Noncovalent self-assembly in aqueous medium: Mechanistic insights from time-resolved cryogenic electron microscopy

Haim Weissman, Boris Rybtchinski

Research output: Contribution to journalReview articlepeer-review

24 Citations (Scopus)


Supramolecular systems based on noncovalent bonds are adaptive due to the reversible nature of the noncovalent interactions, enabling stimuli responsiveness, self-healing, facile fabrication, and recyclability. There is much effort devoted to developing new synthetic tools in supramolecular chemistry. Progress in mechanistic understanding is of crucial importance for rational design targeting functional noncovalent nanoscale assemblies. So far, insufficient insight into evolution of noncovalent assemblies hindered our ability to make progress in the field. The typical paradigm in the case of non-covalent self-assembling systems involves the concept of rapid equilibration at ambient conditions. However, when strong noncovalent interactions are involved, kinetic control may dominate the outcome of the self-assembly processes. The ability of water to impose very strong hydrophobic interactions leads to slow transformations between different structural motifs, amenable to structural mechanistic studies. Cryo-TEM emerges as a method that enables direct structural analysis via imaging of "frozen" evolving assemblies. In this review we focus on cryo-TEM imaging of intermediate structures that evolve along a supramolecular transformation pathway. The structures investigated were trapped and directly visualized, in some cases with subnanometer resolution. Direct structural information obtained by time-resolved cryo-TEM proves to be critical for mechanistic understanding of complex multistep self-assembly processes. Such knowledge is necessary to address the challenge related to rational design of novel functional self-assembled materials.

Original languageEnglish
Pages (from-to)330-342
Number of pages13
JournalCurrent Opinion in Colloid and Interface Science
Issue number6
Publication statusPublished - Dec 1 2012


  • Cryo-TEM
  • Kinetic control
  • Pathway dependent self-assembly
  • Self-assembly
  • Water

ASJC Scopus subject areas

  • Surfaces and Interfaces
  • Physical and Theoretical Chemistry
  • Polymers and Plastics
  • Colloid and Surface Chemistry

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