Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Feb 1;111(4):720-30.
doi: 10.1021/jp066478s.

Why urea eliminates ammonia rather than hydrolyzes in aqueous solution

Anastassia N Alexandrova  1 , William L Jorgensen
Affiliations

Why urea eliminates ammonia rather than hydrolyzes in aqueous solution

Anastassia N Alexandrova et al. J Phys Chem B. .

Abstract

A joint QM/MM and ab initio study on the decomposition of urea in the gas phase and in aqueous solution is reported. Numerous possible mechanisms of intramolecular decomposition and hydrolysis have been explored; intramolecular NH3 elimination assisted by a water molecule is found to have the lowest activation energy. The solvent effects were elucidated using the TIP4P explicit water model with free energy perturbation calculations in conjunction with QM/MM Monte Carlo simulations. The explicit representation of the solvent was found to be essential for detailed resolution of the mechanism, identification of the rate-determining step, and evaluation of the barrier. The assisting water molecule acts as a hydrogen shuttle for the first step of the elimination reaction. The forming zwitterionic intermediate, H3NCONH, participates in 8-9 hydrogen bonds with water molecules. Its decomposition is found to be the rate-limiting step, and the overall free energy of activation for the decomposition of urea in water is computed to be approximately 37 kcal/mol; the barrier for hydrolysis by an addition/elimination mechanism is found to be approximately 40 kcal/mol. The differences in the electronic structure of the transition states of the NH3 elimination and hydrolysis were examined via natural bond order analysis. Destruction of urea's resonance stabilization during hydrolysis via an addition/elimination mechanism and its preservation in the rearrangement to the H3NCONH intermediate were identified as important factors in determining the preferred reaction route.

PubMed Disclaimer

Figures

Figure 1
Figure 1
(a) Projection of the gas phase PDDG PES for the unimolecular elimination of ammonia on the two reaction-coordinates, the difference of the two N-H distances, and R(C-N). (b) PDDG reaction profile for urea decomposition via elimination of ammonia in the gas phase (red curve) and including GB/SA hydration (blue curve).
Figure 2
Figure 2
Reaction pathway for urea decomposition via elimination of ammonia with one H2O assisting the H-shuttling: (a) PDDG results for the gas-phase reaction (red curve) and with GB/SA hydration (blue curve); QM/MM/FEP reaction profiles (b) for the first step of the reaction (TS structures are shown in Figure 3), and (c) for the final NH3 departure.
Figure 3
Figure 3
Structures of the TSs on the decomposition paths of urea: NH3-elimination (a) in the gas phase (B3LYP/6-311++G**), and (b) in solution (snapshots from the MC/FEP simulations); addition-elimination hydrolysis (c) in the gas phase (B3LYP/6-311++G**), and (d) in solution (snapshots from the MC/FEP simulations).
Figure 4
Figure 4
Two views of a snapshot from a QM/MM simulation of the H3NCONH zwitterion in TIP4P water just showing the nine hydrogen-bonded water molecules.
Figure 5
Figure 5
Reaction pathway for urea decomposition via elimination of ammonia in the gas phase with two water molecules assisting the hydrogen shuttling. PDDG results with (blue curve) and without (red curve) GB/SA hydration.
Figure 6
Figure 6
Hydrolysis of urea. Enthalpy profiles: red – in the gas phase (PDDG), blue - in implicit solvent (PDDG + GB/SA). In green, the free energy profile from the QM/MM/FEP simulations in explicit TIP4P water. TS structures are shown in Figure 3.
Figure 7
Figure 7
Hydrolysis of urea in the gas phase assisted by two water molecules (PDDG results).
See this image and copyright information in PMC

References

    1. Shaw WHR, Bordeaux JJ. J Am Chem Soc. 1955;77:4729–4734.
    1. Amell AR. J Am Chem Soc. 1956;78:6234–6238.
    1. Shaw WHR, Walker DG. J Am Chem Soc. 1958;80:5337–5342.
    2. Shaw WHR, Walker DG. J Am Chem Soc. 1956;78:5769–5772.
    3. Shaw WHR, Walker DG. J Am Chem Soc. 1957;79:2681–2684.
    4. Shaw WHR, Walker DG. J Am Chem Soc. 1957;79:3683–3686.
    5. Shaw WHR, Walker DG. J Am Chem Soc. 1957;79:4329–4331.
    1. Lynn KR. J Phys Chem. 1965;69:687–689.
    1. Sizer IW. J Am Chem Soc. 1939;71:209–218.

Publication types

LinkOut - more resources