A Piperine-Based Scaffold as a Novel Starting Point to Develop Inhibitors against the Potent Molecular Target OfChtI.

The insect chitinase OfChtI from the agricultural pest Ostrinia furnacalis (Asian corn borer) is a promising target for green insecticide design. OfChtI is a critical chitinolytic enzyme for the cuticular chitin degradation at the stage of molting. In this study, piperine, a natural amide compound isolated from black pepper, Piper nigrum L., was discovered for the first time to have inhibitory activity toward OfChtI. The compound-enzyme interaction was presumed to take place between the piperine benzo[d][1,3] dioxole skeleton and subsite -1 of the substrate-binding pocket of OfChtI. Hence, on the basis of the deduced inhibitory mechanism and crystal structure of the substrate-binding cavity of OfChtI, compounds 5a-f were designed and synthesized by introducing a butenolide scaffold into the lead compound piperine. The enzymatic activity assay indicated that compounds 5a-f (Ki = 1.03-2.04 µM) exhibited approximately 40-80-fold higher inhibitory activity than the lead compound piperine (I) (Ki = 81.45 µM) toward OfChtI. The inhibitory mechanism of the piperonyl butenolide compounds was elucidated by molecular dynamics, which demonstrated that the introduced butenolide skeleton improved the binding affinity to OfChtI. Moreover, the in vivo activity assay indicated that these compounds also displayed moderate insecticidal activity toward O. furnacalis. This work introduces the natural product piperine as a starting point for the development of novel insecticides targeting OfChtI.

Photocatalytic H2 generation based on noble-metal-free binuclear cobalt complexes using visible-light.

Two new binuclear cobalt complexes, namely {[Co(dmgH)(dmgH2)]2L1} (I) and {[Co(dmgH)(dmgH2)]2L2} (II) (dmgH = dimethylglyoximate monoanion; dmgH2 = dimethylglyoxime, L1 = 1,3-bis(4-pyridyl)propane), L2 = 1,3-bis(imidazol-1-ylmethyl)benzene), have been synthesized by the self-assembly of [Co(dmgH)(dmgH2)] and L1 or L2, respectively. An efficient photocatalytic system was constructed by combining a noble-metal-free cobalt complex as the catalyst with Eosin Y dye (EY(2-)) as the photosensitizer to give an efficient H2 generating system under visible-light irradiation (λ > 420 nm) using triethanolamine (TEOA) as a sacrificial electron donor. The maximum amount of H2 generated was 1013 TON for I and 1134 TON for II over a 2 h irradiation period (λ > 420 nm) under the conditions of pH 8.0, 5% TEOA (v/v), an EY(2-) concentration of 4.0 × 10(-4) M and a catalyst concentration of 4.0 × 10(-4) M in the mixed solvent system of CH3CN-H2O (3 : 1, v/v). In addition, the mechanism of H2 generation in the photolysis system was briefly discussed.