Hydrogen bond donor, acceptor

This study supports rate-determining H-OH bond breaking, which constrasts with previous reports that identified vinylidene isomerization as the key step in catalytic alkyne activation. The results indicate an enzyme-like mechanism is operative involving cooperative substrate activation by a metal center and proximal hydrogen bond donor/acceptors. In the future we will apply these principles to the activation of additional species. 

Phenomenex (see 2006 Catalog, SPE products) Strata-X Polar functionalized styrene-divinylbenzene polymer Reversed phase with weakly acidic, hydrogen bond donor, acceptor, and dipolar interactions Cetirizine (76) pyridoxine (77) omeprazole (78) mycophenolic acid (79) 25-hydroxy-vitamin D3 (80)... 

C. Emmeluth, V. Dyczmons, and M. A. Suhm, Tuning the hydrogen bond donor/acceptor isomerism in jet cooled mixed dimers of aliphatic alcohols. J. Phys. Chem. A 110, 2906 2915... 

The condensation reaction yields an imine 88 with the appropriate set of hydrogen bond donor/acceptor groups to template its own formation via a ternary complex (involving the product and the two reactants). Closer inspection to this reaction has revealed that the tertiary complex is actually more stable (in some of the reaction studied) than the duplex formed between the template and the product. Consequently, once the templation has taken place, the duplex is separated and both the product and original template are ready to accelerate the reaction of the two reactants. Since the number of templates has now doubled, the enhancement of the reaction could in principle follow an exponential rate. 

In cases where hydrogen bond donor/acceptor functions are attached to a (chiral) scaffold, they can steer the assembly of a well defined catalyst-substrate complex. The positions of hydrogen bond donors and acceptors determine the stereoselectivity of the reaction. 

Fig. 4 The piperazine scaffold space offered by IMCR. (Above) The relationship of 16 different piperazine scaffolds based on different heterocyclic systems and also including hydrogen bond donor-acceptor features and sp character is depicted right column). (Below) Several piperazine scaffolds are shown with their immanent 2D hydrogen bond donor-acceptor propensity blue and red arrows, H-hond acceptors and donors, respectively)... 

As points of reference, we will take two well-established hydrogen-bond donor/ acceptors, H2O and NH3. Their computed gas-phase Vs,max and Vs,mm are in Table 5, along with the same data for all of the molecules that have been discussed hydroxylamine (5), dimethylhydroxylamine (6), acetoxime (7), acetohydroxamic acid (8), and the isomeric pairs of oximes examined in the last section. Finally, we included an additional hydroxamic acid, 11, to see the effects of the strongly electron-withdrawing cyano group. 

In the model cAPK with bound staurosporine inhibitor, the lactam amide group of the inhibitor functions as a bidentate hydrogen bond donor-acceptor... 

Other attempts to refine or improve Lipinski s rule set have appeared in the literature. One notable factor for consideration is the number of rotatable bonds in a hit. Increased molecular flexibility can reduce the ability of a molecule to cross a membrane. The maximum number of rotatable bonds has been suggested as 10. The polar surface area, often abbreviated as PSA, of a molecule is another important factor. Polar surface area is tightly correlated to the number of hydrogen-bond donors and acceptors contained in a molecule. A maximum polar surface area of 140 A2 or the equivalent of 12 hydrogen-bond donors/ acceptors has been suggested. This is in line with Lipinski s rules.22... 

Lipinski s rules Lipinski s rules describe the maximum advisable molecular weight, lipophilicity, and hydrogen bond donors/ acceptors in compounds that are likely to show high oral bioavailability. 

Chemical functionality (hydrogen bond donor, acceptor) with geometric constraint ++ +... 

---