Molecular knot

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In chemistry, a molecular knot is a mechanically interlocked molecular architecture that is analogous to a macroscopic knot. [1] Naturally-forming molecular knots are found in organic molecules like DNA, RNA, and proteins. It is not certain that naturally occurring knots are evolutionarily advantageous to nucleic acids or proteins, though knotting is thought to play a role in the structure, stability, and function of knotted biological molecules. [2] The mechanism by which knots naturally form in molecules, and the mechanism by which a molecule is stabilized or improved by knotting, is ambiguous. [3] The study of molecular knots involves the formation and applications of both naturally occurring and chemically synthesized molecular knots. Applying chemical topology and knot theory to molecular knots allows biologists to better understand the structures and synthesis of knotted organic molecules. [1]

Contents

The term knotane was coined by Vögtle et al. in 2000 to describe molecular knots by analogy with rotaxanes and catenanes, which are other mechanically interlocked molecular architectures. [1] [4] The term has not been broadly adopted by chemists and has not been adopted by IUPAC.

Crystal structure of a molecular trefoil knot with two copper(I) templating ions bound within it reported by Jean Pierre Sauvage and coworkers Molecular Knot RecTravChimPays-Bas 427 1993 commons.png
Crystal structure of a molecular trefoil knot with two copper(I) templating ions bound within it reported by Jean Pierre Sauvage and coworkers
Crystal structure of a molecular trefoil knot reported by Vogtle and coworkers in the Angew. Chem. Int. Ed., 2000, 1616-1618. Molecular Knot Angew 1616 2000 commons.jpg
Crystal structure of a molecular trefoil knot reported by Vögtle and coworkers in the Angew. Chem. Int. Ed., 2000, 1616–1618.

Naturally occurring molecular knots

Organic molecules containing knots may fall into the categories of slipknots or pseudo-knots. [2] They are not considered mathematical knots because they are not a closed curve, but rather a knot that exists within an otherwise linear chain, with termini at each end. Knotted proteins are thought to form molecular knots during their tertiary structure folding process, and knotted nucleic acids generally form molecular knots during genomic replication and transcription, [6] though details of knotting mechanism continue to be disputed and ambiguous. Molecular simulations are fundamental to the research on molecular knotting mechanisms.

Knotted DNA was found first in single-stranded, circular, bacterial DNA, though double-stranded circular DNA has been found to also form knots. Naturally knotted RNA has not yet been reported.[ citation needed ] [7]

A number of proteins containing naturally occurring molecular knots have been identified. The knot types found to be naturally occurring in proteins are the and knots, as identified in the KnotProt database of known knotted proteins. [8]

Chemically synthesized molecular knots

Several synthetic molecular knots have been reported. [9] [10] [11] [12] [13] [14] Knot types that have been successfully synthesized in molecules are and 819 knots. Though the and knots have been found to naturally occur in knotted molecules, they have not been successfully synthesized. Small-molecule composite knots have also not yet been synthesized. [7]

Artificial DNA, RNA, and protein knots have been successfully synthesized. DNA is a particularly useful model of synthetic knot synthesis, as the structure naturally forms interlocked structures and can be easily manipulated into forming knots [15] control precisely the raveling necessary to form knots. Molecular knots are often synthesized with the help of crucial metal ion ligands. [7]

KnotYearReference
31 1989 [16] [17]
41 2014 [18] [17]
51 2012 [19] [17] [20]
52 2020 [21] [17] [22]
71 2020 [23] [17]
74 2021 [24] [25]
818 2018 [26] [17]
819 2017 [27] [17] [28]

History

The first researcher to suggest the existence of a molecular knot in a protein was Jane Richardson in 1977, who reported that carbonic anhydrase B (CAB) exhibited apparent knotting during her survey of various proteins' topological behavior. [29] However, the researcher generally attributed with the discovery of the first knotted protein is Marc. L. Mansfield in 1994, as he was the first to specifically investigate the occurrence of knots in proteins and confirm the existence of the trefoil knot in CAB. Knotted DNA was found first by Liu et al. in 1981, in single-stranded, circular, bacterial DNA, though double-stranded circular DNA has been found to also form knots. [30]

In 1989, Sauvage and coworkers reported the first synthetic knotted molecule: a trefoil synthesized via a double-helix complex with the aid of Cu+ ions. [16]

Vogtle et al. was the first to describe molecular knots as knotanes in 2000. [1] Also in 2000 was William Taylor's creation of an alternative computational method to analyze protein knotting that set the termini at a fixed point far enough away from the knotted component of the molecule that the knot type could be well-defined. In this study, Taylor discovered a deep knot in a protein. [31] With this study, Taylor confirmed the existence of deeply knotted proteins.

In 2007, Eric Yeates reported the identification of a molecular slipknot, which is when the molecule contains knotted subchains even though their backbone chain as a whole is unknotted and does not contain completely knotted structures that are easily detectable by computational models. [32] Mathematically, slipknots are difficult to analyze because they are not recognized in the examination of the complete structure.

A pentafoil knot prepared using dynamic covalent chemistry was synthesized by Ayme et al. in 2012, which at the time was the most complex non-DNA molecular knot prepared to date. [19] Later in 2016, a fully organic pentafoil knot was also reported, including the very first use of a molecular knot to allosterically regulate catalysis. [33] In January 2017, an 819 knot was synthesized by David Leigh's group, making the 819 knot the most complex molecular knot synthesized. [27]

An important development in knot theory is allowing for intra-chain contacts within an entangled molecular chain. Circuit topology has emerged as a topology framework that formalises the arrangement of contacts as well as chain crossings in a folded linear chain. As a complementary approach, Colin Adams. et al., developed a singular knot theory that is applicable to folded linear chains with intramolecular interactions. [34]

Applications

Many synthetic molecular knots have a distinct globular shape and dimensions that make them potential building blocks in nanotechnology.

See also

References

  1. 1 2 3 4 Lukin, Oleg; Vögtle, Fritz (25 February 2005). "Knotting and Threading of Molecules: Chemistry and Chirality of Molecular Knots and Their Assemblies". Angewandte Chemie International Edition. 44 (10): 1456–1477. doi:10.1002/anie.200460312. PMID   15704147.
  2. 1 2 Lim, Nicole C. H.; Jackson, Sophie E. (20 August 2015). "Molecular knots in biology and chemistry". Journal of Physics: Condensed Matter. 27 (35): 354101. Bibcode:2015JPCM...27I4101L. doi: 10.1088/0953-8984/27/35/354101 . ISSN   0953-8984. PMID   26291690.
  3. ↑ Xu, Yan; Li, Shixin; Yan, Zengshuai; Luo, Zhen; Ren, Hao; Ge, Baosheng; Huang, Fang; Yue, Tongtao (2018-11-06). "Stabilizing Effect of Inherent Knots on Proteins Revealed by Molecular Dynamics Simulations". Biophysical Journal. 115 (9): 1681–1689. Bibcode:2018BpJ...115.1681X. doi:10.1016/j.bpj.2018.09.015. ISSN   0006-3495. PMC   6225051 . PMID   30314655.
  4. ↑ Safarowsky O, Nieger M, Fröhlich R, Vögtle F (2000). "A Molecular Knot with Twelve Amide Groups - One-Step Synthesis, Crystal Structure, Chirality". Angewandte Chemie International Edition . 39 (9): 1616–1618. doi:10.1002/(SICI)1521-3773(20000502)39:9<1616::AID-ANIE1616>3.0.CO;2-Y. PMID   10820452.
  5. ↑ Albrecht-Gary, A. M.; Meyer, M.; Dietrich-Buchecker, C. O.; Sauvage, J. P.; Guilhem, J.; Pascard, C. (2 September 2010). "Dicopper (I) trefoil knots: Demetallation kinetic studies and molecular structures". Recueil des Travaux Chimiques des Pays-Bas. 112 (6): 427–428. doi:10.1002/recl.19931120622.
  6. ↑ Qi, Xiaodong; Zhang, Fei; Su, Zhaoming; Jiang, Shuoxing; Han, Dongran; Ding, Baoquan; Liu, Yan; Chiu, Wah; Yin, Peng; Yan, Hao (2018-11-02). "Programming molecular topologies from single-stranded nucleic acids". Nature Communications. 9 (1): 4579. Bibcode:2018NatCo...9.4579Q. doi:10.1038/s41467-018-07039-7. ISSN   2041-1723. PMC   6214983 . PMID   30389935.
  7. 1 2 3 Fielden, Stephen D. P.; Leigh, David A.; Woltering, Steffen L. (2017-09-04). "Molecular Knots". Angewandte Chemie International Edition. 56 (37): 11166–11194. doi:10.1002/anie.201702531. ISSN   1433-7851. PMC   5582600 . PMID   28477423.
  8. ↑ Jamroz, Michal; Niemyska, Wanda; Rawdon, Eric J.; Stasiak, Andrzej; Millett, Kenneth C.; Sułkowski, Piotr; Sulkowska, Joanna I. (2015-01-28). "KnotProt: a database of proteins with knots and slipknots". Nucleic Acids Research. 43 (Database issue): D306 –D314. doi:10.1093/nar/gku1059. ISSN   0305-1048. PMC   4383900 . PMID   25361973.
  9. ↑ Ashton, Peter R.; Matthews, Owen A.; Menzer, Stephan; Raymo, Françisco M.; Spencer, Neil; Stoddart, J. Fraser; Williams, David J. (December 1997). "Molecular Meccano, 27. A Template-directed Synthesis of a Molecular Trefoil Knot". Liebigs Annalen. 1997 (12): 2485–2494. doi:10.1002/jlac.199719971210.
  10. ↑ Rapenne, Gwénaël; Dietrich-Buchecker, and Jean-Pierre Sauvage *, Christiane; Sauvage, Jean-Pierre (February 1999). "Copper(I)- or Iron(II)-Templated Synthesis of Molecular Knots Containing Two Tetrahedral or Octahedral Coordination Sites". Journal of the American Chemical Society. 121 (5): 1002–1015. Bibcode:1999JAChS.121..994R. doi:10.1021/ja982239+.
  11. ↑ Feigel, Martin; Ladberg, Rüdiger; Engels, Simon; Herbst-Irmer, Regine; Fröhlich, Roland (25 August 2006). "A Trefoil Knot Made of Amino Acids and Steroids". Angewandte Chemie International Edition. 45 (34): 5698–5702. doi:10.1002/anie.200601111. PMID   16856201.
  12. ↑ Guo, Jun; Mayers, Paul C.; Breault, Gloria A.; Hunter, Christopher A. (7 February 2010). "Synthesis of a molecular trefoil knot by folding and closing on an octahedral coordination template". Nature Chemistry. 2 (3): 218–222. Bibcode:2010NatCh...2..218G. doi:10.1038/nchem.544. PMID   21124480.
  13. ↑ Barran, Perdita E.; Cole, Harriet L.; Goldup, Stephen M.; Leigh, David A.; McGonigal, Paul R.; Symes, Mark D.; Wu, Jhenyi; Zengerle, Michael (16 December 2011). "Active-Metal Template Synthesis of a Molecular Trefoil Knot". Angewandte Chemie International Edition. 50 (51): 12280–12284. doi:10.1002/anie.201105012. PMID   21919173.
  14. ↑ Carina, Riccardo F.; Dietrich-Buchecker, Christiane; Sauvage, Jean-Pierre (January 1996). "Molecular Composite Knots". Journal of the American Chemical Society. 118 (38): 9110–9116. Bibcode:1996JAChS.118.9110C. doi:10.1021/ja961459p.
  15. ↑ Sauvage, Jean-Pierre; Amabilino, David B. (2012), "Templated Synthesis of Knots and Ravels", Supramolecular Chemistry, American Cancer Society, doi:10.1002/9780470661345.smc085, ISBN   978-0-470-66134-5
  16. 1 2 Dietrich-Buchecker, Christiane O.; Sauvage, Jean-Pierre (1989). "A Synthetic Molecular Trefoil Knot". Angewandte Chemie International Edition in English. 28 (2): 189–192. doi:10.1002/anie.198901891. ISSN   1521-3773.
  17. 1 2 3 4 5 6 7 Schaufelberger, Fredrik (2020-12-04). "Open questions in functional molecular topology". Communications Chemistry. 3 (1): 182. Bibcode:2020CmChe...3..182S. doi:10.1038/s42004-020-00433-7. ISSN   2399-3669. PMC   9814244 . PMID   36703419.
  18. ↑ Ponnuswamy, Nandhini; Cougnon, Fabien B. L.; Pantoş, G. Dan; Sanders, Jeremy K. M. (2014-06-11). "Homochiral and meso Figure Eight Knots and a Solomon Link". Journal of the American Chemical Society. 136 (23): 8243–8251. Bibcode:2014JAChS.136.8243P. doi:10.1021/ja4125884. ISSN   0002-7863. PMID   24831779.
  19. 1 2 Ayme, Jean-François; Beves, Jonathon E.; Leigh, David A.; McBurney, Roy T.; Rissanen, Kari; Schultz, David (6 November 2011). "A synthetic molecular pentafoil knot". Nature Chemistry. 4 (1): 15–20. Bibcode:2012NatCh...4...15A. doi:10.1038/nchem.1193. PMID   22169866.
  20. ↑ "Tying Molecules in Knots". www.catenane.net. Retrieved 2023-12-03.
  21. ↑ Leigh, David A.; Schaufelberger, Fredrik; Pirvu, Lucian; Stenlid, Joakim Halldin; August, David P.; Segard, Julien (2020-08-27). "Tying different knots in a molecular strand". Nature. 584 (7822): 562–568. Bibcode:2020Natur.584..562L. doi:10.1038/s41586-020-2614-0. ISSN   0028-0836. PMID   32848222. S2CID   221346706.
  22. ↑ "Molecular 5-2 Knot". www.catenane.net. Retrieved 2023-12-03.
  23. ↑ Inomata, Yuuki; Sawada, Tomohisa; Fujita, Makoto (January 2020). "Metal-Peptide Torus Knots from Flexible Short Peptides". Chem. 6 (1): 294–303. Bibcode:2020Chem....6..294I. doi: 10.1016/j.chempr.2019.12.009 . S2CID   213401688.
  24. ↑ Leigh, David A.; Danon, Jonathan J.; Fielden, Stephen D. P.; Lemonnier, Jean-François; Whitehead, George F. S.; Woltering, Steffen L. (February 2021). "A molecular endless (74) knot". Nature Chemistry. 13 (2): 117–122. doi:10.1038/s41557-020-00594-x. ISSN   1755-4330. PMID   33318672. S2CID   229163544.
  25. ↑ "Endless Knot". www.catenane.net. Retrieved 2023-12-03.
  26. ↑ Kim, Dong Hwan; Singh, Nem; Oh, Jihun; Kim, Eun-Hee; Jung, Jaehoon; Kim, Hyunuk; Chi, Ki-Whan (2018-05-14). "Coordination-Driven Self-Assembly of a Molecular Knot Comprising Sixteen Crossings". Angewandte Chemie International Edition. 57 (20): 5669–5673. doi:10.1002/anie.201800638. ISSN   1433-7851. PMID   29569315.
  27. 1 2 Danon, Jonathan J.; Krüger, Anneke; Leigh, David A.; Lemonnier, Jean-François; Stephens, Alexander J.; Vitorica-Yrezabal, Iñigo J.; Woltering, Steffen L. (2017-01-13). "Braiding a molecular knot with eight crossings". Science. 355 (6321): 159–162. Bibcode:2017Sci...355..159D. doi:10.1126/science.aal1619. ISSN   0036-8075. PMID   28082585. S2CID   206654419.
  28. ↑ "A Synthetic Molecular 819 Knot". www.catenane.net. Retrieved 2023-12-03.
  29. ↑ Richardson, Jane S. (August 1977). "β-Sheet topology and the relatedness of proteins". Nature. 268 (5620): 495–500. Bibcode:1977Natur.268..495R. doi:10.1038/268495a0. ISSN   1476-4687. PMID   329147. S2CID   4287690.
  30. ↑ Liu, L F; Davis, J L; Calendar, R (1981-08-25). "Novel topologically knotted DNA from bacteriophage P4 capsids: studies with DNA topoisomerases". Nucleic Acids Research. 9 (16): 3979–3989. doi:10.1093/nar/9.16.3979. ISSN   0305-1048. PMC   327409 . PMID   6272191.
  31. ↑ Faísca, Patrícia F. N. (2015-01-01). "Knotted proteins: A tangled tale of Structural Biology". Computational and Structural Biotechnology Journal. 13: 459–468. doi:10.1016/j.csbj.2015.08.003. ISSN   2001-0370. PMC   4556803 . PMID   26380658.
  32. ↑ King, Neil P.; Yeates, Eric O.; Yeates, Todd O. (2007-10-12). "Identification of Rare Slipknots in Proteins and Their Implications for Stability and Folding". Journal of Molecular Biology. 373 (1): 153–166. doi:10.1016/j.jmb.2007.07.042. ISSN   0022-2836. PMID   17764691.
  33. ↑ Marcos, Vanesa; Stephens, Alexander J.; Jaramillo-Garcia, Javier; Nussbaumer, Alina L.; Woltering, Steffen L.; Valero, Alberto; Lemonnier, Jean-François; Vitorica-Yrezabal, Iñigo J.; Leigh, David A. (2016-06-24). "Allosteric initiation and regulation of catalysis with a molecular knot". Science. 352 (6293): 1555–1559. Bibcode:2016Sci...352.1555M. doi:10.1126/science.aaf3673. ISSN   0036-8075. PMID   27339983. S2CID   206647890.
  34. ↑ Colin Adams, Judah Devadoss, Mohamed Elhamdadi and Alireza Mashaghi, Knot theory for proteins: Gauss codes, quandles and bondles. Journal of Mathematical Chemistry volume 58, pages1711–1736(2020)
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