Proactively Reducing Anti‐Drug Antibodies via Immunomodulatory Bioconjugation

Although PEGylation reduces the immunogenicity of protein drugs to some extent, its limitations for highly immunogenic biotherapeutics have been demonstrated. Herein, a proactive strategy to alleviate the development of anti‐drug antibodies (ADAs) against protein drugs by immunomodulatory bioconjugation is reported. Rapamycin was conjugated to a PEGylated protein therapeutic via a cleavable disulfide linker. The conjugated rapamycin can be released from the bioconjugate and prevent immune responses once the bioconjugate is uptaken by antigen‐presenting cells. The immunomodulatory bioconjugate significantly reduced the titers of ADAs compared with a PEGylated protein. The inhibition of immune responses was specific to the conjugated antigen, avoiding systemic immune suppression and the risk of increased susceptibility to infections. The reported approach breaks the limitations of PEGylation by the proactive prevention of ADAs.     

Synthesis and characterization of binuclear palladium(II) and platinum(II) complexes with a bridging hydroxypyridinate ligand

Summary Binuclear Pd^II and Pt^II complexes of the type [M₂Cl₂(-Opy)₂(PR₃)₂] [M = Pd or Pt; Opy = 2-OC₅H₄N (2-hydroxypyridinate ion); PR₃ = PEt₃, Pn-Bu₃, PMe₂Ph or PMePh₂] were synthesized and characterized by elemental analysis, ¹H- and ³¹P-n.m.r. spectroscopies. The Pd complexes exist in the sym trans form, whereas the corresponding Pt complexes were generated as different isomers.     

All Solid State Chromium(III) Selective Potentiometric Sensor Based on 2‐(1‐(2‐((3‐(2‐Hydroxyphenyl)‐1H‐pyrozol‐1‐yl)methyl)benzyl)‐1H‐pyrazol‐3‐yl)phenol

Highly selective all solid state electrochemical sensor based on a synthesized compound i.e. 2‐(1‐(2‐((3‐(2‐hydroxyphenyl)‐1H‐pyrozol‐1‐yl)methyl)benzyl)‐1H‐pyrazol‐3‐yl)phenol (I) as an ionophore has been prepared and investigated for the selective quantification of chromium(III) ions. The effect of various plasticizers, viz. dibutyl phosphonate (DBP), dibutyl(butyl) phosphonate (DBBP), nitrophenyl octyl ether (NPOE), tris‐(2‐ethylhexyl)phosphonate (TEP), tri‐butyl phosphonate (TBP), dioctyl phthalate (DOP), dioctyl sebacate (DOS), benzyl acetate (BA) and acetophenone (AP) along with anion excluders NaTPB (sodium tetraphenyl borate) and KClTPB (potassium(tetrakis‐4‐chlorophenyl)borate was also studied. The optimum composition of the best performing membrane contained (I):KClTPB:NPOE:PVC in the ratio 15 : 3 : 40 : 42 w/w. The sensor exhibited near Nernstian slope of 20.1±0.2 mV/decade of activity in the working concentration range of 1.2×10^?7–1.0×10^?1 M, and in a pH range of 3.8–4.5. The sensor exhibited a fast response time of 10 s and could be used for about 5 months without any considerable divergence in potentials. The proposed sensor showed very good selectivity over most of the common cations including Na⁺, Li⁺, K⁺, Cu²⁺, Sr²⁺, Ni²⁺, Co²⁺, Ba²⁺, Hg²⁺, Pb²⁺, Zn²⁺, Cs⁺, Mg²⁺, Cd²⁺, Al³⁺, Fe³⁺and La³⁺. The activity of Cr(III) ions was successfully determined in the industrial waste samples by using this sensor.     

Study of the mesomorphism of benzoates and cinnamates

Two ester homologous series of carboxy (-COO-) and ethylene-carboxy (-CH=CH-COO-) mesogens, viz. α-4-[4’-n-alkoxybenzoyloxy] phenyl β-4’’-methoxy benzoyl ethylenes (1) and α-4-[4’-n-alkoxy cinnamoyloxy phenyl β-4’’-methoxy benzoyl ethylenes (2)] are discussed. Series (1) and (2) differ at their central linking group. Mesophase are observed at four and five number members in both homologue series. Enantiotropic nematogenic property is observed in both series (1) and (2), while some smectic property is exhibited in series (2). Thermal stability of nematic-isotropic in series (1) is relatively low as compared to (2), smectogenic property is totally absent in series (2). In phase diagram, solid-nematic, solid-isotropic, and nematic-isotropic curve follow zigzag path rising and falling. Transition temperatures are observed through hot stage polarizing microscope. Analytical data supports the structure of molecules. Threaded, Schlieren-type textures of homologues are observed through microscope.     

Effect of Molecular Interactions on Electron‐Transfer and Antioxidant Activity of Bis(alkanol)selenides: A Radiation Chemical Study

Understanding electron‐transfer processes is crucial for developing organoselenium compounds as antioxidants and anti‐inflammatory agents. To find new redox‐active selenium antioxidants, we have investigated one‐electron‐transfer reactions between hydroxyl (^.OH) radical and three bis(alkanol)selenides (SeROH) of varying alkyl chain length, using nanosecond pulse radiolysis. ^.OH radical reacts with SeROH to form radical adduct, which is converted primarily into a dimer radical cation (>Se∴Se<)⁺ and α‐{bis(hydroxyl alkyl)}‐selenomethine radical along with a minor quantity of an intramolecularly stabilized radical cation. Some of these radicals have been subsequently converted to their corresponding selenoxide, and formaldehyde. Estimated yield of these products showed alkyl chain length dependency and correlated well with their antioxidant ability. Quantum chemical calculations suggested that compounds that formed more stable (>Se∴Se<)⁺, produced higher selenoxide and lower formaldehyde. Comparing these results with those for sulfur analogues confirmed for the first time the distinctive role of selenium in making such compounds better antioxidants.     

Kinetics of Catalytic Hydrogenation of 5‐Hydroxymethylfurfural to 2,5‐bis‐Hydroxymethylfuran in Aqueous Solution over Ru/C

5‐Hydroxymethylfurfural (5‐HMF) is a cellulosic product of the hydrolysis of biomass, and it is widely considered for the production of several interesting chemicals and derivatives. In the present work, catalytic hydrogenation of 5‐hydroxymethylfurfural to 2,5‐bis‐hydroxymethylfuran was investigated using 5% Ru/C in the aqueous phase. Kinetic data were experimentally obtained over a wide range of temperatures (313–343 K), H₂ partial pressure (0.69–2.07 MPa), initial HMF concentration (19.8–59.5 mM), and catalyst loading (0.3–0.7 kg/m³) in a three‐phase slurry reactor. Disappearance of initial 5‐HMF concentrations was modeled using the power law and Langmuir–Hinshelwood–Hougen–Watson models. A model based on the competitive adsorption of molecular H₂ and HMF was proposed. It is presumed that surface reaction between nondissociatively chemisorbed H₂ and 5‐HMF was rate determining. This model provided the best fit for the kinetic data. From the Arrhenius equation, the activation energy for the surface reaction was found to be 104.9 kJ/mol.     

A difference-equation formalism for the nodal domains of separable billiards

Recently, the nodal domain counts of planar, integrable billiards with Dirichlet boundary conditions were shown to satisfy certain difference equations in Samajdar and Jain (2014). The exact solutions of these equations give the number of domains explicitly. For complete generality, we demonstrate this novel formulation for three additional separable systems and thus extend the statement to all integrable billiards.