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Not Your Usual Bioisostere: Solid State Study of 3D Interactions in Cubanes
Author(s) -
Flanagan Keith J.,
Bernhard Stefan S. R.,
Plunkett Shane,
Senge Mathias O.
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201806432
Subject(s) - cubane , halogen , chemistry , hydrogen bond , solid state , halogen bond , crystallography , hydrogen , stereochemistry , molecule , crystal structure , organic chemistry , alkyl
Previous studies by Desiraju and co‐workers have implicated the acidic hydrogen atoms of cubane as a support network for hydrogen bonding groups. Herein we report a detailed structural analysis of all currently available 1,4‐disubstituted cubane structures with an emphasis on how the cubane scaffold interacts in its solid‐state environment. In this regard, the interactions between the cubane hydrogen atoms and acids, ester, halogens, ethynyl, nitrogenous groups, and other cubane scaffolds were cataloged. The goal of this study was to investigate the potential of cubane as a substitute for phenyl. This could be achieved by analyzing all contacts that are directed by the cubane hydrogen atoms in the X‐ray crystal structures. As a result, we have established several new cubane interaction profiles, such as the catemer formation seen in esters, the preferences of halogen–hydrogen contacts over direct halogen bonding, and the stabilizing effects caused by the cubane hydrogen atoms interacting with ethynyl groups. These interaction profiles can then be used as a guide for designing cubane bioisosteres of known materials and drugs containing phenyl moieties.