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Atomically precise organomimetic cluster nanomolecules assembled via perfluoroaryl-thiol SNAr chemistry

Nature Chemistry volume 9, pages 333–340 (2017)Cite this article

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Abstract

The majority of biomolecules are intrinsically atomically precise, an important characteristic that enables rational engineering of their recognition and binding properties. However, imparting a similar precision to hybrid nanoparticles has been challenging because of the inherent limitations of existing chemical methods and building blocks. Here we report a new approach to form atomically precise and highly tunable hybrid nanomolecules with well-defined three-dimensionality. Perfunctionalization of atomically precise clusters with pentafluoroaryl-terminated linkers produces size-tunable rigid cluster nanomolecules. These species are amenable to facile modification with a variety of thiol-containing molecules and macromolecules. Assembly proceeds at room temperature within hours under mild conditions, and the resulting nanomolecules exhibit high stabilities because of their full covalency. We further demonstrate how these nanomolecules grafted with saccharides can exhibit dramatically improved binding affinity towards a protein. Ultimately, the developed strategy allows the rapid generation of precise molecular assemblies to investigate multivalent interactions.

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Figure 1: Comparison of features between the thiol-capped AuNPs and the OCNs.
Figure 2: Synthesis and characterization of the perfluoroaryl-perfunctionalized dodecaborate clusters and the subsequent modification with thiols.
Figure 3: Characterization of the PEGylated OCNs 2i–2k and 3i–3k.
Figure 4: Multivalent binding of the glycosylated OCN 2l to the lectin ConA.

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Acknowledgements

A.M.S. acknowledges the University of California, Los Angeles (UCLA) Department of Chemistry and Biochemistry for start-up funds, 3M for a Non-Tenured Faculty Award and the American Chemical Society Petroleum Research Fund (56562-DNI3) for the Doctoral New Investigator Grant. E.A.Q. thanks the US Public Health Service of the National Institutes of Health (NIH) for the Predoctoral Training Fellowship through the UCLA Chemistry-Biology Interface Training Program under the National Research Service Award (T32GM008496). A.S. is funded by the CARE Scholars Programs (NIH grant GM055052). M.S.M. is grateful to the National Science Foundation (NSF) for the Bridge-to-Doctorate and the Predoctoral (GRFP) fellowships. P.K. acknowledges the NSF Division of Materials Research grant 1506886. H.D.M. thanks the NSF (CHE-1507735) for funding. We thank UCLA Molecular Instrumentation Center for mass spectrometry and NMR spectroscopy (NIH grant 1S10OD016387-01, NSF grant CHE-1048804). We also thank the Electron Imaging Center for Nanomachines at the UCLA California NanoSystems Institute for electron microscopy (NIH grant 1S10RR23057) and the UCLA Biochemistry Instrumentation Facility for SPR.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of California, Los Angeles, 90095, California, USA

    Elaine A. Qian, Alex I. Wixtrom, Jonathan C. Axtell, Azin Saebi, Dahee Jung, Elamar Hakim Moully, Daniel Mosallaei, Sylvia Chow, Marco S. Messina, Jing Yang Wang, Heather D. Maynard & Alexander M. Spokoyny

  2. Department of Bioengineering, University of California, Los Angeles, 90095, California, USA

    Elaine A. Qian

  3. California NanoSystems Institute, University of California, Los Angeles, 90095, California, USA

    Elaine A. Qian, Dahee Jung, Marco S. Messina, Heather D. Maynard & Alexander M. Spokoyny

  4. Department of Chemistry, University of Illinois at Chicago, Chicago, 60607, Illinois, USA

    Pavel Rehak, Yanxiao Han & Petr Král

  5. Department of Chemistry, University of West Florida, Pensacola, 32514, Florida, USA

    A. Timothy Royappa

  6. Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, 92093, California, USA

    Arnold L. Rheingold

  7. Department of Physics, University of Illinois at Chicago, Chicago, 60607, Illinois, USA

    Petr Král

  8. Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, 60612, Illinois, USA

    Petr Král

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  1. Elaine A. Qian
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Contributions

A.M.S. developed the concept and supervised and guided the research. E.A.Q. and A.M.S. designed the experiments. E.A.Q. performed the majority of the experimental work. A.I.W., J.C.A., A.S. and J.Y.W. contributed to the synthesis of 2 and 3. A.T.R and A.L.R. performed the crystallographic characterization of compound 3. A.S., E.H.M. and D.M. contributed to the synthesis of 2j and 3j. S.C. assisted with optimizing the reaction conditions of 2a–2f, 2i, 2l, 3a–3f, 3i and 3l. A.I.W. and E.H.M. contributed to the purification of the OCNs. D.J. conducted and interpreted the TEM experiments. M.S.M. and H.D.M. assisted with the GPC experiments. P.R., Y.H. and P.K. designed, conducted and interpreted the computational experiments. E.A.Q., A.I.W. and A.M.S. co-wrote the manuscript. All of the authors commented on the manuscript during its preparation.

Corresponding author

Correspondence to Alexander M. Spokoyny.

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Qian, E., Wixtrom, A., Axtell, J. et al. Atomically precise organomimetic cluster nanomolecules assembled via perfluoroaryl-thiol SNAr chemistry. Nature Chem 9, 333–340 (2017). https://doi.org/10.1038/nchem.2686

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