated, as it can be obtained in controlled amounts and with less environmental impact. Although there are small changes in a photophysical context comparing natural versus synthetic curcumins, we did not observe statistical differences in the photoinactivation of S.aureus bacteria, and reproducibility in biomedical contexts is better achieved with the synthetic analogue.

Regulatory mechanisms of stem cell differentiation: Biotechnological applications for neurogenesis.

The world population's life expectancy is growing, and neurodegenerative disorders common in old age require more efficient therapies. In this context, neural stem cells (NSCs) are imperative for the development and maintenance of the functioning of the nervous system and have broad therapeutic applicability for neurodegenerative diseases. Therefore, knowing all the mechanisms that govern the self-renewal, differentiation, and cell signaling of NSC is necessary. This review will address some of these aspects, including the role of growth and transcription factors, epigenetic modulators, microRNAs, and extracellular matrix components. Furthermore, differentiation and transdifferentiation processes will be addressed as therapeutic strategies showing their significance for stem cell-based therapy.

Self-Disinfecting Urethral Catheter to Overcome Urinary Infections: From Antimicrobial Photodynamic Action to Antibacterial Biochemical Entities.

Medical-device-related infections are considered a worldwide public health problem. In particular, urinary catheters are responsible for 75% of cases of hospital urinary infections (a mortality rate of 2.3%) and present a high cost for public and private health systems. Some actions have been performed and described aiming to avoid it, including clinical guidelines for catheterization procedure, antibiotic prophylaxis, and use of antimicrobial coated-urinary catheters. In this review paper, we present and discuss the functionalization of urinary catheters surfaces with antimicrobial entities (e.g., photosensitizers, antibiotics, polymers, silver salts, oxides, bacteriophage, and enzymes) highlighting the immobilization of photosensitizing molecules for antimicrobial photodynamic applications. Moreover, the characterization techniques and (photo)antimicrobial effects of the coated-urinary catheters are described and discussed. We highlight the most significant examples in the last decade (2011-2021) concerning the antimicrobial coated-urinary catheter and their potential use, limitations, and future perspectives.

New Insights on Glutathione's Supramolecular Arrangement and Its In Silico Analysis as an Angiotensin-Converting Enzyme Inhibitor.

Angiotensin-converting enzyme (ACE) inhibitors are one of the most active classes for cardiovascular diseases and hypertension treatment. In this regard, developing active and non-toxic ACE inhibitors is still a continuous challenge. Furthermore, the literature survey shows that oxidative stress plays a significant role in the development of hypertension. Herein, glutathione's molecular structure and supramolecular arrangements are evaluated as a potential ACE inhibitor. The tripeptide molecular modeling by density functional theory, the electronic structure by the frontier molecular orbitals, and the molecular electrostatic potential map to understand the biochemical processes inside the cell were analyzed. The supramolecular arrangements were studied by Hirshfeld surfaces, quantum theory of atoms in molecules, and natural bond orbital analyses. They showed distinct patterns of intermolecular interactions in each polymorph, as well as distinct stabilizations of these. Additionally, the molecular docking study presented the interactions between the active site residues of the ACE and glutathione via seven hydrogen bonds. The pharmacophore design indicated that the hydrogen bond acceptors are necessary for the interaction of this ligand with the binding site. The results provide useful information for the development of GSH analogs with higher ACE inhibitor activity.

Synthesis of Photosensitizers Based on Tetrapyrrolic Macrocycles for Combination with Antibiotics: Dual Inactivation of Bacteria.

The combination of photodynamic therapy with antibiotics or antimicrobial peptides for inactivation of bacteria is an area of growing interest due to the synergistic effect already observed by many authors. It has been shown that the efficiency of this dual antimicrobial therapy is highly dependent on the structure of the photosensitizer, being tetrapyrrolic macrocycles the ones with most promising results. There are a few review articles in the recent literature describing the main microbiological results concerning this dual inactivation of bacteria, but none of them focus on the synthetic processes of these photosensitizers and their remarkable chemical versatility. Therefore, herein we present an overview on synthetic methodologies for preparation of tetrapyrrolic macrocycles and their conjugates with antibiotics or antimicrobial peptides, for use in dual inactivation of bacteria. This review will be divided in two sections concerning the physical or covalent combinations of PS with antibiotic/cationic peptides, followed by brief critical analysis on their corresponding antimicrobial outcomes.

Theoretical analysis of the effects of counterions on the supramolecular arrangement of sulfamethoxazole.

Active pharmaceutical ingredients are formulated as the salt form, aiming to modulate their physicochemical properties. In this regard, the optimization and choice of the salt former have a strong influence on toxicity, therapeutic efficiency, and bioavailability. Sulfamethoxazole (SMZ) salts with Na+, Cl-, and Br- counterions influence in the supramolecular arrangement as well as in their thermodynamic and kinetic parameters. Herein, we analyzed the interactions of the Na+, Cl-, and Br- counterions on the supramolecular arrangement of the sulfamethoxazole salts by Hirshfeld surfaces, fingerprint plots, and theoretical methods-quantum theory of atoms in molecules and natural bond orbitals. Moreover, we evaluated their electronic structure by density functional theory using calculation of the frontier molecular orbitals. Molecular electrostatic potential maps were also obtained to predict the interactions of the counterions along crystalline arrangements. We observed that the structures of [SMZ]+ and [SMZ]- ions differ slightly from the SMZ. The chemical reactivity indices show that the SMZ is kinetically more stable than its respective ions, while its anion is more polarizable, and its cation has a higher global electrophilicity index. The molecular electrostatic potential maps show high charge density in the sulfonyl group (nucleophilic region) and the heterocyclic amino group (electrophilic region). Although the molecular skeleton is identical among the three SMZ species and the presence of different counterions in the formation of the crystalline structure of the salts results in supramolecular arrangements with different patterns of intermolecular interactions, despite being very similar in terms of intensities.

Photodisinfection of material surfaces and bacterial skin infections by a detergent loaded with curcumin.

The development of technologies and therapeutic strategies is needed to combat skin infections and pathogenic microorganisms present on material surfaces that are still responsible for serious public health problems. In this study, detergents loaded with curcumin were prepared by a simple approach and characterized by UV-vis spectroscopy and fluorescence spectroscopy. Their antibacterial photodynamic effects were evaluated against Staphylococcus aureus in planktonic medium and in vivo (skin infection model), and showed a reduction up to 8 logs and 2 logs, respectively. Additionally, the curcumin-detergents were applied on photodisinfection of material surfaces such as wood, rubber, and stainless steel resulting in an efficient photoinactivation up to 3 logs. These developed detergents loaded with curcumin can improve the decontamination of material surfaces and skin infections (in vivo) when illuminated.

Synergic dual phototherapy: Cationic imidazolyl photosensitizers and ciprofloxacin for eradication of in vitro and in vivo E. coli infections.

The emergence of new microorganisms with resistance to current antimicrobials is one of the key issues of modern healthcare that must be urgently addressed with the development of new molecules and therapies. Photodynamic inactivation (PDI) in combination with antibiotics has been recently regarded as a promising wide-spectrum therapy for the treatment of localized topical infections. However, further studies are required regarding the selection of the best photosensitizer structures and protocol optimization, in order to maximize the efficiency of this synergic interaction. In this paper, we present results that demonstrate the influence of the structure of cationic imidazolyl-substituted photosensitizers and light on the enhancement of ciprofloxacin (CIP) activity, for the inactivation of Escherichia coli. Structure-activity studies have highlighted the tetra cationic imidazolyl porphyrin IP-H-Me4+ at sub-bactericide concentrations (4-16 nM) as the most promising photosensitizer for combination with sub-inhibitory CIP concentration (<0.25 mg/L). An optimized dual phototherapy protocol using this photosensitizer was translated to in vivo studies in mice wounds infected with E. coli. This synergic combination reduced the amount of photosensitizer and ciprofloxacin required for full E. coli inactivation and, in both in vitro and in vivo studies, the combination therapy was clearly superior to each monotherapy (PDI or ciprofloxacin alone). Overall, these findings highlight the potential of cationic imidazolyl porphyrins in boosting the activity of antibiotics and lowering the probability of resistance development, which is essential for a sustainable long-term treatment of infectious diseases.

Formulations of curcumin and d-mannitol as a photolarvicide against Aedes aegypti larvae: Sublethal photolarvicidal action, toxicity, residual evaluation, and small-scale field trial.

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 (LC50-24h = 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.

Features of third generation photosensitizers used in anticancer photodynamic therapy: Review.

Cancer remains a main public health issue and the second cause of mortality worldwide. Photodynamic therapy is a clinically approved therapeutic option. Effective photodynamic therapy induces cancer damage and death through a multifactorial manner including reactive oxygen species-mediated damage and killing, vasculature damage, and immune defense activation. Anticancer efficiency depends on the improvement of photosensitizers drugs used in photodynamic therapy, their selectivity, enhanced photoproduction of reactive species, absorption at near-infrared spectrum, and drug-delivery strategies. Both experimental and clinical studies using first- and second-generation photosensitizers had pointed out the need for developing improved photosensitizers for photodynamic applications and achieving better therapeutic outcomes. Bioconjugation and encapsulation with targeting moieties appear as a main strategies for the development of photosensitizers from their precursors. Factors influencing cellular biodistribution and uptake are briefly discussed, as well as their roles as cancer diagnostic and therapeutic (theranostics) agents. The two-photon photodynamic approach using third-generation photosensitizers is present as an attempt in treating deeper tumors. Although significant advances had been made over the last decade, the development of next-generation photosensitizers is still mainly in the developmental stage.

Learning from Nature: Bioinspired Chlorin-Based Photosensitizers Immobilized on Carbon Materials for Combined Photodynamic and Photothermal Therapy.

Chlorophylls, which are chlorin-type photosensitizers, are known as the key building blocks of nature and are fundamental for solar energy metabolism during the photosynthesis process. In this regard, the utilization of bioinspired chlorin analogs as photosensitizers for photodynamic therapy constitutes an evolutionary topic of research. Moreover, carbon nanomaterials have been widely applied in photodynamic therapy protocols due to their optical characteristics, good biocompatibility, and tunable systematic toxicity. Herein, we review the literature related to the applications of chlorin-based photosensitizers that were functionalized onto carbon nanomaterials for photodynamic and photothermal therapies against cancer. Rather than a comprehensive review, we intended to highlight the most important and illustrative examples over the last 10 years.

Avoiding ventilator-associated pneumonia: Curcumin-functionalized endotracheal tube and photodynamic action.

Hospital-acquired infections are a global health problem that threatens patients' treatment in intensive care units, causing thousands of deaths and a considerable increase in hospitalization costs. The endotracheal tube (ETT) is a medical device placed in the patient's trachea to assist breathing and delivering oxygen into the lungs. However, bacterial biofilms forming at the surface of the ETT and the development of multidrug-resistant bacteria are considered the primary causes of ventilator-associated pneumonia (VAP), a severe hospital-acquired infection for significant mortality. Under these circumstances, there has been a need to administrate antibiotics together. Although necessary, it has led to a rapid increase in bacterial resistance to antibiotics. Therefore, it becomes necessary to develop alternatives to prevent and combat these bacterial infections. One possibility is to turn the ETT itself into a bactericide. Some examples reported in the literature present drawbacks. To overcome those issues, we have designed a photosensitizer-containing ETT to be used in photodynamic inactivation (PDI) to avoid bacteria biofilm formation and prevent VAP occurrence during tracheal intubation. This work describes ETT's functionalization with curcumin photosensitizer, as well as its evaluation in PDI against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli A significant photoinactivation (up to 95%) against Gram-negative and Gram-positive bacteria was observed when curcumin-functionalized endotracheal (ETT-curc) was used. These remarkable results demonstrate this strategy's potential to combat hospital-acquired infections and contribute to fighting antimicrobial resistance.

COVID-19: Beyond the virus. The use of photodynamic therapy for the treatment of infections in the respiratory tract.

•The World today is facing a great effort for the control of infections.•Nowadays COVID-19 is the large global outbreak and is the major public health issue.•This letter to Editor highlighted the well-established photodynamic therapy protocol as a tool to decrease the viral and bacterial load in the respiratory tract.

Bioinspired-Metalloporphyrin Magnetic Nanocomposite as a Reusable Catalyst for Synthesis of Diastereomeric (-)-Isopulegol Epoxide: Anticancer Activity Against Human Osteosarcoma Cells (MG-63).

In the present study, we developed a green epoxidation approach for the synthesis of the diastereomers of (-)-isopulegol benzyl ether epoxide using molecular oxygen as the oxidant and a hybrid manganese(III)-porphyrin magnetic reusable nanocomposite as the catalyst. High activity, selectivity, and stability were obtained, with up to four recycling cycles without the loss of activity and selectivity for epoxide. The anticancer effect of the newly synthesized isopulegol epoxide diastereomers was evaluated on a human osteosarcoma cell line (MG-63); both diastereomers showed similar in vitro potency. The measured IC50 values were significantly lower than those reported for other monoterpene analogues, rendering these epoxide isomers as promising anti-tumor agents against low prognosis osteosarcoma.

A Green Protocol for Microwave-Assisted Extraction of Volatile Oil Terpenes from Pterodon emarginatus Vogel. (Fabaceae).

Microwave-assisted extraction of volatile oils (MAE) potentially offers a more efficient and bio-sustainable method than conventional extraction by Clevenger apparatus (CE). This study aimed to optimise the MAE of the volatile oil from Pterodon emarginatus fruits and characterise the volatile compounds. A 2³ full-factorial central composite design and response surface methodology were used to evaluate the effects of time (min), moisture (%) and microwave power (W) on the extraction yield. The process optimisation was based on the desirability function approach. The reaction time and moisture conditions were standardised in these analyses. The volatile oil composition was analysed by Gas Chromatography/Mass Spectrometry (GC/MS) in order to compare techniques extractions influences. Microwave irradiation showed excellent performance for extraction of the volatile oil from Pterodon emarginatus and there were some advantages in compare to conventional method with respect to the time (14 times), energy (6 times), reagents amounts and waste formation. About chemical composition presents significant differences with the type of extraction. Caryophyllene (25.65%) and trans-α-bisabolol (6.24%) were identified as major components in MAE sample while caryophyllene (6.75%) and γ-elemene (7.02%) are the components with higher relative percentage in CE samples. The microwaves assisted process shown an increase of economic interested compounds present in volatile oil.