Building blocks have been identified that can be functionalised by sequential nucleophilic aromatic substitution. Some examples are reported that involve the formation of cyclic benzodioxin and phenoxathiine derivatives from 4,5-difluoro-1,2-dinitrobenzene, racemic quinoxaline thioethers, and sulfones from 2,3-dichloroquinoxaline and (2-aminophenylethane)-2,5-dithiophenyl-4-nitrobenzene from 1-(2-aminophenylethane)-2-fluoro-4,5-dinitrobenzene. Four X-ray single-crystal structure determinations are reported, two of which show short intermolecular N-O…N \"π hole\" contacts.

Molecular interaction fields (MIFs) are three-dimensional interaction maps that describe the intermolecular interactions expected to be formed around target molecules. In this paper, a method for the fast computation of MIFs using the approximation functions of quantum mechanics-level MIFs of small model molecules is proposed. MIF functions of N-methylacetamide with chlorobenzene, bromobenzene, and iodobenzene probes were precisely approximated and used to calculate the MIFs on protein surfaces. This method appropriately reproduced halogen-bond-formable areas around the ligand-binding sites of proteins, where halogen bond formation was suggested in a previous study.

A new type of catalyst containing magnesium oxide modified with various modifiers ranging from bromine and iodine, to interhalogen compounds, hydrohalogenic acids, and alkyl halides have been prepared using chemical vapor deposition (CVD) and wet impregnation methods. The obtained systems were characterized using a number of methods: determination of the concentration of X- ions, surface area determination, powder X-ray diffraction (PXRD), surface acid-base strength measurements, TPD of probe molecules (acetonitrile, pivalonitrile, triethylamine, and n-butylamine), TPD-MS of reaction products of methyl iodide with MgO, and Fourier transform infrared spectroscopy (FTIR). The catalysts\' activity and chemoselectivity during transfer hydrogenation from ethanol to acrolein to allyl alcohol was measured. A significant increase in the activity of modified MgO (up to 80% conversion) in the transfer hydrogenation of acrolein was found, while maintaining high chemoselectivity (>90%) to allyl alcohol. As a general conclusion, it was shown that the modification of MgO results in the suppression of strong basic sites of the oxide, with a simultaneous appearance of Brønsted acidic sites on its surface. Independently, extensive research on the reaction progress of thirty alkyl halides with MgO was also performed in order to determine its ability to neutralize chlorinated wastes.

Understanding the distribution of halogenated organic compounds (HOCs) in marine sediments is essential for understanding the marine carbon and halogen cycling, and also important for assessing the ecosystem health. In this study, a method based on combustion-ion chromatography was developed for determination of the composition and abundance of HOCs in marine sediments. The method showed high accuracy, precision and reproducibility in determining the content of adsorbable organic halogens (AOX), including fluorine, chlorine and bromine (AOF, AOCl, AOBr) and the corresponding insoluble organic halogens (IOF, IOCl, IOBr, IOX), as well as total organic halogen contents (TOX). Application of the method in coastal and deep-sea sediments revealed high ratios of organic halogens in the organic carbon pool of marine sediments, suggesting that organic halogen compounds represent an important yet previously overlooked stock of carbon and energy in marine sediments. Both the TOX and the proportion of organohalogens in organic carbon (X:C ratio) showed an increasing trend from the coast to the deep-sea sediments, indicating an increased significance of HOCs in deep-sea environments. The developed method and the findings of this study lay the foundation for further studies on biogeochemical cycling of HOCs in the ocean.

The epidermal growth factor receptor (EGFR) is a pivotal target in cancer therapy due to its significance within the tyrosine kinase family. EGFR inhibitors like AG-1478 and PD153035, featuring a 4-anilinoquinazoline moiety, have garnered global attention for their potent therapeutic activities. While pre-clinical studies have highlighted the significant impact of halogen substitution at the C3\'-anilino position on drug potency, the underlying mechanism remains unclear. This study investigates the influence of halogen substitution (X = H, F, Cl, Br, I) on the structure, properties, and spectroscopy of halogen-substituted 4-anilinoquinazoline tyrosine kinase inhibitors (TKIs) using time-dependent density functional methods (TD-DFT) with the B3LYP functional. Our calculations revealed that halogen substitution did not induce significant changes in the three-dimensional conformation of the TKIs but led to noticeable alterations in electronic properties, such as dipole moment and spatial extent, impacting interactions at the EGFR binding site. The UV-visible spectra show that more potent TKI-X compounds typically have shorter wavelengths, with bromine\'s peak wavelength at 326.71 nm and hydrogen, with the lowest IC50 nM, shifting its lambda max to 333.17 nm, indicating a correlation between potency and spectral characteristics. Further analysis of the four lowest-lying conformers of each TKI-X, along with their crystal structures from the EGFR database, confirms that the most potent conformer is often not the global minimum structure but one of the low-lying conformers. The more potent TKI-Cl and TKI-Br exhibit larger deviations (RMSD > 0.65 Å) from their global minimum structures compared to other TKI-X (RMSD < 0.15 Å), indicating that potency is associated with greater flexibility. Dipole moments of TKI-X correlate with drug potency (ln(IC50 nM)), with TKI-Cl and TKI-Br showing significantly higher dipole moments (>8.0 Debye) in both their global minimum and crystal structures. Additionally, optical spectral shifts correlate with potency, as TKI-Cl and TKI-Br exhibit blue shifts from their global minimum structures, in contrast to other TKI-X. This suggests that optical reporting can effectively probe drug potency and conformation changes.

In this study, Fe3O4 nanoparticles (FeNPs) decorated with halogenated perylene diimides (PDIs) have been used for capturing VOCs (volatile organic compounds) through noncovalent binding. Concretely, we have used tetrachlorinated/brominated PDIs as well as a nonhalogenated PDI as a reference system. On the other hand, methanol, ethanol, propanol, and butanol were used as VOCs. Experimental studies along with theoretical calculations (the BP86-D3/def2-TZVPP level of theory) pointed to two possible and likely competitive binding modes (lone pair-π through the π-acidic surface of the PDI and a halogen bond via the σ-holes at the Cl/Br atoms). More in detail, thermal desorption (TD) experiments showed an increase in the VOC retention capacity upon increasing the length of the alkyl chain, suggesting a preference for the interaction with the PDI aromatic surface. In addition, the tetrachlorinated derivative showed larger VOC retention times compared to the tetrabrominated analog. These results were complemented by several state-of-the-art computational tools, such as the electrostatic surface potential analysis, the Quantum Theory of Atoms in Molecules (QTAIM), as well as the noncovalent interaction plot (NCIplot) visual index, which were helpful to rationalize the role of each interaction in the VOC···PDI recognition phenomena.

Fragment-based drug design using X-ray crystallography is a powerful technique to enable the development of new lead compounds, or probe molecules, against biological targets. This study addresses the need to determine fragment binding orientations for low-occupancy fragments with incomplete electron density, an essential step before further development of the molecule. Halogen atoms play multiple roles in drug discovery due to their unique combination of electronegativity, steric effects and hydrophobic properties. Fragments incorporating halogen atoms serve as promising starting points in hit-to-lead development as they often establish halogen bonds with target proteins, potentially enhancing binding affinity and selectivity, as well as counteracting drug resistance. Here, the aim was to unambiguously identify the binding orientations of fragment hits for SARS-CoV-2 nonstructural protein 1 (nsp1) which contain a combination of sulfur and/or chlorine, bromine and iodine substituents. The binding orientations of carefully selected nsp1 analogue hits were focused on by employing their anomalous scattering combined with Pan-Dataset Density Analysis (PanDDA). Anomalous difference Fourier maps derived from the diffraction data collected at both standard and long-wavelength X-rays were compared. The discrepancies observed in the maps of iodine-containing fragments collected at different energies were attributed to site-specific radiation-damage stemming from the strong X-ray absorption of I atoms, which is likely to cause cleavage of the C-I bond. A reliable and effective data-collection strategy to unambiguously determine the binding orientations of low-occupancy fragments containing sulfur and/or halogen atoms while mitigating radiation damage is presented.

This study reveals a new non-covalent interaction called a π-hole halogen bond, which is directional and potentially non-linear compared to its sister analog (σ-hole halogen bond). A π-hole is shown here to be observed on the surface of halogen in halogenated molecules, which can be tempered to display the aptness to form a π-hole halogen bond with a series of electron density-rich sites (Lewis bases) hosted individually by 32 other partner molecules. The [MP2/aug-cc-pVTZ] level characteristics of the π-hole halogen bonds in 33 binary complexes obtained from the charge density approaches (quantum theory of intramolecular atoms, molecular electrostatic surface potential, independent gradient model (IGM-δginter)), intermolecular geometries and energies, and second-order hyperconjugative charge transfer analyses are discussed, which are similar to other non-covalent interactions. That a π-hole can be observed on halogen in halogenated molecules is substantiated by experimentally reported crystals documented in the Cambridge Crystal Structure Database. The importance of the π-hole halogen bond in the design and growth of chemical systems in synthetic chemistry, crystallography, and crystal engineering is yet to be fully explicated.

Herein we have investigated the formation and interplay of several noncovalent interactions (NCIs) involved in the inhibition of human monoamine oxidase B (MAO B). Concretely, an inspection of the Protein Data Bank (PDB) revealed the formation of a halogen bond (HlgB) between a diphenylene iodonium (DPI) inhibitor and a water molecule present in the active site, in addition to a noncovalent network of interactions (e. g. lone pair-π, hydrogen bonding, OH-π, CH-π and π-stacking interactions) with surrounding protein residues. Several theoretical models were built to understand the strength and directionality features of the HlgB in addition to the interplay with other NCIs present in the active site of the enzyme. Besides, a computational study was carried out using DPI as HlgB donor and several electron rich molecules (CO, H2O, CH2O, HCN, pyridine, OCN-, SCN-, Cl- and Br-) as HlgB acceptors. The results were analyzed using several state-of-the-art computational tools. We expect that our results will be useful for those scientists working in the fields of rational drug design, chemical biology as well as supramolecular chemistry.

Mulching to conserve moisture has become an important agronomic practice in saline soil cultivation, and the effects of the dual stress of salinity and microplastics on soil microbes are receiving increasing attention. In order to investigate the effect of polyethylene microplastics on the microbial community of salinized soils, this study investigated the effects of different types (chloride and sulphate) and concentrations (weak, medium, and strong) of polyethylene (PE) microplastics (1% and 4% of the dry weight mass of the soil sample) on the soil microbial community by simulating microplastic contamination in salinized soil environments indoors. The results showed that:PE microplastics reduced the diversity and abundance of microbial communities in salinized soils and were more strongly affected by sulphate saline soil treatments. The relative abundance of each group of bacteria was more strongly changed in the sulphate saline soil treatment than in the chloride saline soil treatment. At the phylum level, the relative abundance of Proteobacteria was positively correlated with the abundance of fugitive PE microplastics, whereas the relative abundances of Bacteroidota, Actinobacteriota, and Acidobacteria were negatively correlated with the abundance of fugitive PE microplastics. At the family level, the relative abundances of Flavobacteriaceae, Alcanivoracaceae, Halomonadaceae, and Sphingomonasceae increased with increasing abundance of PE microplastics. The KEGG metabolic pathway prediction showed that the relative abundance of microbial metabolism and genetic information functions were reduced by the presence of PE microplastics, and the inhibition of metabolic functions was stronger in sulphate saline soils than in chloride saline soils, whereas the inhibition of genetic information functions was weaker than that in chloride saline soils. The secondary metabolic pathways of amino acid metabolism, carbohydrate metabolism, and energy metabolism were inhibited. It was hypothesized that the reduction in metabolic functions may have been caused by the reduced relative abundance of the above-mentioned secondary metabolic pathways. This study may provide a theoretical basis for the study of the effects of microplastics and salinization on the soil environment under the dual pollution conditions.