RESUMO
Ice formation is a critical challenge across multiple fields, from industrial applications to biological preservation. Inspired by natural antifreeze proteins, we designed and synthesized a new class of small-molecule antifreezes based on α-helical p-terphenyl scaffolds with guanidine side chains. These p-terphenyl guanidines 1, among the smallest molecules that mimic α-helical structures, exhibit potent ice recrystallization inhibition (IRI) activity, similar to that of existing large α-helical antifreeze compounds. The most effective compound, 1a, with four C1-carbon guanidine moieties, demonstrated a superior IRI activity of 0.46 (1 mg/mL). Using molecular dynamics simulations with density-functional theory and separate pKa calculations, we elucidated the mechanisms underlying their antifreeze properties.
Assuntos
Guanidinas , Simulação de Dinâmica Molecular , Guanidinas/química , Guanidinas/síntese química , Proteínas Anticongelantes/química , Compostos de Terfenil/química , Compostos de Terfenil/farmacologia , Compostos de Terfenil/síntese química , Desenho de Fármacos , Estrutura Molecular , Teoria da Densidade Funcional , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/farmacologia , Gelo , Cristalização , Crioprotetores/química , Crioprotetores/farmacologiaRESUMO
We present a viable approach for the cross-dehydrogenative coupling of Het-SF4-alkynes with tetrahydroisoquinolines under oxidative conditions, using TBHP and copper catalysts. These newly developed conditions boast enhanced yields and a more extensive range of substrates, demonstrating tolerance to various functional groups and addressing the limitations of earlier reports. Consequently, this method should increase opportunities for the exploration of SF4-containing compounds and their potential applications in drug discovery, materials science, and as alternatives to PFAS.
RESUMO
This study introduces a dual-catalytic method for cross-dehydrogenative coupling (CDC) between tetrahydroisoquinolines and Py-SF4-alkyne using visible-light photoredox catalysis. This protocol enables selective C(sp3)-H alkynylation, expanding the synthetic toolkit for SF4-based molecules. Demonstrating efficiency and substrate versatility, this approach opens new avenues in hexacoordinated tetrafluorinated sulfur chemistry and CDC strategies and holds significant promise for drug discovery and materials science.