Proposed Hydrogen-Bonding Index of Donor or Acceptor Reflecting Its Intrinsic Contribution to Hydrogen-Bonding...

In this work, we tentatively propose that the hydrogen-bonding strength E_HB (referring to the minimal hydrogen-bonding energy) and its corresponding hydrogen-bond (HB) distance (referring to the optimal HB distance d_HB) for simple mono-HB systems have an exponential relationship on the basis of MP2 and DFT computational results. We take a step further and propose that the hydrogen-bonding indices of the donor (I_donor) and acceptor (I_acceptor), reflecting their intrinsic contributions to hydrogen-bonding strength, also have an exponential relation with the hypothetical effective hydrogen-bond radii of the donor (r_donor) and acceptor (r_acceptor), respectively. On the basis of extensive quantum-mechanical calculations, relevant assumptions about the hydrogen-bonding index are rationalized. Moreover, the hydrogen-bonding index is also suggested as an additional prefiltering criterion for virtual screening besides the widely accepted Lipinski's rule of five. Finally, a "Hydrogen-Bond Index Estimator (HBIE)" module has been implemented in our Visual Force Field Derivation Toolkit (VFFDT) program to approximately and rapidly estimate the hydrogen-bonding indices of any small molecules in batch and screen possible stronger donors or acceptors from the small-molecule database. To the best of our knowledge, the concept of the hydrogen-bonding index and its potential application are proposed here for the first time.