Face-Fusion of Icosahedral Boron Hydride Increases Affinity to γ-Cyclodextrin: closo,closo-[B21H18]− as an Anion with Very Low Free Energy of Dehydration

The supramolecular recognition of closo,closo-[B₂₁H₁₈]⁻ by cyclodextrins (CDs) has been studied in aqueous solution by isothermal titration calorimetry and nuclear magnetic resonance spectroscopy. These solution studies follow up on previous mass-spectrometric measurements and computations, which indicated the formation and stability of CD ⋅ B₂₁H₁₈⁻ complexes in the gas phase. The thermodynamic signature of solution-phase binding is exceptional, the association constant for the γ-CD complex with B₂₁H₁₈⁻ reaches 1.8×10⁶ M⁻¹, which is on the same order of magnitude as the so far highest observed value for the complex between γ-CD and a metallacarborane. The nature of the intermolecular interaction is also examined by quantum-mechanical computational protocols. These suggest that the desolvation penalty, which is particularly low for the B₂₁H₁₈⁻ anion, is the decisive factor for its high binding strength. The results further suggest that the elliptical macropolyhedral boron hydride is another example of a CD binder, whose extraordinary binding affinity is driven by the chaotropic effect, which describes the intrinsic affinity of large polarizable and weakly solvated chaotropic anions to hydrophobic cavities and surfaces in aqueous solution.     

Conductance of Lithium and Sodium Perchlorates and Tetraphenylborates in 2-Butanone from −35 to 25°C

Conductances of dilute solutions of LiClO₄, NaClO₄, LiBPh₄ and NaBPh₄ in 2-butanone were measured at seven temperatures from ?35 to 25°C. The limiting molar conductivities and association constants were evaluated using the conductance equation of Fuoss and Justice (including the Chen effect). The distance parameter was fixed at the Bjerrum distance. The limiting ionic conductivities, determined by assuming equal ionic conductivities of the i-Am₃ BuN⁺ and BPh ₄ ^? ions at all temperatures, were related to the crystallographic ionic radii using the Hubbard–Onsager model of dielectric friction corrected for the inhomogeneity of the electric field. The activation enthalpy of ionic transport in 2-butanone is almost independent of the nature of the electrolyte. The Walden products do not vary with the temperature. The correction to the conductance parameters for dielectric saturation computed for M⁺ClO ₄ ^? associates was found to be small. Thermodynamic functions characterizing the association process were evaluated from K _A data and their dependences on the temperature. The short-range, noncoulombic contributions to the Gibbs energy were estimated using Bjerrum's theory.     

On the geometry of orthonormal frame bundles II

We study the geometry of orthonormal frame bundles OM over Riemannian manifolds (M, g). The former are equipped with some modifications of the Sasaki-Mok metric depending on one real parameter c ≠ 0. The metrics are “strongly invariant” in some special sense. In particular, we consider the case when (M, g) is a space of constant sectional curvature K. Then, for dim M > 2, we find always, among the metrics , two strongly invariant Einstein metrics on OM which are Riemannian for K > 0 and pseudo-Riemannian for K < 0. At least one of them is not locally symmetric. We also find, for dim M ≥ 2, two invariant metrics with vanishing scalar curvature.      

Rapid separation and identification of the subtypes of swine and equine influenza A viruses by electromigration techniques with UV and fluorometric detection

Influenza A is viral disease, which is a cause of yearly epidemics and, potentially, pandemics. The conventional techniques used today are equipment-demanding, time-consuming and laborious. Recently, we have confirmed that the capillary isoelectric focusing is a suitable fast alternative for the verifying of virus purity. In the wide pH gradient of pH range 2.0-7.5 the isoelectric points for subtypes of equine (H3N8) and swine (H1N2) influenza A viruses were determined approximately as 6.6 and 6.5, respectively. In this contribution we have verified these findings using different isolates of different viral subtypes of swine influenza, H1N1, H1N2, and of equine influenza, H3N8, H7N7, which were separated by capillary zone electrophoresis (CZE) and capillary isoelectric focusing (CIEF) in the narrow pH gradient pH range from 6.0 to 7.0. It was found that the isoelectric points of different isolates and subtypes of equine and swine influenza are almost independent of their origin. The electromigration velocities of subtypes of equine or swine influenza viruses were dependent on the antigenic subtypes of their surface glycoproteins. The detection sensitivity of the influenza viruses labeled by the fluorescent non-ionogenic tenside based on poly(ethylene glycol)pyrenebutanoate for fluorometric detection was increased and down to ten labeled viruses were detected. The isoelectric points of the native and labeled equine and swine influenza A viruses and their subtypes do not differ. According to our experiments these methods appear to be useful for the fast preliminary differentiation of influenza viruses in future.     

Antitumor Efficacy of Colon‐Specific HPMA Copolymer/9‐Aminocamptothecin Conjugates in Mice Bearing Human‐Colon Carcinoma Xenografts

The antitumor activity of a colon‐specific N‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymer – 9‐aminocamptothecin (9‐AC) conjugate (P‐9‐AC) was assessed in orthotopic and subcutaneous animal (HT29 xenograft) tumor models. P‐9‐AC treatment of mice bearing orthotopic colon tumors, with a dose of 3 mg/kg of 9‐AC equivalent every other day for 6 weeks, resulted in regression of tumors in 9 of 10 mice. A lower dose of P‐9‐AC (1.25 mg/kg of 9‐AC equivalent) every other day for 8 weeks inhibited subcutaneous tumor growth in all mice. No liver metastases were observed. Colon‐specific release of 9‐AC from polymer conjugates enhanced antitumor activity and minimized the systemic toxicity.

     

Evaluation of Electrochemical Stability of Sulfonated Anthraquinone-Based Acidic Electrolyte for Redox Flow Battery Application

Despite intense research in the field of aqueous organic redox flow batteries, low molecular stability of electroactive compounds limits further commercialization. Additionally, currently used methods typically cannot differentiate between individual capacity fade mechanisms, such as degradation of electroactive compound and its cross-over through the membrane. We present a more complex method for in situ evaluation of (electro)chemical stability of electrolytes using a flow electrolyser and a double half-cell including permeation measurements of electrolyte cross-over through a membrane by a UV–VIS spectrometer. The method is employed to study (electro)chemical stability of acidic negolyte based on an anthraquinone sulfonation mixture containing mainly 2,6- and 2,7-anthraquinone disulfonic acid isomers, which can be directly used as an RFB negolyte. The effect of electrolyte state of charge (SoC), current load and operating temperature on electrolyte stability is tested. The results show enhanced capacity decay for fully charged electrolyte (0.9 and 2.45% per day at 20 °C and 40 °C, respectively) while very good stability is observed at 50% SoC and lower, even at 40 °C and under current load (0.02% per day). HPLC analysis conformed deep degradation of AQ derivatives connected with the loss of aromaticity. The developed method can be adopted for stability evaluation of electrolytes of various organic and inorganic RFB chemistries.     

Crosslinking of CD38 Receptors Triggers Apoptosis of Malignant B Cells

Recently, we designed an inventive paradigm in nanomedicine—drug-free macromolecular therapeutics (DFMT). The ability of DFMT to induce apoptosis is based on biorecognition at cell surface, and crosslinking of receptors without the participation of low molecular weight drugs. The system is composed of two nanoconjugates: a bispecific engager, antibody or Fab’ fragment—morpholino oligonucleotide (MORF1) conjugate; the second nanoconjugate is a multivalent effector, human serum albumin (HSA) decorated with multiple copies of complementary MORF2. Here, we intend to demonstrate that DFMT is a platform that will be effective on other receptors than previously validated CD20. We appraised the impact of daratumumab (DARA)- and isatuximab (ISA)-based DFMT to crosslink CD38 receptors on CD38+ lymphoma (Raji, Daudi) and multiple myeloma cells (RPMI 8226, ANBL-6). The biological properties of DFMTs were determined by flow cytometry, confocal fluorescence microscopy, reactive oxygen species determination, lysosomal enlargement, homotypic cell adhesion, and the hybridization of nanoconjugates. The data revealed that the level of apoptosis induction correlated with CD38 expression, the nanoconjugates meet at the cell surface, mitochondrial signaling pathway is strongly involved, insertion of a flexible spacer in the structure of the macromolecular effector enhances apoptosis, and simultaneous crosslinking of CD38 and CD20 receptors increases apoptosis.     

Classification of locally homogeneous affine connections with arbitrary torsion on 2-dimensional manifolds

The aim of this paper is to classify (locally) all locally homogeneous affine connections with arbitrary torsion on two-dimensional manifolds. Herewith, we generalize the result given by B. Opozda for torsion-less case in [(2004) Classification of locally homogeneous connections on 2-dimensional manifolds. Diff Geom Appl 21: 173–198]. Authors’ addresses: Teresa Arias-Marco, Department of Geometry and Topology, University of Valencia, Vicente Andrés Estellés 1, 46100 Burjassot, Valencia, Spain; Oldřich Kowalski, Faculty of Mathematics and Physics of the Charles University, Sokolovská 83, 18600 Praha 8, Czech Republic     

Synthesis and Characterization of Enzymatically Degradable PEG‐Based Peptide‐Containing Hydrogels

Biodegradable hydrogels were synthesized by the click reaction of 4‐arm azido‐terminated PEG differing in molecular weight (2 100 and 8 800) and two alkyne‐terminated peptides: [alkyne]‐GFLGK‐[alkyne] and ([alkyne]‐GFLG)₂K. The physical properties of in situ formed hydrogels were examined. The hydrogels were highly elastic as determined by rheological and microrheological studies. Swelling degree and enzymatic degradation by papain were dependent on the molecular weight of the PEG, but not the peptide. For PEG8800‐based hydrogels, time‐course analysis of degradation showed that the molecular weight of the soluble fraction quickly reached the PEG precursor value. These findings may guide future design of hydrogels with controllable mechanical properties and enzymatic degradability.

     

Aminoxyl Radicals from N-Phenyl-1-(2-oxo-1-azacycloalkyl)-methanesulfonamides

Summary. The synthesis and reaction with two oxidation agents is described for N-phenyl-1-(2-oxo-1-azacycloalkyl)methanesulfonamides. Their oxidation was carried out using radicals and 3-chloroperbenzoic acid. In both cases, the EPR spectra of corresponding aminoxyl radicals were recorded. Their simulation confirmed that the –SO₂– group in the neighbourhood of the – – fragment does not prevent the interaction of the unpaired electron with the methylene protons and the nitrogen atom of the heterocyclic ring.