Sumanene-carbazole conjugate with push-pull structure and its chemoreceptor application.

The first-of-its-kind tetra-substituted sumanene derivative, featuring the push-pull chromophore architecture, has been successfully designed. The inclusion of both strong electron-withdrawing (CF3) and electron-donating (carbazole) moieties in this buckybowl compound has enhanced the charge transfer characteristics of the molecule. This enhancement was supported by ultraviolet-visible (UV-Vis) and emission spectra analyses along with density functional theory (DFT) calculations. The application of the title sumanene-carbazole push-pull chromophore as a selective recognition material for cesium cations (Cs+) was also presented. The title compound exhibited effective and selective Cs+-trapping ability, characterized by a high apparent binding constant value (at the level of 105) and a low limit of detection (0.09-0.13 µM). Owing to the tuned optical properties of the title push-pull chromophore, this study marks the first time in sumanene-tethered chemoreceptor chemistry where efficient tracking of Cs+ binding was possible with both absorption and fluorescence spectroscopies. This work introduces a new approach toward tuning the structure of bowl-shaped optical chemoreceptors.

Monoclonal antibody-navigated carbon-encapsulated iron nanoparticles used for MRI-based tracking integrin receptors in murine melanoma.

Integrin beta-3 is a cell adhesion molecule that mediate cell-to-cell and cell-to-extracellular matrix communication. The major goal of this study was to explore melanoma cells (B16F10) based upon specific direct targeting of the ß3 subunit (CD61) in the integrin αvß3 receptor using carbon-encapsulated iron nanoparticles decorated with monoclonal antibodies (Fe@C-CONH-anti-CD61 and Fe@C-(CH2)2-CONH-anti-CD61). Both melanoma cells treated with nanoparticles as well as C57BL/6 mice bearing syngeneic B16-F10 tumors intravenously injected with nanoparticles were tested in preclinical MRI studies. The as-synthesized carbon-encapsulated iron nanoparticles functionalized with CD61 monoclonal antibodies have been successfully used as a novel targeted contrast agent for MRI-based tracking melanoma cells expressing the ß3 subunit of the integrin αvß3 receptor.

Supramolecular Chemistry of Sumanene.

Sumanene is a buckybowl molecule that is continuously attracting the attention of the scientific community because of its unique geometrical and physicochemical properties. This Minireview systematically summarizes advances and considerations regarding the applied supramolecular chemistry of sumanene. This work highlights the major fields in which potential or real applications of sumanene molecule have been reported to date, such as the design of sumanene-containing functional supramolecular materials and architectures, sumanene-based drug-delivery systems, or sumanene-tethered ion-selective molecular receptors. An assessment of the current status in the applied supramolecular chemistry of sumanene is provided, together with an emphasis on the key advances being made. Discussion on those milestones that are still to be achieved within this emerging field is also provided.

Graphene-encapsulated iron nanoparticles as a non-viral vector for gene delivery into melanoma cells.

The rapid progress of nanotechnology has led to use different nanomaterials for biomedical applications. Among them, graphene-encapsulated magnetic nanoparticles (GEMNS) are recognized as next generation carbon nanomaterials in translation cancer research. In this study, we utilized green fluorescence protein (GFP) expression plasmid DNA (pDNA) and GEMNS decorated with branched polyethyleneimine (PEI) to yield a novel transporter (GEMNS-PEI/pDNA) for gene delivery into melanoma cells (B16F10). The efficiency of transfection was examined using PCR and confocal microscopy. The studies show that the as-designed GEMNS-PEI construct is successfully used to transfect the melanoma cells with pDNA and it should be considered as a potent non-viral vector for introducing naked nucleic acids into eucaryotic cells.

Application of Monoferrocenylsumanenes Derived from Sonogashira Cross-Coupling or Click Chemistry Reactions in Highly Sensitive and Selective Cesium Cation Electrochemical Sensors.

This paper reports the synthesis and characterization of novel monoferrocenylsumanenes obtained by means of the Sonogashira cross-coupling or click chemistry reaction as well as their application in cesium cation electrochemical sensors. A new synthetic protocol based on Sonogashira cross-coupling was developed for the synthesis of monoferrocenylsumanene or ethynylsumanene. The click chemistry reaction was introduced to the sumanene chemistry through the synthesis of 1,2,3-triazole containing monoferrocenylsumanene. The designed synthetic methods for the modification of sumanene at the aromatic position proved to be efficient and proceeded under mild conditions. The synthesized sumanene derivatives were characterized by detailed spectroscopic analyses of the synthesized sumanene derivatives. The supramolecular interactions between cesium cations and the synthesized monoferrocenylsumanenes were spectroscopically and electrochemically investigated. Furthermore, the design of the highly selective and sensitive cesium cation fluorescence and electrochemical sensors comprising the synthesized monoferrocenylsumanenes as receptor compounds was analyzed. The tested cesium cation electrochemical sensors showed excellent limit of detection values in the range of 6.0-9.0 nM. In addition, the interactions between the synthesized monoferrocenylsumanenes and cesium cations were highly selective, which was confirmed by emission spectroscopy, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), and cyclic voltammetry.

Ultrasensitive voltammetric detection of SARS-CoV-2 in clinical samples.

In every pandemic, it is critical to test as many people as possible and keep track of the number of new cases of infection. Therefore, there is a need for novel, fast and unambiguous testing methods. In this study, we designed a sandwich-type voltammetric immunosensor based on unlabeled- and labeled with a redox probe antibodies against virus spike protein for fast and ultrasensitive detection of SARS-CoV-2. The process of the preparation of the sensor layer included chemisorption of cysteamine layer and covalent anchoring of antibody specific for the S1 subunit of the S protein. The source of the voltametric signal was the antibody labeled with the redox probe, which was introduced onto biosensor surface only after the recognition of the virus. This easy-to-handle immunosensor was characterized by a wide analytical range (2.0·10-7 to 0.20 mg·L-1) and low detection limit (8.0·10-8 mg·L-1 ≡ 0.08 pg·mL-1 ≡ 4 virions·µL-1). The utility of the designed device was also evidenced by the detection of SARS-CoV-2 in the clinical samples. Moreover, the main advantage and a huge novelty of the developed device, compared to those already existing, is the moment of generating the analytical signal of the redox probe that appears only after the virus recognition. Thus, our diagnostic innovation may considerably contribute to controlling the COVID-19 pandemic. The as-developed immunosensor may well offer a novel alternative approach for viral detection that could complement or even replace the existing methods.

Foliate-Targeting Quantum Dots-ß-Cyclodextrin Nanocarrier for Efficient Delivery of Unsymmetrical Bisacridines to Lung and Prostate Cancer Cells.

Targeted drug delivery by nanocarriers molecules can increase the efficiency of cancer treatment. One of the targeting ligands is folic acid (FA), which has a high affinity for the folic acid receptors, which are overexpressed in many cancers. Herein, we describe the preparation of the nanoconjugates containing quantum dots (QDs) and ß-cyclodextrin (ß-CD) with foliate-targeting properties for the delivery of anticancer compound C-2028. C-2028 was bound to the nanoconjugate via an inclusion complex with ß-CD. The effect of using FA in QDs-ß-CD(C-2028)-FA nanoconjugates on cytotoxicity, cellular uptake, and the mechanism of internalization in cancer (H460, Du-145, and LNCaP) and normal (MRC-5 and PNT1A) cells was investigated. The QDs-ß-CD(C-2028)-FA were characterized using DLS (dynamic light scattering), ZP (zeta potential), quartz crystal microbalance with dissipation (QCM-D), and UV-vis spectroscopy. The conjugation of C-2028 with non-toxic QDs or QDs-ß-CD-FA did not change the cytotoxicity of this compound. Confocal microscopy studies proved that the use of FA in nanoconjugates significantly increased the amount of delivered compound, especially to cancer cells. QDgreen-ß-CD(C-2028)-FA enters the cells through multiple endocytosis pathways in different levels, depending on the cell line. To conclude, the use of FA is a good self-navigating molecule in the QDs platform for drug delivery to cancer cells.

Aromatic Dendrimers Bearing 2,4,6-Triphenyl-1,3,5-triazine Cores and Their Photocatalytic Performance.

The synthesis of two novel aromatic dendrimers structurally derived from 1,3,5-tri[1,3-diphenyl(phenyl-5-yl)phenyl-4'-yl]benzene and bearing 2,4,6-triphenyl-1,3,5-triazine cores is reported. The obtained dendrimers were used for the OLEDs construction, as well as in the role of innovative photocatalysts for the very efficient and selective oxidation of various benzylamines to respective N-benzylidene benzylamines under mild conditions.

Controlled Drug Release and Cytotoxicity Studies of Beta-Lapachone and Doxorubicin Loaded into Cyclodextrins Attached to a Polyethyleneimine Matrix.

This work presents a new look at the application of cyclodextrins (CD) as a drug nanocarrier. Two different cyclodextrins (αCD, ßCD) were covalently conjugated to branched polyethylenimine (PEI), which was additionally functionalized with folic acid (PEI-ßCD-αCD-FA). Here, we demonstrated that the combination of αCD and ßCD enabled to load and control release of two anticancer drugs: doxorubicin (DOX) and beta-lapachone (beta-LP) (DOX in ß-CD and beta-LP into α-CD) via host-guest inclusion. The PEI-ßCD(DOX)-αCD-FA nanoconjugate was used to transport anticancer drugs into A549 lung cancer cells for estimation the cytotoxic and antitumor effect of this nanoconjugate. The presence of FA molecules should facilitate the penetration of studied nanoconjugate into the cell. Whereas, the non-cellular experiments proved that the drugs are released from the carrier mainly in the pH 4.0. The release mechanism is found to be anomalous in all studied cases.

Supramolecular Interactions between ß-Cyclodextrin and the Nucleobase Derivatives of Ferrocene.

Novel conjugates of ferrocene with uracil, 5-fluorouracil, tegafur, or acyclovir are reported. Their synthesis involved (i) the azide-alkyne 1,3-dipolar cycloaddition or (ii) the formation of the ester linkage. For the first time, we present an in-depth insight into the supramolecular interactions between ß-cyclodextrin and ferrocene-nucleobase derivatives. Spectroscopic and voltammetric analyses performed within this work suggested that the ferrocene or adamantane unit of the conjugates interacted with the ß-cyclodextrin's inner cavity. The methods applied for the supramolecular studies included 1H-1H ROESY NMR, 1H NMR titration, Fourier-transform infrared spectroscopy, cyclic voltammetry, fluorescence spectra titration, and 1H DOSY NMR. 1H DOSY NMR was also employed to evaluate the apparent binding constants for all the complexes. The ferrocene-acyclovir conjugate Fc-5 featured the highest apparent binding constant value among all the complexes tested.

Functionalization of graphene: does the organic chemistry matter?

Reactions applying amidation- or esterification-type processes and diazonium salts chemistry constitute the most commonly applied synthetic approaches for the modification of graphene-family materials. This work presents a critical assessment of the amidation and esterification methodologies reported in the recent literature, as well as a discussion of the reactions that apply diazonium salts. Common misunderstandings from the reported covalent functionalization methods are discussed, and a direct link between the reaction mechanisms and the basic principles of organic chemistry is taken into special consideration.

Novel non-covalent stable supramolecular ternary system comprising of cyclodextrin and branched polyethylenimine.

ABSTRACT: The synthesis of a novel supramolecular system comprising of branched polyethylenimine and cyclodextrin, is presented. The synthesis route is based on the self-assembly phenomena with the inclusion of solvent molecules. The systems are formed by a hydrogen-bonding network and host-guest type interactions between the building blocks. It was found that the native cyclodextrin and polyethylenimine are able to form stable systems when the reaction medium constitutes a polar solvent forming host-guest type complexes with cyclodextrin. A special consideration was paid on the detailed spectroscopic analyses of the obtained water-soluble constructs, including ROESY and diffusion-ordered (DOSY) NMR spectroscopy studies. The versatility and significance of DOSY technique for the analysis of the cyclodextrin complexes and its non-covalent systems with branched polymers, were presented. It was also found that the guest molecules that were incorporated in the complexes exhibited enhanced thermal stability. The morphological details in the solid state were obtained by scanning electron microscope.

Grind, shine and detect: mechanochemical synthesis of AIE-active polyaromatic amide and its application as molecular receptor of monovalent anions or nucleotides.

A mechanochemical synthesis of novel polyaromatic amide consisting of 1,3,5-triphenylbenzene and 1,1',2,2'-tetraphenylethylene skeletons has been established. The designed mechanochemical approach using readily available and low-cost equipment allowed a twofold increase in reaction yield, a 350-fold reduction in reaction time and a significant reduction in the use of harmful reactants in comparison to the solution synthesis method. The parameters of Green Chemistry were used to highlight the advantages of the developed synthesis method over the solution-based approach. The title compound was found to exhibit attractive optical properties related to the Aggregation-induced emission (AIE) behaviour. Taking the advantage of AIE-active properties of the synthesized polyaromatic amide, its application as effective and versatile molecular receptor towards detection of monovalent anions, as well as bio-relevant anions - nucleotides, has been demonstrated. The values of the binding constants were at the satisfactory level of 104, the detection limit values were low and ranged from 0.2 µM to 19.9 µM.

Expanding the library of sumanene molecular receptors for caesium-selective potentiometric sensors.

This paper reports the synthesis and characterization of eight sumanene molecular receptors for the selective recognition of caesium cations (Cs+). The sumanene derivatives differed in the number (from one to nine), type (electron donating or electron withdrawing) and method of the attachment (functionalization of sumanene at the benzylic or aromatic carbons) of substituents in the sumanene skeleton. The ultimate goal of this work was to investigate the prospective use of various sumanene derivatives in the design of Cs+-selective potentiometric sensors, thus, expanding the library of sumanene receptors for such applications. Spectroscopic fluorescence titration with caesium hexafluorophosphate revealed that the formation of sandwich complexes is highly favourable, but the steric hindrance of bulky substituents can disrupt this preference. In the case of triaryl-substituted sumanene derivatives, theoretical calculations show that, indeed, sandwich complexes are energetically more advantageous by 2.3 times than 1 : 1 complexes. Furthermore, such functionalization significantly increases receptor solubility in the polymeric membrane of the potentiometric sensors, which was quantitatively evaluated with the COSMO model.

Metal cations recognition by bowl-shaped N-pyrrolic polycyclic aromatic hydrocarbons.

Bowl-shaped, nitrogen-doped polycyclic aromatic hydrocarbons were examined for the first time as molecular receptors for the recognition of metal cations. Potentiometric and spectrofluorimetric assays, supported with density functional theory computations, revealed that the title compounds recognise metal cations with a special focus on caesium (Cs+) cations.

In vitro biological evaluation of a novel folic acid-targeted receptor quantum dot-ß-cyclodextrin carrier for C-2028 unsymmetrical bisacridine in the treatment of human lung and prostate cancers.

BACKGROUND: Traditional small-molecule chemotherapeutics usually do not distinguish tumors from healthy tissues. However, nanotechnology creates nanocarriers that selectively deliver drugs to their site of action. This work is the next step in the development of the quantum dot-ß-cyclodextrin-folic acid (QD-ß-CD-FA) platform for targeted and selected delivery of C-2028 unsymmetrical bisacridine in cancer therapy. METHODS: Herein, we report an initial biological evaluation (using flow cytometry and light microscopy) as well as cell migration analysis of QD-ß-CD(C-2028)-FA nanoconjugate and its components in the selected human lung and prostate cancer cells, as well as against their respective normal cells. RESULTS: C-2028 compound induced apoptosis, which was much stronger in cancer cells compared to normal cells. Conjugation of C-2028 with QDgreen increased cellular senescence, while the introduction of FA to the conjugate significantly decreased this process. C-2028 nanoencapsulation also reduced cell migration. Importantly, QDgreen and QDgreen-ß-CD-FA themselves did not induce any toxic responses in studied cells. CONCLUSIONS: In conclusion, the results demonstrate the high potential of a novel folic acid-targeted receptor quantum dot-ß-cyclodextrin carrier (QDgreen-ß-CD-FA) for drug delivery in cancer treatment. Nanoplatforms increased the amount of delivered compounds and demonstrated high suitability.

Click Chemistry Derived Hexa-ferrocenylated 1,3,5-Triphenylbenzene for the Detection of Divalent Transition Metal Cations.

The 1,3-dipolar cycloaddition reaction (click chemistry approach) was employed to create a hexa-ferrocenylated 1,3,5-triphenylbenzene derivative. Leveraging the presence of metal-chelating sites associated with 1,2,3-triazole moieties and 1,4-dinitrogen systems (ethylenediamine-like), as well as tridentate chelating sites (1,4,7-trinitrogen, diethylene triamine-like) systems, the application of this molecule as a chemosensor for divalent transition metal cations was investigated. The interactions were probed voltammetrically and spectrofluorimetrically against seven selected cations: iron(II) (Fe2+), cobalt(II) (Co2+), nickel(II) (Ni2+), copper(II) (Cu2+), zinc(II) (Zn2+), cadmium(II) (Cd2+), and manganese(II) (Mn2+). Electrochemical assays revealed good detection properties, with very low limits of detection (LOD), for Co2+, Cu2+, and Cd2+ in aqueous solution (0.03-0.09 µM). Emission spectroscopy experiments demonstrated that the title compound exhibited versatile detection properties in solution, specifically turn-off fluorescence behavior upon the addition of each tested transition metal cation. The systems were characterized by satisfactory Stern-Volmer constant values (105-106 M-1) and low LOD, especially for Zn2+ and Co2+ (at the nanomolar concentration level).

Surface-Bioengineered Extracellular Vesicles Seeking Molecular Biotargets in Lung Cancer Cells.

Personalized medicine is a new approach to modern oncology. Here, to facilitate the application of extracellular vesicles (EVs) derived from lung cancer cells as potent advanced therapy medicinal products in lung cancer, the EV membrane was functionalized with a specific ligand for targeting purposes. In this role, the most effective heptapeptide in binding to lung cancer cells (PTHTRWA) was used. The functionalization process of EV surface was performed through the C- or N-terminal end of the heptapeptide. To prove the activity of the EVs functionalized with PTHTRWA, both a model of lipid membrane mimicking normal and cancerous cell membranes as well as human adenocarcinomic alveolar basal epithelial cells (A549) and human normal bronchial epithelial cells (BEAS-2B) have been exposed to these bioconstructs. Magnetic resonance imaging (MRI) showed that the as-bioengineered PTHTRWA-EVs loaded with superparamagnetic iron oxide nanoparticle (SPIO) cargos reach the growing tumor when dosed intravenously in NUDE Balb/c mice bearing A549 cancer. Molecular dynamics (MD) in silico studies elucidated a high affinity of the synthesized peptide to the α5ß1 integrin. Preclinical safety assays did not evidence any cytotoxic or genotoxic effects of the PTHTRWA-bioengineered EVs.

Lack of cytotoxic and genotoxic effects of mPEG-silane coated iron(III) oxide nanoparticles doped with magnesium despite cellular uptake in cancerous and noncancerous lung cells.

Cytotoxic and genotoxic effects of novel mPEG-silane coated iron(III) oxide nanoparticles doped with magnesium (Mg0.1-γ-Fe2O3(mPEG-silane)0.5) have been investigated on human adenocarcinomic alveolar basal epithelial (A549) and human normal bronchial epithelial (BEAS-2B) cells. In the studies several molecular and cellular targets addressing to cell membrane, cytoplasm organelles and nucleus components were served as toxicological endpoints. The as-synthesized nanoparticles were found to be stable in the cell culture media and were examined for different concentration and exposure times. No cytotoxicity of the tested nanoparticles was found although these nanoparticles slightly increased reactive oxygen species in both cell types studied. Mg0.1-γ-Fe2O3(mPEG-silane)0.5 nanoparticles did not produce any DNA strand breaks and oxidative DNA damages in A549 and BEAS-2B cells. Different concentration of Mg0.1-γ-Fe2O3(mPEG-silane)0.5 nanoparticles and different incubation time did not affect cell migration. The lung cancer cells' uptake of the nanoparticles was more effective than in normal lung cells. Altogether, the results evidence that mPEG-silane coated iron(III) oxide nanoparticles doped with magnesium do not elucidate any deleterious effects on human normal and cancerous lung cells despite cellular uptake of these nanoparticles. Therefore, it seems reasonable to conclude that these novel biocompatible nanoparticles are promising candidates for further development towards medical applications.