Water molecules which apparently accept no hydrogen bonds are systematically involved in C-H...O interactions

The hydrogen-bond acceptor functions are analyzed for 672 water molecules in crystal structures of hydrated small biological molecules. Of the 672 water molecules, 26 neither accept hydrogen bonds from O-H or N-H donors, nor coordinate to metal ions. As compensation, they satisfy their acceptor potential with up to four C-H.O hydrogen bonds. They are found in hydrated amino acids, purines and pyrimidines, and alkaloids, but not in carbohydrates, nucleosides, nucleotides and steroids. As for conventional hydrogen bonds, the preferred coordination geometry is tetrahedral. No example of a true non-accepting water molecule is found. A particularly strong C-H hydrogen-bond donor occurring in many biological molecules is C-H neighbouring protonated N.