Helical polyisocyanides have attracted considerable attention due to their stable helical conformations, yet incorporating acidic sulfonamide groups remains synthetically challenging. Herein, we report the first sulfonamide-functionalized helical polyisocyanide (Poly-PE-SA-PI). The key monomer was prepared via sulfonyl fluoride (SuFEx) click chemistry, followed by polymerization. The monomer exhibits unexpected stability due to hydrogen-bonded dimerization-a self-protection mechanism that challenges conventional notions of functional group incompatibility. The polymer adopts a stable one-handed helical conformation stabilized by aromatic pi-pi interactions rather than hydrogen bonding, as confirmed by TFA titration, and exhibits certain solvent polarity responsiveness: the helical structure becomes more compact, and the circular dichroism signal intensifies with increasing solvent polarity. Poly-PE-SA-PI displays highly selective fluoride ion (F-) recognition, with visible color change, UV-vis red-shift, and CD signal attenuation. Mechanism studies reveal that F-induces deprotonation of the sulfonamide groups, while the bulky tetrabutylammonium cation acts as a "cation-wedging" effector that cooperatively drives the conformational reorganization of the helix, enabling efficient and selective fluoride sensing. This work not only overcomes the synthetic challenges associated with polyisocyanides containing sulfonamide side chains but also provides a new class of materials toward helical polymers with precise ion-recognition capabilities. It holds promise for potential applications in chemical sensing, chiral separation, and smart optical devices.

BACKGROUND:Diabetes mellitus is a major global health concern. DPP-4 (dipeptidyl peptidase-4) inhibitors containing a 2-cyanopyrrolidine scaffold are in clinical use; however, systematic evaluation of amides derived from amino acids adjacent to the N-2 position of GLP-1 (glucagon-like peptide-1) has not been reported. METHODS:A total of eight 2-cyanopyrrolidine derivatives, grouped into three series, were synthesized from N-Boc-protected amino acids via condensation with 2-cyanopyrrolidine followed by deprotection. The compounds were characterized by nuclear magnetic resonance (NMR), elemental analysis, and mass spectrometry (MS). DPP-4 inhibitory activity was evaluated in vitro using a DPP-IV Glo™ assay, with sitagliptin as a control. IC50 (Half Maximal Inhibitory Concentration) values were determined from three independent replicates (n = 3) and calculated by nonlinear regression. RESULTS:Compounds 4d, 4g, and 4h exhibited excellent DPP-4 inhibition, with IC50 values of 1.36 ± 0.09, 5.24 ± 0.31, and 4.83 ± 0.22 nM, respectively. Compound 4d (histidine) was more potent than sitagliptin (6.13 ± 0.42 nM). The bis-cyanopyrrolidine derivatives 4g and 4h also showed strong activity. The remaining compounds (4a-4c, 4e, 4f) displayed moderate inhibition (IC50 112-181 nM). CONCLUSIONS:Aminoacyl-2-cyanopyrrolidine derivatives bearing an imidazole or bis-cyanopyrrolidine structure are potent DPP-4 inhibitors. These findings highlight the importance of neighboring GLP-1 amino acid residues (positions 1 and 3) in inhibitor design. Further cellular and in vivo studies are warranted to evaluate the therapeutic potential of these compounds.

2-Hydroxymethyl piperazine is a crucial structural unit and essential intermediate in the drug development process. However, there are few reported methods for synthesizing 2-hydroxymethyl piperazine substituted at position 5. Herein, the 2-hydroxymethyl piperazines are synthesized from serine methyl ester hydrochloride and N-Boc-L-amino acids through a four-step reaction of condensation, deprotection, cyclisation, and reduction. This synthetic route has several advantages, including mild reaction conditions, availability of reagents, non-racemic composition, and the potential for gram-scale synthesis. In this study, we present a mild and effective synthetic method for preparing para-substituted 2-hydroxymethyl piperazine.

Novel conjugated polymers with aza-15-crown-5 as pendant groups, P1 were synthesized by the Sonogashira coupling reaction. The polymer P1 was found to show fluorescence enhancement response towards Ba2+. The gradual recovery and turning-point of emission intensity of polymers appeared in the addition of Ba2+, which provided good evidence for the fluorescence amplification mechanism of conjugated polymers.