Molecular tweezers
From Wikipedia, the free encyclopedia
Trinitrofluorene bound in molecular tweezers reported by
Lehn and coworkers.
[1]
Molecular tweezers, and
molecular clips, are noncyclic
host molecules with open cavities capable of binding guest molecules.
The term "molecular tweezers" was first used by Howard J. Whitlock,
[3] but the class of hosts was developed and popularized by Steven C. Zimmerman in the mid-1980s to early 1990s
[4][5][6] and later by Frank-Gerrit Klärner and Colleagues.
[7] The open cavity of the molecular tweezers may bind guests using
non-covalent bonding which includes
hydrogen bonding, metal coordination,
hydrophobic forces,
van der Waals forces,
π-π interactions, and/or electrostatic effects. These complexes are a subset of
macrocyclic molecular receptors
and their structure is that the two "arms" that bind the guest molecule
between them are only connected at one end leading to a certain
flexibility of these receptor molecules (induced fit model).
Examples
One example of molecular tweezers has been reported by
Lehn and coworkers. This molecule is capable of binding
aromatic guests.
[1] The molecular tweezers are composed of two
anthracene arms held at a distance that allows aromatic guests to gain π-π interactions from both.
Another class of molecular tweezers is composed of two substituted
porphyrin macrocycles tethered by an amide linker with a variable
length. This example of a molecular tweezer shows the potential mobility
of this class of molecules, as the orientation of the porphyrin planes
which comprise the tweezer can be altered by the guest which is bound
[8]
Yet another structure for molecular tweezers which specifically bind
fullerenes is called a buckycatcher and has been reported.
[2] This molecular tweezer is composed of two concaved
corannulene pincers that complement the surface of the
convex fullerene guest. An
association constant (Ka) of 8600 M
−1 between the host buckycatcher and a C60 fullerene was calculated using
1H
NMR spectroscopy.
The water-soluble phosphate-substituted tweezer binds to the
positively charged aliphatic sidechains of basic amino acids very
selectively (to lysine stronger than to arginine)
[9]
whereas the molecular clip prefers to clip flat pyridinium rings (for
example the nicotinamide ring from NAD(P)+) between its plane
naphthalene sidewalls
[10]
These mutually excluding binding modes make these compounds valuable
tools to probe critical biological interactions of lysines in peptides
and on protein surfaces as well as of NAD(P)+ cofactors. For example,
both compounds inhibit the oxidation reactions of ethanol or
glucose-6-phosphate by NAD(P)+, which are catalyzed by alcohol
dehydrogenase or glucose-6-phosphate dehydrogenase
[11]
respectively. In addition, the tweezer, but not the clip, prevents
formation of misfolded oligomers and aggregates of amyloidogenic
proteins, including those of amyloid β-protein (Aβ) and tau
[12][13] and α-synuclein
[14] which are thought to cause Alzheimer’s and Parkinson’s diseases, respectively.
The above examples show the potential reactivity and specificity of
these molecules. The binding site between the planes of the tweezer can
evolve to bind to an appropriate guest with resulting high association
constants and consequent stability, depending on the configuration of
the tweezer. That makes this overall class of macromolecule truly a
synthetic molecular receptor.
[citation needed]
See also
References
A.
Petitjean, R. G. Khoury, N. Kyritsakas and J. M. Lehn (2004). "Dynamic
Devices. Shape Switching and Substrate Binding in Ion-Controlled
Nanomechanical Molecular Tweezers". J. Am. Chem. Soc. 126 (21): 6637–6647. doi:10.1021/ja031915r
. PMID 15161291
.
- Prabhudesai
S, Sinha S, Attar A, Kotagiri A, Fitzmaurice AG, Lakshmanan R, Ivanova
MI, Loo JA, Klärner FG, Schrader T, Stahl M, Bitan G, Bronstein JM
(2012) A novel "molecular tweezer" inhibitor of α-synuclein
neurotoxicity in vitro and in vivo. Neurotherapeutics 9:464-476.
10.1007/s13311-012-0105-1.
External links
A. Sygula, F. R. Fronczek, R. Sygula, P. W. Rabideau and M. M. Olmstead (2007). "A Double Concave Hydrocarbon Buckycatcher". J. Am. Chem. Soc. 129 (13): 3842–3843. doi:10.1021/ja070616p
. PMID 17348661
.
Chen
C.-W.; Whitlock H. W. "Molecular Tweezers - A Simple-Model of
Bifunctional Intercalation," J. Am. Chem. Soc. 1978, 100, 4921
Zimmerman,
S. C.; VanZyl, C. M. "Rigid molecular tweezers: synthesis,
characterization, and complexation chemistry of a diacridine," J. Am.
Chem. Soc. 1987, 109, 7894.
Zimmerman,
S. C.; Wu, W. "A rigid molecular tweezers with an active site
carboxylic acid: exceptionally efficient receptor for adenine in an
organic solvent," J. Am. Chem. Soc. 1989, 111, 8054.
Zimmerman, S. C. "Rigid molecular tweezers as hosts for the complexation of neutral guests," Top. Curr. Chem. 1993, 165, 71.
F.-G.
Klärner & B. Kahlert (2003). "Molecular Tweezers and Clips as
Synthetic Receptors. Molecular Recognition and Dynamics in
Receptor-Substrate Complexes". Acc. Chem. Res. 36 (12): 919–932. doi:10.1021/ar0200448
. PMID 14674783
.
X.
Huang, N. Fujioka, G. Pescitelli, F. Koehn, R. T. Williamson, K.
Nakanishi and N. Berova (2002). "Absolute Configurational Assignments of
Secondary Amines by CD-sensitive Dimeric Zinc Porphyrin Host". J. Am. Chem. Soc. 124 (17): 10320–10335. doi:10.1021/ja020520p
.
P.
Talbiersky; F. Bastkowski; F.-G. Klärner; T. Schrader (2008).
"Molecular Clip and Tweezer Introduce New Mechanisms of Enzyme
Inhibition". J. Am. Chem. Soc. 130 (30): 9824–9828. doi:10.1021/ja801441j
.
J.
Polkowska; F. Bastkowski; T. Schrader; F.-G. Klärner; J. Zienau; F.
Koziol; C. Ochsenfeld (2009). "A combined experimental and theoretical
study of the pH-dependent binding mode of NAD+ by water-soluble
molecular clips". J. Phys. Org. Chem. 22 (30): 779–790. doi:10.1002/poc.1519
.
M.
Kirsch; P. Talbiersky; J. Polkowska; F. Bastkowski; T. Schaller; H. de
Groot; F.-G. Klärner; T. Schrader (2009). "A Mechanism of Efficient G6PD
Inhibition by a Molecular Clip". Angew. Chem. Int. Ed. 48: 2886–2890. doi:10.1002/anie.200806175
.
S.
Sinha, D. H. J. Lopes, Z. Du, E. S. Pang, A. Shanmugam, A. Lomakin, P.
Talbiersky, A. Tennstaedt, K. McDaniel, R. Bakshi, P.-Y. Kuo, M.
Ehrmann, G. B. Benedek, J. A. Loo, F. –G. Klärner, T. Schrader, C. Wang,
G. Bitan (2011) (2011). "Lysine-Specific Molecular Tweezers Are
Broad-Spectrum Inhibitors ofAssembly and Toxicity of Amyloid Proteins". J. Am. Chem. Soc. 133 (42): 16958–16969. doi:10.1021/ja206279b
.
Attar
A, Ripoli C, Riccardi E, Maiti P, Li Puma DD, Liu T, Hayes J, Jones MR,
Lichti-Kaiser K, Yang F, Gale GD, Tseng CH, Tan M, Xie CW, Straudinger
JL, Klärner FG, Schrader T, Frautschy SA, Grassi C, Bitan G (2012)
Protection of primary neurons and mouse brain from Alzheimer's pathology
by molecular tweezers. Brain 135:3735-3748. 10.1093/brain/aws289.
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