Theoretical evaluation of the unusual entropy change during formation
of calix[6]arene-phenol host-guest complexes
a
a
a
a
b
Sándor Kunsági-Máté, Beáta Lemli, Kornélia Szabó, Géza Nagy, László Kollár
a
Department of General and Physical Chemistry, University of Pécs, Ifjúság 6., H-7624 Pécs, Hungary
E-mail: [email protected]
b
Department of Inorganic Chemistry, University of Pécs, Ifjúság 6., H-7624 Pécs, Hungary
SO3Na
[
CH3
NO2
Cl
OH
OH
OH
OH
2a
2b
2c
2d
]
OH
6
1
Figure 1. Calix[6]arene-hexasulfonate salt 1 and different phenol derivatives (2a-2d)
were chosen as host and guests, respectively (2a: p-nitrophenol, 2b: p-chlorophenol, 2c:
phenol and 2d : p-cresol)
ABSTRACT
The complex formation of calix[6]arene-hexasulfonate host with para-substituted phenol derivatives was studied by DFT/B3LYP/6-31++G method
and molecular dynamics simulation. The complex formation and the stability of the complex were evaluated considering the Hammett parameters of
the substituents of the guest. In agreement with related experiments, theoretical results show similar dependence of the interaction energy between the
host and guest on the electron density of the aromatic ring of the phenol guest molecules. The entropy term of the complex formation was studied by
simulation of the molecular rearrangement of solvent water molecules around the calixarene host when the phenols with their differently charged
aromatic rings are entered into the calixarene cavity. The results show a more ordered structure of the water molecules when the aromatic ring of the
entering guest molecule is more charged. This property fits well to the experimental observation. These results are applicable in the development of
selective and sensitive chemical sensors for neutral organic aromatics.
INTRODUCTION
The selectivity character of calixarene complexes is mostly based on stereochemical effects, on the steric hindrance at most. Therefore, the selectivity of these molecules can be modified by changing the cavity size by the different
functionalization at the lower and/or upper rims of the molecule. Among several related works in our recent papers [1-6] the factors controlling the thermodynamic and kinetic stability or selectivity of some calixarene derivatives towards
neutral p-electron deficient aromatics were reported. The inclusion complexation of calix[6]arene hexasulfonate with different neutral aromatics (Fig. 1) in aqueous media have been studied recently by PL (Photoluminescence), DSC
(Differential Scanning Calorimetry) and quantum-chemical methods [7,8]. To tune the electron density (Fig. 2) on the guest's aromatic rings, the phenol parent compound was functionalized in the para-position with different electronwithdrawing groups, such as NO2, Cl, as well as H and CH3 groups. Although the enthalpy change predicts strong interaction between the host and the guest, the Gibbs free energy change of the complex formation is small, resulting in a
relatively low complex stability. This property is due to the high and negative entropy change during the complex formation. Since the interactions of calixarene with neutral species involve competition between complexation and solvation
processes, it was obvious to assume that redistribution of the electron density of calixarene rings, followed by the reordering of the solvent molecules can be a background of this unexpected entropy change at molecular level.
Methods
The equilibrium conformations of calixarene 1 and their complexes with phenol derivatives (2a-2d) were studied at DFT/B3LYP/6-31++G level by using GAUSSIAN 03 package. The PCM (Polarizable Continuum
Model) method was used to consider the solvent effect. The Fletcher-Reeves geometry optimization method was used for the investigation of the conformers.
The temperature-dependent molecular dynamic simulations were performed with AMBER forcefield. The TIP3P method is used to explicitly consider the solvent water molecules. For this calculation a cubic box with 20 Ĺ
side length is used. The box contained 265 water molecules according to the water density at 298K. To find an appropriate initial condition for molecular dynamics a 'heating' algorithm implemented in HyperChem package
was used. This procedure heats up the molecular system smoothly from lower temperatures to the temperature T at which molecular dynamics simulation is desired to perform. The starting geometry for this heating phase is
a static initial structure. We used the optimized geometry derived from semiempirical AM1 calculations as an initial structure. The temperature step and the time step in the heating phase were set to 2K and 0.1 fs,
respectively. After equilibration at the given temperature, the MD simulations were run in 1 ps time intervals with resolution of 0.1 fs. The simulation time step was 0.1 fs. Ten thousand points were calculated in each run.
Five water molecules locating closest to the calixarene's phenolic unit was chosen for data analysis. The inclination angles of the C2 symmetry axis of the water molecules, related to the directions perpendicular to the planes
of the appropriate phenolic units of calixarene molecules, were collected during the simulation. The average values of these angles were used to represent the freedom of water molecules around the calixarene rings.
Single point calculations and ab initio geometry optimizations were carried out with the GAUSSIAN 03 code, while molecular dynamics simulations are performed by the HyperChem Professional 7 program package.
Figure 2. Charge density map of different phenol derivatives (2a-2d) applied as guests in this study.
Calculations were performed with ab-initio DFT/6-31G** method.
Equilibrium conformation of the host-guest complexes
The complexes formed during the interactions of the calixarene 1 and different phenol derivatives (2a-2d) are
preferably stabilized by two attractive forces. Either by the p-p interaction between the aromatic p-electron systems
of calixarene phenolic units and that of the aromatic guest molecules, or by weak attractive interaction between the
OH groups at the lower rim also participates in the stabilization. In all cases, the orientation of the different phenol
derivatives inside the calixarene cavity was found to be always the same: the para substituents located at the top and
the phenolic OH at the bottom. This is probably due to the diminished repulsive interaction between the negatively
charged sulfonate groups of the calixarene and the nitro- or chloro-groups of the guests 2a and 2b. The decrease in
repulsive interaction would be explained by the protonation of the sulfonate groups closest to the guest.
a
b
c
d
Figure 3. Top and side views of the equilibrium conformations of
calix[6]arene hexasulfonate phenol complexes. Calculations
were performed at DFT/B3LYP/6-31++G level considering the
solvent effect by the PCM (Polarizable Continuum Model)
method. The complexes of 2a-2d with 1 are depicted Fig. 4.a-4.d,
respectively.
Interaction energies between the host and guest
Figure 4 shows the calculated interaction energy values of the host-guest complexes in comparison with the appropriate measured Gibbs free energies and
entalpies. Hammett parameter is used as a quantitative peculiarity of the electron withdrawing and electron releasing feature of the substituents on the aromatic
ring of phenols. It can be clearly seen that the Gibbs free energy change, therefore the stability of the host-guest complex increases with the electron density of
the aromatic rings of the guest molecules. Note, that all thermodynamic values reflect to the formation of the complex, i.e. the values in the Figure 4 show the
Gibbs free energy of the complex (product) subtracted with the Gibbs free energy of the separated species (reactants). These values are negative. Since the
dependence of the enthalpy change on the mentioned electron density of the guest shows opposite tendency, the stability of the complex can be increased only if
the entropy would compensate the decrease of the enthalpy changes. However, the entropy change of the complex formation is also negative showing a more
ordered structure after the complex was formed. Consequently, the entropy term of the complexation decreases the complex stability. However, the entropy
change decreases fast with the electron density of the aromatic rings of the different guests and this change overcompensates the stability-decreasing effect of
enthalpy.
Consequences on the rotation of water molecules around the complex
~85
0
~265
0
Figure 4. The experimental Gibbs free energy (squares) and enthalpy (closed circles) changes, also the
calculated interaction energy (open circles), (left axis) and the measured entropy (triangles) changes
(right axis) obtained for the formation of the host-guest complexes as function of the Hammett
substituent constants. Experimental values were taken from the ref. 8.
The optimized structures of the host-guest complexes show that the phenol molecule entering into the calixarene cavity lies between the two aromatic rings of the
calix[6]arene (Figure 3). The three parallel aromatic rings form a sandwich-type structure. Results confirm that this structure is stabilized either by the p-p interaction or
by hydrogen bonds between the aromatic rings or the OH groups of the phenolic units of host and the guest, respectively. To obtain appropriate data for room temperature
(298 K), molecular dynamic calculations were performed by the AMBER forcefield. This forcefield is used since both the hydrogen bonding and the coulomb-type
interaction are parametrized quite correctly to the system studied here. For quantitative description, the angles of the C2 symmetry axis of water molecules, relating to the
directions perpendicular to the planes of the appropriate phenolic units of calixarene molecules, were collected during the simulation. The deviation from the average
values of these angles of five water molecules closest to the appropriate phenolic ring of calixarene were used to represent the freedom of water molecules around the
calixarene rings. It was found that the average
rotation of the water molecules is nearly three times less in the case when the p-nitrophenol guest with its electron
deficient
0
0
aromatic ring is entered into the cavity (85 ), while, for comparison, the average rotation value for the nearly neutral p-methylphenol was found to be 265 (Fig. 5). It
means, that the solvent water molecules, which lie in the outer side of the calixarene rings, has much higher ordered structure after the guest with charged phenolic unit is
entered into the cavity.
This observation is summarized on Figure 6. The Hammett parameter is used again to describe the electron releasing/withdrawing character of the substituents. The
observed rotation have shown, that water molecules coordinated to the calixarene-p-nitrophenol complex are much more hindered than that of the case of the calixarenep-methylphenol complex. These results are in good agreement with the experiments and therefore can be considered as a microscopic background of the unexpected
entropy change obtained experimentally on the same molecular systems.
References :
CONCLUSION
Figure 5. Schematic microscopic view of the entropy change during the complexation of
phenols by calixarene. Upper figure is about the complexation of p-nitrophenol, where the
aromatic ring of the guest molecule is positively charged due to the electron-withdrawing effect
of the nitro- group. Bottom figure relates to the complexation of phenol, where the aromatic ring
is nearly uncharged. The change in the electron density of the calixarene rings results in a higher
ordered structure in the former case. The average rotation of the water molecules reduces when
the guest having charged aromatic ring enters into the cavity.
Figure 6. The calculated average rotation of water molecules located closest to the calixarene
ring as function of the Hammett parameters related to the different guests entered into the
calixarene cavity.
Experimental investigation on the effect of electron density of the aromatic ring of
different phenol guest molecules during complexation with calix[6]arenehexasulfonate host has shown the significant role of the entropy change during
complex formation. According to the experiments, in this theoretical work the
interaction between the above host and guest molecules was studied by
DFT/B3LYP/6-31++G method and molecular dynamics simulation. The electron
density of the aromatic ring of the phenol derivatives was varied by replacing a
hydrogen atom in the para-position to the OH group with different electronwithdrawing groups, such as NO2, Cl, as well as CH3 groups. In all cases the
calculated interaction energies are comparable with the directly measured molar
enthalpy of inclusion process. Furthermore, the interaction of the calixarene with
the solvent molecules is modified when a guest molecule enters into the cavity.
The attractive force of water molecules towards the calixarene phenolic ring
preferably based on hydrogen bonding in case when p-methylphenol guest
molecule enters into the calixarene cavity. In the case of p-nitrophenol guest
probably the attractive coulomb-type interaction between the positively charged
aromatic ring of the calixarene and the lone pair electrons of the water molecules is
determinant in the stabilization of the water solvent molecules. As a result, the
increased interaction induced by the p-nitrophenol guest results that the rotation of
the water molecules is significantly hindered. As a consequence, a more ordered
structure is formed when the aromatic ring of the entering guest molecule is more
electron deficient. This property fits well to the experimental observation.
Overall, the calculated molecular properties of the complex formation show
Hammett-type correlation. These results are applicable in the development of
selective and sensitive chemical sensors for neutral organic aromatics.
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The financial support of the Hungarian Scientific Research Fund (OTKA
Grant TS044800) and that of the joint project of the European Union Hungarian National Development Program (Grant GVOP-3.2.1-2004-040200/3.0) is highly appreciated. Calculations were performed on SunFire
15000 supercomputer located in the Supercomputer Center of the
Hungarian National Infrastructure Development Program Office.