The role of halogen oxides is substantial in the stratosphere, especially for ozone depletion. It is important to make clear the interaction of halogen oxides with other gaseous molecules. This work performed quantum chemical calculations to investigate the intermolecular interactions between XmOn (X = Cl or Br, m, n = 1 or 2) and ammonia. The chlorine and bromine oxides selected in this paper include typical halogen oxides which can influence the atmospheric processes. For each complex, two different types of interactions, halogen and hydrogen bonds were identified. A π-hole interaction was also found in the XO2···NH3 complex. The interaction energy implies that the strength of the halogen bond is far more stronger than the hydrogen bond. A prominent difference exists between the halogen oxides of singlet or doublet state, which can be ascribed to the electron spin density distribution. The nature of the intermolecular interactions was identified by an independent gradient model based on Hirshfeld partition (IGMH) analysis. Symmetry-adapted perturbation theory (SAPT) calculation indicates that electrostatic interaction dominates the halogen-bonded complex, and hydrogen bond is driven by electrostatic interaction and dispersion.

A novel magnetic nanoadsorbent (Fe3O4@SiO2@PAA-SO3H) was synthesized by grafting acrylic acid and sulfonic group to Fe3O4@SiO2 using a facile cross-link technology. The adsorbent presented water-stability and biocompatibility in wastewater, which exhibited high-selectivity capture for Pb(II) and Cu(II) of 182.5 mg/g and 250.7 mg/g, respectively, at pH 6.0. Furthermore, the adsorption-desorption processes show that nanoadsorbent still retains high uptake capacity after 6 cycles, revealing structural stability and advanced recycling. Effects from other ions existed weak interference in removal of Pb(II) and Cu(II). Meanwhile, the mechanism was further analyzed from both electrostatic potential (ESP) and average local ionization energy (ALIE) based on the density functional theory (DFT). The results indicate that interaction among nanoadsorbent and heavy metal ions is bridged by oxygen active sites. As the Fe3O4@SiO2@PAA-SO3H adsorbent is a hierarchical, highly water-dispersible and biocompatible adsorbent, it is a potential new treatment option for wastewater.

Due to the dramatic increase in the number of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), designing new selective and sensitive sensors for the detection of this virus is of importance. In this research, by employing full atomistic molecular dynamics (MD) simulations, the interactions of the receptor-binding domain (RBD) of the SARS-CoV-2 with phosphorene and graphene nanosheets were analyzed to investigate their sensing ability against this protein. Based on the obtained results, the RBD interactions with the surface of graphene and phosphorene nanosheets do not have important effects on the folding properties of the RBD but this protein has unique dynamical behavior against each nanostructure. In the presence of graphene and phosphorene, the RBD has lower stability because due to the strong interactions between RBD and these nanostructures. This protein spreads on the surface and has lower structural compaction, but in comparison with graphene, RBD shows greater stability on the surface of the phosphorene nanosheet. Moreover, RBD forms a more stable complex with phosphorene nanosheet in comparison with graphene due to greater electrostatic and van der Waals interactions. The calculated Gibbs binding energy for the RBD complexation process with phosphorene and graphene are -200.37 and -83.65 kcal mol-1, respectively confirming that phosphorene has higher affinity and sensitivity against this protein than graphene. Overall, the obtained results confirm that phosphorene can be a good candidate for designing new nanomaterials for selective detection of SARS-CoV-2.

The highly anionic synthetic pentasaccharide fondaparinux (FDPX) - representing the antithrombin binding sequence of heparin - is in clinical use as a potent anticoagulant. Contrary to the unfractionated heparin, FDPX lacks potent antidote completely reversing its anticoagulant activity, therefore it is of great importance to identify new structures exhibiting strong intermolecular interactions towards FDPX. The polycationic heptakis(6-amino-6-deoxy)-beta-cyclodextrin (NH2-β-CD) can serve as an excellent model compound to mimic these interactions between the oppositely charged oligosaccharides. Herein, extensive NMR spectroscopic and nano-electrospray ionization mass spectrometric (nESI-MS) studies were conducted to understand the molecular-level interactions in the FDPX - NH2-β-CD systems. NMR experiments were performed at pD 7.4 and 2.0. Job\'s method of continuous variation and 1H NMR titration experiments suggested the formation of FDPX∙NH2-β-CD complex at pD 7.4, while the presence of multiple complexes was assumed at pD 2.0. Stability constants were determined by separate 1H NMR titrations, yielding log β11=3.65 ± 0.02 at pD 7.4, while log β11 ≥ 4.9 value suggested a high-affinity system at pD 2.0. 2D NOESY NMR studies indicated spatial proximities between the anomeric resonance α-l-iduronic acid residue and the cyclodextrin\'s methylene unit in the proximity of the cationic amino function. Acidic degradation of FDPX was investigated by NMR and MS for the first time in detail confirming that desulfation occurs involving one to two sulfate moieties. The desulfation of FDPX was inhibited by the cationic cyclodextrin in the case of equimolar ratio at pD 2.0. This is the first report on the stabilizing effect of cyclodextrin complexation on heparin degradation.

Vegetables are considered to be a sustainable source of promising biomaterials such as proteins and polysaccharides. In this study, four protein isolates (amaranth protein isolate API, amaranth globulin-rich protein isolate AGR, bean protein isolate BPI, and bean phaseolin-rich protein isolate BPR) were structurally characterized under different pH conditions (2-12) and their compatibility behavior with xanthan gum (XG) in aqueous medium was described. All protein isolates showed β turn and β sheet (78.24-81.11%), as the major secondary structures without statistically significant difference under the pH conditions surveyed. Protein isolates show solubility at pH ≤ 3 (40.4-85.1%) and pH ≥ 8 (57.6-99.9%) and surface hydrophobicity results suggest protein denaturation at pH ≤ 3. In the compatibility study, API/XG ratios between 1:1 and 5:1 at pH from 7 to 9 and the BPI/XG ratios from 1:1 to 20:1 at pH 7 form gels that do not require heating nor crosslinking agent addition. Zeta potential results, on the other hand, evidenced that formation of gels is driven by attractive electrostatic interaction of the charged regions of both biopolymers and intermolecular interactions such as hydrogen bonds.

Budesonide is a BCS class II drug with low water solubility (0.045 mg/mL) and low oral bioavailability (6-8%) due to high first pass effect. The aim is to prepare cross-linked chitosan-dextran sulfate nanoparticles and/or nanodispersion. Nebulizable cross-linked nanodispersion was prepared by the solvent evaporation technique and characterized through XRPD, FTIR, mean particle size (MPS), polydispersity index (PDI), zeta potential (ZP), drug loading, entrapment efficiency, SEM, % production yield, in vitro diffusion, aerodynamic and stability study. The optimization of formulation was done by using central composite rotatable design to study the effect of independent variables, concentration of chitosan (X1) and concentration dextran sulfate (X2) on the dependent variables, MPS (Y1), drug loading (Y2) and % CDR (% cumulative drug release) (Y3). The MPS, PDI, and ZP of budesonide-loaded nanoparticles were 160.8 ± 0.27 nm, 0.36 ± 0.04, and 13 ± 0.894 mV, respectively. The percent drug loading of all the batches was found in range of 10-16%. The emitted drug in target region (alveoli) was measured by using HPLC and it was found to be 18.26%. It was found that, nanodispersion had the optimum in vitro aerodynamic behavior. Stability study results showed no significant change in MPS, PDI, ZP, and % CDR after three month storage. In conclusion, cross-linked chitosan-dextran sulfate nanoparticles had properties suitable for nebulizable dispersion of increased drug loading, in vitro drug release and avoiding the first pass effect.

Thioxanthone and its derivatives are the most remarkable molecules due to their vast variety of application such as radiation curing that is, until using them as a therapeutic drug. Therefore, in this study it was intended to use 2-Thioxanthone acetic acid with and without NaCl in Tris HCl buffer solution (pH:7.0) to represent the interaction with ct-DNA. The UV-vis absorption spectra of TXCH2COOH in the presence of ct-DNA showed hypochromism and the intrinstic binding constant (Kb) was determined as 6 × 103 L mol-1. The fluoresence intensity of TXCH2COOH with ct-DNA clearly increased up to 101% which indicated that the fluorescence intensity was very sensitive to ct-DNA concentration. The binding constant (K) and the values of number of binding sites (n) and were calculated as 1.8 × 103 L mol-1 and 0.69, respectively. When the quenching constants (Ksv) of free TXCH2COOH and TXCH2COOH, which were bonded with ct-DNA were compared, slightly changed values of Ksv were seen. Moreover, displacement assay with Hoechst 33,258 and viscosity measurements in the presence and absence of NaCl salt also confirmed the binding mode which noted the electrostatic interaction following groove binding between TXCH2COOH and ct-DNA. Last but not least, the salt effect was examined on ct-DNA binding with TXCH2COOH. The results of the experiments indicated that the groove binding was strengthened by NaCl whereas in the high NaCl concentration, the binding ability of TXCH2COOH to ct-DNA was inversely affected.

OBJECTIVE: A simple, selective and sensitive hydrophilic interaction liquid chromatography-MS/MS method is developed for the simultaneous determination of metformin (MET) and teneligliptin (TEN) in human plasma using deuterated internal standards. The mechanism of retention of analytes was studied by varying the proportion of organic diluent, buffer strength, pH of the mobile phase and temperature.
RESULTS: The results showed a mixed-mode mechanism comprising of hydrophilic (partition) and electrostatic interaction (ion exchange) for MET and essentially hydrophilic for TEN. The linear calibration curves were established in the concentration range of 1.0-1000 ng/ml for MET and 0.50-750 ng/ml for TEN.
CONCLUSIONS: The method was applied to determine plasma concentration of MET and TEN in healthy subjects.

New experimental results are reported on the self-assembling behavior of EAK16-II, the first discovered ionic self-complementary peptide, incubated at ultralow concentration (10-6 M) at neutral pH onto differently charged surfaces. It is found that strongly negatively charged surfaces promote the self-assembly of flat, micrometer-long mono-molecular fibers of side-on assembled sequences, lying onto a continuous monolayer of flat-on EAK16-II molecules. These results suggest that the monomolecular EAK16-II self-assembly is driven by the peculiar matching condition between peptide and surface electrostatic properties. Molecular Mechanics simulations of the basic bimolecular interactions confirmed the experimental inferences, showing that the flat-on state is the most stable arrangement for two interacting EAK16-II sequences onto strongly negatively charged surfaces, where indeed EAK16-II β-sheet conformation is stabilized, while the weak electrostatic interactions with mildly charged substrates promote an \"entangled\" EAK16-II geometry. Molecular Dynamics simulations further showed that the mobility and diffusional freedom of the peptides from the surfaces are ruled by the relative strength of peptide-surface electrostatic interactions, so that desorption probability for the peptide sequences is negligible from strongly-charged surfaces and high from mildly-charged surfaces. Furthermore, it has been found that an oligopeptide sequence lying onto two flat-on EAK16-II molecules, gains a remarkable lateral mobility, while remaining weakly bound to the surface, thus allowing the further molecular self-alignment responsible for the micrometer-long fiber formation. The reported results pave the way to the understanding and control of the subtle peptide-surface structural motifs matching enabling the formation of micrometer-long, but nanometer-wide monomolecular fibers.

The binding of cationic peptides of the sequence (KX)4K to lipid vesicles of negatively charged dipalmitoyl-phosphatidylglycerol (DPPG) was investigated by differential scanning calorimetry (DSC) and temperature dependent Fourier-transformed infrared (FT-IR) spectroscopy. The hydrophobicity of the uncharged amino acid X was changed from G (glycine) over A (alanine), Abu (α-aminobutyric acid), V (valine) to L (leucine). The binding of the peptides caused an increase of the phase transition temperature (Tm) of DPPG by up to 20°C. The shift depended on the charge ratio and on the hydrophobicity of the amino acid X. Unexpectedly, the upward shift of Tm increased with increasing hydrophobicity of X. FT-IR spectroscopy showed a shift of the CH2 stretching vibrations of DPPG to lower frequency, particularly for bilayers in the liquid-crystalline phase, indicating an ordering of the hydrocarbon chains when the peptides were bound. Changes in the lipid C=O vibrational band indicated a dehydration of the lipid headgroup region after peptide binding. (KG)4K was bound in an unordered structure at all temperatures. All other peptides formed intermolecular antiparallel β-sheets, when bound to gel phase DPPG. However, for (KA)4K and (KAbu)4K, the β-sheets converted into an unordered structure above Tm. In contrast, the β-sheet structures of (KV)4K and (KL)4K remained stable even at 80°C when bound to the liquid-crystalline phase of DPPG. Strong aggregation of DPPG vesicles occurred after peptide binding. For the aggregates, we suggest a structure, where aggregated single β-sheets are sandwiched between opposing DPPG bilayers with a dehydrated interfacial region.