Fragment linking

The acidic hydrogen in terminal alkynes can readily be replaced by silver, in a diagnostic test. [(Me3P)Ag(C=CPh)] has a polymeric structure while [(Ph3P)Ag(C=CPh)]4 is made of [Ag(PPh3)2]+ and [Ag(C=CPh)2] fragments linked so that the silver atoms form a square [147]. 

Another promising way of transmembrane PET includes intramolecular electron transfer along bridge molecule D-PC-A which spans the bilayer and contains PC, D and A fragments linked by covalent bonds [17]. 

Fig. 1 Schematic representations of the two general FBDD approaches, (a) Evolution of the fragment in the binding site of a generic target, (b) Fragment-linking approach...

F.G.A. Stone With increasing frequency, as our work in this area develops, we are observing reactions in which the metal alkylidyne fragments link to form C-C bonds Please refer to compounds (39) and (40), and the relevant references to these species. 

Restriction enzymes, sequence-dependent cleavage of DNA by, 12 497—498 Restriction fragment linked polymorphism (RFLP), 12 500 procedure, 12 103-104 Restriction sites, as genetic markers, 12 500... 

The first cyclopentadienylzinc compound that was structurally characterized by an X-ray crystallographic study is cyclopentadienyl(methyl)zinc, Cp(Me)Zn (57) ". The structure of 57 in the solid state consists of puckered chains of methylzinc fragments, linked by bridging cyclopentadienyl groups (Figure 28). 

CAVEAT (39, 40) are examples of software using the linking approach. ReCore (41) and Scaffold Replacement are capable of performing both fragment linking and building. 

A dye developer is a compound composed of a silver halide developer fragment linked via an insulating group (Z) to a dye moiety. The compounds are intrinsically soluble in alkali because of acid functions contained in the developer fragment, normally a hydroquin-one. On interaction with exposed silver halide the hydroquinone becomes oxidized to the corresponding quinone. This renders the compound insoluble in alkali (Scheme 7). The reaction can be enhanced by the use of a mobile auxiliary developer such as p-methylphenyl-hydroquinone. In the areas of the emulsion layer where there has been no exposure of silver halide, the dye developer cannot be oxidized. It therefore remains soluble and free to transfer to the mordant layer. Thus, the transfer of dye is inversely proportional to the amount of exposed silver halide and the overall result is a positive of an original scene on the receiver. 

Howard, N., et al., Application of fragment screening and fragment linking to the discovery of novel thrombin inhibitors. J Med Chem, 2006,49, 1346-1355. 

Fig. 3. Extended carbon networks containing diyne fragments linked by (a) sp3 carbons, (b) sp2 carbons, and (c) [3]-radialenes.

---