Intermolecular complexes of HXeOH with water: stabilization and destabilization effects

Theoretical and matrix-isolation studies of intermolecular complexes of HXeOH with water molecules are presented. The structures and possible decomposition routes of the HXeOH-(H(2)O)(n)(n = 0, 1, 2, 3) complexes are analyzed theoretically. It is concluded that the decay of these metastable species may proceed through the bent transition states (TSs), leading to the global minima on the respective potential energy surfaces, Xe + (H(2)O)(n+1). The respective barrier heights are 39.6, 26.6, 11.2, and 0.4 kcal/mol for n = 0, 1, 2, and 3. HXeOH in larger water clusters is computationally unstable with respect to the bending coordinate, representing the destabilization effect. Another decomposition channel of HXeOH-(H(2)O)(n), via a linear TS, leads to a direct break of the H-Xe bond of HXeOH. In this case, the attached water molecules stabilize HXeOH by strengthening the H-Xe bond. Due to the stabilization, a large blue shift of the H-Xe stretching mode upon complexation of HXeOH with water molecules is featured in calculations. On the basis of this computational result, the IR absorption bands at 1681 and 1742 cm(-1) observed after UV photolysis and annealing of multimeric H(2)O/Xe matrixes are assigned to the HXeOH-H(2)O and HXeOH-(H(2)O)(2) complexes. These bands are blue-shifted by 103 and 164 cm(-1) from the known monomeric HXeOH absorption.     

Exploring new 129Xe chemical shift ranges in HXeY compounds: hydrogen more relativistic than xenon

Among rare gases, xenon features an unusually broad nuclear magnetic resonance (NMR) chemical shift range in its compounds and as a non-bonded Xe atom introduced into different environments. In this work we show that (129)Xe NMR chemical shifts in the recently prepared, matrix-isolated xenon compounds appear in new, so far unexplored (129)Xe chemical shift ranges. State-of-the-art theoretical predictions of NMR chemical shifts in compounds of general formula HXeY (Y = H, F, Cl, Br, I, -CN, -NC, -CCH, -CCCCH, -CCCN, -CCXeH, -OXeH, -OH, -SH) as well as in the recently prepared ClXeCN and ClXeNC species are reported. The bonding situation of Xe in the studied compounds is rather different from the previously characterized cases as Xe appears in the electronic state corresponding to a situation with a low formal oxidation state, between I and II in these compounds. Accordingly, the predicted (129)Xe chemical shifts occur in new NMR ranges for this nucleus: ca. 500-1000 ppm (wrt Xe gas) for HXeY species and ca. 1100-1600 ppm for ClXeCN and ClXeNC. These new ranges fall between those corresponding to the weakly-bonded Xe(0) atom in guest-host systems (δ < 300 ppm) and in the hitherto characterized Xe molecules (δ > 2000 ppm). The importance of relativistic effects is discussed. Relativistic effects only slightly modulate the (129)Xe chemical shift that is obtained already at the nonrelativistic CCSD(T) level. In contrast, spin-orbit-induced shielding effects on the (1)H chemical shifts of the H1 atom directly bonded to the Xe center largely overwhelm the nonrelativistic deshielding effects. This leads to an overall negative (1)H chemical shift in the range between -5 and -25 ppm (wrt CH(4)). Thus, the relativistic effects induced by the heavy Xe atom appear considerably more important for the chemical shift of the neighbouring, light hydrogen atom than that of the Xe nucleus itself. The predicted NMR parameters facilitate an unambiguous experimental identification of these novel compounds.     

Participation of xenon guest in hydrogen bond network of β-hydroquinone crystal

In the β-hydroquinone (β-HQ)-Xe crystal, the Xe guest is placed between two hexagonal rings of coupled [···O-H···O-](6) H-bonds. This clathrate is treated as the model for monitoring the H-bonding system with the Xe participation. Three kinds of isotope effects due to the H/D substitution in the [···O-H···O-](6) bonds are considered: (i) structural changes in the clathrate (X-ray diffraction), (ii) variations of (129)Xe NMR signal of the guest (CP MAS), and (iii) variations of selected vibrations of the host (IR). This study predicts subtle inclination of every other hydroxyl group of the [···O-H···O-](6) rings into the Xe atom and formation of six Xe···H-O pairs in every cage, the frequency shift of the γOH mode due to these contacts, -ΔγOH(Xe···H) > 74 cm(-1), as well as the enthalpy formation, -ΔH(Xe···H) > 6-8 kJ mol(-1). Our IR results reveal a tendency of the Xe atom to form the H-bond-like network inside its cage and much weaker Xe···D-O interactions in the H/D substituted crystal. The (129)Xe NMR results do not reflect this kind of interactions due to averaging of the (129)Xe shielding phenomena, probably. We also predict elongation of the O···O distances due to the β-HQ-Xe crystal heating and the Xe escape.     

Theoretical predictions of nuclear magnetic resonance parameters in a novel organo-xenon species: chemical shifts and nuclear quadrupole couplings in HXeCCH

We calibrate the methodology for the calculation of nuclear magnetic resonance (NMR) properties in novel organo-xenon compounds. The available state-of-the-art quantum-chemical approaches are combined and applied to the HXeCCH molecule as the model system. The studied properties are (129)Xe, (1)H, and (13)C chemical shifts and shielding anisotropies, as well as (131)Xe and (2)H nuclear quadrupole coupling constants. The aim is to obtain, as accurately as currently possible, converged results with respect to the basis set, electron correlation, and relativistic effects, including the coupling of relativity and correlation. This is done, on one hand, by nonrelativistic correlated ab initio calculations up to the CCSD(T) level and, on the other hand, for chemical shifts and shielding anisotropies by the leading-order relativistic Breit-Pauli perturbation theory (BPPT) with correlated ab initio and density-functional theory (DFT) reference states. BPPT at the uncorrelated Hartree-Fock level as well as the corresponding fully relativistic Dirac-Hartree-Fock method are found to be inapplicable due to a dramatic overestimation of relativistic effects, implying the influence of triplet instability in this multiply bonded system. In contrast, the fully relativistic second-order Moller-Plesset perturbation theory method can be applied for the quadrupole coupling, which is a ground-state electric property. The performance of DFT with various exchange-correlation functionals is found to be inadequate for the nonrelativistic shifts and shielding anisotropies as compared to the CCSD(T) results. The relativistic BPPT corrections to these quantities can, however, be reasonably predicted by DFT, due to the improved triplet excitation spectrum as compared to the Hartree-Fock method, as well as error cancellation within the five main BPPT contributions. We establish three computationally feasible models with characteristic error margins for future calculations of larger organo-xenon compounds to guide forthcoming experimental NMR efforts. The predicted (129)Xe chemical shift in HXeCCH is in a novel range for this nucleus, between weakly bonded or solvated atomic xenon and xenon in the hitherto characterized molecules.     

Quantum chemical study of the hydrogen-bonded HXeOH–H2O complex

A combined MP2 and DFT/B3LYP study of the HXeOH–H₂O complex is presented. These computational methods have been used to extract information on the structural, energetical and vibrational properties of the complex. Additionally, we have applied anharmonic vibrational calculations based on the MP2-computed intermolecular potential energy surface. Large perturbations both on the subunit structures and their fundamental vibrational modes are found upon complexation. Large changes of anharmonicity of the HXeOH subunit reflects the perturbation of the molecule's electronic structure. The computed BSSE-corrected interaction energies are −40.23 and −38.94 kJ mol⁻¹ at the CCSD(T)//MP2 and CCSD(T)//B3LYP levels of theory, respectively. The estimated deformation energy contribution to the interaction energy is about 5%, which is very large compared with classical hydrogen-bonded complexes. The topological analysis of the Electron Localization Function (ELF) was applied to study further the hydrogen-bonded interaction between the two complex partners. The obtained interaction pattern suggests that the interaction between HXeOH and H₂O is a typical hydrogen bond interaction driven mainly by electrostatic interactions.     

Studies on the structure, stability, and spectral signatures of hydride ion-water clusters

The gas-phase structure, stability, spectra, and electron density topography of H(-)W(n) clusters (where n = 1-8) have been calculated using coupled-cluster CCSD(T) and M?ller-Plesset second-order perturbation (MP2) theory combined with complete basis set (CBS) approaches. The performance of various density functional theory (DFT) based methods such as B3LYP, M05-2X, M06, M06-L, and M06-2X using 6-311++G(d,p), and aug-cc-pVXZ (aVXZ, where X = D, T, and Q) basis sets has also been assessed by considering values calculated using CCSD(T)/CBS limit as reference. The performance of the functionals has been ranked based on the mean signed/unsigned error. The comparison of geometrical parameters elicits that the geometrical parameters predicted by B3LYP/aVTZ method are in good agreement with those values obtained at MP2/aVTZ level of theory. Results show that M05-2X functional outperform other functionals in predicting the energetics when compared to CCSD(T)/CBS value. On the other hand, values predicted by M06-2X, and M06 methods, are closer to those values obtained from MP2/CBS approach. It is evident from the calculations that H(-)W(n) (where n = 5-8) clusters adopt several interesting structural motifs such as pyramidal, prism, book, Clessidra, cubic, cage, and bag. The important role played by ion-water (O-H···H(-)) and water-water (O-H···O) interactions in determining the stability of the clusters has also been observed. Analysis of the results indicates that the most stable cluster is made up of minimum number of O-H···H(-) interaction in conjugation with the maximum number of O-H···O interactions. The Bader theory of atoms in molecules (AIM) and natural bond orbital (NBO) analyses has also been carried out to characterize the nature of interactions between hydride ion and water molecules. It can be observed from the vibrational spectra of H(-)W(n) clusters, the stretching frequencies involving ion-water interaction always exhibit larger redshift and intensities than that of water-water (inter solvent) interactions.     

Effects of a single water molecule on the OH + H2O2 reaction

The effect of a single water molecule on the reaction between H(2)O(2) and HO has been investigated by employing MP2 and CCSD(T) theoretical approaches in connection with the aug-cc-PVDZ, aug-cc-PVTZ, and aug-cc-PVQZ basis sets and extrapolation to an ∞ basis set. The reaction without water has two elementary reaction paths that differ from each other in the orientation of the hydrogen atom of the hydroxyl radical moiety. Our computed rate constant, at 298 K, is 1.56 × 10(-12) cm(3) molecule(-1) s(-1), in excellent agreement with the suggested value by the NASA/JPL evaluation. The influence of water vapor has been investigated by considering either that H(2)O(2) first forms a complex with water that reacts with hydroxyl radical or that H(2)O(2) reacts with a previously formed H(2)O·OH complex. With the addition of water, the reaction mechanism becomes much more complex, yielding four different reaction paths. Two pathways do not undergo the oxidation reaction but an exchange reaction where there is an interchange between H(2)O(2)·H(2)O and H(2)O·OH complexes. The other two pathways oxidize H(2)O(2), with a computed total rate constant of 4.09 × 10(-12) cm(3) molecule(-1) s(-1) at 298 K, 2.6 times the value of the rate constant of the unassisted reaction. However, the true effect of water vapor requires taking into account the concentration of the prereactive bimolecular complex, namely, H(2)O(2)·H(2)O. With this consideration, water can actually slow down the oxidation of H(2)O(2) by OH between 1840 and 20.5 times in the 240-425 K temperature range. This is an example that demonstrates how water could be a catalyst in an atmospheric reaction in the laboratory but is slow under atmospheric conditions.     

Structure and stability of xenon insertion compounds of hypohalous acids, HXeOX [X=F, Cl, and Br]: an ab initio investigation

The structure and stability of xenon-inserted hypohalous acids HXeOX (X=F, Cl, and Br) have been investigated theoretically using ab initio molecular orbital calculations. All these molecules are found to consist of a nearly linear HXeO moiety and a bend XeOX fragment. Geometrical parameters of HXeOX are comparable with that of experimentally observed HXeOH species. The dissociation energies corresponding to the lowest-energy fragmentation products, HOX+Xe have been computed to be -398.1, -385.5, and -386.7 kJmol for HXeOF, HXeOCl, and HXeOBr, respectively, at the MP2 level of theory. The respective barrier heights corresponding to the bent transition states (H-Xe-O bending mode) have been calculated to be 138.1, 138.4, and 138.2 kJmol with respect to HXeOX minimum. These species are found to be metastable in their respective potential-energy surface, and the dissociation energies corresponding to the H+Xe+OX products are found to be 56.8, 66.0, and 80.8 kJmol for HXeOF, HXeOCl, and HXeOBr, respectively. The energies corresponding to the H+Xe+O+X dissociation channel have been computed to be 272.0, 309.3, and 299.7 kJmol for HXeOF, HXeOCl, and HXeOBr, respectively, at the same level of theory. Energetics as well as geometrical considerations suggests that it may be possible to prepare these species experimentally similar to that of HXeOH species at low-temperature laser photolysis experiments.     

Electron affinities of uracil: microsolvation effects and polarizable continuum model

We present adiabatic electron affinities (AEAs) and the vertical detachment energies (VDEs) of the uracil molecule interacting with one to five water molecules. Credibility of MP2 and DFT/B3LYP calculations is supported by comparison with available benchmark CCSD(T) data. AEAs and VDEs obtained by MP2 and DFT/B3LYP methods copy trends of benchmark CCSD(T) results for the free uracil and uracil-water complexes in the gas phase being by 0.20 - 0.28 eV higher than CCSD(T) values depending on the particular structure of the complex. AEAs and VDEs from MP2 are underestimated by 0.09-0.15 eV. For the free uracil and uracil-(H(2)O)(n) (n = 1,2,3,5) complexes, we also consider the polarizable continuum model (PCM) and discuss the importance of the microsolvation when combined with PCM. AEAs and VDEs of uracil and uracil-water complexes enhance rapidly with increasing relative dielectric constant (ε) of the solvent. Highest AEAs and VDEs of the U(H(2)O)(5) complexes from B3LYP with ε = 78.4 are 2.03 and 2.81 eV, respectively, utilizing the correction from CCSD(T). Specific structural features of the microsolvated uracil-(H(2)O)(n) complexes and their anions are preserved also upon considering PCM in calculations of AEAs and VDEs.     

DFT study of the NMR properties of xenon in covalent compounds and van der waals complexes-implications for the use of 129Xe as a molecular probe

The NMR properties (chemical shift and spin-spin coupling constants) of (129)Xe in covalent compounds and weakly bound complexes have been investigated by DFT methods including relativistic effects. For covalent species, a good agreement between experimental and calculated results is achieved without scalar relativistic effects, but their inclusion (with a triple-zeta, double-polarization basis set) leads to some improvement in the quality of the correlation. The spin-orbit coupling term has a significant effect on the shielding constant, but makes a small contribution to the chemical shift. Coupling constants contain substantial contributions from the Fermi contact and paramagnetic spin-orbit terms; unlike light nuclei the spin-dipole term is also large, whereas the diamagnetic spin-orbit term is negligible. For van der Waals dimers, the dependence of the xenon chemical shift and anisotropy is calculated as a function of the distance. Small (<1 Hz) but non-negligible through-space coupling constants between (129)Xe and (13)C or (1)H are predicted. Much larger couplings, of the order of few Hz, are calculated between xenon and (17)O in a model silicate residue.     

Theoretical investigation of the binding energies of the iodide ion and xenon atom with decaborane

The interaction of decaborane (B(10)H(14)) with the I(-) ion and the (isoelectronic) Xe atom is investigated using a number of theoretical methods: MP2, CCSD(T), CCSD, spin-orbit CISD, and DFT using the B3LYP, B3PW91, PW91PW91, and PBE0 methods. All non-DFT and some DFT methods agree that B(10)H(14)I(-) is bound by charge-dipole electrostatic forces, charge- and dipole-induced-dipole forces, and dispersion forces, while B(10)H(14)Xe is bound by dipole-induced-dipole forces and dispersion forces. Counterpoise corrections are necessary to obtain reliable results. Relativistic effective core potentials were used for the I, Xe, and B atoms. Basis sets for use with these potentials are discussed as is the question of basis set balance in molecules. We find B(10)H(14)I(-) to be bound by 19.8 kcal/mol and B(10)H(14)Xe by 1.1 kcal/mol, indicating that the charge and polarizability of I(-) play the major role in the interaction energy.     

Theoretical study of the 1:1 and 2:1 (homo- and heterochiral) complexes of XOOX' (X, X' = H, CH3) with lithium cation

A theoretical study of the 1:1 and 2:1 complexes of XOOX' (X, X' = H, CH(3)) with the lithium cation has been carried out by means of ab initio computational methods up to the MP2/aug-cc-pVTZ level. The optical rotatory power and NMR parameters (absolute chemical shielding and indirect coupling constants) have been calculated. In addition, the racemization barriers within the complexes formed have been evaluated. Special attention has been paid concerning the differences between the 2:1 homo- and heterochiral complexes.     

Interaction of dihydrogen with small and light molecules

Second-order M?ller-Plesset (MP2) calculations (using the approximate resolution of the identity, RI-MP2), explicitly correlated MP2 (MP2-R12) calculations, and coupled-cluster calculations including all single and double excitations with a perturbative estimate of triple excitations [CCSD(T)] are performed to study the interaction of molecular hydrogen with the small molecules HF, H2O, NH3, and LiOH. Different adsorption positions are studied. In the cases of H2O and NH3, the most favorable configuration places H2 in an end-on fashion on the O or N atom, respectively. In the cases of HF and LiOH, the H2 molecule takes a side-on position on the H atom of HF or the Li atom. With respect to MP2 calculations in a triple-zeta basis, both the enlargement of the basis set and the extension of the correlation treatment (CCSD(T) vs MP2) increase the interaction energy. The basis set limit CCSD(T) estimates of the interaction energy of H2 with the HF, H2O, NH3, and LiOH molecules amount to 4.40, 2.67, 3.02, and 10.74 kJ mol-1, respectively. The interaction energy for the simultaneous interaction of H2 with two LiOH molecules does not significantly exceed the value obtained for the interaction with a single LiOH molecule. Furthermore, the interaction energies (by MP2) of H2 with glycine, the glycine dimer, and imidazolium chloride amount to 2.78, 5.00, and 6.30 kJ mol-1, respectively.     

Interfacing Q-Chem and CHARMM to perform QM/MM reaction path calculations

A hybrid quantum mechanical/molecular mechanical (QM/MM) potential energy function with Hartree-Fock, density functional theory (DFT), and post-HF (RIMP2, MP2, CCSD) capability has been implemented in the CHARMM and Q-Chem software packages. In addition, we have modified CHARMM and Q-Chem to take advantage of the newly introduced replica path and the nudged elastic band methods, which are powerful techniques for studying reaction pathways in a highly parallel (i.e., parallel/parallel) fashion, with each pathway point being distributed to a different node of a large cluster. To test our implementation, a series of systems were studied and comparisons were made to both full QM calculations and previous QM/MM studies and experiments. For instance, the differences between HF, DFT, MP2, and CCSD QM/MM calculations of H2O...H2O, H2O...Na+, and H2O...Cl- complexes have been explored. Furthermore, the recently implemented polarizable Drude water model was used to make comparisons to the popular TIP3P and TIP4P water models for doing QM/MM calculations. We have also computed the energetic profile of the chorismate mutase catalyzed Claisen rearrangement at various QM/MM levels of theory and have compared the results with previous studies. Our best estimate for the activation energy is 8.20 kcal/mol and for the reaction energy is -23.1 kcal/mol, both calculated at the MP2/6-31+G(d)//MP2/6-31+G(d)/C22 level of theory.     

An ab initio study of van der Waals potential energy parameters for silver clusters

We employ ab initio calculations of van der Waals complexes to study the potential energy parameters (C(6) coefficients) of van der Waals interactions for modeling of the adsorption of silver clusters on the graphite surface. Electronic structure calculations of the (Ag(2))(2), Ag(2)-H(2), and Ag(2)-C(6)H(6) complexes are performed using a coupled-cluster approach that includes single, double, and perturbative triple excitations (CCSD(T)), M?ller-Plesset second-order perturbation theory (MP2), and spin-component-scaled MP2 (SCS-MP2) methods. Using the atom pair approximation, the C(6) coefficients for silver-silver, silver-hydrogen, and silver-carbon atom systems are obtained after subtracting the energies of quadrupole-quadrupole interactions from the total electronic energy.     

Calculated spectroscopic and electric properties of the alkali metal-ammonia complexes from Kn-NH3 to Frn-NH3 (n=0,+1)

The newly developed Stuttgart small-core scalar relativistic pseudopotentials for the alkali metals are used to study spectroscopic and electric properties of the heavier alkali metal-ammonia complexes from K(n)-NH(3) to Fr(n)-NH(3) (n=0,+1) at the second-order Moller-Plesset (MP2) and coupled cluster [CCSD(T)] levels of theory. Equilibrium geometries and dissociation energies computed at the MP2 level are in reasonable agreement with their CCSD(T) counterparts, whereas for the dipole polarizabilities MP2 is not performing well overestimating significantly electron correlation effects. The bond distances increase monotonically with increasing mass of the metal atom as relativistic effects are small in these systems. However, the dipole polarizabilities are more sensitive to such effects and we find a decrease in this property from Cs-NH(3) to Fr-NH(3). Combination of CCSD(T) harmonic frequencies and MP2 anharmonic corrections obtained from a perturbative vibrational treatment leads to fundamental frequencies in good agreement with experimental results obtained by Suzer and Andrews [J. Am. Chem. Soc. 109, 300 (1986)]. We also present the results of variational calculations with a three-dimensional vibrational Hamiltonian, making use of CCSD(T) potential energy and electric dipole moment surfaces. Complexation of NH(3) to the metal causes a strong infrared intensification of the symmetric NH(3) stretching mode in the neutral complexes, which is absent in the charged species.     

Normal halogen dependence of 13C NMR chemical shifts of halogenomethanes revisited at the four‐component relativistic level

The ‘Normal Halogen Dependence’ of ¹³C NMR chemical shifts in the series of halogenomethanes is revisited at the four‐component relativistic level. Calculations of ¹³C NMR chemical shifts of 70 halogenomethanes have been carried out at the density functional theory (DFT) and MP2 levels with taking into account relativistic effects using the four‐component relativistic theory of Dirac‐Coulomb within the different computational methods (4RPA, 4OPW91) and hybrid computational schemes (MP2 + 4RPA, MP2 + 4OPW91). The most efficient computational protocols are derived for practical purposes. Relativistic shielding effect reaches as much as several hundreds of ppm for heavy halogenomethanes, and to account for this effect in comparison with experiment at the qualitative level, relativistic Dyall's basis sets of triple‐zeta quality or higher are to be used within the framework of the four‐component relativistic theory taking into account solvent effects. Relativistic geometrical optimization (as compared with the non‐relativistic level) is essential for the molecules containing at least two iodines at one carbon atom. Copyright © 2016 John Wiley & Sons, Ltd.     

Halogen bonded complexes between volatile anaesthetics (chloroform, halothane, enflurane, isoflurane) and formaldehyde: a theoretical study

The structures and intermolecular interactions in the halogen bonded complexes of anaesthetics (chloroform, halothane, enflurane and isoflurane) with formaldehyde were studied by ab initio MP2 and CCSD(T) methods. The CCSD(T)/CBS calculated binding energies of these complexes are between -2.83 and -4.21 kcal mol(-1). The largest stabilization energy has been found for the C-Br···O bonded halothane···OCH(2) complex. In all complexes the C-X bond length (where X = Cl, Br) is slightly shortened, in comparison to a free compound, and an increase of the C-X stretching frequency is observed. The electrostatic interaction was excluded as being responsible for the C-X bond contraction. It is suggested that contraction of the C-X bond length can be explained in terms of the Pauli repulsion (the exchange overlap) between the electron pairs of oxygen and halogen atoms in the investigated complexes. This is supported by the DFT-SAPT results, which indicate that the repulsive exchange energy overcompensates the electrostatic one. Moreover, the dispersion and electrostatic contributions cover about 95% of the total attraction forces, in these complexes.     

CH···π interactions do not contribute to hydrogen transfer catalysis by glycerol dehydratase

The role of the nonbonded CH···π interaction in the hydrogen abstraction from glycerol by the coenzyme B(12)-independent glycerol dehydratase (GDH) was examined using the QM/MM (ONIOM), MP2, and CCSD(T) methods. The studied CH···π interaction included the hydrogen atom of the -C(2)H(OH)- group of the glycerol substrate and the tyrosine-339 residue of the dehydratase. A contribution of this interaction to the stabilization of the transition state for the transfer of a hydrogen atom from the adjacent terminal C(1)H(2)(OH) group to cysteine 433 was determined by ab initio HF, MP2, and CCSD(T) calculations with the aug-cc-pvDZ basis set for the corresponding methane/benzene, methanol/phenol, and glycerol radical/phenol subsystems. The calculated CH···π distance, defined as the distance between the H atom and the center of the phenol ring, shortened from 2.62 to 2.52 ? upon going from the ground- to the transition-state of the GDH-catalyzed reaction. However, this shortening was not accompanied by the expected lowering of the CH···π interaction free energy. Instead, this interaction remained weak (about -1 kcal/mol) along the entire reaction coordinate. Additionally, the mutual orientation of the CH group and the phenol ring did not change significantly during the reaction. These results suggest that the phenol group of the tyrosine-339 does not contribute to lowering the activation barrier in the enzyme, but do not exclude the possibility that tyrosine 339 facilitates proper orientation of glycerol for the electrostatic catalysis, or inhibits side-reactions of the reactive glycerol radical intermediate.