Knotted molecules

Most of the known synthetic receptors, such as cryptands, cyclophanes, and cages, are homo-oligomeric structures, although more complex and unconventional topologies, such as interlocked and knotted molecules have recently proved their... 

Figure 10. Dependence of the equilibrium fraction of knotted molecules on DNA effective diameter, d, for closed DNA containing 14 Kuhn lengths (lower curve), 20 Kuhn lengths (middle curve) and 30 Kuhn lengths (upper curve). The data are from Klenin et al. (1988) [36]. The diameter is measured in Kuhn lengths so, to obtain the d value in nanometers one has to multiply the figures on the abscissa by the factor of 100.

Knotted molecules were hrst detected in preparations of single-stranded circular DNAs after they had been treated under special conditions with a type I topoisomerase (Liu et ah, 1976 [41]). This was the hrst case when a knotted molecule was observed. However, the problem of knotting of normal, double-stranded DNAs continued to be very intriguing. It turned out that there is a special subclass of topoisomerases called type II topoisomerases, which are capable of untying and tying knots in ccDNAs. Moreover, these enzymes catalyze the formahon of catenanes from pairs or from a larger number of molecules of ccDNA. Here entire networks are formed, similarly to those observed in vivo in kinetoplasts. 

The folding of a protein explained in the Introduction to this chapter creates an intertwined chemical structure. Ponnuswamy et al. (2012) fabricated knotted molecules, similar to protein structure, which took advantage of hydrophobic interactions. The molecular structure was comprised of three hydrophobic naphthalene diimides held together with alanine linkers and anchored at both ends with cysteine amino acid. 

The knot can also be prepared using a stepwise synthesis, which helps to determine the route by which it is formed in the one-step reaction. The string-like molecule 14 (Figure 13) was prepared in order to ascertain whether indeed it is an intermediate on the pathway to knot 13. Indeed, reaction of this open knot with di-acid chloride 9 generates the knot 13 in 11% yield. Clearly, the possibility of using the open knot as a reagent with different di-acid chlorides is possible, and leads to a variety of substituted knot molecules. ... 

The knots based on neutral, purely organic molecules are obviously not prone to classical diastereomer resolution, and, while chromatographic methods were not suitable for the separation of the two enantiomers of the metal-templated trefoil knot, they have been proved successful in the amide-containing knots. As far as these knotted molecules are concerned, it must be noted that they incorporate classical stereogenic centers (carbon atoms), which makes them very different from the copper-based systems in terms of chirality. In the first instance, the separation of the two enantiomers of six different knots was achieved with a colunm that was not conunercially available (chiral-AD type). Trichloromethane was needed to obtain an optimal separation. The silica gel and the chiral stationary phase were covalently bound so that the material did not bleed out when the lipophilic eluent was used. Moreover, comparison of the experimental CD of the pure enantiomers of a knot with a theoretically calculated CD (based on X-ray structure and a fiiUy optimized AMI geometry) permitted assignment of the absolute configuration of this knot. The latter preparation of soluble knots based on substitution of the 5-position of the pyridine moieties in 13 afforded molecules that were soluble in solvents which could be used in commercially available chiral columns." On the other hand, the substitution of a racemic mixture of knots with chiral auxiliaries allows the separation of the diastereomeric product." ... 

ABSTRACT. Knots and interlaced designs have been part of human artistry and culture since the earliest times. In chemistry, knots have been the focus of theoretical investigations for several decades. In pandlel, a few experimental approaches have been attempted by synthetic chemists. Until recent years, the only preparative routes pursued used the tools of classical organic chemistry. Despite their intellectual elegance, they have not succeeded. By taking advantage of the three-dimensional template effect of a transition metal (copper I), it has recently been possible to interlace two molecular threads prior to cyclisation and formation of a dimetallic trefoil knot. The demetallated knotted molecule and its di-copper(I) precursor have been fully characterized and studied. The X-ray structure of the dimetallic trefoil knot has been solved. It confirms the topology of the system. 

Knotted molecules are certainly among the most fascinating topologically novel entities of chemistry. They belong also to the realm of mathematics where highly elaborated modem theories have recently been developed for their description.[43]... 

Another particularity of knotted molecules is that the double-helical multimetallic complex that has been used as a templating core will be more or less frozen. In other words, the stability of the double helix will be insured by tying the molecular string used to make the knot in such a way as to make ligand exchange, helicity inversion, etc... 

Molecular knots, such as 37, are another variation of these molecules. The... 

This molecule has no chiral carbons, nor does it have a rigid shape, but it too has neither a plane nor an alternating axis of symmetry. Compound 32 has been synthesized and has, in fact, been shown to be chiral. Rings containing 50 or more members should be able to exist as knots (33, and see 37 on p. 114 in Chapter 3). Such a knot would be nonsuperimposable on its mirror image. Calixarenes, ° crown ethers, catenanes, and rotaxanes (see p. 113) can also be chiral if suitably substituted. For example, A and B are nonsuperimposable mirror images. 

For a review of chirality in Mobius-strip molecules catenanes, and knots, see Walba, D.M. Tetrahedron, 1985, 41, 3161. 

In the model Figure 18.19, the points A, B, and C correspond to the knots in the string and play a role to stop the shding of the molecule between the adjacent carbon particles. 

The synthesis of a molecular knot 6 [11], olympiadane 7 [12], and many other topological molecules discussed in Sections 2.3 and 8.1 would not be possible without preorganization of substrates forcing their appropriate orientation. In this case the preorganization is accomplished by the complexation of phenanthroline fragments with a metal ion (Figure 1.2). 

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