Dynamic building block design

The head-to-tail-coupling reactions described above are potentially useful in the design of dynamic combinatorial libraries. Features of these reactions include the rapid and reversible formation of carbon-carbon bonds, multifunctional ene-imine building blocks, and formation of stereo centers upon ene-imine linkage. Support for template-directed synthesis utilizing ene-imine building blocks is the formation of a poly ene-imine species that could recognize 3 -GGA-5 sequences of DNA.48 It is noteworthy that some polyene-imines are helical and could form a triple helix with DNA. 

Via recognition-directed association and self-organization processes, supramolecular chemistry has opened new perspectives in materials science towards the design and engineering of supramolecular materials. These, again, are dynamic by nature, whereas molecular materials must be rendered dynamic by introduction of reversible covalent connections between building blocks. Because of their intrinsic ability to exchange their components, they may in principle select them in response to external stimuli or environmental factors and therefore behave as adaptive materials of either molecular or supramolecular nature [7-9]. 

Fig. 4 Structure of the building blocks for a DCL designed to generate possible UDP-galactose mimics. Amplification of the constitutional dynamic library (CDL) against catalytically active al,3GalT and pi,4GalT enzymes (adapted from [45])...

Fragments derived from drug-like molecules are often correlated with biological activity and a good pharmacokinetic and -dynamic profile. Novel compounds designed from these building-blocks are expected to behave in the same way. 

Once a stochastic molecular dynamics-based framework is developed it is possible to modify it or use it as a building block in order to enhance sampling efficiency. One can for example incorporate these methods into kinetic Monte-Carlo, other metropolized schemes, or various advanced path sampling techniques. Thus the design of good molecular SDE methods is the cornerstone of much of modern molecular modelling. 

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