Molecular tweezers

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Trinitrofluorene bound in molecular tweezers, published by Lehn et al.
Fullerene bound in a "buckycatcher" published by Sygula et al.

Molecular tweezers are non-cyclic host molecules with open cage structures that are able to bind a guest molecule. The term molecular tweezers was first used by Howard J. Whitlock, but the type of host molecule was developed and made popular by Steven C. Zimmermann in the mid-1980s to the 1990s and later by Frank-Gerrit Klärner et al. The open cage structure of the molecular tweezers can bind guests using non-covalent bonds such as hydrogen bonds , metal coordination, van der Waals forces , π-π interactions, and electrostatic effects. These complexes are a subset of macrocyclic molecular receptors , and their structure is such that two arms can bind the guest molecule, being connected at only one end, which gives these receptor molecules a certain flexibility.

Examples

An example of molecular tweezers was published by Jean-Marie Lehn et al. This host molecule is able to bind aromatic guests. The molecular tweezers consist of two anthracene arms, spaced a certain distance apart, which allows aromatic guests π-π interactions between the two. Another class of molecular tweezers was synthesized from two substituted porphyrin macromolecules linked by amide bridges of different lengths. This example of molecular tweezers shows the flexibility of this class of substances, as the orientation of the porphrin planes that make up the tweezers adapts to the bound guest.

Another structure of molecular tweezers that can specifically bind fullerenes has been published, the so-called "buckycatcher". This molecule consists of two concave Corannunlenes as tweezers, which can enclose the entire surface of the convex fullerene guest. The association constant Ka between the host, the “buckycatcher” and the C60 fullerene as a guest was calculated by NMR and is 8600 M −1 .

Water-soluble phosphate-substituted tweezers bind to the positively charged side chains of amino acids very selectively (lysine more strongly than arginine). The molecular tweezers prefer to bind flat pyridine rings (for example the nicotinamide ring of the NAD +) between planar naphthalenes . These binding properties make the molecular tweezers a valuable tool to use interactions with lysines in peptides and on protein surfaces, as well as with NAD (P) + cofactors. For example, both compounds prevent the oxidation of glucose-6-phosphate by NAD (P) +, which is catalyzed by alcohol dehydrogenase. In addition, the tweezers prevent the formation of misfolded oligomers and aggregates of amyloidogenic proteins, including those of amyloid α-protein and β-synuclein, which are believed to be the causes of Alzheimer's and Parkinson's diseases.

The above examples demonstrate the potential reactivity and specificity of these molecules. The binding surface between the planes of the forceps can enable a suitable guest to be bound with a resulting high association constant and stability, depending on the configuration of the forceps. This makes the compound class of these macromolecules a true synthetic molecular receptor.

Individual evidence

  1. ↑ a b A. Petitjean, RG Khoury, N. Kyritsakas, JM Lehn: Dynamic Devices. Shape Switching and Substrate Binding in Ion-Controlled Nanomechanical Molecular Tweezers . In: J. Am. Chem. Soc. tape 126 , no. 21 , 2004, p. 6637-6647 , doi : 10.1021 / ja031915r , PMID 15161291 .
  2. ↑ a b A. Sygula, FR Fronczek, R. Sygula, PW Rabideau, MM Olmstead: A Double Concave Hydrocarbon Buckycatcher . In: J. Am. Chem. Soc. tape 129 , no. 13 , 2007, p. 3842-3843 , doi : 10.1021 / ja070616p , PMID 17348661 .
  3. ↑ C.-W. Chen, HW Whitlock: Molecular Tweezers - A Simple-Model of Bifunctional Intercalation. In: J. Am. Chem. Soc. 100, 1978, p. 4921.
  4. ↑ SC Zimmerman, CM VanZyl: Rigid molecular tweezers: synthesis, characterization, and complexation chemistry of a diacridine. In: J. Am. Chem. Soc. 109, 1987, p. 7894.
  5. ^ SC Zimmerman, W. Wu: A rigid molecular tweezers with an active site carboxylic acid: exceptionally efficient receptor for adenine in an organic solvent. In: J. Am. Chem. Soc. 111, 1989, p. 8054.
  6. ↑ SC Zimmerman: Rigid molecular tweezers as hosts for the complexation of neutral guests. In: Top. Curr. Chem. 165, 1993, p. 71.
  7. ↑ F.-G. Klärner, B. Kahlert: Molecular Tweezers and Clips as Synthetic Receptors. Molecular Recognition and Dynamics in Receptor-Substrate Complexes . In: Acc. Chem. Res. Volume 36 , no. 12 , 2003, p. 919-932 , doi : 10.1021 / ar0200448 , PMID 14674783 .
  8. ↑ X. Huang, N. Fujioka, G. Pescitelli, F. Koehn, RT Williamson, K. Nakanishi, N. Berova: Absolute Configurational Assignments of Secondary Amines by CD-sensitive Dimeric Zinc Porphyrin Host . In: J. Am. Chem. Soc. tape 124 , no. 17 , 2002, p. 10320-10335 , doi : 10.1021 / ja020520p .
  9. ↑ P. Talbiersky, F. Bastkowski, F.-G. Klärner, T. Schrader: Molecular Clip and Tweezer Introduce New Mechanisms of Enzyme Inhibition . In: J. Am. Chem. Soc. tape 130 , no. 30 , 2008, p. 9824-9828 , doi : 10.1021 / ja801441j .
  10. ↑ a b J. Polkowska, F. Bastkowski, T. Schrader, F.-G. Klärner, J. Zienau, F. Koziol, C. Ochsenfeld: A combined experimental and theoretical study of the pH-dependent binding mode of NAD + by water-soluble molecular clips . In: J. Phys. Org. Chem. Band 22 , no. 30 , 2009, p. 779-790 , doi : 10.1002 / poc.1519 .
  11. ↑ M. Kirsch, P. Talbiersky, J. Polkowska, F. Bastkowski, T. Schaller, H. de Groot, F.-G. Klärner, T. Schrader: A Mechanism of Efficient G6PD Inhibition by a Molecular Clip . In: Angew. Chem. Int. Ed. tape 48 , 2009, p. 2886-2890 , doi : 10.1002 / anie.200806175 .
  12. ↑ S. Sinha, DHJ Lopes, Z. Du, ES Pang, A. Shanmugam, A. Lomakin, P. Talbiersky, A. Tennstaedt, K. McDaniel, R. Bakshi, P.-Y. Kuo, M. Ehrmann, GB Benedek, JA Loo, F.-G. Klärner, T. Schrader, C. Wang, G. Bitan: Lysine-Specific Molecular Tweezers Are Broad-Spectrum Inhibitors of Assembly and Toxicity of Amyloid Proteins . In: J. Am. Chem. Soc. tape 133 , no. 42 , 2011, p. 16958-16969 , doi : 10.1021 / ja206279b .
  13. ↑ A. Attar, C. Ripoli, E. Riccardi, P. Maiti, DD Li-Puma, T. Liu, J. Hayes, MR Jones, K. Lichti-Kaiser, F. Yang, GD Gale, CH Tseng, M Tan, CW Xie, JL Straudinger, FG Klärner, T. Schrader, SA Frautschy, C. Grassi, G. Bitan: Protection of primary neurons and mouse brain from Alzheimer's pathology by molecular tweezers. In: Brain. 135, 2012, pp. 3735-3748, doi : 10.1093 / brain / aws289 .