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Nanocrystal synthesis with alkoxy reagents for dispersion in polar and non-polar solvents

Nature Synthesis volume 4, pages 826–835 (2025)Cite this article

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Abstract

Applications of colloidal nanocrystals in polar solvents often require nanocrystals synthesized in non-polar solvents. However, solvent transfer processes are problematic and deteriorate nanocrystal quality. Here we report syntheses of nanocrystals with nearly universal solvent dispersibility using ligands and solvents with alkoxy repeating units. Core syntheses, shell deposition and cation exchange proceed similarly to traditional methods while products are more stable in aqueous solution than those generated by solvent transfer. (CdSe)CdZnS nanocrystals retain photoluminescence in cells for single-particle tracking experiments and outperform other nanocrystal classes in diffusion metrics reflecting stability and resistance to non-specific binding. Distinct reaction classes yield nanocrystals with either methoxy or hydroxy ligand terminations, both of which can be purified by aqueous methods that are chemically greener than traditional methods. These reactions can further generate nanocrystals with diverse oxide, sulfide and selenide compositions, shapes and spectral bands with wide dispersibility that may make applications in polar solvents more widely accessible.

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Fig. 1: Chemical structures of compounds used in alkyl or alkoxy reaction systems for nanocrystal synthesis.
Fig. 2: Differences in solvent dispersibility of (core)shell (CdSe)CdZnS nanocrystals with shells grown by alkyl or alkoxy reactions.
Fig. 3: Purification of nanocrystals from alkoxy reactions.
Fig. 4: Comparison between (CdSe)CdZnS nanocrystals from alkoxy-based shell growth reactions using ligand 1a and structurally equivalent (CdSe)CdZnS nanocrystals synthesized by alkyl-based shell growth reactions and then coated with ligand 1a or other hydrophilic coatings.
Fig. 5: Alkoxy reactions for shell growth on diverse nanocrystals originating from alkyl reactions to generate widely dispersible and photoluminescent nanocrystals with tunable photophysical properties and shapes.
Fig. 6: Syntheses of oxide, sulfide and selenide nanocrystals through nucleation in alkoxy-based reactions.

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Relevant data are provided within the Supplementary Information. Source data are provided with this paper.

References

  1. Murray, C. B., Norris, D. J. & Bawendi, M. G. Synthesis and characterization of nearly monodisperse CdE (E = S, Se, Te) semiconductor nanocrystallites. J. Am. Chem. Soc. 115, 8706–8715 (1993).

    Article  CAS  Google Scholar 

  2. Yin, Y. & Alivisatos, A. P. Colloidal nanocrystal synthesis and the organic–inorganic interface. Nature 437, 664–670 (2005).

    Article  CAS  PubMed  Google Scholar 

  3. Nasilowski, M., Mahler, B., Lhuillier, E., Ithurria, S. & Dubertret, B. Two-dimensional colloidal nanocrystals. Chem. Rev. 116, 10934–10982 (2016).

    Article  CAS  PubMed  Google Scholar 

  4. Kwon, S. G. & Hyeon, T. Colloidal chemical synthesis and formation kinetics of uniformly sized nanocrystals of metals, oxides, and chalcogenides. Acc. Chem. Res. 41, 1696–1709 (2008).

    Article  CAS  PubMed  Google Scholar 

  5. Mocatta, D. et al. Heavily doped semiconductor nanocrystal quantum dots. Science 332, 77–81 (2011).

    Article  CAS  PubMed  Google Scholar 

  6. Drake, G. A., Keating, L. P. & Shim, M. Design principles of colloidal nanorod heterostructures. Chem. Rev. 123, 3761–3789 (2022).

    Article  PubMed  Google Scholar 

  7. McCormick, C. R., Katzbaer, R. R., Steimle, B. C. & Schaak, R. E. Combinatorial cation exchange for the discovery and rational synthesis of heterostructured nanorods. Nat. Synth. 2, 152–161 (2023).

    Article  CAS  Google Scholar 

  8. Kagan, C. R., Lifshitz, E., Sargent, E. H. & Talapin, D. V. Building devices from colloidal quantum dots. Science 353, aac5523 (2016).

    Article  PubMed  Google Scholar 

  9. Liu, M. et al. Colloidal quantum dot electronics. Nat. Electron. 4, 548–558 (2021).

    Article  Google Scholar 

  10. Park, Y.-S., Roh, J., Diroll, B. T., Schaller, R. D. & Klimov, V. I. Colloidal quantum dot lasers. Nat. Rev. Mater. 6, 382–401 (2021).

    Article  CAS  Google Scholar 

  11. Chan, W. C. W. & Nie, S. M. Quantum dot bioconjugates for ultrasensitive nonisotopic detection. Science 281, 2016–2018 (1998).

    Article  CAS  PubMed  Google Scholar 

  12. Bruchez, M., Moronne, M., Gin, P., Weiss, S. & Alivisatos, A. P. Semiconductor nanocrystals as fluorescent biological labels. Science 281, 2013–2016 (1998).

    Article  CAS  PubMed  Google Scholar 

  13. Dubertret, B. et al. In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 298, 1759–1762 (2002).

    Article  CAS  PubMed  Google Scholar 

  14. Wu, X. Y. et al. Immunofluorescent labeling of cancer marker Her2 and other cellular targets with semiconductor quantum dots. Nat. Biotechnol. 21, 41–46 (2003).

    Article  CAS  PubMed  Google Scholar 

  15. Stavis, S. M., Fagan, J. A., Stopa, M. & Liddle, J. A. Nanoparticle manufacturing—heterogeneity through processes to products. ACS Appl. Nano Mater. 1, 4358–4385 (2018).

    Article  CAS  Google Scholar 

  16. Shen, Y., Gee, M. Y. & Greytak, A. B. Purification technologies for colloidal nanocrystals. Chem. Commun. 53, 827–841 (2017).

    Article  CAS  Google Scholar 

  17. Lim, H. et al. Continuous purification of colloidal quantum dots in large-scale using porous electrodes in flow channel. Sci. Rep. 7, 43581 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Jokerst, J. V., Lobovkina, T., Zare, R. N. & Gambhir, S. S. Nanoparticle PEGylation for imaging and therapy. Nanomedicine 6, 715–728 (2011).

    Article  CAS  PubMed  Google Scholar 

  19. De Roo, J. et al. Probing solvent–ligand interactions in colloidal nanocrystals by the NMR line broadening. Chem. Mater. 30, 5485–5492 (2018).

    Article  Google Scholar 

  20. Larsen, T. H., Sigman, M., Ghezelbash, A., Doty, R. C. & Korgel, B. A. Solventless synthesis of copper sulfide nanorods by thermolysis of a single source thiolate-derived precursor. J. Am. Chem. Soc. 125, 5638–5639 (2003).

    Article  CAS  PubMed  Google Scholar 

  21. Jun, S., Jang, E. J. & Chung, Y. S. Alkyl thiols as a sulfur precursor for the preparation of monodisperse metal sulfide nanostructures. Nanotechnology 17, 4806–4810 (2006).

    Article  CAS  Google Scholar 

  22. Ma, L. et al. Multidentate polymer coatings for compact and homogeneous quantum dots with efficient bioconjugation. J. Am. Chem. Soc. 138, 3382–3394 (2016).

    Article  CAS  PubMed  Google Scholar 

  23. Ithurria, S. & Talapin, D. V. Colloidal atomic layer deposition (c-ALD) using self-limiting reactions at nanocrystal surface coupled to phase transfer between polar and nonpolar media. J. Am. Chem. Soc. 134, 18585–18590 (2012).

    Article  CAS  PubMed  Google Scholar 

  24. Aldana, J., Wang, Y. A. & Peng, X. G. Photochemical instability of CdSe nanocrystals coated by hydrophilic thiols. J. Am. Chem. Soc. 123, 8844–8850 (2001).

    Article  CAS  PubMed  Google Scholar 

  25. Pellegrino, T. et al. Hydrophobic nanocrystals coated with an amphiphilic polymer shell: a general route to water soluble nanocrystals. Nano Lett. 4, 703–707 (2004).

    Article  CAS  Google Scholar 

  26. Smith, A. M. & Nie, S. M. Minimizing the hydrodynamic size of quantum dots with multifunctional multidentate polymer ligands. J. Am. Chem. Soc. 130, 11278–11279 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Turo, M. J. & Macdonald, J. E. Crystal-bound vs surface-bound thiols on nanocrystals. ACS Nano 8, 10205–10213 (2014).

    Article  CAS  PubMed  Google Scholar 

  28. Zahid, M. U., Ma, L., Lim, S. J. & Smith, A. M. Single quantum dot tracking reveals the impact of nanoparticle surface on intracellular state. Nat. Comm. 9, 1830 (2018).

    Article  Google Scholar 

  29. Cai, E. et al. Stable small quantum dots for synaptic receptor tracking on live neurons. Angew. Chem. Int. Ed. 53, 12484–12488 (2014).

    Article  CAS  Google Scholar 

  30. Etoc, F. et al. Non-specific interactions govern cytosolic diffusion of nanosized objects in mammalian cells. Nat. Mater. 17, 740–746 (2018).

    Article  CAS  PubMed  Google Scholar 

  31. Katrukha, E. A. et al. Probing cytoskeletal modulation of passive and active intracellular dynamics using nanobody-functionalized quantum dots. Nat. Comm. 8, 14772 (2017).

    Article  CAS  Google Scholar 

  32. Zhu, Z. J. et al. Stability of quantum dots in live cells. Nat. Chem. 3, 963–968 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cai, R. et al. Dynamic intracellular exchange of nanomaterials’ protein corona perturbs proteostasis and remodels cell metabolism. Proc. Natl Acad. Sci. USA 119, e2200363119 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Pietryga, J. M. et al. Utilizing the lability of lead selenide to produce heterostructured nanocrystals with bright, stable infrared emission. J. Am. Chem. Soc. 130, 4879–4885 (2008).

    Article  CAS  PubMed  Google Scholar 

  35. Lim, S. J. et al. Lipoprotein nanoplatelets: brightly fluorescecent, zwitterionic probes with rapid cellular entry. J. Am. Chem. Soc. 138, 64–67 (2016).

    Article  CAS  PubMed  Google Scholar 

  36. Nasilowski, M., Nienhaus, L., Bertram, S. N. & Bawendi, M. G. Colloidal atomic layer deposition growth of PbS/CdS core/shell quantum dots. Chem. Commun. 53, 869–872 (2017).

    Article  CAS  Google Scholar 

  37. Smith, A. M., Mancini, M. C. & Nie, S. M. Second window for in vivo imaging. Nat. Nanotech. 4, 710–711 (2009).

    Article  CAS  Google Scholar 

  38. Wohlfarth, C. in Static Dielectric Constants of Pure Liquids and Binary Liquid Mixtures (ed. Lechner, M. D.) 138 (Springer-Verlag, 2015).

  39. Wohlfarth, C. in Static Dielectric Constants of Pure Liquids and Binary Liquid Mixtures (ed. Lechner, M. D.) 184 (Springer-Verlag, 2015).

  40. Monego, D. et al. When like destabilizes like: inverted solvent effects in apolar nanoparticle dispersions. ACS Nano 14, 5278–5287 (2020).

    Article  CAS  PubMed  Google Scholar 

  41. Ito, D., Yokoyama, S., Zaikova, T., Masuko, K. & Hutchison, J. E. Synthesis of ligand-stabilized metal oxide nanocrystals and epitaxial core/shell nanocrystals via a lower-temperature esterification process. ACS Nano 8, 64–75 (2014).

    Article  CAS  PubMed  Google Scholar 

  42. Chen, J., Spear, S. K., Huddleston, J. G. & Rogers, R. D. Polyethylene glycol and solutions of polyethylene glycol as green reaction media. Green Chem. 7, 64–82 (2005).

    Article  CAS  Google Scholar 

  43. Ahmed, S. F. et al. Green approaches in synthesising nanomaterials for environmental nanobioremediation: technological advancements, applications, benefits and challenges. Environ. Res. 204, 111967 (2022).

    Article  CAS  PubMed  Google Scholar 

  44. Varma, R. S. Greener and sustainable trends in synthesis of organics and nanomaterials. ACS Sustain. Chem. Eng. 4, 5866–5878 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Chen, O. et al. Synthesis of metal-selenide nanocrystals using selenium dioxide as the selenium precursor. Angew. Chem. Int. Ed. 47, 8638–8641 (2008).

    Article  CAS  Google Scholar 

  46. Lim, S. J. et al. Brightness-equalized quantum dots. Nat. Comm. 6, 8210 (2015).

    Article  CAS  Google Scholar 

  47. Jaqaman, K. et al. Robust single-particle tracking in live-cell time-lapse sequences. Nat. Methods 5, 695–702 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by funds from the National Institutes of Health (grant nos. R01CA227699, R01GM131272, R01EB032249 and R01EB032725 to A.M.S.) and the National Science Foundation (grant nos. 2232681 to A.M.S. and 1746047 to E.I.H.A.). This work used the Delta system at the National Center for Supercomputing Applications through allocation MAT230021 from the Advanced Cyberinfrastructure Coordination Ecosystem: Services & Support (ACCESS) program, supported by National Science Foundation grants (nos. 2138259, 2138286, 2138307, 2137603 and 2138296). We are grateful to L. Zhu for valuable help with NMR experiments.

Author information

Authors and Affiliations

  1. Department of Bioengineering, University of Illinois Urbana-Champaign, Urbana, IL, USA

    Suresh Sarkar, Opeyemi H. Arogundade, Yuxiao Cui & Andrew M. Smith

  2. Holonyak Micro and Nanotechnology Laboratory, University of Illinois Urbana-Champaign, Urbana, IL, USA

    Suresh Sarkar, Opeyemi H. Arogundade, Yuxiao Cui & Andrew M. Smith

  3. Department of Chemistry, Indian Institute of Technology Jodhpur, Rajasthan, India

    Suresh Sarkar

  4. Department of Materials Science and Engineering, University of Illinois Urbana-Champaign, Urbana, IL, USA

    Erick I. Hernandez Alvarez, André Schleife & Andrew M. Smith

  5. Materials Research Laboratory, University of Illinois Urbana-Champaign, Urbana, IL, USA

    André Schleife

  6. National Center for Supercomputing Applications, University of Illinois Urbana-Champaign, Urbana, IL, USA

    André Schleife

  7. Cancer Center at Illinois, University of Illinois Urbana-Champaign, Urbana, IL, USA

    Andrew M. Smith

  8. Carl R. Woese Institute for Genomic Biology, University of Illinois Urbana-Champaign, Urbana, IL, USA

    Andrew M. Smith

  9. Carle Illinois College of Medicine, Urbana, IL, USA

    Andrew M. Smith

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  1. Suresh Sarkar
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Contributions

S.S. and A.M.S. conceived and designed the experiments, characterizations and contributed to the chemical theory. S.S. performed all chemical syntheses and optical characterizations. O.H.A. performed all studies related to living cells including single-particle tracking and cytotoxicity experiments and related data analyses. Y.C. synthesized urea-based reagents and performed NMR characterizations and related data analyses. E.I.H.A. performed CdS nanocrystal syntheses as well as XPS characterization and related data analyses. E.I.H.A. and A.S. designed and performed DFT simulations. S.S. and A.M.S. wrote the paper. All authors edited the manuscript.

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Correspondence to Andrew M. Smith.

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Nature Synthesis thanks Emil A. Hernandez-Pagan and the other, anonymous, reviewer(s) for their contribution to the peer review of this work. Primary Handling Editor: Alexandra Groves, in collaboration with the Nature Synthesis team.

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Sarkar, S., Arogundade, O.H., Cui, Y. et al. Nanocrystal synthesis with alkoxy reagents for dispersion in polar and non-polar solvents. Nat. Synth 4, 826–835 (2025). https://doi.org/10.1038/s44160-025-00764-0

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