Pyrazine‐2,3‐dicarboxamide

In the crystal structure of the title di­amide, C₆H₆N₄O₂, linear tapes of carbox­amide N—H?O and pyrazine C—H?N hydrogen‐bond dimers are connected by N—H?O bonds to form a staircase‐like pattern.     

Dynamic Jahn-teller effect in a Fe-N6 cage molecule

Mössbauer spectroscopic studies of [Fe(di(amH)-sar)](NO₃)_4·H₂O where di(amH)-sar represents 1,8 diamino 3,6,10,13,16,19-hexaza bicyclo [6,6,6] icosane in the temperature range of 4.2 to 300 K suggest that it undergoes a dynamic Jahn-Teller effect as revealed from the plots of temperature dependent quadrupole coupling constant, chemical shift and line width values. The spectrum down to 4.2 K, shows a quadrupole doublet with no magnetic hyperfine splitting.     

A convenient synthesis of the novel 5H-thieno[2,3-e]-4,1,2-oxathiazepine ring system via an alkoxycarbenium ion intermediate

3-(Methoxymethoxymethyl)-2-thiophenesulfonamides and 3-hydroxymethyl-N-methoxymethyl-2-thiophenesulfonamides have been shown to undergo cyclization when treated under anhydrous acidic conditions to provide the novel 2,3-dihydro-5H-thieno[2,3-e]-4,1,2-oxathiazepine ring system. Incorporation of a primary sulfonamide group into position seven of the molecule provided compounds which inhibit human carbonic anhydrase II.     

Normal flow boundary conditions in 3D circulation models

The problem of enforcing normal transport conditions on 3D velocity fields is considered in the context of ‘wave equation’ finite element models. A procedure for strong enforcement of the transport constraint is given. The procedure is identical for Neumann (transport known) and Dirichlet (pressure known) problems, which are treated reversibly. All local mass and force balance relations are retained in the FEM system. A global mass conservation property is proven for the general 3D, discrete-time case. Examples demonstrate the quality of the solutions and the practicality of the approach. © 1997 John Wiley & Sons, Ltd.     

Inhibitor binding influences the protonation states of histidines in SARS-CoV-2 main protease

The main protease (M^pro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an attractive target for antiviral therapeutics. Recently, many high-resolution apo and inhibitor-bound structures of M^pro, a cysteine protease, have been determined, facilitating structure-based drug design. M^pro plays a central role in the viral life cycle by catalyzing the cleavage of SARS-CoV-2 polyproteins. In addition to the catalytic dyad His41–Cys145, M^pro contains multiple histidines including His163, His164, and His172. The protonation states of these histidines and the catalytic nucleophile Cys145 have been debated in previous studies of SARS-CoV M^pro, but have yet to be investigated for SARS-CoV-2. In this work we have used molecular dynamics simulations to determine the structural stability of SARS-CoV-2 M^pro as a function of the protonation assignments for these residues. We simulated both the apo and inhibitor-bound enzyme and found that the conformational stability of the binding site, bound inhibitors, and the hydrogen bond networks of M^pro are highly sensitive to these assignments. Additionally, the two inhibitors studied, the peptidomimetic N3 and an α-ketoamide, display distinct His41/His164 protonation-state-dependent stabilities. While the apo and the N3-bound systems favored N_δ (HD) and N_ϵ (HE) protonation of His41 and His164, respectively, the α-ketoamide was not stably bound in this state. Our results illustrate the importance of using appropriate histidine protonation states to accurately model the structure and dynamics of SARS-CoV-2 M^pro in both the apo and inhibitor-bound states, a necessary prerequisite for drug-design efforts.

The main protease (M^pro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an attractive target for antiviral therapeutics.