Halogen Bonding inside a Molecular Container

The synthetic macrocycle cucurbit[6]­uril forms host–guest
inclusion complexes with molecular dibromine and diiodine. As evidenced
by their crystal structures, the encapsulated dihalogens adapt a tilted
axial geometry and are held in place by two different types of halogen-bonding
interactions, one with a water molecule (bond distances 2.83 Å
for O···Br and 3.10 Å for O···I)
and the other one with the ureido carbonyl groups of the molecular
container itself (bond distances 3.33 Å for O···Br
and 3.49 Å for O···I). While the former is of
the conventional type, involving the lone electron pair of an oxygen
donor, the latter is perpendicular, involving the π-system of
the carbonyl oxygen (N–CO···X dihedrals
ca. 90°). Such perpendicular interactions resemble those observed
in protein complexes of halogenated ligands. A statistical analysis
of small-molecule crystal structural data, as well as quantum-chemical
calculations with urea as a model (MP2/aug-cc-pVDZ-PP), demonstrates
that halogen bonding with the π-system of the carbonyl oxygen
can become competitive with the commonly favored lone-pair interaction
whenever the carbonyl group carries electron-donating substitutents,
specifically for ureas, amides, and esters, and particularly when
the lone pairs are engaged in orthogonal hydrogen bonding (hX bonds). The calculations further demonstrate that the
perpendicular interactions remain significantly attractive also for
nonlinear distortions of the O···X–X angle to
ca. 140°, the angle observed in the two reported crystal structures.
The structural and theoretical data jointly support the assignment
of the observed dihalogen–carbonyl contacts as genuine halogen
bonds.