Bifunctional Inhibitors of Influenza Virus Neuraminidase: Molecular Design of a Sulfonamide Linker

The growing resistance of the influenza virus to widely used competitive neuraminidase inhibitors occupying the active site of the enzyme requires the development of bifunctional compounds that can simultaneously interact with other regulatory sites on the protein surface. When developing such an inhibitor and combining structural fragments that could be located in the sialic acid cavity of the active site and the adjacent 430-cavity, it is necessary to select a suitable linker not only for connecting the fragments, but also to ensure effective interactions with the unique arginine triad Arg118-Arg292-Arg371 of neuraminidase. Using molecular modeling, we have demonstrated the usefulness of the sulfonamide group in the linker design and the potential advantage of this functional group over other isosteric analogues.

Anti-adhesive membranes based on crosslinked carboxymethyl cellulose

In recent times, new anti-adhesion devices including devices based on carboxymethyl cellulose (CMC), which have “barrier” effect are being developed and actively introduced into surgical practice. The “barrier” should be completely resorbed after the time required to healing the morphofunctional integrity of the injured peritoneum, be economically available and easy to use (including laparoscopic technologies). But the time when the CMC is in the body is insufficient to prevent the formation of adhesions, particularly in the presence of non-absorbable rigid implants. The reactive functional groups in CMC allow to transform the CMC-macromolecule into a spatial structure. For this are required the using of bifunctional (bicarboxylic or aminocarboxylic) acids and the transform of a part of the carboxyl groups from the Na-form to the hardly soluble H-form, i.e., it is necessary to crosslink CMC-macromolecules. Adipic acid and glutaric acid, aminoacetic acid and amino capronic acid used are linking agents. The influence of modification parameters on the degree of polymers swelling in water is studied. As a result, to obtain membranes designed for the treatment of adhesive disease, it is recommended to use additives in CMC of bifunctional compounds.

Methods for Synthesis of α-Alkyl α,β-Unsaturated Aldehydes

α-Substituted α,β-unsaturated aldehydes represent a highly reactive class of compounds with a broad scope of application. Therefore, the development of methods for the synthesis of these bifunctional compounds is a dynamically progressing area of research. This review summarizes and highlights methods for the synthesis of α-alkyl α,β-alkenals.

Synthesis and characterization of two bifunctional pyrazole-phosphonic acid ligands

The bifunctional compounds 3,5-dimethyl-4-(4-phosphonophenyl)-1H-pyrazole 1 and 4-(4-phosphonophenyl)-1H-pyrazole 2 were synthesized via Suzuki-Miyaura coupling, starting from a Boc-protected pyrazolylboronic acid ester and the iodoarylphosphonate. The target compounds were isolated after acidic hydrolysis in the form of the hydrochloride salts 1 · HCl and 2 · HCl · H2O with a yield of 81% and 86%, respectively. Pd(dppf)Cl2 was found to be superior to Pd(PPh3)4 as a catalyst; dry 1,4-dioxane as a solvent, Cs2CO3 as a base, and no co-ligands were the best found conditions. The alternative routes through iodoarylphosphonate of iodoarylpyrazole, with the crucial steps based on the copper-catalyzed coupling with acetylacetone or the Arbuzov reaction were proven inefficient. The structures of the isolated hydrochloride salts 1 · HCl and 2 · HCl · H2O feature hydrogen-bonded networks involving the chloride anions.

Excited-state proton transfer relieves antiaromaticity in molecules

Baird’s rule explains why and when excited-state proton transfer (ESPT) reactions happen in organic compounds. Bifunctional compounds that are [4n + 2] π-aromatic in the ground state, become [4n + 2] π-antiaromatic in the first 1ππ* states, and proton transfer (either inter- or intramolecularly) helps relieve excited-state antiaromaticity. Computed nucleus-independent chemical shifts (NICS) for several ESPT examples (including excited-state intramolecular proton transfers (ESIPT), biprotonic transfers, dynamic catalyzed transfers, and proton relay transfers) document the important role of excited-state antiaromaticity. o-Salicylic acid undergoes ESPT only in the “antiaromatic” S1 (1ππ*) state, but not in the “aromatic” S2 (1ππ*) state. Stokes’ shifts of structurally related compounds [e.g., derivatives of 2-(2-hydroxyphenyl)benzoxazole and hydrogen-bonded complexes of 2-aminopyridine with protic substrates] vary depending on the antiaromaticity of the photoinduced tautomers. Remarkably, Baird’s rule predicts the effect of light on hydrogen bond strengths; hydrogen bonds that enhance (and reduce) excited-state antiaromaticity in compounds become weakened (and strengthened) upon photoexcitation.