Molecular Mislow

Mislow, K., Gust, D., Finocchiaro, P., and Boettcher, R. J. Stereochemical Correspondence Among Molecular Propellers. 47, 1-22 (1974). 

Mislow, who discussed MM in some detail in his textbook (64), has performed excellent systematic studies of overcrowded methanes (3) (molecular propellers) and ethanes (4) and their metal analogs by the combination of dynamic NMR with MM calculations. Since his own reviews have been published (65,66), only very recent results are mentioned. 

Mislow and Bickart (258) have recently discussed the properties, and specified the limitations and essential features, of models that can be used for the prediction of chirality of a molecular system. In the simplified and idealized representation of molecular stracture, nonessential features are deliberately left out the model summarizes some selected aspects of the system and completely disregards or even falsifies, others. The model must be adequate to the time scale in which the phenomenon is observed. In particular, in mobile conformational systems it should refer to a time-averaged structure. In other words, the model can have a higher symmetry than that observed under static conditions (e.g., by X-ray diffraction in the crystalline state or by NMR under slow exchange conditions) (259). 

Gust, D. Mislow, K. J. Am. Chem. Soc. 1973,95,1535 Mislow, K. Acc. Chem. Res. 1976,9,26. Theoretical computations were performed with the software package CERIUS 2, v. 1.6 from Molecular Simulations Inc. 

Liang and Mislow s idea of contracting naphthalenes can be formalized if we consider the molecular cell complex rather than the molecular graph of triple layered naphthalenophane. We obtain a cell complex G by replacing each naphthalene by a pair of cells. We shall now prove by contradiction that this mo-... 

Using this theorem we can prove that various molecular graphs are intrinsically chiral. We shall illustrate by proving that the graphs of a ferrocenophane derivative molecule [26] and the Simmons-Paquette molecule [29, 30] are both intrinsically chiral. (Note that Liang and Mislow observed the intrinsic chirality of this ferrocenophane derivative as well as many other molecules [21].)... 

Recently, Liang and Mislow have presented fascinating discussions on knots and links in relation to chirality [19, 20], This breakthrough should help bridge the gap between the mathematical topologist and molecular chemist communities. 

Figure 14. Top row Molecular structures of (a) twistane, (b) tritwistane, (c) [6]chochin. Bottom row planar images of the corresponding molecular graphs.71 Reprinted with permission from K. Mislow, Croat. Chem. Acta 1996, 69, 485. Copyright 1996, Croatian Chemical Society.

This first example inspired the design of many other similar systems, most famously those investigated in the 1970s and 1980s by Mislow and Iwamura [19]. Later, the structurally complex but conceptually similar molecular turnstiles 3-5 (Fig. 2) were introduced by Moore [20]. Variable temperature XH NMR studies on the methylene protons, ffa and H, showed that the central aromatic ring of 4 spins rapidly on the NMR timescale at room temperature, while spindle rotation does not occur in turnstile 5 even at 85 °C due to steric constraints. 

Molecular fragments, like whole molecules, may display steric relationships, as pioneered by Hanson [20] and Mislow [18]. When such fragments are considered in isolation, namely separated from the remainder of the molecule, morphic relationships arise. When the partial structures are considered in an intact molecule or in different intact molecules, one speaks of topic relationships. 

Three criteria are useful when assessing topic relationships, namely (a) the molecular environment, (b) symmetry considerations, and (c) the substitution criterion. When two topic groups in a molecule have stereoisomeric environments, the molecule is said to possess elements of prostereoisomerism. Mislow and Raban have given a definitive classification of topic relationships [62], and the following discussion is based on this classification. 

---