Design and preparation of co-crystals utilizing the R2 4(8) hydrogen-bonding motif

Joel Bernstein, Juan J. Novoa, Roland Boese, Sebastian A. Cirkel

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


An investigation of the feasibility of utilizing a specific, and previously largely unrecognized, hydrogenbonded synthon for the design and preparation of co-crystals is reported. Structural evidence (i.e., >12000 instances) indicated the robustness of the cyclic R24(8) hydrogen-bonded motif containing, in most cases, four individual (either identical or different) molecules, in which the donor substituent (e.g., an amine) can provide two hydrogen-bond donors, and the acceptor (e.g., a carbonyl oxygen) can provide two hydrogen-bond acceptors. The energetic robustness of the motif with respect to chemical substitution and charge on the component molecules was investigated and confirmed in a series of fully optimized calculations at the MP2/6-31+G(d) level. A proof-ofconcept experiment to prepare a cocrystal between a prototypical ketone and a primary amine yielded the crystal structure reported herein, in which the hydrogen bonds between the co-crystal components indeed exhibit exclusively the designed and sought-after R24(8) motif.

Original languageEnglish
Pages (from-to)9047-9055
Number of pages9
JournalChemistry - A European Journal
Issue number30
StatePublished - 19 Aug 2010


  • Computational energetics
  • Crystal engineering
  • Graph sets
  • Hydrogen bonds
  • Supramolecular chemistry

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry


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