Dynamic combinatorial chemistry

Definition

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 |

    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
  • 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
  • Research |

    Self-replicating molecules provide a simple molecular level system to study the processes occurring in speciation. Now it is shown that in a pool of interconverting macrocycles, constructed from two building blocks, two distinct sets of self-replicating molecules emerge, and that one is a descendant of the other.

    • Jan W. Sadownik
    • , Elio Mattia
    • , Piotr Nowak
    •  & Sijbren Otto
    Nature Chemistry 8, 264–269

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