Design, Synthesis, and Photophysical Characterization of Biocompatible Thermally Activated Delayed Fluorescent Carbazole-Coumarins for Sensing Applications.

A series of fluorescent carbazole-coumarins exhibiting good photoluminescence quantum yields and thermally activated delayed fluorescence (TADF) properties have been designed and synthetized using computer-aided density functional theory calculations. The TADF characteristics of the carbazole-coumarins were systematically explored both in solution and in the solid state, utilizing poly(methyl methacrylate) (PMMA) as a matrix. The study revealed that the introduction of carbazole units onto the coumarin benzene ring led to compounds with thermally induced reverse intersystem crossing and delayed fluorescence. The study further demonstrated the potential utility of these compounds in practical applications by incorporating them into a Cmr-PMMA-based sensor for molecular oxygen detection. The resulting sensor exhibited promising performance, highlighting the adaptability and efficacy of the synthesized TADF-carbazole-coumarin compounds for reversible molecular oxygen sensing.

Advances in Hybrid Composites for Photocatalytic Applications: A Review.

Heterogeneous photocatalysts have garnered extensive attention as a sustainable way for environmental remediation and energy storage process. Water splitting, solar energy conversion, and pollutant degradation are examples of nowadays applications where semiconductor-based photocatalysts represent a potentially disruptive technology. The exploitation of solar radiation for photocatalysis could generate a strong impact by decreasing the energy demand and simultaneously mitigating the impact of anthropogenic pollutants. However, most of the actual photocatalysts work only on energy radiation in the Near-UV region (<400 nm), and the studies and development of new photocatalysts with high efficiency in the visible range of the spectrum are required. In this regard, hybrid organic/inorganic photocatalysts have emerged as highly potential materials to drastically improve visible photocatalytic efficiency. In this review, we will analyze the state-of-art and the developments of hybrid photocatalysts for energy storage and energy conversion process as well as their application in pollutant degradation and water treatments.

Continuous-Flow Synthesis of Arylthio-Cyclopropyl Carbonyl Compounds.

The straightforward, continuous-flow synthesis of cyclopropyl carbaldehydes and ketones has been developed starting from 2-hydroxycyclobutanones and aryl thiols. This acid-catalyzed mediated procedure allows access to the multigram and easily scalable synthesis of cyclopropyl adducts under mild conditions, using reusable Amberlyst-35 as a catalyst. The resins, suitably ground and used for filling steel columns, have been characterized via TGA, ATR, SEM and BET analyses to describe the physical-chemical properties of the packed bed and the continuous-flow system in detail. To highlight the synthetic versatility of the arylthiocyclopropyl carbonyl compounds, a series of selective oxidation reactions have been performed to access sulfoxide and sulfone carbaldehyde cyclopropanes, oxiranes and carboxylic acid derivatives.

Synthesis and Antiproliferative Effect of Halogenated Coumarin Derivatives.

A series of 6- and 6,8-halocoumarin derivatives have been investigated as potential antiproliferative compounds against a panel of tumor and normal cell lines. Cytotoxic effects were determined by the MTT method. To investigate the potential molecular mechanism involved in the cytotoxic effect, apoptosis assay, cell cycle analysis, reactive oxygen species (ROS), and reduced glutathione analysis were performed. Among the screened compounds, coumarins 6,8-dibromo-2-oxo-2H-chromene-3-carbonitrile 2h and 6,8-diiodo-2-oxo-2H-chromene-3-carbonitrile 2k exhibited the most antiproliferative effect in thyroid cancer-derived cells TPC-1. The apoptosis assay showed that both 2h and 2k induced apoptosis in TPC-1 thyroid cancer cells. According to these experiments, both coumarins induced a slight increase in TPC-1 cells in the G2/M phase and a decrease in the S phase. A significant increase in ROS levels was observed in TPC-1 treated with diiodocoumarin 2k, while the dibromocoumarin 2h induced a decrease in ROS in a dose and time-dependent manner.

A Brønsted acid catalyzed tandem reaction for the diastereoselective synthesis of cyclobuta-fused tetrahydroquinoline carboxylic esters.

A novel Brønsted acid catalyzed tandem reaction provides highly functionalized cyclobuta-fused tetrahydroquinoline carboxylic esters from anilines and 2-alkylenecyclobutanones in good to high yield. During the reaction a dynamic diastereoselective cyclization is achieved, resulting in the formation of three contiguous stereocenters with high stereoselectivity.

Lithiated three-membered heterocycles as chiral nucleophiles in the enantioselective synthesis of 1-oxaspiro[2,3]hexanes.

The reaction between configurably stable α-lithiated oxiranes and 3-substituted cyclobutanones allows obtaining enantiomerically enriched cyclobutanols (er > 98 : 2). These adducts, subjected to base-mediated Payne rearrangement, lead to the synthesis of a new class of oxaspirohexanes, useful precursors of 2,4-disubstituted cyclopentanones.

Visible light promoted continuous flow photocyclization of 1,2-diketones.

The continuous flow Norrish-Yang photocyclization of 1,2-diketones has been developed and used for the synthesis of a large number of functionalized 2-hydroxycyclobutanones, under blue light irradiation and employing acetone as a solvent. This eco-friendly procedure represents a valid alternative to the reactions carried out in batches thus reducing the reaction times, the formation of secondary products and simplifying the purification steps. The use of differently substituted diketone compounds has allowed us to obtain a wide range of 2 and 3-functionalized cyclobutanones, thus allowing the evaluation of the scope and limitations of this procedure.

Synthesis of ß-sulfinyl cyclobutane carboxylic amides via a formal α to ß sulphoxide migration process.

An original tandem reaction consisting of a thermal elimination-addition process was developed. Highly substituted ß-sulfinyl cyclobutane carboxylic acid derivatives were obtained from isomeric α-sulfinyl derivatives in a single operation in good to high yields and with high trans diastereoselectivity.

Preparation of Cyclobutene Acetals and Tricyclic Oxetanes through Photochemical Tandem and Cascade Reactions.

We describe a photochemical reaction using two starting materials, a cyclopent-2-enone and an alkene, which are transformed in a controlled manner via the initial [2+2]-photocycloaddition adducts into cyclobutene aldehydes (conveniently trapped as stable acetals) or unprecedented angular tricyclic 4:4:4 oxetane-containing skeletons. These compounds are formed through tandem or triple cascade photochemical reaction processes, respectively. Small libraries of each compound class were prepared, thus suggesting that this photochemistry approach opens new opportunities for synthesis design and for widening molecular diversity.

Acid-catalyzed reaction of 2-hydroxycyclobutanone with benzylic alcohols.

The acid-promoted syntheses of 2-(benzyloxy)cyclobutanones and bis(benzyloxy)dioxatricyclo decanes were achieved starting from 2-hydroxycyclobutanone and variously functionalized benzyl alcohols. The reaction sequences afforded the desired products in good to high yields and in a solvent-dependent chemoselective fashion.

Synthesis of 2,2-bis(pyridin-2-yl amino)cyclobutanols and their conversion into 5-(pyridin-2-ylamino)dihydrofuran-2(3H)-ones.

A two-step protocol is presented for the preparation of 5-(pyridin-2-ylamino)dihydrofuran-2(3H)-ones from 2-hydroxycyclobutanone and some 2-aminopyridines via a catalyst-free synthesis of 2,2-bis(pyridin-2-ylamino)cyclobutanols followed by Dess-Martin periodinane mediated ring expansion.

Deracemizing organocatalyzed Michael addition reactions of 2-(arylthio)cyclobutanones with ß-nitrostyrenes.

Organocatalyzed Michael addition reactions of 2-(arylthio)cyclobutanones with trans-ß-nitrostyrenes have been carried out using a bifunctional thiourea-primary amine catalyst, providing diastereoisomerically and enantiomerically enriched 2-alkyl-2-(arylthio)cyclobutanones having two contiguous stereocenters of which one is a chiral quaternary center. The absolute configuration of these novel adducts was assigned by X-ray diffraction analysis and a transition-state model is proposed to explain the observed stereoselectivities.

Exploring the Antiviral Potential of Esters of Cinnamic Acids with Quercetin.

Severe acute respiratory syndrome-related Coronavirus 2 (SARS-CoV-2) has infected more than 762 million people to date and has caused approximately 7 million deaths all around the world, involving more than 187 countries. Although currently available vaccines show high efficacy in preventing severe respiratory complications in infected patients, the high number of mutations in the S proteins of the current variants is responsible for the high level of immune evasion and transmissibility of the virus and the reduced effectiveness of acquired immunity. In this scenario, the development of safe and effective drugs of synthetic or natural origin to suppress viral replication and treat acute forms of COVID-19 remains a valid therapeutic challenge. Given the successful history of flavonoids-based drug discovery, we developed esters of substituted cinnamic acids with quercetin to evaluate their in vitro activity against a broad spectrum of Coronaviruses. Interestingly, two derivatives, the 3,4-methylenedioxy 6 and the ester of acid 7, have proved to be effective in reducing OC43-induced cytopathogenicity, showing interesting EC50s profiles. The ester of synaptic acid 7 in particular, which is not endowed with relevant cytotoxicity under any of the tested conditions, turned out to be active against OC43 and SARS-CoV-2, showing a promising EC50. Therefore, said compound was selected as the lead object of further analysis. When tested in a yield reduction, assay 7 produced a significant dose-dependent reduction in viral titer. However, the compound was not virucidal, as exposure to high concentrations of it did not affect viral infectivity, nor did it affect hCoV-OC43 penetration into pre-treated host cells. Additional studies on the action mechanism have suggested that our derivative may inhibit viral endocytosis by reducing viral attachment to host cells.

Stereocontrolled synthesis and functionalization of cyclobutanes and cyclobutanones.

In the last decade a certain number of new cyclobutane and cyclobutanone synthesis and functionalization protocols have been published. Organo- and biocatalyzed eco-friendly approaches to cyclobutane-containing molecules have been developed with interesting results. Also, successful new total synthesis of bioactive compounds and drugs have been recently reported where a four membered ring represented the key intermediate. Therefore, the rising interest in this field represents a great point of discussion for the scientific community, disclosing the synthetic potential of strained four membered ring carbocyclic compounds. Herein we report a critical survey on the literature concerning the enantiocontrolled synthesis and functionalization of cyclobutane derivatives, with particular attention to metal-free, low impact methodologies, published during the period 2000-2013.

SARS-CoV-2 Fusion Peptide Conjugated to a Tetravalent Dendrimer Selectively Inhibits Viral Infection.

Fusion is a key event for enveloped viruses, through which viral and cell membranes come into close contact. This event is mediated by viral fusion proteins, which are divided into three structural and functional classes. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein belongs to class I fusion proteins, characterized by a trimer of helical hairpins and an internal fusion peptide (FP), which is exposed once fusion occurs. Many efforts have been directed at finding antivirals capable of interfering with the fusion mechanism, mainly by designing peptides on the two heptad-repeat regions present in class I viral fusion proteins. Here, we aimed to evaluate the anti-SARS-CoV-2 activity of the FP sequence conjugated to a tetravalent dendrimer through a classical organic nucleophilic substitution reaction (SN2) using a synthetic bromoacetylated peptide mimicking the FP and a branched scaffold of poly-L-Lysine functionalized with cysteine residues. We found that the FP peptide conjugated to the dendrimer, unlike the monomeric FP sequence, has virucidal activity by impairing the attachment of SARS-CoV-2 to cells. Furthermore, we found that the peptide dendrimer does not have the same effects on other coronaviruses, demonstrating that it is selective against SARS-CoV-2.

Organocatalytic asymmetric tandem condensation-intramolecular rearrangement-protonation: an approach to optically active α-amino thioester derivatives.

An unprecedented and conceptually novel chiral Brønsted base/Brønsted acid catalytic method for the enantioselective synthesis of α-amino thioesters through a tandem condensation-intramolecular rearrangement-protonation has been developed which provides a number of important synthetic building blocks in good yield and with moderate to good enantioselectivities.

Very high stereoselectivity in organocatalyzed desymmetrizing aldol reactions of 3-substituted cyclobutanones.

N-Phenylsulfonyl (S)-proline catalyzes the direct aldol reaction of 3-substituted cyclobutanones and aryl aldehydes in good yield and with excellent diastereoselectivity and enantioselectivity. This desymmetrization process provides highly functionalized cyclobutanones with control over three contiguous stereogenic centers.

Towards N-N-Doped Carbon Dots: A Combined Computational and Experimental Investigation.

The introduction of N doping atoms in the carbon network of Carbon Dots is known to increase their quantum yield and broaden the emission spectrum, depending on the kind of N bonding introduced. N doping is usually achieved by exploiting amine molecules in the synthesis. In this work, we studied the possibility of introducing a N-N bonding in the carbon network by means of hydrothermal synthesis of citric acid and hydrazine molecules, including hydrated hydrazine, di-methylhydrazine and phenylhydrazine. The experimental optical features show the typical fingerprints of Carbon Dots formation, such as nanometric size, excitation dependent emission, non-single exponential decay of photoluminescence and G and D vibrational bands in the Raman spectra. To explain the reported data, we performed a detailed computational investigation of the possible products of the synthesis, comparing the simulated absorbance spectra with the experimental optical excitation pattern. The computed Raman spectra corroborate the hypothesis of the formation of pyridinone derivatives, among which the formation of small polymeric chains allowed the broad excitation spectra to be experimentally observed.

One-ligand catalytic asymmetric deprotonation of a phosphine borane: synthesis of P-stereogenic bisphosphine ligands.

A new protocol for the catalytic asymmetric deprotonation of a phosphine borane using s-BuLi and substoichiometric quantities of chiral diamines is reported. The method involves three sequential additions of s-BuLi, and use of (-)-sparteine or the (+)-sparteine surrogate facilitates access to P-stereogenic phosphines with opposite configuration. The method is exemplified by the catalytic asymmetric synthesis of each enantiomer of precursors to QuinoxP*, trichickenfootphos, and Mini-PHOS.

4-Nitrophenol Efficient Photoreduction from Exfoliated and Protonated Phenyl-Doped Graphitic Carbon Nitride Nanosheets.

The photoreduction of 4-nitrophenol to 4-aminophenol by means of protonated and exfoliated phenyl-doped carbon nitride is reported. Although carbon nitride-based materials have been recognized as efficient photocatalysts, the photoreduction of 4-nitrophenol to 4-aminophenol is not allowed because of the high recombination rate of the photogenerated electron-hole pairs. In this paper, we show the morphology effects on the photoactivity in phenyl-doped carbon nitride. Structural (TEM, XRD, Raman) and optical characterization (absorption, photoluminescence) of the protonated and exfoliated phenyl-doped carbon nitride (hereafter pePhCN) is reported. The increased photocatalytic efficiency, with respect to the bulk material, is underlined by the calculation of the kinetic constant of the photoreduction process (2.78 × 10-1 min-1 and 3.54 × 10-3 min-1) for pePhCN and bulk PhCN, respectively. Finally, the detailed mechanism of the photoreduction process of 4-nitrophenol to 4-aminophenol by modified phenyl carbon nitride is proposed.