Local Electronic Charge Transfer in the Helical Induction of Cis-Transoid Poly(4-carboxyphenyl)acetylene by Chiral Amines.

Understanding the phenomena that lead to the formation of a specific helicity in helical polymers remains a challenge even today. Various polymers have been shown to assume different helical screw-senses depending on different stimuli. Acid-base chiral amines, for example, can induce helical conformations on cis-transoid poly(4-carboxyphenyl)acetylene yielding high-intensity circular dichroism signals. There have been many experimental attempts to elucidate the driving forces involved, but the induction process remains unclear. Here, we investigate the mechanism of helical polymer formation by both Molecular Dynamics (MD) and Density Functional Theory (DFT) approaches. We find that DFT calculations and the dissociation energies between 4 monomer polymers and amines show a clear trend in the affinity of R and S conformers with clockwise and counterclockwise polymer screw-senses, respectively. The charge analysis revealed that the local charge transfer effect plays a crucial role that leads to the helical polymer-amine induction.

Enantiomeric Separation of Semiconducting Single-Walled Carbon Nanotubes by Acid Cleavable Chiral Polyfluorene.

Helical wrapping by conjugated polymer has been demonstrated as a powerful tool for the sorting of single-walled carbon nanotubes (SWCNTs) according to their electronic type, chiral index, and even handedness. However, a method of one-step extraction of left-handed (M) and right-handed (P) semiconducting SWCNTs (s-SWCNTs) with subsequent cleavage of the polymer has not yet been published. In this work, we designed and synthesized one pair of acid cleavable polyfluorenes with defined chirality for handedness separation of s-SWCNTs from as-produced nanotubes. Each monomer contains a chiral center on the fluorene backbone in the 9-position, and the amino and carbonyl groups in the 2- and 7-positions maintain the head-to-tail regioselective polymerization resulting in polyimines with strictly all-(R) or all-(S) configuration. The obtained chiral polymers exhibit a strong recognition ability toward left- or right-handed s-SWCNTs from commercially available CoMoCAT SWCNTs with a sorting process requiring only bath sonication and centrifugation. Interestingly, the remaining polymer on each single nanotube, which helps to prevent aggregation, does not interfere with the circular dichroism signals from the nanotube at all. Therefore, we observed all four interband transition peaks (E11, E22, E33, E44) in the circular dichroism (CD) spectra of the still wrapped optically enriched left-handed and right-handed (6,5) SWCNTs in toluene. Binding energies obtained from molecular dynamics simulations were consistent with our experimental results and showed a significant preference for one specific handedness from each chiral polymer. Moreover, the imine bonds along the polymer chains enable the release of the nanotubes upon acid treatment. After s-SWNT separation, the polymer can be decomposed into monomers and be cleanly removed under mild acidic conditions, yielding dispersant-free handedness sorted s-SWNTs. The monomers can be almost quantitatively recovered to resynthesize the chiral polymer. This approach enables high selective isolation of polymer-free s-SWNT enantiomers for their further applications in carbon nanotube (CNT) devices.

Targeting α -(1,4)-Glucosidase in Diabetes Mellitus Type 2: The Role of New Synthetic Coumarins as Potent Inhibitors.

Diabetes mellitus type 2 (DMT2) is a metabolic disease characterized by a chronic increase in glycemia that promotes several long-term complications and high mortality. Some enzymes involved in glycaemic control, such as α -(1,4)-glucosidase, have now been established as novel pharmacological targets. Coumarins have shown benefits in attenuating signs and complications of DMT2, including inhibition of this enzyme. In this work, new synthetic coumarins (bearing different amide and aryl substituents) were studied in vitro as inhibitors of α-(1,4)-glucosidase. Among them, five molecules proved to be excellent α-(1,4)-glucosidase inhibitors, being compound 7 (IC50 = 2.19 µM) about 200 times more potent than acarbose, a drug currently used for the treatment of DMT2. In addition, most of the coumarins presented uncompetitive inhibition for the α-(1,4)-glucosidase. Molecular docking studies revealed that coumarins bind to the active site of the enzyme in a more external area comparing to the substrate, without interfering with it, and displaying aromatic and hydrophobic interactions, as well as some hydrogen bonds. According to the results, aromatic interactions with two phenylalanine residues, 157 and 177, were the most common among the studied coumarins. This study is a step forward for the understanding of coumarins as potential anti-diabetic compounds displaying α-(1,4)-glucosidase inhibition.