Dynamic combinatorial chemistry

Dynamic combinatorial chemistry is an approach to molecular design in which building blocks combine through reversible chemical reactions to form libraries of complex structures. These dynamic combinatorial libraries are responsive to external influence (biomolecules, for example), which alter the relative thermodynamic stabilities of members of the library and can shift product distributions.

Latest Research and Reviews

  • Research |

    Light can selectively drive and control the reversible reaction between a nitrogen nucleophile and a photoswitchable carbonyl electrophile by inducing wavelength-specific tautomerization cycles. This enables external and bidirectional regulation of closed dynamic covalent systems via C=N exchange, resembling a light-powered bidirectional molecular-scale Dean–Stark trap.

    • Michael Kathan
    • , Fabian Eisenreich
    • , Christoph Jurissek
    • , Andre Dallmann
    • , Johannes Gurke
    •  & Stefan Hecht
    Nature Chemistry 10, 1031-1036
  • Research | | open

    Selection and persistence of chemical non-equilibrium species is crucial for the emergence of life and the exact mechanisms remain elusive. Here the authors show that phase separation is an efficient way to control selection of chemical species when primitive carboxylic acids are brought out-of-equilibrium by high-energy condensing agents.

    • Marta Tena-Solsona
    • , Caren Wanzke
    • , Benedikt Riess
    • , Andreas R. Bausch
    •  & Job Boekhoven
  • Research | | open

    Container-molecules capable of recognizing charged species possess great potential as sensors, but are typically limited by their rigid frameworks. Here, Sun and co-workers design a family of adaptive metal-organic macrocycles that exhibit shape and size induced-fit transformations upon anion-binding.

    • Ting Zhang
    • , Li-Peng Zhou
    • , Xiao-Qing Guo
    • , Li-Xuan Cai
    •  & Qing-Fu Sun
  • Research |

    Di- and tripeptide building blocks in which the C-terminus has been converted into an aldehyde are shown to form dynamic chemical networks through imine condensation followed by the formation of cyclic N,N-acetals. The networks exhibit multi-phase growth of prion-like assemblies that template the formation of chain-length-specific peptide-like oligomers.

    • Chenrui Chen
    • , Junjun Tan
    • , Ming-Chien Hsieh
    • , Ting Pan
    • , Jay T. Goodwin
    • , Anil K. Mehta
    • , Martha A. Grover
    •  & David G. Lynn
    Nature Chemistry 9, 799-804
  • Research |

    It has now been shown that amines and thiols can be tethered together through a Meldrum's acid-derived conjugate acceptor for applications ranging from dynamic combinatorial chemistry to biochemistry to polymer chemistry. Furthering the utility of this chemistry, the ability to then chemically ‘declick' back to the unaltered amine and thiol components is also demonstrated.

    • Katharine L. Diehl
    • , Igor V. Kolesnichenko
    • , Scott A. Robotham
    • , J. Logan Bachman
    • , Ye Zhong
    • , Jennifer S. Brodbelt
    •  & Eric V. Anslyn
    Nature Chemistry 8, 968-973

News and Comment

  • News and Views |

    'Click' chemistry allows for the linking together of chemical modules, however, there are currently no methods that also allow for facile 'declicking' to unlink them. Now, a method has been developed to click together amines and thiols, and then allow a chemically triggered declick reaction to release the original molecular components.

    • David A. Fulton
    Nature Chemistry 8, 899-900
  • News and Views |

    The scope of dynamic combinatorial chemistry is somewhat limited by the small number of predictably reversible reactions. Now, secondary alcohols are shown to quickly and reversibly react with iminium ions to form hemiaminal ethers, opening up opportunites for their use in the construction of complex — and functional — dynamic architectures.

    • Ognjen Š. Miljanić
    Nature Chemistry 3, 909-910