Some molecular tweezers bind
aromatic guests. These molecular tweezers consist of a pair of
anthracene arms held at a distance that allows aromatic guests to gain π–π interactions from both (see Figure). Other molecular tweezers feature a pair of tethered
porphyrins. Yet another type of molecular tweezers binds
fullerenes. These "
buckycatchers" are composed of two
corannulene pincers that complement the surface of the
convex fullerene guest (Figure 2). An
association constant (
Ka) of 8,600 M−1 was calculated using 1H
NMR spectroscopy. Stoermer and co-workers described clefts capable of capturing cyclohexane or chloroform molecules. Intriguingly, pi interactions played key roles in guest capture as well as cleft formation rate. File:Lysine+tweezer.jpg|thumb| Figure 3. The aliphatic sidechain of lysine bound inside the cavity of the phosphate-substituted molecular benzene tweezer by electrostatic, CH-p and hydrophobic interactions reported by Klärner, Schrader, and coworkers.[9,10] Water-soluble phosphate-substituted molecular tweezers made of alternating
phenyl and
norbornenyl substituents bind to positively charged aliphatic side chains of basic amino acids, such as
lysine and
arginine (Figure 3). Similar compounds called "molecular clips", whose side walls are flat rather than convex, prefer to enclose flat pyridinium rings (for example the nicotinamide ring of NAD(P)+) between their plane naphthalene sidewalls (Figure 4). These mutually exclusive binding modes make these compounds valuable tools for probing critical biological interactions of basic amino acid side chains in peptides and proteins as well as of NAD(P)+ and similar cofactors. For example, both types of compounds inhibit the oxidation reactions of ethanol by
alcohol dehydrogenase or of glucose-6-phosphate by
glucose-6-phosphate dehydrogenase, respectively. File:NAD+clip.jpg|thumb| Figure 4. The double-sandwich host–guest complex of the phosphate-substituted molecular clip and nicotinamide adenine dinucleotide (NAD+, the cofactor of many redox enzymes). The nicotinamide ring (the active site of NAD+) is bound between the clip naphthalene sidewalls, as reported by Klärner, Schrader, Ochsenfeld, and coworkers.[11] The molecular tweezers, but not the clips, efficiently inhibit the formation of toxic oligomers and aggregates by amyloidogenic proteins associated with different diseases. Examples include the proteins involved in
Alzheimer's disease – amyloid β-protein (Aβ) and tau; α-synuclein, which is thought to cause
Parkinson's disease and other
synucleinopathies and is involved in
spinal-cord injury; mutant huntingtin, which causes Huntington's disease; islet amyloid polypeptide (amylin), which kills pancreatic β-cells in
type-2 diabetes;
transthyretin (TTR), which causes familial amyloid polyneuropathy, familial amyloid cardiomyopathy, and senile systemic amyloidosis; aggregation-prone mutants of the tumor-suppressor protein
p53; and semen proteins whose aggregation enhances
HIV infection. Importantly, the molecular tweezers have been found to be effective and safe not only in the test tube but also in animal models of different diseases, suggesting that they may be developed as drugs against diseases caused by abnormal protein aggregation, all of which currently have no cure. They were also shown to destroy the membranes of enveloped viruses, such as HIV, herpes, and hepatitis C, == See also ==