Cu(I)-thioether coordination complexes based on a chiral cyclic ß-amino acid ligand.

Coordination complexes, particularly metalloproteins, highlight the significance of metal-sulfur bonds in biological processes. Their unique attributes inspire efforts to synthetically reproduce these intricate metal-sulfur motifs. Here, we investigate the synthesis and characterization of copper(I)-thioether coordination complexes derived from copper(I) halides and the chiral cyclic ß-amino acid trans-4-aminotetrahydrothiophene-3-carboxylic acid (ATTC), which present distinctive structural properties and ligand-to-metal ratios. By incorporating ATTC as the ligand, we generated complexes that feature a unique chiral conformation and the capacity for hydrogen bonding, facilitating the formation of distinct geometric structures. Through spectroscopic analyses and density functional theory (DFT) calculations, we studied the complexes' optical properties, including their emission bands and variable second-harmonic generation (SHG) efficiencies, which vary based on the halide used. Our findings underscore the potential of the ATTC ligand in creating unusual coordination complexes and pave the way for further investigations into their potential applications, particularly within materials science.

Versatile Post-synthetic Modifications of Helical ß-Peptide Foldamers Derived from a Thioether-Containing Cyclic ß-Amino Acid.

We introduce a novel cyclic ß-amino acid, trans-(3S,4R)-4-aminotetrahydrothiophene-3-carboxylic acid (ATTC), as a versatile building block for designing peptide foldamers with controlled secondary structures. We synthesized and characterized a series of ß-peptide hexamers containing ATTC using various techniques, including X-ray crystallography, circular dichroism, and NMR spectroscopy. Our findings reveal that ATTC-containing foldamers can adopt 12-helical conformations similar to their isosteres and offer the possibility of fine-tuning their properties via post-synthetic modifications. In particular, chemoselective conjugation strategies demonstrate that ATTC provides unique post-synthetic modification opportunities, which expand their potential applications across diverse research areas. Collectively, our study highlights the versatility and utility of ATTC as an alternative to previously reported cyclic ß-amino acid building blocks in both structural and functional aspects, paving the way for future research in the realm of peptide foldamers and beyond.

Directing Foldamer Self-Assembly with a Cyclopropanoyl Cap.

The rational design of self-assembling organic materials is extremely challenging due to the difficulty in precisely predicting solid-state architectures from first principles, especially if synthons are conformationally flexible. A tractable model system to study self-assembly was constructed by appending cyclopropanoyl caps to the N termini of helical α/ß-peptide foldamers, designed to form both N-H⋅⋅⋅O and Cα -H⋅⋅⋅O hydrogen bonds, which then rapidly self-assembled to form foldectures (foldamer architectures). Through a combined analytical and computational investigation, cyclopropanoyl capping was observed to markedly enhance self-assembly in recalcitrant substrates and direct the formation of a single intermolecular N-H⋅⋅⋅O/Cα -H⋅⋅⋅O bonding motif in single crystals, regardless of peptide sequence or foldamer conformation. In contrast to previous studies, foldamer constituents of single crystals and foldectures assumed different secondary structures and different molecular packing modes, despite a conserved N-H⋅⋅⋅O/Cα -H⋅⋅⋅O bonding motif. DFT calculations validated the experimental results by showing that the N-H⋅⋅⋅O/Cα -H⋅⋅⋅O interaction created by the cap was sufficiently attractive to influence self-assembly. This versatile strategy to harness secondary noncovalent interactions in the rational design of self-assembling organic materials will allow for the exploration of new substrates and speed up the development of novel applications within this increasingly important class of materials.