Copper-Catalyzed Selective Arylation of Oxadiazolones by Diaryliodonium Salts

The direct N-arylation of cyclic amides can be considered a pivotal issue for modern organic chemistry. Here, we report the method for copper-catalyzed <i>N</i>-arylation of diverse oxadiazolones by diaryliodonium salts in mild conditions in high yields (up to 92%) using available CuI as a catalyst. The developed method allows to efficiently utilize both symmetric and unsymmetric diaryliodonium salts bearing auxiliary groups such as 2,4,6-trimethoxyphenyl (TMP). The evaluation of steric effects in aryl moieties to the chemoselectivity of <i>N</i>- and <i>O</i>-arylation of the 1,2,4-oxadiazol-5(4<i>H</i>)-ones exhibited the high potential of mesityl-substituted diaryliodonium salts as a selective arylation reagent. The structural study suggests that steric accessibility of <i>N</i>-atom in 1,2,4-oxadiazol-5(4<i>H</i>)-ones impact to arylation with sterically hindered diaryliodonium salts. The synthetic application of proposed method was also demonstrated on selective arylation of 1,3,4-oxadiazol-2(3<i>H</i>)-ones and 1,2,4-oxadiazole-5-thiol.

Copper-Catalyzed Selective Arylation of Oxadiazolones by Diaryliodonium Salts

The direct N-arylation of cyclic amides can be considered a pivotal issue for modern organic chemistry. Here, we report the method for copper-catalyzed <i>N</i>-arylation of diverse oxadiazolones by diaryliodonium salts in mild conditions in high yields (up to 92%) using available CuI as a catalyst. The developed method allows to efficiently utilize both symmetric and unsymmetric diaryliodonium salts bearing auxiliary groups such as 2,4,6-trimethoxyphenyl (TMP). The evaluation of steric effects in aryl moieties to the chemoselectivity of <i>N</i>- and <i>O</i>-arylation of the 1,2,4-oxadiazol-5(4<i>H</i>)-ones exhibited the high potential of mesityl-substituted diaryliodonium salts as a selective arylation reagent. The structural study suggests that steric accessibility of <i>N</i>-atom in 1,2,4-oxadiazol-5(4<i>H</i>)-ones impact to arylation with sterically hindered diaryliodonium salts. The synthetic application of proposed method was also demonstrated on selective arylation of 1,3,4-oxadiazol-2(3<i>H</i>)-ones and 1,2,4-oxadiazole-5-thiol.

Computational epitope map of SARS-CoV-2 spike protein

The primary immunological target of COVID-19 vaccines is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface and mediates viral entry into the host cell. To identify possible antibody binding sites, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation, and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for structure-based vaccine design. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics. The protective glycan shield and the high flexibility of its hinges give the stalk overall low epitope scores. Our computational epitope-mapping procedure is general and should thus prove useful for other viral envelope proteins whose structures have been characterized.

The structures of secretory and dimeric immunoglobulin A

Secretory (S) Immunoglobulin (Ig) A is the predominant mucosal antibody, which binds pathogens and commensal microbes. SIgA is a polymeric antibody, typically containing two copies of IgA that assemble with one joining-chain (JC) to form dimeric (d) IgA that is bound by the polymeric Ig-receptor ectodomain, called secretory component (SC). Here, we report the cryo-electron microscopy structures of murine SIgA and dIgA. Structures reveal two IgAs conjoined through four heavy-chain tailpieces and the JC that together form a β-sandwich-like fold. The two IgAs are bent and tilted with respect to each other, forming distinct concave and convex surfaces. In SIgA, SC is bound to one face, asymmetrically contacting both IgAs and JC. The bent and tilted arrangement of complex components limits the possible positions of both sets of antigen-binding fragments (Fabs) and preserves steric accessibility to receptor-binding sites, likely influencing antigen binding and effector functions.

Map of SARS-CoV-2 spike epitopes not shielded by glycans

The severity of the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, calls for the urgent development of a vaccine. The primary immunological target is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface to mediate viral entry into the host cell. To identify possible antibody binding sites not shielded by glycans, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for vaccine development. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics in epitope mapping.

The Structures of Secretory and Dimeric Immunoglobulin A

Secretory (S) Immunoglobulin (I) A is the predominant mucosal antibody, which binds pathogens and commensal microbes. SIgA is a polymeric antibody, typically containing two copies of IgA that assemble with one joining-chain (JC) to form dimeric (d) IgA that is bound by the polymeric Ig-receptor ectodomain, called secretory component (SC). Here we report the cryo-electron microscopy structures of murine SIgA and dIgA. Structures reveal two IgAs conjoined through four heavy-chain tailpieces and the JC that together form a β-sandwich-like fold. The two IgAs are bent and tilted with respect to each other, forming distinct concave and convex surfaces. In SIgA, SC is bound to one face, asymmetrically contacting both IgAs and JC. The bent and tilted arrangement of complex components limits the possible positions of both sets of antigen binding fragments (Fabs) and preserves steric accessibility to receptor binding sites, likely influencing antigen binding and effector functions.

EFFECT OF STERIC ACCESSIBILITY OF EXCHANGE CENTER OF HIGHER QUATERNARY AMMONIUM SALTS AND PLASTICIZER NATURE ON CHARACTERISTICS OF ELECTRODES, REVERSIBLE TO DOUBLE-CHARGED ANIONS

The effect of the steric accessibility of the exchange center of higher quaternary ammonium salts and plasticizer nature on the selectivity and the limit of detection for film electrodes reversible to hydrophilic double-charged anions was studied. It was established the decrease in selectivity coefficients lgKi,jPot by 2.8−3.8 order of magnitude and low detection limit by 2−3 order of magnitude in the series of QAS: TOD≤TC<TL<TNODA<TB<TE<TM< DCPBTM. Also, the increase in low detection limit by 1−0.7 order of magnitude in the series of plasticizers: DBP>DDP>o-NPDE>1-BN was established. The composition of membranes of ion-selective electrodes was optimized.