Do Docking Sites Persist Upon Fluorination? The Diadamantyl Ether‐Aromatics Challenge for Rotational Spectroscopy and Theory

Abstract

Fluorinated derivatives of biological molecules have proven to be highly efficient at modifying the biological activity of a given protein through changes in the stability and the kind of docking interactions. These interactions can be hindered or facilitated based on the hydrophilic/hydrophobic character of a particular protein region. Diadamantyl ether (C20H30O) possesses both kinds of docking sites, serving as a good template to model these important contacts with aromatic fluorinated counterparts. In this work, an experimental study on the structures of several complexes between diadamantyl ether and benzene as well as a series of fluorinated benzenes is reported to analyze the effect of H→F substitution on the interaction and structure of the resulting molecular clusters using rotational spectroscopy. All experimentally observed complexes are largely dominated by London dispersion interactions with the hydrogen‐terminated surface areas of diadamantyl ether. Already single substitution of one hydrogen atom with fluorine changes the preferred docking site of the complexes. However, the overall contributions of the different intermolecular interactions are similar for the different complexes, contrary to previous studies focusing on the difference in interactions using fluorinated and non‐fluorinated molecules.

The Role of Non‐Covalent Interactions on Cluster Formation: Pentamer, Hexamers and Heptamer of Difluoromethane

“…This field is complex and the properties exhibited by weakly bound molecular aggregates help to bridge the gap between the different states of matter [21–24] . The gas‐phase approach can facilitate the design and generation of tailor‐made molecular clusters to study the specific behavior of NCIs.…”

“…This field is complex and the properties exhibited by weakly bound molecular aggregates help to bridge the gap between the different states of matter. [ 21 , 22 , 23 , 24 ] The gas‐phase approach can facilitate the design and generation of tailor‐made molecular clusters to study the specific behavior of NCIs. However, despite their conceptual potential, in practice there are very few examples with molecular homoclusters larger than two units,[ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ] with the water pentadecamer (H 2 O) 15 being the largest cluster observed rotationally to date.…”

Sustainable Synthesis of Diamondoid Ethers by High-Temperature Ball Milling

“…While selective chemical functionalization of diamondoids has been systematically described in the literature, ,− there exist only a few examples of direct linking of two or more diamondoid cages via heteroatoms. − For instance, 1,1′-diadamantyl ether ( 1 ) was first reported as a side product in the synthesis of aryl adamantly ethers . Afterward, the preparation of 1 was reported by several other authors, but mainly as a by-product of various reactions. − Only recently was its first targeted synthesis reported. ,, We were intrigued by a possible preparation scope for the derivatives consisting of two diamondoid cages connected by an oxygen atom. We recently reported on the synthesis and spontaneous self-assembly of ethers 1 , 2 , and 4 on the highly oriented pyrolytic graphite (HOPG) surface, shedding light on the importance of London dispersion interactions for on-surface supramolecular systems of this type .…”

“…37−40 Only recently was its first targeted synthesis reported. 13,41,42 We were intrigued by a possible preparation scope for the derivatives consisting of two diamondoid cages connected by an oxygen atom. We recently reported on the synthesis and spontaneous self-assembly of ethers 1, 2, and 4 on the highly oriented pyrolytic graphite (HOPG) surface, shedding light on the importance of London dispersion interactions for on-surface supramolecular systems of this type.…”

The Role of Non‐Covalent Interactions on Cluster Formation: Pentamer, Hexamers and Heptamer of Difluoromethane

“…This field is complex and the properties exhibited by weakly bound molecular aggregates help to bridge the gap between the different states of matter. [21][22][23][24] The gas-phase approach can facilitate the design and generation of tailormade molecular clusters to study the specific behavior of NCIs. However, despite their conceptual potential, in practice there are very few examples with molecular homoclusters larger than two units, [25][26][27][28][29][30][31][32][33] with the water pentadecamer (H 2 O) 15 being the largest cluster observed rotationally to date.…”