Templating molecule charge

The definition of pharmacophores is done manually by applying so-called schemes using a Pharmacophore Query Editor. A template molecule is generally used for this purpose. In the MOE environment, a scheme is a collection of functions that define how each ligand is annotated. This is accessed via an SVL function. The default scheme is called PCH (Polarity-Charged-Hydrophobicity). New schemes can be created to represent certain molecules better, e.g. Planar-Polar-Charged- Hydrophobiaty [91]. 

It is surprising that in all cases, the Al/M ratio is very high. This clearly indicates that the AlO - framework negative centers must also be compensated by positive charges stemming from the template molecules. It is indeed probable that under the relatively low pH values that characterize our synthesis batches (11—11.5), the diamines are at least partly protonated (36). Araya and Lowe also concluded... 

A molecular model of the template molecule is made and charges for each atom are calculated and the structure of the template is refined using MM. 

In-house experience with Cresset has shown that FieldPoint patterns can be particularly sensitive to conformation and charge. In the absence of a bioactive conformation for the template molecule, a suitable conformation and charge state... 

A classic example of the formation of a macrocycle by a neutral template is that of the versatile host compound and component of molecular machines, the so-called blue box, or cyclobis paraquat-para-phenylene. Reaction of the horseshoe precursor with dibromo-para-xylene leads to the formation of a tricationic intermediate that is capable of binding the template molecule (Scheme 3), which closes the macrocycle to form the tetracationic cyclophane. The jT-ir interactions of the charge-transfer variety (the complex of the product and template is colored, whereas the components are not) assisted by the charge on ihe product are a major driving force in the process, as revealed in X-ray structures of complexes. It should be noted that the interaction is of the jr-n type assisted by the complementary positive charge on the bipyridinium residues and r-electron-rich nature of the template. This supramolecu-lar synthon can be used for other cyclophanes, catenanes, and rotaxanes (see Self-Assembly of Macromolecular Threaded Systems, Self-Assembled Links Catenanes, and Rotaxanes—Self-Assembled Links, Self-Processes). 

Flexibility, Basicity, Amphiphily, and Charge of Templating Molecules... 

---