Cryogenic infrared spectroscopy reveals remarkably short NH+⋯F hydrogen bonds in fluorinated phenylalanines

In past decades, hydrogen bonds involving organic fluorine have been a highly disputed topic. Obtaining clear evidence for the presence of fluorine-specific interactions is generally difficult because of their weak nature. Today, the existence of hydrogen bonds with organic fluorine is widely accepted and supported by numerous studies. However, strong bonds with short H⋯F distances remain scarce and are primarily found in designed model compounds. Using a combination of cryogenic gas-phase infrared spectroscopy and density functional theory, we here analyze a series of conformationally unrestrained fluorinated phenylalanine compounds as protonated species. The results suggest proximal NH+⋯F hydrogen bonds with an exceptionally close H⋯F distance (1.79 Å) in protonated ortho-fluorophenylalanine

Neighboring Group Participation of Benzoyl Protecting Groups in C3- and C6-Fluorinated Glucose

Fluorination is a potent method to modulate chemical properties of glycans. Here, we study how C3- and C6-fluorination of glucosyl building blocks influence the structure of the intermediate of the glycosylation reaction, the glycosyl cation. Using a combination of gas-phase infrared spectroscopy and first-principles theory, glycosyl cations generated from fluorinated and non-fluorinated monosaccharides are structurally characterized. The results indicate that neighboring group participation of the C2-benzoyl protecting group is the dominant structural motif for all building blocks, correlating with the β-selectivity observed in glycosylation reactions. The infrared signatures indicate that participation of the benzoyl group in enhanced by resonance effects. Participation of remote acyl groups such as Fmoc or benzyl on the other hand is unfavored. The introduction of the less bulky fluorine leads to a change in the conformation of the ring pucker, whereas the structure of the active dioxolenium site remains unchanged

Emergence of low-symmetry foldamers from single monomers

Self-assembly is a powerful method to obtain large discrete functional molecular architectures. When using a single building block, self-assembly generally yields symmetrical objects in which all the subunits relate similarly to their neighbours. Here we report the discovery of a family of self-constructing cyclic macromolecules with stable folded conformations of low symmetry, which include some with a prime number (13, 17 and 23) of units, despite being formed from a single component. The formation of these objects amounts to the production of polymers with a perfectly uniform length. Design rules for the spontaneous emergence of such macromolecules include endowing monomers with a strong potential for non-covalent interactions that remain frustrated in competing entropically favoured yet conformationally restrained smaller cycles. The process can also be templated by a guest molecule that itself has an asymmetrical structure, which paves the way to molecular imprinting techniques at the level of single polymer chains

Spontaneous and Template-Directed Emergence of Low-Symmetry Foldamers from Dynamic Homomeric Sequences

Creating large objects from simple subunits rarely results in structures that are of low symmetry as well as of low polydispersity. We now report the spontaneous and uniquely selective oligomerization of simple monomer units into oligomers that are of uniform length, have complex low symmetry structures and are conformationally well-defined. The occurrence of such structures is both frequent and diverse. It is driven by the spontaneous folding into three-dimensional shapes akin to those exhibited by biopolymers. We also show that templates can direct the formation of new functional foldamers. The resulting structures carry imprints of the templates and are therefore capable of binding these. This behavior resembles that of molecularly imprinted polymers (MIPs), with the important distinction that the selected oligomers are uniform and conformationally well-defined, whereas MIPs suffer from heterogeneity in structure, shape and size

CCDC 1999456: Experimental Crystal Structure Determination

Related Article: Charalampos G. Pappas, Pradeep K. Mandal, Bin Liu, Brice Kauffmann, Xiaoming Miao, Dávid Komáromy, Waldemar Hoffmann, Christian Manz, Rayoon Chang, Kai Liu, Kevin Pagel, Ivan Huc, Sijbren Otto|2020|Nature Chemistry|12|1180|doi:10.1038/s41557-020-00565-

CCDC 1942977: Experimental Crystal Structure Determination

Related Article: Charalampos G. Pappas, Pradeep K. Mandal, Bin Liu, Brice Kauffmann, Xiaoming Miao, Dávid Komáromy, Waldemar Hoffmann, Christian Manz, Rayoon Chang, Kai Liu, Kevin Pagel, Ivan Huc, Sijbren Otto|2020|Nature Chemistry|12|1180|doi:10.1038/s41557-020-00565-