Operating a collection of prototype molecular machines within a dendritic macromolecule

Published in Chemistry
Operating a collection of prototype molecular machines within a dendritic macromolecule

The paper in Nature Communications is here: http://rdcu.be/GiGs

Mechanical bonds are a novel and exciting class of non-covalent bonds similar to familiar chains and hooks, for example. A series of novel hyperbranched macromolecules with at most 15 mechanical bonds at the branching unit was reported. These macromolecules can induce an overall extension-contraction or breathing molecular motion via collective and controllable molecular back-and-forth shuttling, providing the ability to encapsulate drug molecules and release them actively by acidic stimuli. These new molecules were characterised by mass spectrometry and their physical properties were also verified with supercomputer simulations. This smart material combines molecular machines and dendrimers (rotaxane dendrimers) with a new breakthrough in synthesis as well as controlled and active drug release. With its complexity and size, this synthetic molecule resembles a small virus.  

Rotaxane dendrimers are molecular interlocked molecules that combine hyperbranched macromolecules with molecular machines. Among various types of rotaxane dendrimer, type III-B possesses the most complicated molecular structure and exhibits the largest extension-contraction properties. The syntheses of most compounds required the in situ rotaxane formation followed by careful purification. The breakthrough in the high-yielding synthesis and the control of particle size of higher-generation rotaxane dendrimers could give scientists an insight to develop more sophisticated molecular machines to be applied in functional materials and nanotechnology, such as the delivery of drugs or biomolecules.  

This world-first breakthrough on the design and synthesis of a smart globular molecular machine gives insight to targeted therapy drugs such as Chlorambucil in the treatment of leukemia. In current leukemia treatment, drugs are delivered to kill leukemia cells that may be present in the blood and bone marrow. The amount of drugs released to kill the free-floating cancer cells cannot be effectively controlled, however. The 15 mechanical bonds resemble 15 mechanical arms that actively control the delivery and amount of drugs released to targeted cancer cells. Due to the relatively low toxicity of this smart globular molecular vehicle, it can also serve as a potential ideal long-term drug delivery molecular machine submerged in the human body.

The paper in Nature Communications (DOI: 10.1038/s41467-018-02902-z) is here: http://go.nature.com/2EI1IjI

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