Determination of Hydrogen Bond Structure in Water versus Aprotic Environments To Test the Relationship Between Length and Stability

Hydrogen
bonds profoundly influence the architecture and activity
of biological macromolecules. Deep appreciation of hydrogen bond contributions
to biomolecular function thus requires a detailed understanding of
hydrogen bond structure and energetics and the relationship between
these properties. Hydrogen bond formation energies (ΔGf) are enormously more favorable
in aprotic solvents than in water, and two classes of contributing
factors have been proposed to explain this energetic difference, focusing
respectively on the isolated and hydrogen-bonded species: (I) water
stabilizes the dissociated donor and acceptor groups much better than
aprotic solvents, thereby reducing the driving force for hydrogen
bond formation; and (II) water lengthens hydrogen bonds compared to
aprotic environments, thereby decreasing the potential energy within
the hydrogen bond. Each model has been proposed to provide a dominant
contribution to ΔGf, but incisive tests that distinguish the importance of these contributions
are lacking. Here we directly test the structural basis of model II.
Neutron crystallography, NMR spectroscopy, and quantum mechanical
calculations demonstrate that O–H···O hydrogen
bonds in crystals, chloroform, acetone, and water have nearly identical
lengths and very similar potential energy surfaces despite ΔGf differences >8 kcal/mol
across
these solvents. These results rule out a substantial contribution
from solvent-dependent differences in hydrogen bond structure and
potential energy after association (model II) and thus support the
conclusion that differences in hydrogen bond ΔGf are predominantly determined by solvent
interactions with the dissociated groups (model I). These findings
advance our understanding of universal hydrogen-bonding interactions
and have important implications for biology and engineering.