Molecular cleft ligands

Silver(I) complexes with macrocyclic nitrogen ligands are also very numerous. Mono- or homodi-nuclear silver-containing molecular clefts can be synthesized from the cyclocondensation of functionalized alkanediamines or triamines with 2,6-diacetylpyridine, pyridine-2,6-dicarbalde-hyde, thiophene-2,5-dicarbaldehyde, furan-2,5-dicarbaldehyde, or pyrrole-2,5-dicarbaldehyde in the presence of silver(I).486 97 The clefts are derived from bibracchial tetraimine Schiff base macrocycles and have been used, via transmetallation reactions, to complex other metal centers. The incorporation of a range of functionalized triamines has provided the conformational flexibility to vary the homodinuclear intermetallic separation from ca. 3 A to an excess of 6 A, and also to incorporate anions as intermetallic spacers. Some examples of the silver(I) complexes obtained are shown in Figure 5. 

The chelation of small molecules described above may be extended to metal ions. The convergence of the carboxyls within the molecular clefts provides a microenvironment ideal for divalent metals. A special structural feature of the new ligands involves stereoelectronic effects at carboxyl oxygen. Classical chelates such as EDTA present the less anti lone pairs to the metal ion, but the new structures offer the more basic syn lone pairs. Metals such as Ca and Mg are tightly bound and readily transported across liquid membranes (Scheme 6). In addition, the mode of binding within the new ligands is exclusively trans, a feature which is likely to lead to altered reactivity of the bound metal ions as catalysts. 

The lacunar cyclidene ligands are the first family of totally synthetic ligands to form both iron(II) and cobalt(II) Oj carriers. The molecular structure of the lacunar cyclidene complexes is most simply represented by the flat projection (la), while the stereochemistry is shown in Ib. Cyclidene refers to the parent macrocycle encircling the metal ion and the lacuna is the permanent void created by bridging the cleft arising from the saddle shape of the cyclidene macrocycle. 

In rat liver ADH the presence of multiple molecular forms has been correlated to disulfide bridges involving the ligands to this zinc atom (Section II,B,3). These forms are active in ethanol oxidation (62). The lobe region which binds zinc is thus, in all probability, not essential for the catalytic action of alcohol oxidation. It has been suggested (133,134) that the extra zinc atom is essential for the structural stability of the enzyme. There is no evidence in the structure that this lobe region is necessary either for tertiary or quaternary structure stabilization. From the structural point of view, this region looks much more like a second catalytic center. The zinc atom is situated in one side of an obvious cleft into which the lone pair electrons of the sulfur atom of Cys-97 project. 

The deduced preselection of the dipolar species in the electric field of the receptor may be assumed to enormously accelerate the diffusional approach of dipolar ligands [153]. The resulting formation of a diffusional encounter complex Figure 4.8) represents the initial step in molecular recognition and selection which is followed by a sequence of consecutive steps, during which more and more substructures make contact with the subsites of the receptor cleft, which eventually may fully encompass an inhibitor molecule when being complementary. 

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