Competing hydrogen-bond and halogen-bond donors in crystal engineering

Abstract

aIn order to study the structure-directing competition between hydrogen-and halogen-bond donors we 5 have synthesized two ligands, 3,3'-azobipyridine and 4,4'-azobipyridine, and co-crystallized them with a series of bi-functional donor molecules comprising an activated halogen-bond donor (I or Br) as well as a hydrogen-bond donor (acid, phenol or oxime) on the same backbone. Based on the subsequent singlecrystal analysis, 5 of 6 co-crystals of 3,3'-azobipyridine are assembled using hydrogen bonds as the primary driving force accompanied by weaker secondary (C-XO) interactions. However, in 5 out of the 10 6 co-crystals of 4,4'-azobipyridine, both hydrogen bonds (O-HN) and halogen bonds (C-XN) are present as comparable structure-directing interactions leading to 1-D chains. Since the charges on the acceptor sites in 3,3'-and 4,4'-azobipyridine are very similar, i.e. -174 and -172 kJ/mol respectively, the observed difference in binding behaviour highlights the importance of binding-site location on the acceptor molecules (anti-parallel in 3,3'-azobipyridine and co-linear in 4,4'-azobipyridine) as a direct 15 influence over the structural balance between hydrogen-and halogen-bond donors.

A Protein Data Bank Survey Reveals Shortening of Intermolecular Hydrogen Bonds in Ligand-Protein Complexes When a Halogenated Ligand Is an H-Bond Donor

“…These values agree with energies estimated by IR spectroscopy, for CF 3 -X•••N(CH 3 ) 3 in liquid noble gases, which are the best models for a non-polar solvent that does not interfere with solute-solute interactions: 2.1, 4.4 and 6.8 kcal/mol for X-bonds involving Cl, Br and I, respectively [31]–[33]. These halogen bonds can compete with hydrogen bonding, as well documented for numerous low-mass complexes in silico [34], [35], in solution [36], [37], and in the solid state [17], [38], [39].…”

Integrated kinetic studies and computational analysis on naphthyl chalcones as mushroom tyrosinase inhibitors

“…[24][25][26][27] Also, oximes upon deprotonation, can act as strongly coordinating ligands in metalcoordination chemistry. 28,29 Classically, oximes are prepared by refluxing an alcoholic solution of a carbonyl compound with hydroxylamine hydrochloride and pyridine.…”

Halogen and Hydrogen Bonding in Multicomponent Crystals of Tetrabromo-1H-Benzotriazole

“…This may help in identifying new CCFs generating TBBT pharmaceutical cocrystals with solubility higher than the original API. When an API-CCF adduct is formed, the recognition and binding phenomena typically occur between molecules displaying a wealth of different functional moieties, which may compete with each other in the formation of the interactions [17][18][19][20]. The evaluation of the specific role of the moieties characterized by a similar supramolecular behavior is thus fundamental to identify the most reliable supramolecular synthetic strategies.…”