Search Results (31)

The increasing prevalence of drug-resistant microorganisms has prompted research into novel antimicrobial compounds, with 2-thiophene carboxylic acid thiourea derivatives showing promise for future therapeutic applications. However, the poor water solubility of these compounds limits their practical use. This study investigates the formation and characterization of inclusion complexes between 2-hydroxypropyl-β-cyclodextrin (HPβCD) and 2-thiophene carboxylic acid-halogenated (chlorine-, bromine-, and iodine-) thiourea derivatives, seeking to improve their physicochemical properties. The dynamic light scattering (DLS) measurements and UV-Vis spectroscopy provided information related to thiourea–HPβCD aggregates and stoichiometry. Solid-state inclusion compounds and physical mixtures were prepared in two different molar ratios (thioureas:HPβCD = 1:1 and 1:2), and the morphology of the resulting powders was observed by scanning electron microscopy (SEM). Thermogravimetry (TG) and differential scanning calorimetry (DSC) (TG-DSC) coupled analysis were used to analyze thermal profiles in the temperature range of 25 °C to 600 °C, while the spectral data obtained by Fourier transform infrared spectroscopy (FTIR) provided the characteristic vibrational bands of the pure guest molecules and data corresponding to the structural and chemical changes in the host–guest systems. The structural and thermal analyses revealed significant interactions between the host and thioureas molecules, with evidence of possible interactions involving two cyclodextrin molecules. The results demonstrate the presence of intermediate stoichiometry in the inclusion compounds, with possible enhancement of the therapeutic potential of these thiourea derivatives. Full article

The molecular electrostatic surface potential (MESP) has become a key theoretical tool for probing reactivity in chemical systems. It reveals electrophilic and nucleophilic regions on molecular surfaces, underpinning the understanding of noncovalent interactions such as hydrogen, triel, tetrel, pnictogen, chalcogen, halogen, matere, and aerogen bonding, among many others. These interactions, driven by Coulombic attraction, govern aggregation in molecular and supramolecular systems across solid, liquid, and gas phases. MESP applications span crystal engineering, polymers, biology, catalysis, photovoltaics, and drug discovery. While limitations exist—such as the arbitrariness in defining isodensity surfaces—its impact on advancing both theoretical and applied chemical research is substantial. This review outlines the conceptual foundations of MESP and highlights its broad relevance across the chemical sciences. Full article

The emergence of drug-resistant Candida species has created an urgent need for non-toxic molecules that inhibit fungal growth, biofilm development, and hyphal formation. In this study, fifty multi-halogenated indole derivatives were screened against ten Candida species, including azole-resistant C. albicans, C. auris, C. glabrata, and C. parapsilosis. Among them, 4,6-dibromoindole and 5-bromo-4-chloroindole exhibited the strongest antifungal and antibiofilm effects, with minimum inhibitory concentration (MIC) values of 10–50 µg/mL, outperforming ketoconazole and comparable to miconazole. Both di-halogenated indoles markedly inhibited cell aggregation, yeast-to-hyphae transition, and induced reactive oxygen species (ROS) accumulation, contributing to fungicidal activity. Microscopic analyses revealed the disruption of hyphal networks and reduced biofilm biomass. They showed moderate cytotoxicity in human hepatocellular carcinoma (HepG2) cells (median lethal dose, LD₅₀ = 35.5 µg/mL and 75.3 µg/mL) and low phytotoxicity in plant assays. The quantitative structure–activity relationship (QSAR) model identified halogen substitution at C4, C5, and C6 positions as optimal for antifungal activity due to enhanced hydrophobic and electron-withdrawing effects. Together, these findings demonstrate that di-halogenated indoles serve as potent, low-toxicity inhibitors of Candida growth, biofilms, and morphogenesis, providing a promising scaffold for next-generation antifungal agents targeting drug-resistant Candida species. Full article

As an eco-friendly flame-retardant additive, magnesium hydroxide (MH) is widely employed in low-smoking, halogen-free polymer materials due to its environmentally benign nature. In order to enhance flame retardancy performance, the modified MH was modified with tetrakis(hydroxymethyl)phosphonium sulfate (THPS) by a one-pot hydrothermal method. The resulting morphology was characterized using scanning electron microscopy (SEM), and it shows the dispersion of nanometer particles and almost no aggregation. The X-ray photoelectron spectroscopy (XPS) along with Raman spectroscopy show that the THPS is connected with the Mg(OH)₂ by chemical bond. The sample was incorporated into ethylene–vinyl acetate (EVA) to evaluate the flame retardancy was assessed via limiting oxygen index (LOI) and vertical burning tests (UL-94). The results show that THPS modified MH effectively enhanced the flame retardancy, achieving a V-0 rating and an LOI value of 31.3%. In addition, the composites retain good mechanical integrity. The thermal analysis with TGA and DTG shows the formation of the MgO decomposition product, along with water vapor and phosphorus-containing radicals released by modified MH in the combustion process, forming a strong flame-retardant protective layer. In addition, the maximum smoke density of EVA/MHP-3 composite was 155.4, lower than 411.3 for EVA/MH, with a 62.2% reduction in total smoke production. The result shows that THPS is effective for improving the flame-retardant efficiency of inorganic metal hydroxide in polymer composites. Full article

Perovskite as an emerging semiconductor luminescent material has attracted widespread attention due to its simple preparation, high luminescence quantum yield, high color purity, tunable spectrum, and ability to cover the entire visible light band. However, due to the influence of water or other highly polar solvents, oxygen, temperature, and radiation, perovskite nanocrystals will aggregate or collapse in the lattice, eventually leading to luminescence quenching. This study starts from the postprocessing of perovskite, uses methyl methacrylate as the monomer and TPO as the photoinitiator, and encapsulates the perovskite powder prepared by the hot injection method through ultraviolet light initiation. A method is proposed to improve the luminescence and crystal structure stability of perovskite. By eliminating the influence of environmental factors on perovskite nanocrystals through the dense structure formed by organic polymers, the resistance of perovskite to strong polar solvents such as water will be greatly improved, and it has great potential in the protection of perovskite. Finally, by changing the proportion of halogen elements in the perovskite resin to change the color of the luminescent resin, a fluorescent coating emitting light in all visible light bands is prepared. Fluorescent coatings are widely used in life and industry fields such as plastics, sol, and paper. Full article

Fentanyl (FTN) and synthetic analogs of FTN continue to ravage populations across the globe, including in the United States where opioids are increasingly being used and abused and are causing a staggering and growing number of overdose deaths each year. This growing pandemic is worsened by the ease with which FTN can be derivatized into numerous derivatives. Understanding the chemical properties/behaviors of the FTN class of compounds is critical for developing effective chemical detection schemes using nanoparticles (NPs) to optimize important chemical interactions. Halogen bonding (XB) is an intermolecular interaction between a polarized halogen atom on a molecule and e⁻-rich sites on another molecule, the latter of which is present at two or more sites on most fentanyl-type structures. Density functional theory (DFT) is used to identify these XB acceptor sites on different FTN derivatives. The high toxicity of these compounds necessitated a “fragmentation” strategy where smaller, non-toxic molecules resembling parts of the opioids acted as mimics of XB acceptor sites present on intact FTN and its derivatives. DFT of the fragments’ interactions informed solution measurements of XB using ¹⁹F NMR titrations as well as electrochemical measurements of XB at self-assembled monolayer (SAM)-modified electrodes featuring XB donor ligands. Gold NPs, known as monolayer-protected clusters (MPCs), were also functionalized with strong XB donor ligands and assembled into films, and their interactions with FTN “fragments” were studied using voltammetry. Ultimately, spectroscopy and TEM analysis were combined to study whole-molecule FTN interactions with the functionalized MPCs in solution. The results suggested that the strongest XB interaction site on FTN, while common to most of the drug’s derivatives, is not strong enough to induce NP-aggregation detection but may be better exploited in sensing schemes involving films. Full article

The α-synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of α-synuclein aggregates (α-syn) in the brain. Currently, there is no suitable tracer to enable a definitive early diagnosis of these diseases. We reported candidates based on 4,4′-disarylbisthiazole (DABTA) scaffold with a high affinity towards α-syn and excellent selectivity over Aβ and tau fibrils. Based on prior in silico studies, a focused library of 23 halogen-containing and O-methylated DABTAs was prepared. The DABTAs were synthesized via a modified two-step Hantzsch thiazole synthesis, characterized, and used in competitive binding assays against [³H]PiB and [³H]DCVJ. The DABTAs were obtained with an overall chemical yield of 15–71%, and showed a calculated lipophilicity of 2.5–5.7. The ligands demonstrated an excellent affinity to α-syn with both [³H]PiB and [³H]DCVJ: K_i 0.1–4.9 nM and up to 20–3900-fold selectivity over Aβ and tau fibrils. It could be concluded that in silico simulation is useful for the rational design of a new generation of DABTAs. Further investigation of the leads in the next step is encouraged: radiolabeling of the ligands with radioisotopes such as fluorine-18 or carbon-11 for in vivo, ex vivo, and translational research and for further in vitro experiments on human-derived protein aggregates. Full article

Statistical analysis of halogen...halogen intermolecular distances was performed for three sets of homomolecular crystals under normal conditions: C–Hal1...Hal2–C distances in crystals consisting of: (i) organic compounds (set Org); (ii) organometallic compounds (set Orgmet); and (iii) distances M1–Hal1...Hal2–M2 (set MHal) (in all cases Hal1 = Hal2, and in MHal M1 = M2, M is any metal). When analyzing C–Hal...Hal–C distances, a new method for estimating the values of van der Waals radii is proposed, based on the use of two subsets of distances: (i) the shortest distances from each substance less than a threshold; and (ii) all C–Hal...Hal–C distances less than the same threshold. As initial approximations for these thresholds for different Hal, the R_agg values previously introduced in investigations with the participation of the author were used (R_agg values make it possible to perform a statistical assessment of the presence of halogen aggregates in crystals). The following values are recommended in this work to be used as universal values for crystals of organic and organometallic compounds: R_F = 1.57, R_Cl = 1.90, R_Br = 1.99, and R_I = 2.15 Å. They are in excellent agreement with the results of some other works but significantly (by 0.10–0.17 Å) greater than the commonly used values. For the Orgmet set, slightly lower values for R_I (2.11–2.09 Å) were obtained, but number of the C–I...I–C distances available for analysis was significantly smaller than in the other subgroups, which may be the reason for the discrepancy with value for the Org set (2.15 Å). Statistical analysis of the M–Hal...Hal–M distances was performed for the first time. A Hal-aggregation coefficient for M–Hal bonds is proposed, which allows one to estimate the propensity of M–Hal groups with certain M and Hal to participate in Hal-aggregates formed by M–Hal...Hal–M contacts. In particular, it was found that, for the Hg–Hal groups (Hal = Cl, Br, I), there is a high probability that the crystals have Hg–Hal...Hal–Hg distances with length ≤ R_agg. Full article

The development of high-performance fluorescence probes has been an active area of research. In the present work, two new pH sensors Zn-3,5-Cl-saldmpn and Zn-3,5-Br-saldmpn based on a halogenated Schiff ligand (3,5-Cl-saldmpn = N, N${}^{\prime }$-(3,3${}^{\prime }$-dipropyhnethylamine) bis (3,5-chlorosalicylidene)) with linearity and a high signal-to-noise ratio were developed. Analyses revealed an exponential intensification in their fluorescence emission and a discernible chromatic shift upon pH increase from 5.0 to 7.0. The sensors could retain over 95% of their initial signal amplitude after 20 operational cycles, demonstrating excellent stability and reversibility. To elucidate their unique fluorescence response, a non-halogenated analog was introduced for comparison. The structural and optical characterization suggested that the introduction of halogen atoms can create additional interaction pathways between adjacent molecules and enhance the strength of the interaction, which not only improves the signal-to-noise ratio but also forms a long-range interaction process in the formation of the aggregation state, thus enhancing the response range. Meanwhile, the above proposed mechanism was also verified by theoretical calculations. Full article

The synthesis and spectroscopic characterisation of six bis(5-X-pyridine-2-yl)isophthalamides (X = H, F, Br, Cl, I, NO₂) are reported, together with five crystal structure analyses (for X = H, F to I). The isophthalamides span a range of conformations as syn/anti (H-DIP; I-DIP), anti/anti- (F-DIP; Br-DIP) and with both present in ratio 2:1 in Cl-DIP. The essentially isostructural F-DIP and Br-DIP molecules (using strong amide…amide interactions) aggregate into 2D molecular sheets that align with either F/H or Br atoms at the sheet surfaces (interfaces), respectively. Sheets are linked by weak C-H⋯F contacts in F-DIP and by Br⋯Br halogen bonding interactions as a ‘wall of bromines’ at the Br atom rich interfaces in Br-DIP. Cl-DIP is an unusual crystal structure incorporating both syn/anti and anti/anti molecular conformations in the asymmetric unit (Z’ = 3). The I-DIP•½(H₂O) hemihydrate structure has a water molecule residing on a twofold axis between two I-DIPs and has hydrogen and N⋯I (N_c = 0.88) halogen bonding. The hydrate is central to an unusual synthon and involved in six hydrogen bonding interactions/contacts. Contact enrichment analysis on the Hirshfeld surface demonstrates that F-DIP, Cl-DIP and Br-DIP have especially over-represented halogen···halogen interactions. With the F-DIP, Cl-DIP and Br-DIP molecules having an elongated skeleton, the formation of layers of halogen atoms in planes perpendicular to the long unit cell axis occurs in the crystal packings. All six DIPs were analysed by ab initio calculations and conformational analysis; comparisons are made between their minimized structures and the five crystal structures. In addition, physicochemical properties are compared and assessed. Full article

Unraveling the binding preferences involved in the formation of a supramolecular complex is key to properly understand molecular recognition and aggregation phenomena, which are of pivotal importance to biology. The halogenation of nucleic acids has been routinely carried out for decades to assist in their X-ray diffraction analysis. The incorporation of a halogen atom on a DNA/RNA base not only affected its electronic distribution, but also expanded the noncovalent interactions toolbox beyond the classical hydrogen bond (HB) by incorporating the halogen bond (HalB). In this regard, an inspection of the Protein Data Bank (PDB) revealed 187 structures involving halogenated nucleic acids (either unbound or bound to a protein) where at least 1 base pair (BP) exhibited halogenation. Herein, we were interested in disclosing the strength and binding preferences of halogenated A···U and G···C BPs, which are predominant in halogenated nucleic acids. To achieve that, computations at the RI-MP2/def2-TZVP level of theory together with state of the art theoretical modeling tools (including the computation of molecular electrostatic potential (MEP) surfaces, the quantum theory of “Atoms in Molecules” (QTAIM) and the non-covalent interactions plot (NCIplot) analyses) allowed for the characterization of the HB and HalB complexes studied herein. Full article

Current antiplatelet therapies have several clinical complications and are mostly irreversible in terms of suppressing platelet activity; hence, there is a need to develop improved therapeutic agents. Previous studies have implicated RhoA in platelet activation. Here, we further characterized the lead RhoA inhibitor, Rhosin/G04, in platelet function and present structure–activity relationship (SAR) analysis. A screening for Rhosin/G04 analogs in our chemical library by similarity and substructure searches revealed compounds that showed enhanced antiplatelet activity and suppressed RhoA activity and signaling. A screening for Rhosin/G04 analogs in our chemical library using similarity and substructure searches revealed compounds that showed enhanced antiplatelet activity and suppressed RhoA activity and signaling. SAR analysis revealed that the active compounds have a quinoline group optimally attached to the hydrazine at the 4-position and halogen substituents at the 7- or 8-position. Having indole, methylphenyl, or dichloro-phenyl substituents led to better potency. Rhosin/G04 contains a pair of enantiomers, and S-G04 is significantly more potent than R-G04 in inhibiting RhoA activation and platelet aggregation. Furthermore, the inhibitory effect is reversible, and S-G04 is capable of inhibiting diverse-agonist-stimulated platelet activation. This study identified a new generation of small-molecule RhoA inhibitors, including an enantiomer capable of broadly and reversibly modulating platelet activity. Full article

Recent literature on this topic highlights the significance of adding malononitrile moiety and halogen substituents to the squaraine scaffold to create redshifted fluorophores into the near-infrared optical region. Herein, a redshifted hydrophobic squaraine dye is synthesized via a three-step pathway. The reported dye is characterized by spectroscopic techniques, such as ¹H NMR, ¹⁹F NMR, ¹³C NMR, and high-resolution mass spectroscopy. Optical properties are also reported using absorbance and fluorescence studies. The hydrophobicity of the dye was studied with absorbance and fluorescence spectroscopy in water–methanol mixtures and showed J-aggregates as the water concentration increased. Density functional theory calculations were conducted to assess its electron delocalization as well as observe the three-dimensional geometry of the dye as a result of the dicyanomethylene modification and the two bulky phenyl groups. Full article

The fluorination strategy is one of the most efficient and popular molecular modification methods to develop new materials for organic photovoltaic (OPV) cells. For OPV materials, it is a broad agreement that fluorination can reduce the energy level and change the morphology of active layers. To explore the effect of fluorination on small molecule acceptors, we selected two non-fullerene acceptors (NFA) based bulk heterojunction (BHJ) films, involving PM6:Y6 and PM6:Y5 as model systems. The electron mobilities of the PM6:Y5 and PM6:Y6 BHJ films are 5.76 × 10⁻⁷ cm²V⁻¹s⁻¹ and 5.02 × 10⁻⁵ cm²V⁻¹s⁻¹ from the space-charge-limited current (SCLC) measurements. Through molecular dynamics (MD) simulation, it is observed that halogen bonds can be formed between Y6 dimers, which can provide external channels for electron carrier transfer. Meanwhile, the “A-to-A” type J-aggregates are more likely to be generated between Y6 molecules, and the π–π stacking can be also enhanced, thus increasing the charge transfer rate and electron mobility between Y6 molecules. Full article

The crystal structure of (1,2,3-trimethylpyridnium)₂Cu₅Br₁₂ provides the second reported example of a fully halogenated, linear, quasi-planar, bibridged pentacopper(II) oligomer. The oligomers are aggregated into crosshatched layers that defy traditional notions and notations for quasi-planar oligomer stacking. The regularly arranged voids in the layers are occupied by inversion-related organic cation pairs similar to eggs in an egg-tray. The cross-hatched layer structure arises from a particular stacking of mixed organic cation/pentacopper oligomer sheets. The sheets consist of oligomers placed in a herringbone arrangement separated by zipper-like ribbons of organic cations in a structural motif similar to that found in other 1,2,3- or 1,2,6-trimethylpyridinium halidocuprate(II) structures. Alternative stacking of the sheets leads, on the other hand, to a conventional stacking pattern that conforms to traditional stacking descriptions. Interpretation of these structures in terms of the stacking of mixed cation/anion sheets, as is often performed for ABX₃ systems, provides a complementary method for understanding these structures as well as providing a means to describe systems that are not easily described by traditional stacking notation. Full article