Lorenz Canaval, University of Innsbruck

Combining Quantum Mechanical Molecular Dynamics
with a Dissociative Water Model for the
Description of Hydrolyzing Systems
Lorenz R. Canaval and Thomas S. Hofer*
Theoretical Chemistry Division, Institute of General, Inorganic and Theoretical Chemistry,
University of Innsbruck, Austria || *T.Hofer@uibk.ac.at || www.theochem.at
BACKGROUND & METHODOLOGY
One particularly challenging application for QM/MM simulations is the study of
hydrolysis phenomena. Although a quantum chemical treatment is capable of
describing proton transfer (PT) events occurring within the QM region, the
majority of molecular mechanical methods does not enable an adequate
+
−
treatment of oxonium (H3O ) and hydroxide (OH ) ions. Until now QM/MM
simulations had to be aborted as soon as one of the (de-)protonated species
migrated into the MM region. We herein present the first successful simulation
employing the dissociative water model developed by Garofalini [1] in the MM
region of a QM/MM study, applying the RI-MP2 level of theory in the QM region.
The target of the investigation was the three-step hydrolysis of As 3+ resulting in
arsenous acid H3AsO3.
In order to achieve a dissociative description of the solvent, no distinction
between intra- and intermolecular contributions is made. The potential functions
apply in the same manner to all interactions, irrespective of whether the atoms are
part of the same residue (hydroxide, water, oxonium, ...) or not. In addition to the
partial charge q assigned to the atoms, each particle is surrounded by a Gaussian
charge distribution carrying a charge qd of opposite sign to reduce the overall
Coulombic potential at increased distances. A screened, cosine-harmonic three-
Figure 1: Snapshots taken from the simulation trajectory showing the starting structure
(hydrated As3+) and the product after three hydrolysis steps (arsenous acid H3AsO3).
body potential is employed in addition to the pairwise interactions.
For QM/MM applications, an automated topology update has to be employed in
order to assign solvent molecules as a whole either to the QM or the MM region.
For such a book-keeping, a criterion has to be found determining whether a proton
is still part of its donor molecule, or if it has already been transferred to the
acceptor molecule. The ratio of the projected donor–hydrogen and donor–acceptor
distances proofed to be a simple yet effective criterion to identify PT events. [2]
RESULTS AND DISCUSSION
Figure 2a depicts selected interatomic distances as a function of time for the first
hydrolysis reaction observed after 144 fs of simulation time (t T1), resulting in a
deprotonation of a water molecule coordinated to As(III). The transfer of this proton
is indicated by a sharp increase of the donor–hydrogen, and a likewise decrease
of the acceptor–hydrogen distance. In addition, a significant decrease of the
donor–acceptor distance at the time of the PT is observed. A decrease of the
arsenic–donor distance is starting even shortly before the PT occurs, resulting in a
distance of approx. 1.75 Å, being in full agreement with experimental data for As–
O distances in hydroxo-species.
The influence of the geometries of H-bonds formed by two water molecules
adjacent to the acceptor molecule (figures 2b and 2c) has also been studied. A
strong hydrogen bond between the latter and a neighboring molecule was
identified at the moment of PT (tT1, figure 2b). A significant decrease of the
corresponding donor–acceptor and acceptor–hydrogen distances coupled with a
nearly linear arrangement of the acceptor–hydrogen–donor atoms highlights the
importance of this H-bond to stabilize the PT reaction. In contrast, the second
water molecule did not show any particular promoting influence.
As both the arsenic-hydroxo-complex and the newly formed oxonium ion are
positively charged, they tend to part, either by diffusion or by further proton
hopping processes. Such an hopping event is observed 550 fs after the initial PT
event (tH1, figure 2c). In contrast to the first two hydrolysis events taking place very
soon, a number of hydrolysis attempts were observed during 10 ps before the third
successful PT reaction occurred after approx. 12 ps (tT3b, figure 3a). An
unsuccessful PT event was found 25 fs earlier (tT3a, figure 3a). Considering the
respective distance plots does not reveal any significant differences between these
two events in terms of stabilization via H-bonding by the two neighboring water
molecules. However, the analysis of the corresponding H-bond angles reveals that
during the first transfer attempt (tT3a) only one H-bond shows an angle close to
180°, whereas the second one is weak, amounting only to 138°. In contrast, both Hbond angles show values close to linearity for the successful attempt (t T3b). It can be
concluded that this near perfect alignment maximally stabilises the final hydrolysis
step, resulting in the product arsenous acid H3AsO3.
Figure 4 shows the evolution of
selected
quantum-mechanically
derived partial charges. Due to
charge–transfer effects, which are
intrinsically accounted for in the
quantum-mechanical
treatment,
the formal charge of As(III) is
reduced to approx. +2 at the
beginning. As can be seen in plot
4a, the partial charge of the metal
ion drops to +1.85 before the first
proton transfer event takes place,
and then a short stagnation at this
level lasting about 80 fs is
observed. During this time interval
the first successful hydrolysis Figure 4: Evolution of quantum-mechanically
event
takes
place
(tT1). derived partial charges for selected atoms for the
first and second hydrolysis event (tT1 and tT2)
Subsequent continuous dischargincluding subsequent H-hopping (tH1), and the third
ing of the center ion is observed.
hydrolysis event (tT3a/b).
CONCLUSION
✔
✔
✔
✔
Figure 2 (left) and Figure 3 (right): Selected interatomic distances characterizing the first
(figure 2) and third (figure 3) proton transfer reactions of the hydrolysis of As(III) for a) the
transferring proton, b,c) H-bonds to neighboring water molecules of the acceptor species, and
d) corresponding to H-Bond angles.
✔
QMCF-MD simulation using dissociative water model
suitable for hydrolysis studies
numerous hydrolysis attempts, three successful hydrolysis steps
a number of proton-hopping reactions
monitoring of partial charges reveals charge-transfer effects
properties of product in excellent agreement with experimental work
(1) Mahadevan, T. S.; Garofalini, S. H. J. Phys. Chem. B 2007, 111, 8919
(2) Hofer, T.S., Hitzenberger M., Randolf B.R. J. Chem. Theory Comput. 2012, 8, 3586
Financial support from a PhD grant of the Leopold-Franzens-University of Innsbruck (Rector Univ.-Prof. Dr. Dr.hc.mult. Tilmann D. Märk) for Lorenz R. Canaval is gratefully acknowledged.