Novel Type of Tetranitrosyl Iron Salt: Synthesis,Structure and Antibacterial Activity of Complex [FeL’2(NO)2][FeL’L”(NO)2] with L’-thiobenzamide and L”-thiosulfate

In this work a new donor of nitric oxide (NO) with antibacterial properties, namely nitrosyl iron complex of [Fe(C₆H₅C-SNH₂)₂(NO)₂][Fe(C₆H₅C-SNH₂)(S₂O₃)(NO)₂] composition (complex I), has been synthesized and studied. Complex I was produced by the reduction of the aqueous solution of [Fe₂(S₂O₃)₂(NO)₂]²⁻ dianion by the thiosulfate, with the further treatment of the mixture by the acidified alcohol solution of thiobenzamide. Based on the structural study of I (X-ray analysis, quantum chemical calculations by NBO and QTAIM methods in the frame of DFT), the data were obtained on the presence of the NO…NO interactions, which stabilize the DNIC dimer in the solid phase. The conformation properties, electronic structure and free energies of complex I hydration were studied using B3LYP functional and the set of 6–31 + G(d,p) basis functions. The effect of an aquatic surrounding was taken into account in the frame of a polarized continuous model (PCM). The NO-donating activity of complex I was studied by the amperometry method using an “amiNO-700” sensor electrode of the “inNO Nitric Oxide Measuring System”. The antibacterial activity of I was studied on gram-negative (Escherichia coli) and gram-positive (Micrococcus luteus) bacteria. Cytotoxicity was studied using Vero cells. Complex I was found to exhibit antibacterial activity comparable to that of antibiotics, and moderate toxicity to Vero cells.     

A Comprehensive Study of N-Butyl-1H-Benzimidazole

Imidazole derivatives have found wide application in organic and medicinal chemistry. In particular, benzimidazoles have proven biological activity as antiviral, antimicrobial, and antitumor agents. In this work, we experimentally and theoretically investigated N-Butyl-1H-benzimidazole. It has been shown that the presence of a butyl substituent in the N position does not significantly affect the conjugation and structural organization of benzimidazole. The optimized molecular parameters were performed by the DFT/B3LYP method with 6-311++G(d,p) basis set. This level of theory shows excellent concurrence with the experimental data. The non-covalent interactions that existed within our compound N-Butyl-1H-benzimidazole were also analyzed by the AIM, RDG, ELF, and LOL topological methods. The color shades of the ELF and LOL maps confirm the presence of bonding and non-bonding electrons in N-Butyl-1H-benzimidazole. From DFT calculations, various methods such as molecular electrostatic potential (MEP), Fukui functions, Mulliken atomic charges, and frontier molecular orbital (HOMO-LUMO) were characterized. Furthermore, UV-Vis absorption and natural bond orbital (NBO) analysis were calculated. It is shown that the experimental and theoretical spectra of N-Butyl-1H-benzimidazole have a peak at 248 nm; in addition, the experimental spectrum has a peak near 295 nm. The NBO method shows that the delocalization of the aσ-electron from σ (C1–C2) is distributed into antibonding σ* (C1–C6), σ* (C1–N26), and σ* (C6–H11), which leads to stabilization energies of 4.63, 0.86, and 2.42 KJ/mol, respectively. Spectroscopic investigations of N-Butyl-1H-benzimidazole were carried out experimentally and theoretically to find FTIR vibrational spectra.     

Radiochemical Synthesis of 4-[18F]FluorobenzylAzide and Its Conjugation with EGFR-Specific Aptamers

Central nervous system tumors related to gliomas are of neuroectodermal origin and cover about 30% of all primary brain tumors. Glioma is not susceptible to any therapy and surgical attack remains one of the main approaches to its treatment. Preoperative tumor imaging methods, such as positron emission tomography (PET), are currently used to distinguish malignant tissue to increase the accuracy of glioma removal. However, PET is lacking a specific visualization of cells possessing certain molecular markers. Here, we report an application of aptamers to enhancing specificity in imaging tumor cells bearing the epidermal growth factor receptor (EGFR). Glioblastoma is characterized by increased EGFR expression, as well as mutations of this receptor associated with active division, migration, and adhesion of tumor cells. Since 2021, EGFR has been included into the WHO classification of gliomas as a molecular genetic marker. To obtain conjugates of aptamers GR20 and GOL1-specific to EGFR, a 4-[¹⁸F]fluorobenzylazide radiotracer was used as a synthon. For the production of the synthon, a method of automatic synthesis on an Eckert & Ziegler research module was adapted and modified using spirocyclic iodonium ylide as a precursor. Conjugation of 4-[¹⁸F]fluorobenzylazide and alkyne-modified aptamers was carried out using Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) with/without the TBTA ligand. As a result, it was possible to obtain ¹⁸F-labelled conjugates with 97% radiochemical purity for [¹⁸F]FB-GR20 and 98% for [¹⁸F]FB-GOL1. The obtained conjugates can be used for further studies in PET analysis on model animals with grafted glioblastoma.     

Evaluation of Genotoxicity and Toxicity of Annona muricata L. Seeds and In Silico Studies

Cancer is a multifactorial organic dysfunction for which great efforts are being devoted in searching for new treatments and therapeutic adjuvants. Annona muricata is a fruit that has promising activity against several types of cancer, as it contains acetogenins, the metabolite group associated with this action. Thus, the objective of this study was to evaluate, in experimental models, the toxic behavior of an extract and fraction rich in acetogenins from A. muricata seeds and study the acetogenin, Annonacin, in silico. Phytochemical characterization was made by thin layer chromatography, spectroscopy in the infrared region and nuclear magnetic resonance. Toxicity was evaluated by tests of Allium cepa and Artemia salina, and in silico studies using the SwissDock servers DockThor, PharmMapper, ADMETLab, PreADME, Osiris and ProTox. The extract and fraction showed genotoxic activity against meristematic cells of A. cepa, reducing the mitotic index; however, the extract produced great deleterious effects on the system, even causing cell necrosis. In A. Saline, the extract was more toxic than the fraction, but both samples were considered toxic. Annonacin was effectively linked to complex I, and presented different activities regarding toxicity. Thus, the results of this study are promising, highlighting the anticancer potential of acetogenins.     

Effect of Negative Ion Generation on Complex Plasma Structure Properties

We propose a low-density discharge plasma model that takes into account the impact of oxygen admixture in typical conditions of complex (dusty) plasmas. Numerical simulations based on this model show that the concentration of negative ions turns out to be very high, and they play an important role in the overall kinetics in this particular range of plasma conditions. The ambipolar diffusion electric field drags these negative ions into the center of the plasma. The density of negative ions is high enough to push the negatively charged dust component out of the center, both by weakening the radial electric field and by increasing the thermophoretic force. This phenomenon was observed in the published experiment and qualitatively supports the proposed model. Additionally, the proposed model allows an alternative explanation of the experiment.     

Exploring the Interplay between Drug Release and Targeting of Lipid-Like Polymer Nanoparticles Loaded with Doxorubicin

Targeted delivery of doxorubicin still poses a challenge with regards to the quantities reaching the target site as well as the specificity of the uptake. In the present approach, two colloidal nanocarrier systems, NanoCore-6.4 and NanoCore-7.4, loaded with doxorubicin and characterized by different drug release behaviors were evaluated in vitro and in vivo. The nanoparticles utilize a specific surface design to modulate the lipid corona by attracting blood-borne apolipoproteins involved in the endogenous transport of chylomicrons across the blood–brain barrier. When applying this strategy, the fine balance between drug release and carrier accumulation is responsible for targeted delivery. Drug release experiments in an aqueous medium resulted in a difference in drug release of approximately 20%, while a 10% difference was found in human serum. This difference affected the partitioning of doxorubicin in human blood and was reflected by the outcome of the pharmacokinetic study in rats. For the fast-releasing formulation NanoCore-6.4, the AUC_0→1h was significantly lower (2999.1 ng × h/mL) than the one of NanoCore-7.4 (3589.5 ng × h/mL). A compartmental analysis using the physiologically-based nanocarrier biopharmaceutics model indicated a significant difference in the release behavior and targeting capability. A fraction of approximately 7.310–7.615% of NanoCore-7.4 was available for drug targeting, while for NanoCore-6.4 only 5.740–6.057% of the injected doxorubicin was accumulated. Although the targeting capabilities indicate bioequivalent behavior, they provide evidence for the quality-by-design approach followed in formulation development.     

The Effect of Blood Contained in the Samples on the Metabolomic Profile of Mouse Brain Tissue: A Study by NMR Spectroscopy

(1) Recently, metabolic profiling of the tissue in the native state or extracts of its metabolites has become increasingly important in the field of metabolomics. An important factor, in this case, is the presence of blood in a tissue sample, which can potentially lead to a change in the concentration of tissue metabolites and, as a result, distortion of experimental data and their interpretation. (2) In this paper, the metabolomic profiling based on NMR spectroscopy was performed to determine the effect of blood contained in the studied samples of brain tissue on their metabolomic profile. We used 13 male laboratory CD-1^® IGS mice for this study. The animals were divided into two groups. The first group of animals (n = 7) was subjected to the perfusion procedure, and the second group of animals (n = 6) was not perfused. The brain tissues of the animals were homogenized, and the metabolite fraction was extracted with a water/methanol/chloroform solution. Samples were studied by high-frequency ¹H-NMR spectroscopy with subsequent statistical data analysis. The group comparison was performed with the use of the Student’s test. We identified 36 metabolites in the brain tissue with the use of NMR spectroscopy. (3) For the major set of studied metabolites, no significant differences were found in the brain tissue metabolite concentrations in the native state and after the blood removal procedure. (4) Thus, it was shown that the presence of blood does not have a significant effect on the metabolomic profile of the brain in animals without pathologies.     

Polyampholytic Graft Copolymers as Matrix for TiO2/Eosin Y/[Mo3S13]2− Hybrid Materials and Light-Driven Catalysis

An effective strategy to enhance the performance of inorganic semiconductors is moving towards organic-inorganic hybrid materials. Here, we report the design of core–shell hybrid materials based on a TiO₂ core functionalized with a polyampholytic (poly(dehydroalanine)-graft-(n-propyl phosphonic acid acrylamide) shell (PDha-g-PAA@TiO₂). The PDha-g-PAA shell facilitates the efficient immobilization of the photosensitizer Eosin Y (EY) and enables electronic interactions between EY and the TiO₂ core. This resulted in high visible-light-driven H₂ generation. The enhanced light-driven catalytic activity is attributed to the unique core–shell design with the graft copolymer acting as bridge and facilitating electron and proton transfer, thereby also preventing the degradation of EY. Further catalytic enhancement of PDha-g-PAA@TiO₂ was possible by introducing [Mo₃S₁₃]²⁻ cluster anions as hydrogen-evolution cocatalyst. This novel design approach is an example for a multi-component system in which reactivity can in future be independently tuned by selection of the desired molecular or polymeric species.     

Organic room-temperature phosphorescence from halogen-bonded organic frameworks: hidden electronic effects in rigidified chromophores

Development of purely organic materials displaying room-temperature phosphorescence (RTP) will expand the toolbox of inorganic phosphors for imaging, sensing or display applications. While molecular solids were found to suppress non-radiative energy dissipation and make the RTP process kinetically favourable, such an effect should be enhanced by the presence of multivalent directional non-covalent interactions. Here we report phosphorescence of a series of fast triplet-forming tetraethyl naphthalene-1,4,5,8-tetracarboxylates. Various numbers of bromo substituents were introduced to modulate intermolecular halogen-bonding interactions. Bright RTP with quantum yields up to 20% was observed when the molecule is surrounded by a Br⋯O halogen-bonded network. Spectroscopic and computational analyses revealed that judicious heavy-atom positioning suppresses non-radiative relaxation and enhances intersystem crossing at the same time. The latter effect was found to be facilitated by the orbital angular momentum change, in addition to the conventional heavy-atom effect. Our results suggest the potential of multivalent non-covalent interactions for excited-state conformation and electronic control.

The number and position of halogen substituents in purely organic π–π* chromophores critically affect the efficiency of phosphorescence.     

Stereoselective synthesis of unnatural α-amino acid derivatives through photoredox catalysis

A protocol for stereoselective C-radical addition to a chiral glyoxylate-derived N-sulfinyl imine was developed through visible light-promoted photoredox catalysis, providing a convenient method for the synthesis of unnatural α-amino acids. The developed protocol allows the use of ubiquitous carboxylic acids as radical precursors without prior derivatization. The protocol utilizes near-stoichiometric amounts of the imine and the acid radical precursor in combination with a catalytic amount of an organic acridinium-based photocatalyst. Alternative mechanisms for the developed transformation are discussed and corroborated by experimental and computational studies.

A protocol for stereoselective C-radical addition to a chiral glyoxylate-derived N-sulfinyl imine was developed through visible light-promoted photoredox catalysis, providing a convenient method for the synthesis of unnatural α-amino acids.