Competing intramolecular vs. intermolecular hydrogen bonds in solution

Abstract

A hydrogen bond for a local-minimum-energy structure can be identified according to the definition of the International Union of Pure and Applied Chemistry (IUPAC recommendation 2011) or by finding a special bond critical point on the density map of the structure in the framework of the atoms-in-molecules theory. Nonetheless, a given structural conformation may be simply favored by electrostatic interactions. The present review surveys the in-solution competition of the conformations with intramolecular vs. intermolecular hydrogen bonds for different types of small organic molecules. In their most stable gas-phase structure, an intramolecular hydrogen bond is possible. In a protic solution, the intramolecular hydrogen bond may disrupt in favor of two solute-solvent intermolecular hydrogen bonds. The balance of the increased internal energy and the stabilizing effect of the solute-solvent interactions regulates the new conformer composition in the liquid phase. The review additionally considers the solvent effects on the stability of simple dimeric systems as revealed from molecular dynamics simulations or on the basis of the calculated potential of mean force curves. Finally, studies of the solvent effects on the type of the intermolecular hydrogen bond (neutral or ionic) in acid-base complexes have been surveyed.

Figure 1

The figure shows the projection of the heavy-atom skeleton onto the X–H…Y plane for cases where H-bonding can result in a: (a) Five-member ring; (b) Six-member ring; or (c) Seven-member ring.

Figure 2

Structures with an intramolecular hydrogen bond for: (1) 1,2-Ethanediol; (2) Salicylic acid; (3) Hydroxy-benzoic acid; and (5) β-Alanine zwitterion. Conformations 2, 4, 6 prevent the formation of the intramolecular H-bond and are open for forming intermolecular hydrogen bonds.

Figure 3

OCCN gauche structures with an intramolecular H-bond for 2-aminoethanol (7) and 2-NO₂ ethanol (9); Conformations 8 and 10 indicate disrupted H-bonds after rotations by approximately 120° about the O–C axes.

Figure 4

The free energy perturbation (FEP) curves for the transformations of conformers with an intramolecular H-bond to structures without H-bonds. Shown are 1,2-ethanediol (1) to (2), salicylic acid (3) to (4), and β-alanine zwitterion (5) to (6) where structure numbering is taken from Figure 2.

Figure 5

Structures of the syn (11) and anti (12) acetic acid, the s-cis propenic acid (13) and the s-trans pyruvic acid (14). The carboxylic group is syn for the latter two.

Figure 6

Solute-water pair-energy distribution functions for 2-aminoethanol and 2-NO₂-ethanol with (HB) and without (NHB) an intramolecular H-bond: H₂NetOH HB (7); H₂NetOH NHB (8); O₂NetOH HB (9); O₂NetOH NHB (10). Structure numbers from Figure 3.

Figure 7

Solute-water pair-energy distribution functions for syn acetic acid (11); anti acetic acid (12); s-cis propenic acid (13); and s-trans pyruvic acid (14) with structures shown in Figure 5.

Figure 8

Neurotransmitters portrayed in the neutral form: (a) Histamine; (b) Tyramine; (c) Dopamine; (d) Norepinephrine (R=H), Epinephrine (R=CH₃); and (e) Serotonin.