Hydrogen directionality

Each of the pharmacophore queries consisted of one donor, one acceptor and one of the two hydrophobic points indicated in Figure 1.16. The directionality of hydrogen bonds was inferred from the X-ray structure and reasonably loose tolerances of 1.5 A were used for donor-acceptor distances and 2-2.5 A to the hydrophobe were chosen to allow for the flexibility seen across kinase structures and to maximise the diversity amongst the identified fragments. Four pharmacophore queries were completed and the results were combined. The chosen fragments were further filtered by molecular weight (between 150 and 250), 51og P (between 2.5 and —2.5) and the presence of... 

The H-bonding in the anhydrous 1 Im (Table 24) has topologic properties (Fig. 46) similar to those in the alcohol coordinatoclathrates of 1 with 1 2 host guest stoichiometry (cf. Fig. 17 a). Assuming a perfectly ordered crystal lattice, the resulting central loop of H-bonds should appear to have homodromic directionality with the donor/acceptor functions separated in space. This contrasts to the behavior in the dihydrated l Im where no such characteristic loops are formed. Involvement of the C—H hydrogen atoms of the imidazole molecule, however, is similar in both cases. 

Formally, the lone pairs on molecular nitrogen, hydrogen cyanide, and carbon monoxide are sp hybrid orbitals, whereas NLMO hybridizations calculated even lower p contributions. Hence, these lone pairs have low directionality, the electron density remains close to the coordinating atom and interaction between the lone pair and the Be2+ is comparatively weak. The Be-L bonds are easily disrupted and ligand exchange consequently can proceed with a low activation barrier. A high degree of p character, on the other hand, means that the lone pair is directed toward beryllium, with electron density close to the metal center, and thus well suited for coordination. 

The compounds of carbon and silicon with hydrogen would be expected to be completely covalent according to these models, but the directionality of the bonds, which is towards the apices of a regular tetrahedron, is not explained by these considerations. Another of Pauling s suggestions which accounts for this type of directed covalent bonding involves so-called hybrid bonds. 

Both species exhibit the expected linear geometry that maximizes the dominant n- - a interaction. However, these isomers are rather perplexing from a dipole-dipole viewpoint. The dipole moment of CO is known to be rather small (calculated Fco = 0.072 D), with relative polarity C- 0+. 40 While the linear equilibrium struc-ture(s) may appear to suggest a dipole-dipole complex, robust H-bonds are formed regardless of which end of the CO dipole moment points toward HF This isomeric indifference to dipole directionality shows clearly that classical dipole-dipole interactions have at most a secondary influence on the formation of a hydrogen bond. 

The principal non-covalent interaction in molecule-based crystal engineering is the hydrogen bond. The reason for this preference is simple, the hydrogen bond is the strongest of the non-covalent interactions and possesses a high degree of directionality. Strength and directionality (namely transferability and repro-... 

In this context, the classical hydrogen bonds provide the best combination of strength and directionality, permitting rapid self-organization of molecular building blocks into extended regnlar structnres. This process is very efficient with respect to conventional snpramolecular synthesis nsing covalent bonds. 

Since hydrogen and dihydrogen bonds have comparable energies and directionality, their combination also holds interest for crystal engineers. 

In contrast to the TREN template, 75 with the NTA template preferred the h-cis configuration . This could be caused either due to the inverse directionality of the hydroxamate group, or, more plausibly, because the tripeptide is connected through the amino end, leading to opposite orientation of the hydrogen-bonding network. ... 

Leahy, D.E., Morris, J.J., Taylor, P.J. and Wait, A.R. (1992) Model solvent systems for QSAR. Part 3. An LSER analysis of the critical quartef . New light on hydrogen bond strength and directionality Journal of the Chemical Society-Perkin Transactions 2, 705-722. 

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