We are grateful for financial support from NSF
(CHE-0957607) and from the Johnson Center for Basic
Cancer Research.
Notes and references
z For crystallographic data in tabular format see Table S3 from ESI.w
Fig. 3 Supramolecular heterodimer (A1ꢀB3) extended via combination
of hydrogen bond and halogen bond.
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In five of the six structures (A2ꢀB3 is the exception) the
anti-proton of the amino group is engaged in a hydrogen-bond
to either a carboxylate oxygen atom or the CQO moiety of a
neutral acid (see ESIw).
The facile syntheses of A1–A2 and B2–B3, followed by
co-crystallizations and structure determinations of the resulting
products have allowed us to explore two critical issues in
crystal engineering. By carefully selecting hydrogen-bond
and halogen-bond donor/acceptor moieties with appropriate
complementarity and intermolecular preference, it is possible
to combine both non-covalent interactions in such a way that
no structural crossover or interference takes place. Since the
two cyclic nitrogen atoms in pyrazine have comparable
electrostatic charges, the carboxylic acid is far more likely to
bind to the end that also contains an auxillary amino group,
capable of complementing and strengthening the O–Hꢀ ꢀ ꢀN
contact with a N–H(amino)ꢀ ꢀ ꢀOQC(carbonyl) interaction.
This leaves the 4-nitrogen atom free to act as an acceptor
for either an activated iodine or bromine atom. This latter
interaction is, in all six cases, able to organize either ion-pairs
(A1ꢀB1 and A2ꢀB1) or neutral supermolecules into infinite
chains. The geometry of the resulting assembly is pre-
determined due to the relative position (co-linear) of the two
synthons with respect to each other. The presence of
additional bromine atoms on B2 and B3 does not pose a
supramolecular problem as the bromine/iodine atoms on A1
and A2 (activated by fluorination of the ring) are significantly
better halogen-bond donors and will therefore bind far more
strongly to the remaining N4 atom in aminopyrazine. The
role of charge in controlling the presence/absence of proton
transfer was also emphasized as the acceptor molecule with the
highest negative charge was capable of abstracting a proton
from both A1 and A2, leading to two salts. No sign of proton
transfer was observed in the other structures. These results
demonstrate how it may be possible to build more complex
supramolecular assemblies with a larger number of different
molecules (even ternary co-crystals are still notoriously
difficult to obtain) by combining interactions that can be made
to operate independently of each other both at the level of
molecular recognition, and at the level of overall structural
control. In addition, it is important to note that in order to
meet specific and well-defined supramolecular challenges it is
often necessary to employ custom-designed molecules with the
appropriate functionalities; this led us to develop a very facile
synthetic path to A1 and A2. These molecules combine two
very powerful halogen bond, and halogen bond donors,
respectively, and may therefore find uses in a broad range of
future crystal engineering efforts especially since they promote
and facilitate supramolecular selectivity due to their built-in
geometric differences.
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c
4690 Chem. Commun., 2011, 47, 4688–4690
This journal is The Royal Society of Chemistry 2011