Early DCLs

Lehn developed the dynamic combinatorial approach as a result of his work on metal helicates, observing that the major product in a dynamic mixture of helicates was determined by the nature of the counterion that binds in the center of the helicates [25]. Hue and Lehn then extended their work to include templahng of a ligand by a protein, describing the inhibihon of carbonic anhydrase by a library of imines created in situ [26]. This work was preceded by a publicahon by Venton et al. who used nonspecific proteases to prepare and degrade a set of pephdes 

---

Many of the early proof of concept DCC experiments were carried out on a somewhat ad hoc basis. Several authors quickly came to the realization that it would be useful to develop methodology for simulating DCLs, both as a guide to experimental design and as a way to resolve the question of whether screening a DCL really leads to the identification of the... 

Nevertheless, the product data have been exceptionally interpreted only in these terms. (1) An allylic carbocation can afford significant amounts of 1,2-products. For instance, in the above-mentioned DCl addition, 1,2-adducts were the major products whatever the solvent, (ii) In addition to the electrophile and substituent dependence of the charge distribution in the intermediate, solvent and steric effects probably play an important role in the product-forming step of these reactions, as they do in the reactions of monoenes . (iii) 1,2-Adducts isomerize frequently to the more stable 1,4-adducts. Therefore, the kinetic or thermodynamic control of the product distribution 2.i4 should be questioned. As a consequence, a number of early results were later revised when this problem was recognized, (iv) Finally, it has also been suggested " that 1,4-addition products do not necessarily arise from allylic intermediates but could also result from bridged intermediates via an Sn2 process implying a syn stereochemistry. 

An interesting relationship between building block structure and library diversity was revealed by the early work of the Sanders group on DCLs generated through transesterification. Transesterification under thermodynamic control of building blocks 3 and 4 (Figure 3.2) produced all four possible cyclic trimers in a statistical 1 3 3 1 ratio [33], Hardly any dimers or tetramers were formed. 

A second original concept from the early years of DCC was that exposure of a given DCL of receptors to a variety of guests that amplify the same receptor would produce responses from the libraries that correlate with the binding of those guests to the ampUfied receptor. Again, some early results on amplification of receptors from relatively simple DCLs supported that idea. 

Early metal alkyls such as Cp2TiMc2 are readily cleaved by acid to liberate the alkane a transient alkane complex is the probable intermediate in such cases. Protonation of the alkene complex shown below can occur by two simultaneous paths (1) direct protonation at the metal and (2) initial protonation at the alkene followed by fi elimination. Path 2 leads to incorporation of label from DCl into the alkene ligands. ... 

---