Organocatalytic Synthesis and DNA Interactive Studies of New 1,2,3-triazolyl-thiazolidines Hybrids.

An organocatalytic [3+2] cycloaddition reaction between thiazolidine-containing ß-ketoester 1 and aryl azides 2 was employed to synthesize new 1,2,3-triazolyl-thiazolidine hybrids 3. In this metal-free approach, twelve compounds were isolated in yields ranging from 23 % to 96 % by using diethylamine (10 mol%) and DMSO at 75 °C for 24 hours. DNA-binding assays were conducted through absorption, emission spectroscopy and viscosimetry analysis, to evaluate the interaction capacity of the studied derivatives with nucleic acids. All the synthesized compounds were evaluated for their interactions with a specific group of compounds containing the pharmacophoric groups triazole and thiazolidine through a molecular docking speculative study, aimed at identifying the interaction profile of these compounds with DNA. The obtained results suggest that 1,2,3-triazolyl-thiazolidine hybrids could be a promising approach in the development of novel therapeutic agents targeting DNA-related processes.

Electrophile-Promoted Nucleophilic Cyclization of 2-Alkynylindoles to Give 4-Substituted Oxazinoindolones.

A method for the synthesis of 4-organoselanyl oxazinoindolone derivatives by the cascade cyclization of N-(alkoxycarbonyl)-2-alkynylindoles using iron(III) chloride and diorganyl diselenides as promoters was developed. This protocol was applied to a series of N-(alkoxycarbonyl)-2-alkynylindoles containing different substituents. The reaction conditions also tolerated a variety of diorganyl diselenides having both electron donating and electron withdrawing groups. However, the reaction did not work for diorganyl disulfides and ditellurides. The reaction mechanism seems to proceed via an ionic pathway and the cooperative action between iron(III) chloride and diorganyl diselenides is crucial for successful cyclization. We also found that using the same starting materials, by simply changing the electrophilic source to iodine, led to the formation of 4-iodo-oxazinoindolones. The high reactivity of Csp2 -Se and Csp2 -I bonds were tested under cross-coupling conditions leading to the preparation of a new class of functionalized indole derivatives. In addition, the absorption, emission and electrochemical properties of 4-organoselanyl oxazinoindolones showed an important relationship with the substituents of the aromatic rings. The advantages of the methodology include the use of electrophilic to promote the cyclization reaction and functionalization of the indole ring, and the electronic properties presented by the prepared compounds can be exploited as probes, analyte detectors and optical materials.

Visible Light and Triselenium Dicyanide (TSD): New Horizons in the Synthesis of Organic Selenocyanates.

Herein, we describe a new method for the synthesis of α-carbonyl selenocyanates by reacting triselenium dicyanide (TSD) and styrenes under blue light irradiation and O2 atmosphere. The reactions are triggered by the formation of Se-centered radical species, followed by the addition/oxidation of the styrene π-bond. α-Carbonyl selenocyanates and α-hydroxy selenocyanates were obtained in moderate to excellent yields from aryl- and alkyl-substituted alkenes, respectively. It was demonstrated that α-carbonyl selenocyanates could be used as a synthetic platform in a multicomponent reaction strategy to prepare 2-phenylimidazo[1,2-a]pyridine derivatives, which were evaluated for their photophysical properties. Overall, this new method provides a useful tool for synthesizing α-carbonyl selenocyanates, and demonstrates their potential for use in the synthesis of other compounds, thus giving new synthetic opportunities to construct organic selenocyanate compounds.

Effects of Substituents on the Photophysical/Photobiological Properties of Mono-Substituted Corroles.

The trans-A2B-corrole series was prepared starting with 5-(pentafluorophenyl)dipyrromethene, which was then reacted with respective aryl-substituted aldehyde by Gryko synthesis. It was further characterized by HRMS and electrochemical methods. In addition, we investigated experimental photophysical properties (absorption, emission by steady-state and time-resolved fluorescence) in several solvents and TDDFT calculations, aggregation, photostability and reactive oxygen species generation (ROS), which are relevant when selecting photosensitizers used in photodynamic therapy and many other photo-applications. In addition, we also evaluated the biomolecule-binding properties with CT-DNA and HSA by spectroscopy, viscometry and molecular docking calculations assays.

Bromo-Substituted Diazenyl-pyrazolo[1,5-a]pyrimidin-2-amines: Sonogashira Cross-Coupling Reaction, Photophysical Properties, Bio-interaction and HSA Light-Up Sensor.

A convenient synthesis of a broad series of thirteen examples of alkyne-spacer derivatives 2 from the well-known Sonogashira cross-coupling reaction on diazenyl-pyrazolo[1,5-a]pyrimidin-2-amine compounds 1 is reported. The reactivity of heterocycles 1 due the presence of selected electron-donor (EDG) and electron-withdrawing (EWG) groups attached to different alkynes was evaluated. Also, the reactional versatility due the position variation of the bromo atom at the scaffolds 1 was also investigated. In general, derivatives presented strong absorption bands at the 250-500 nm optical window and UV to cyan emission properties. Also, the redox analysis was recorded by electrochemical cyclic voltammetry technique. For HSA biomacromolecule assays, spectroscopic studies by UV-Vis, steady-state and time-resolved emission fluorescence, and molecular docking calculations evidenced the ability of each compound to establish interactions with human serum albumin (HSA). Finally, the behavior presented for this new class of heterocycles makes them a promising tool as optical sensors for albumins.

Hybridized 4-Trifluoromethyl-(1,2,3-triazol-1-yl)quinoline System: Synthesis, Photophysics, Selective DNA/HSA Bio-interactions and Molecular Docking.

The synthesis, structural analysis, and evaluation of the photophysical properties of twelve novel 2-aryl(heteroaryl)-6-(4-alkyl(aryl)-1H-1,2,3-triazol-1-yl)-4-(trifluoromethyl)quinolines (6-8), where aryl(heteroaryl)=Ph, 4-Me-C6 H4 , 4-F-C6 H4 and 2- furyl; 4-alkyl(aryl)=-CH2 OH, -(CH2 )5 CH3 and Ph, are reported. Hybrid scaffolds 6-8 were synthesized at 77-95 % yields by regioselective copper-catalysed azide-alkyne cycloaddition (CuAAC) reaction of unpublished 6-azido-4-(trifluoromethyl)quinolines (2) with selected terminal alkynes (3-5). Azido intermediates 2 were obtained from the reaction of 6-amino-4-(trifluoromethyl)quinolines (1) and sodium azide at good yields (78-87 %). Compounds 6-8 were structurally fully characterized by 1 H-, 13 C- and 19 F- and 1 H-13 C 2D-NMR (HSQC, HMBC) spectroscopy, X-ray diffraction (SC-XRD) and HRMS analysis. Moreover, the photophysical properties, DNA- and HSA-binding experiments (bio-interactions), and molecular docking studies for compounds 6-8 were performed. These are discussed and compared with similar compounds from recent research.

Biophysical Characterization of the Interaction between a Transport Human Plasma Protein and the 5,10,15,20-Tetra(pyridine-4-yl)porphyrin.

The interaction between human serum albumin (HSA) and the non-charged synthetic photosensitizer 5,10,15,20-tetra(pyridine-4-yl)porphyrin (4-TPyP) was evaluated by in vitro assays under physiological conditions using spectroscopic techniques (UV-vis, circular dichroism, steady-state, time-resolved, synchronous, and 3D-fluorescence) combined with in silico calculations by molecular docking. The UV-vis and steady-state fluorescence parameters indicated a ground-state association between HSA and 4-TPyP and the absence of any dynamic fluorescence quenching was confirmed by the same average fluorescence lifetime for HSA without (4.76 ± 0.11 ns) and with 4-TPyP (4.79 ± 0.14 ns). Therefore, the Stern-Volmer quenching (KSV) constant reflects the binding affinity, indicating a moderate interaction (104 M-1) being spontaneous (ΔG°= -25.0 kJ/mol at 296 K), enthalpically (ΔH° = -9.31 ± 1.34 kJ/mol), and entropically (ΔS° = 52.9 ± 4.4 J/molK) driven. Binding causes only a very weak perturbation on the secondary structure of albumin. There is just one main binding site in HSA for 4-TPyP (n ≈ 1.0), probably into the subdomain IIA (site I), where the Trp-214 residue can be found. The microenvironment around this fluorophore seems not to be perturbed even with 4-TPyP interacting via hydrogen bonding and van der Waals forces with the amino acid residues in the subdomain IIA.

Bis-triazolylchalcogenium-Functionalized Benzothiadiazole Derivatives as Light-up Sensors for DNA and BSA.

A range of bis-triazolylchalcogenium-BTD 3 was synthesized by a copper-catalyzed azide-alkyne cycloaddition of azido arylchalcogenides 1 and 4,7-diethynylbenzo[c][1,2,5]thiadiazole 2. Eight new compounds were obtained in moderate to good yields using 1 mol % of copper(II) acetate monohydrate under mild reaction conditions. In addition, the synthesized bis-triazolylchalcogenium-BTD 3a-3h were investigated regarding their photophysical, electrochemical, and biomolecule binding properties in solution. In general, compounds presented strong absorption bands at the 250-450 nm region and cyan to green emission properties. The redox process attributed to the chalcogen atom was observed by electrochemical analysis (CV techniques). In addition, spectroscopic studies by UV-vis, steady-state emission fluorescence, and molecular docking calculations evidenced the ability of each derivative to establish interactions with calf-thymus DNA (CT-DNA) and bovine serum albumin (BSA). The behavior presented for this new class of compounds makes them a promising tool as optical sensors for biomolecules.

Recent advances in electroanalytical drug detection by porphyrin/phthalocyanine macrocycles: developments and future perspectives.

Porphyrins and phthalocyanines are promising π-conjugated compounds with fantastic photochemical and electrochemical properties which are present in nature in more systems than we are generally aware. The electrochemical properties of these large aromatic molecules are also unique, endowing them with the ability to catalyze a wide range of redox reactions. The macrocycle core of these molecules is extremely favorable for the complexation of several metal ions, resulting in molecules with tunable properties. Porphyrins and phthalocyanines are able to form highly organized films, with high conductivity and great robustness and their use was explored to build a great number of electrochemical and photoelectrochemical sensors for many varied applications, one among them being drug analysis. This review will focus on the potential of the electrodes modified with attractive porphyrins and phthalocyanines for this application. The papers published in the last 3 years were closely evaluated.

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases.

A new series of ten examples of Schiff bases, namely (E)-2-(((2-alkyl(aryl/heteroaryl)-4-(trifluoromethyl)quinolin-6-yl)imino)methyl)phenols 3, was easily synthesized with yields of up to 91% from the reactions involving a series of 2-(R-substituted) 6-amino-4-(trifluoromethyl)quinolines 1 and 4(5)-R1-substituted salicylaldehydes 2 - in which alkyl/aryl/heteroaryl for 2-R-substituents are Me, Ph, 4-MeC6H4, 4-FC6H4, 4-NO2C6H4, and 2-furyl, and R1-substituents are 5-NEt2, 5-OCH3, 4-Br, and 4-NO2. Complementarily, the Schiff bases showed low to good quantum fluorescence yield values in CHCl3 (Φf = 0.12-0.80), DMSO (Φf = 0.20-0.75) and MeOH (Φf = 0.13-0.85). Higher values of Stokes shifts (SS) were observed in more polar solvents (DMSO; 65-150 nm and MeOH; 65-130 nm) than in CHCl3 (59-85 nm). Compounds 3 presented good stability under white-LED irradiation conditions and moderate ROS generation properties were observed.

Photophysical and electrochemical properties of two trans-A2B-corroles: differences between phenyl or pyrenyl groups at the meso-10 position.

The present study reports on the optical and photophysical properties of trans-A2B-corroles possessing pyrenyl units attached at the meso-10-position and compares them with those of model trans-A2B-corroles having phenyl substituents at that position. In contrast to the model meso-substituted corrole, the new pyrenyl-corrole shows slightly red-shifted absorption bands and blue-shifted emission, slightly higher fluorescence quantum yield, and more importantly, it shows better photo-stability under white-light illumination. Theoretical calculations were used to determine the electronic transitions and geometries of the singlet and triplet excited states (TD-DFT and NTO). Moreover, we demonstrate that the pyrenyl-corrole in analogy to previously studied model corroles is able to generate reactive oxygen species (ROS) under visible light using photo-degradation of 1,3-diphenylisobenzofuran (DBPF), a singlet oxygen quencher, and EPR spectroscopy allied with the spin-trapping method is used for identifying singlet oxygen species. The results show that the pyrenyl unit attached at the meso-10-position of the corrole increases the photo-stability and efficiency in ROS generation compared to the phenyl substituent.

Porphyrin Derivative Nanoformulations for Therapy and Antiparasitic Agents.

Porphyrins and analogous macrocycles exhibit interesting photochemical, catalytic, and luminescence properties demonstrating high potential in the treatment of several diseases. Among them can be highlighted the possibility of application in photodynamic therapy and antimicrobial/antiparasitic PDT, for example, of malaria parasite. However, the low efficiency generally associated with their low solubility in water and bioavailability have precluded biomedical applications. Nanotechnology can provide efficient strategies to enhance bioavailability and incorporate targeted delivery properties to conventional pharmaceuticals, enhancing the effectiveness and reducing the toxicity, thus improving the adhesion to the treatment. In this way, those limitations can be overcome by using two main strategies: (1) Incorporation of hydrophilic substituents into the macrocycle ring while controlling the interaction with biological systems and (2) by including them in nanocarriers and delivery nanosystems. This review will focus on antiparasitic drugs based on porphyrin derivatives developed according to these two strategies, considering their vast and increasing applications befitting the multiple roles of these compounds in nature.

Two-photon absorption properties of BODIPY-like compounds based on BF2-naphthyridine complexes.

Boron dipyrromethene type molecules (BODIPYs) are versatile molecules which have been used for applications ranging from photodynamic therapy to solar cells (DSSC). However, these molecules usually do not present high two-photon absorption cross-sections, limiting their use in nonlinear optical applications. Herein, we study a series of BF2-naphthyridine based boron-complexes with electron-donating and withdrawing groups to increase their two-photon absorption. We have found two-photon absorption cross-sections up to approximately 270 GM, which corresponds to an increase of approximately five times in comparison to the average cross-section value reported for molecules with similar conjugation length, indicating such compounds as potential materials for nonlinear applications in both the visible and infrared spectral regions.

meso-Mono-[4-(1,4,7-triazacyclononanyl)]-tri(phenyl)]porphyrin and the respective zinc(ii)-complex: complete characterization and biomolecules binding abilities.

We aimed to synthesize a new series of triazacyclononanyl-porphyrins (4 and 5) with the potential ability to bind DNA. For this, the free-base porphyrin 4 and the corresponding Zn(ii)-complex 5 were synthesized by the Schiff base formation reaction. The binding ability of the porphyrin derivatives 4 and 5 with DNA from calf-thymus was studied by UV-vis and emission spectroscopy. Detailed analysis of the results suggests that the interaction of these systems most probably occurs through π-stacking and secondary hydrogen interaction surface binding with ct-DNA. Moreover, we also demonstrate the substantial ability of porphyrins 4 and 5 to generate (1)O2 and to photocleave plasmid DNA after irradiation.

Encapsulation of metalloporphyrins improves their capacity to block the viability of the human malaria parasite Plasmodium falciparum.

Several synthetic metallated protoporphyrins (M-PPIX) were tested for their ability to block the cell cycle of the lethal human malaria parasite Plasmodium falciparum. After encapsulating the porphyrin derivatives in micro- and nanocapsules of marine atelocollagen, their effects on cultures of red blood cells infected (RBC) with P. falciparum were verified. RBCs infected with synchronized P. falciparum incubated for 48 h showed a toxic effect over a micromolar range. Strikingly, the IC50 of encapsulated metalloporphyrins reached nanomolar concentrations, where Zn-PPIX showed the best antimalarial effect, with an IC50=330 nM. This value is an 80-fold increase in the antimalarial activity compared to the antimalarial effect of non-encapsulated Zn-PPIX. These findings reveal that the incubation of P. falciparum infected-RBCs with 20 µM Zn-PPIX reduced the size of hemozoin crystal by 34%, whereas a 28% reduction was noticed with chloroquine, confirming the importance of heme detoxification pathway in drug therapy. FROM THE CLINICAL EDITOR: In this study, synthetic metalloporphyrins were tested as therapeutics that target Plasmodium falciparum. The IC50 of encapsulated metalloporphyrins was found to be in the nanomolar concentration range, with encapsulated Zn-PPIX showing an 80-fold increase in its antimalarial activity compared to the non-encapsulated form.

Advances in porphyrins and chlorins associated with polysaccharides and polysaccharides-based materials for biomedical and pharmaceutical applications.

Over the last decade, the convergence of advanced materials and innovative applications has fostered notable scientific progress within the biomedical and pharmaceutical fields. Porphyrins and their derivatives, distinguished by an extended conjugated π-electron system, have a relevant role in propelling these advancements, especially in drug delivery systems, photodynamic therapy, wound healing, and (bio)sensing. However, despite their promise, the practical clinical application of these macrocycles is hindered by their inherent challenges of low solubility and instability under physiological conditions. To address this limitation, researchers have exploited the synergistic association of porphyrins and chlorins with polysaccharides by engineering conjugated systems and composite/hybrid materials. This review compiles the principal advances in this growing research field, elucidating fundamental principles and critically examining the applications of such materials within biomedical and pharmaceutical contexts. Additionally, the review addresses the eventual challenges and outlines future perspectives for this poignant research field. It is expected that this review will serve as a comprehensive guide for students and researchers dedicated to exploring state-of-the-art materials for contemporary medicine and pharmaceutical applications.

Photophysical, photobiological, and biomolecule-binding properties of new tri-cationic meso-tri(2-thienyl)corroles with Pt(II) and Pd(II) polypyridyl derivatives.

We report the synthesis and characterization of new tri-cationic corrole derivatives, containing Pt(II) or Pd(II) complexes attached at the peripheral position of thienyl moieties. Corrole derivatives were characterized through microanalysis, electrochemical, spectrometry and spectroscopy analysis. Singlet and triplet excited-states are investigated by photophysical/theoretical calculation methods and photobiological parameters were also evaluated spectroscopic techniques (UV-Vis and EPR). Also, the binding capacity of each corrole derivative with nucleic acids (DNA) and human serum albumin (HSA) was determined by UV-Vis, steady-state, and time-resolved fluorescence spectroscopy, combined with molecular docking analysis. Moreover, the new corroles containing peripheral complexes improve their interactions with biomacromolecules, generate reactive oxygen species under light source irradiation studied and has potential for application in photodynamic therapeutic processes.

First report of trans-A2B-corrole derived from a lapachone derivative: photophysical, TD-DFT and photobiological assays.

In this work, the synthesis, characterization and photophysical assays of a new trans-A2B-corrole derivative from the naturally occurring quinone are described. ß-Lapachone is a naturally occurring quinoidal compound that provides highly fluorescent heterocyclic compounds such as lapimidazoles. The new trans-A2B-corrole compound was obtained from the reaction between 2,3,4,5,6-(pentafluorophenyl)dipyrromethane and the lapimidazole bearing an aldehyde group. The dyad was characterized by high-resolution mass spectrometry (HRMS), NMR spectroscopy (1H, COSY 2D, HMBC, 19F), FT-IR, UV-vis, steady-state and time-resolved fluorescence, electrochemical studies (CV), TD-DFT analysis and photobiological experiments, in which includes aggregation, stability in solution, photostability and partition coefficients assays. Finally, ROS generation assays were performed using 1,3-diphenylisobenzofuran (DPBF) method and the presented compound showed significant photostability and singlet oxygen production.

Synthesis and evaluation of photophysical, electrochemical, and ROS generation properties of new chalcogen-naphthoquinones-1,2,3-triazole hybrids.

This study presents a comprehensive analysis encompassing the synthesis, structural elucidation, photophysical behavior, and electrochemical properties of a novel series of chalcogen-naphthoquinone-1,2,3-triazole hybrids. Employing a meticulously designed protocol, the synthesis of these hybrids, denoted as 11a-j, was achieved with remarkable efficiency (yielding up to 81%). This synthesis used a regioselective copper-catalyzed azide-alkyne cycloaddition reaction (CuAAC). Furthermore, a detailed investigation into the photophysical characteristics, TDDFT calculations, electrochemical profiles, and photobiological attributes of compounds 11a-j was conducted. This exploration aimed to unravel insights into the excited state behaviors of these molecules, as well as their redox properties. Such insights are crucial for future applications of these derivatives in diverse biological assays.

Resolution of isomeric multi-ruthenated porphyrins by travelling wave ion mobility mass spectrometry.

The ability of travelling wave ion mobility mass spectrometry (TWIM-MS) to resolve cationic meta/para and cis/trans isomers of mono-, di-, tri- and tetra-ruthenated supramolecular porphyrins was investigated. All meta isomers were found to be more compact than the para isomers and therefore mixtures of all isomeric pairs could be properly resolved with baseline or close to baseline peak-to-peak resolution (R(p-p)). Di-substituted cis/trans isomers were found, however, to present very similar drift times and could not be resolved. N(2) and CO(2) were tested as the drift gas, and similar α but considerably better values of R(p) and R(p-p) were always observed for CO(2).