Although Lipinski’s rules and related approaches demand that we count any hydrogen bond donor or acceptor (defined in a rather limited way) as equivalent, there is a significant strand of experimental and computational work that has sought to quantify the differences between the acceptor and donor ability of different functional groups. I was first introduced to these ideas in one of the series Hydrogen Bonding, Parts 1 to at least 9. In part 9, Abraham et al. introduced an overview of their measurements made by using a standard donor (4-nitrophenol) or a standard acceptor (N-methylpyrollidinone) in 1,1,1-trichloroethane. A large array of functional group types were studied. Subsequently, these data were found to correlate well with electrostatic potential computed in quantum mechanical calculations by Kenny in two important publications (Acceptors: and Donors:). This work was extended to show how hydrogen bonding strength could be related to differences between partitioning coefficients measured in 1-octanol and partitioning coefficients measured in hexadecane.

In parallel with this activity, mostly undertaken at Astrazeneca, Hunter was using similar considerations to build a unifying model of the nature of interactions between molecules that led to the map shown below in which blue regions represent acceptors (across the top) and donors (down the side) that are able to form attractive interactions in water. The red regions represent those interaction types that involve loss of so much solvation by the more polar partner that the new interaction is unable to compensate for it. 

Hydrogen bonds not the same

Quantifying Intermolecular Interactions: Guidelines for the Molecular Recognition Toolbox

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