Methanol Solvation Effect on the Proton ... - ACS Publications

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Methanol Solvation Effect on the Proton Rearrangement of Curcumin’s Enol Forms: An Ab Initio Molecular Dynamics and Electronic Structure Viewpoint Lauriane G. Santin,†,‡ Eduardo M. Toledo,† Valter H. Carvalho-Silva,*,† Ademir J. Camargo,† Ricardo Gargano,‡ and Solemar S. Oliveira*,† †

Universidade Estadual de Goiás, Campus de Ciências Exatas e Tecnológicas, Grupo de Química Teórica e Estrutural de Anápolis, 75001-970 Anápolis, Brazil ‡ Universidade de Brasília, Instituto de Física, 70904-970 Brasília, Brazil S Supporting Information *

ABSTRACT: The recognition of the solvent effect on the enol−enol tautomerism in curcumin can guide the rationalization of systems of chemical and biological interest. Although the phenomenon is widely studied, the nature of the proton rearrangement involving the explicit solvation remains an important issue. In this study, we describe the phenomenon by an ab initio approach in gas-phase and methanol solution. The mechanism involved in the proton rearrangement has been investigated by Car− Parrinello molecular dynamics and the static M062X/DFT method. The free-energy landscape and potential energy surface in the methanol environment were explored and compared with the gas-phase one. The energy profile in methanol medium shows asymmetrical proton distribution in the curcumin enol forms and, inversely, a symmetrical behavior in the gas phase. The Gilli π-delocalization index and the HOMO orbital shape show a slight decrease in the resonance-assisted hydrogen bond (RAHB) in the solvated enol forms, different from the gas-phase system. The thermal rate constant of the intramolecular proton transfer indicated that the tunneling effect plays an important role when the curcumin molecule is under the influence of methanol. These results suggest a criterion to characterize the symmetry of the potential energy profile for the intramolecular proton transfer.

1. INTRODUCTION The enormous literature on the intramolecular proton transfer indicates a highly challenging topic in chemical processes. Proton rearrangement is particularly important in chemistry, medicine, pharmacology, and molecular biology, where it plays a rate-determining step reaction role in organic synthesis and in biochemical and enzymatic mechanisms.1−4 Special attention has been given to the keto−enol tautomerism, specifically in the intramolecular enol forms of β-diketones.5−13 Several papers have recognized the potential role of enol−enol equilibrium in anti-inflammatory, anticancer, antioxidant activities and in amyloid aggregation.14−21 In refs 16 and 22, experimental and theoretical results suggest that curcumin, a prototypical system of enol−enol tautomerization, inhibits formation of amyloid aggregates, supporting its rational use in clinical trials for preventing or treating Alzheimer’s disease. Moreover, these studies indicate that the unique charge and bonding characteristics of the enol form of curcumin facilitate its penetration into the blood−brain barrier and binding to amyloid. One common drawback associated with enol forms of curcumin is the shape of the potential energy profile. Substantial differences in the potential energy profile in different states of matter have instigated a debate about the dependent parameters involved with this behavior. A series of © XXXX American Chemical Society

papers discussed the influence of the resonance-assisted hydrogen bonds, excited state, tunneling, and solvent effects of this behavior in curcumin-like molecules; however, no consensus has been reached.5,8,11−13,23 There is a need for a greater understanding of the influence of the solvent effect on the symmetries of hydrogen bonds in enol forms. The solvent has an important effect on the formation of tautomers because it can interact with the donor and acceptor of the curcumins. A substantial amount of literature about this subject suggests hydrogen bond asymmetries in solution since the position of the hydrogen is always located on the less solvated oxygen. A similar environment around the β-diketone group in solution does not guarantee proton equidistribution considering that the solution is a disorganized system.12,23 Perrin and co-workers8,23 present several works describing experimental techniques to justify the role of the liquid environment on the symmetry of the hydrogen bonds in enol forms in maleate, phthalate, succinic, and naphthalenediamine anions. More recently, Hupper24,25 employed photophysical techniques to study the Received: March 7, 2016 Revised: August 8, 2016

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DOI: 10.1021/acs.jpcc.6b02393 J. Phys. Chem. C XXXX, XXX, XXX−XXX

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The Journal of Physical Chemistry C luminescence of curcumin in methanol and ethanol, and he found a connection between the luminescence and proton rearrangement in the excited state. Considering the limited number of computational studies of the intramolecular proton transfer in explicit solvent, in this paper we have described the enol−enol tautomerism in the curcumin molecule in the gas phase and methanol solution employing ab initio molecular dynamic and static M062X/DFT simulations. In both approaches, the one-dimensional potential energy profiles of proton rearrangement were described, and the methanol effect on the relative energy profile and geometric parameters in synchronization with a breakdown of the symmetry in the gas phase was discussed. The quantum tunneling effect on the thermal rate constant of conversion between the enolic forms was not neglected, and transition state theory with tunneling corrections was applied to quantify the low barrier at low temperature.

Figure 1. Curcumin and methanol molecular structures and labels. The blue box highlights the intramolecular proton transfer region, and the red box highlights the anchorage of methanol in the curcumin molecule.

intramolecular proton transfer static DFT calculations. Considering how cost-consuming the calculations were, frames of the parallelepiped box were selected that contained only one and two molecules of methanol interacting with one curcumin molecule (see Figure 1; Figures S4 and S5 in SI). All the electronic structure properties of the reactants, products, and transition state were calculated at the M062X/6-31+G* level.37 The stationary points were characterized with analytic harmonic frequency calculations. The absence and existence for one imaginary frequency characterize the optimized structures as a local minimum and transition state, respectively. The quantum chemistry calculations reported in this study were carried out with Gaussian 09.38 Reaction Rate Procedure. The kinetic thermal rate constants (k) were calculated by transition state theory (TST) given by the following equation

2. COMPUTATIONAL PROCEDURES Molecular Dynamics Procedure. The ab initio Car− Parrinello molecular dynamics (CPMD) simulations were carried out using the CP code implemented in the quantum ESPRESSO package version 4.3.1.26−31 The electronic structure was treated within the generalized gradient approximation to density functional theory (DFT), through the Perdew−Burke−Ernzerhof (PBE) exchange-correlation functional.32 Vanderbilt ultrasoft pseudopotentials were employed to represent core−valence electron interactions.33 A plane-wave basis set was used to expand the valence electronic wave function with an energy cutoff of 25 Ry. The equations of motion were integrated using the Verlet scheme with a time step of 5 au (0.121 fs), and the wave function fictitious mass (μ) was set to be 400 au. The boundary conditions and the canonical ensemble NVT were considered in the study. The temperature of the ionic system was controlled by the Nose− Hoover thermostat scheme, to maintain the temperature around 300 K.34 The initial molecular configuration for two systems was regenerated randomly, and it was optimized by the nonlinear conjugate gradient method. The proton distribution in the β-diketone group in the explicit methanol is guaranteed with greater time simulation; i.e., a larger simulation time was needed for an equilibration of the system. A liquid environment simulation using methanol solvent guarantees exclusively the enol form.35 In our simulations, we built two boxes under periodic boundary conditions: (i) a cubic box of 27 Å3 dimensions with one curcumin molecule (C21H20O6), with a simulation time of 30 ps and (ii) a parallelepiped box of 10 × 10 × 22 Å3 dimensions with one curcumin molecule (C21H20O6) and 29 methanol molecules (CH4O), which are significant to resemble a solvated system36 with a simulation time of 48.4 ps. Concerning the number of methanol molecules, three different systems were tested, and we chose a box with 29 methanol molecules as previously described (see details of other systems in SI). The calculated Helmholtz free energy surface was obtained by the trajectory data in the configuration range currently sampled as F = −kBT ln[P(Δr)], where kB is Boltzmann constant, T the simulated temperature, and P(Δr) the proton distribution as a function of reaction coordinate Δr = rO2−H1 − rO6−H1 (see Figure 1) as calculated from the molecular dynamics simulations. Δr = 0 indicates the midpoint of the proton position in the H-bond. Static DFT Procedure. We selected one frame of each system calculated with CPMD simulation to proceed with

kTST =

⎛ E ⎞ kBT QTS† exp⎜ − 0 ⎟ h Q Reac ⎝ kBT ⎠

(1)

where kB is the Boltzmann’s constant; h is the Planck constant; T is the temperature; and E0 is the height barrier. QReac and QTS† are the partition functions of the reactant and transition state, respectively. In order to include quantum tunneling effects along the reaction coordinate into our treatment, the tunneling Wigner (κW),39 Bell 1935 (κB0),40 and Bell 1958 (κB1 and κB2)40 tunneling correction and deformed theory (d-TST)41−44 are used as follows κW = 1 +

κ B0 =

2 1 ⎛ hv† ⎞ ⎜ ⎟ 24 ⎝ kBT ⎠

⎡ E0 ⎢⎣ hv† −

E0 (E0 / kBT − E0 / hv†)⎤ e ⎥⎦ kBT

( − ) ) ) ) − Ee ) ( E0

hv†

κ B1

κ B2

B

hv† 2kBT

( = sin( ( = sin(

(2)

E0 kBT

(3)

hv† 2kBT †

hv 2kBT

hv† 2kBT

0

(4)

(E0 / kBT − E0 / hv†)

E0kBT hv†

− E0

)

(5)


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The Journal of Physical Chemistry C

Figure 2. Time evolution of bond length in C5−O6, C4−C5, C3−C4, O2−C3, O2−O6, O2−H1, and O6−H1 using the CPMD method (a) in the gas phase and (c) with explicit methanol. Time evolution of bonds involved in the intramolecular proton transfer calculated at 300 K using the CPMD method (b) in the gas phase and (d) with explicit methanol.

kTST =

1/ d E ⎞ kBT QTS† ⎛ ⎜1 − d 0 ⎟ , kBT ⎠ h Q Reac ⎝

2 1 ⎛ hv† ⎞ d=− ⎜ ⎟ 3 ⎝ 2E0 ⎠

oscillates between O2 and O6 sites with equal distribution in the gas phase. For the curcumin system in methanol (Figures 2c and 2d) the H1 also oscillates between O2 and O6 sites, but it has preference for the O2 site, where it remains for a total time of about 32 ps and has an average bond length of 1.18 Å. The H1 also remains at the O6 site for about 13 ps, and it has an average hydrogen bond length of 1.36 Å. A breakdown of the symmetry in the proton distribution is observed between oxygens from the β-diketone group due to the anchoring of the methanol in the O6 site of curcumin. This result suggests that there is a lower potential barrier. Figures 2a and 2c also present the bond lengths between the heavy atoms of the β-diketone group, with a slight variation in the gas phase and in explicit methanol. The major changes in the geometric parameters are observed in the region of the intramolecular proton transfer. Figures 2b and 2d show the time evolution of the reaction coordinate (Δr), where we can clearly observe the H1 position during the simulations. From these figures, we observed symmetric and asymmetric distributions of the proton positions between the two sites in the gas phase and in explicit methanol, respectively.

(6) †

where v is the imaginary frequency for crossing the barrier. The crossover temperature, Tc = ℏv†/kB, is the parameter that delimits the degree of tunneling regimes: negligible (T > 4Tc), moderate (Tc < T < 2Tc), and deep (T < Tc).45 A definition of a validity temperature, Td = Tc + d E/2kB, delimits the applicability of deformed theory (d-TST) within the negligible or moderate tunneling regimes.41,46

3. RESULTS AND DISCUSSION 3.1. Geometric and Ressonance-Assisted Parameters. In Figures 2a−d, we present the time evolution of the interatomic distances in the β-diketone region and the reaction coordinate, Δr, in the gas phase and in the explicit methanol. When we evaluated the trajectory of curcumin enol during the CPMD simulation in vacuum, the formation of the intramolecular proton transfer O6−H1···O2/O6···H1−O2 is clearly observed. From Figure 2a and 2b, one can see that the H1 C


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Figure 3. π-Delocalization indexes (Λ and Q) versus rO2−O6 from CPMD simulations (a) in the gas phase and (b) in explicit methanol. HOMO orbital in the intramolecular proton transfer region of the transition state of curcumin calculated at the M062X/6-31+G* level (c) in the gas phase and (d) in explicit methanol.

Figures 2(a) and 2(d)), we find the following values for Q and Λ: 0 Å and 0.5 in the gas phase and +0.02 Å and 0.49 with explicit methanol, respectively. It is important to point out that these delocalization indexes are very similar to that obtained at the static M062X/6-31+G* calculation with explicit methanol: Q = +0.03 Å and Λ = 0.485 (see bond lengths in Table S1 in the Supporting Information). In the gas phase the indexes obtained at the M062X/6-31+G* level are exactly equal to that obtained with CPMD simulations. The π-delocalized character in the β-diketone cycle undergoes a disturbance because of the significant interaction between the methanol and the βdiketone group of the curcumin. The decrease in the πdelocalized character can also be visualized in the asymmetric distribution of the HOMO orbital in O6 interacting with methanol (see Figures 3(c) and 3(d)). The presence of the hydrogen bond mediated by the methanol stabilizes the O6 atom, and consequently, it modifies the resonance distribution of the HOMO orbital. Thus, we can suggest that the intramolecular hydrogen bond in the curcumin can be designed as a RAHB system. However, this behavior presents a decrease in solvated enol forms. The intramolecular hydrogen bond strength, EH‑bond, can corroborate the RAHB in the system; however, its estimation is not trivial. A consensus opinion considers that strong (EH‑Bond = 12−24 kcal mol−1 and 2.50 Å ≤ rO2−O6 ≤ 2.65 Å) and very strong H-bonds (EH‑Bond > 24 kcal mol−1 and rO2−O6 < 2.50 Å) can occur due to rigorous intramolecular charge-assisted or resonance-assisted phenomena.11 A simple empirical formula proposed by ref 48, EH‑Bond = (5.554 × 105)e−4.12 rO2−O6, can be

The effect of solvent on the intramolecular proton mobility in the β-diketone group is observed by the geometrical parameter evolution. Another parameter affected by the solvent effect is the π-conjugated bonds, a cooperativity phenomenon around the hydrogen bond, named the resonance-assisted hydrogen bond (RAHB).11,47 This phenomenon can be analyzed through the Gilli π-delocalization indexes which are defined as Λ=

Q ⎞ 1⎛ ⎜1 − ⎟, ⎝ 2 0.32 ⎠

Q = (rO2 − C3 − rC5 − O6) + (rC4 − C5 − rC3 − C4)

(7)

where rO2−C3, rC5−O6, rC4−C5, and rC3−C4 are the bond lengths presented in Figure 1. According to ref 47, the β-diketone group assumes fully πdelocalized structure (hydrogen bonding forms a continuous cycle in the β-diketone group) when Q = 0 and completely localized structure (hydrogen forms a stable bond with a donator atom in the diketone group) when Q = −0.32 or +0.32 Å. As a consequence of eq 7, Λ = 0.5 indicates π-delocalized structure, and Λ = 0 or 1 indicates localized structure. From CPMD simulations, we obtained Q and Λ values with rO2−O6 dependence in the gas phase and with explicit methanol, as shown in Figures 3(a) and 3(b). The Q and Λ distributions have a symmetric behavior in the gas phase, whereas an asymmetry behavior is observed in the presence of methanol. Considering the average bond lengths for ri, with i = C5−O6, C4−C5, C3−C4, O2−C3, O2−O6, O2−H1, and O6−H1, (see D


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Figure 4. Relative energy profile (kcal mol−1) of the intramolecular proton transfers calculated at PBE/plane-waves level by CPMD simulations (a) in the gas phase and (b) with explicit methanol and calculated at the M062X/6-31+G* level (c) in the gas phase and (d) with explicit methanol.

oxygens from the β-diketone group during the molecular dynamics simulation. However, there is a preference for the O6 site, and this solvation process induces asymmetric behavior from the energy wells. The symmetric methanol distribution around the β-diketone group needs an organized and specific anchoring, and the polarity of methanol is not enough to stabilize this interaction.49 Furthermore, the degree of organization necessary for symmetric methanol interaction requires a considerable negative entropy (a nonspontaneous process). In contrast, the disorder provided by the dynamic evolution solvates one of the carboxyls better than the other, stabilizing the structure with hydrogen on the other carboxyl.8,23 The static DFT calculations with two explicit symmetric or nonsymmetric methanol molecules also were performed, and the results corroborate with negative entropic hypothesis; both provide a larger height barrier when compared with one solvent molecule (see Figures S4 and S5 in SI). The two explicit symmetric and nonsymmetric methanol molecules have a degenerated intramolecular proton transfer height barrier at the M062X/6-31+G* level. Accordingly, the observation of two symmetric methanol molecules stabilizing the β-diketone group is negligible in the dynamic evolution. The static optimization based on the reaction coordinate neglects the environment effect and just considers the atomic positions in the phase space for the process. Differently, the dynamic procedure accounts for the velocity of the molecules

used to estimate the intramolecular hydrogen bond from CPMD simulations in the two calculated conditions: (i) in the gas phase, EH‑Bond = 18.68 kcal mol−1 and rO2−O6 = 2.50 Å and (ii) in methanol, EH‑Bond = 21.14 kcal mol−1 and rO2−O6 = 2.47 Å. The increase in hydrogen bond strength in the methanol environment can be explained by an increase in charge assistance in the O6 because of the methanol interaction, disturbing the resonance assistance in the gas phase. 3.2. Potential Energy Profile and Tunneling Contribution. Figure 4 shows the potential energy profiles calculated using both CPMD and static DFT methods. At the static DFT method, the potential energy profile is described regarding only the curcumin molecule in the vacuum and interacting with one solvent methanol. In agreement with geometric analysis, one observes a significant methanol effect on the symmetry of relative energy profile with a breakdown of the symmetry in the gas phase. In CPMD calculations, the methanol effect changes the barrier value from 0.50 to 0.12 kcal mol−1, which enhances the low-barrier character (see Figures 4(a) and 4(b)). The static M062X/DFT results present an analogous profile compared with CPMD calculations with changes in the barrier value from 2.71 to 1.47 kcal mol−1 (see Figures 4c and 4d). The observed difference in the barrier value in both methods is due to the fact that the static calculation neglects the complete solvation medium and the dynamic process effects. The solvent effect on the potential energy profile lies in the fact that the disorganized liquid methanol medium drives the visit of the two E


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Figure 5. Arrhenius plot (ln k as a function of the reciprocal temperature) of the intramolecular proton transfers with one-dimensional tunneling correction formulations: deformed,40−42 Wigner,38 (1) Bell-1935,39 (2) Bell-1958,39 and (3) Bell-1958−2T39 (a) in the gas phase and (b) in explicit methanol. The purple dashed line is crossover temperature.45

the harmonic analysis is usef ul, it could be rather unrealistic because of the small classical proton transfer energy barrier”. It is interesting to use the barrier calculated to provide an estimate for rate constant by the TST approach. In order to take tunneling effects into account, the transmission coefficients were determined using the correction formulations, as detailed in Section 2. Figures 5(a) and 5(b) show the conventional and tunneling correction TRC for gas-phase and explicit methanol intramolecular proton transfer. The intramolecular proton transfer TRC is temperature-dependent with significant curvature on the Arrhenius plot below the crossover temperature42,45 for all tunneling correction formulations, including d−TST; however, the deviation in the Bell-1935 and Bell-1958 corrections is more pronounced. The magnitude and the negative value of the parameter d in the d−TST formulation account for the contribution from the tunneling effect.42,60 In the explicit methanol d = −0.4052, while in the gas phase d = −0.1255; i.e., the tunneling effect is more pronounced in the presence of methanol. A linear behavior of the TRC is obtained at high temperature when thermal contributions are more pronounced. Considering the tunneling effect as indicated by the curvature on the Arrhenius plot, it is possible to use the

synchronized with the reaction evolution and consequently account for the entropic effect. The entropic effect can change the probable path expected by the intrinsic transition state reaction coordinate.50−55 The proton mobility over the potential barrier is affected by quantum tunneling because of its quantum nature. A traditional procedure to account for the tunneling is multiplying a tunneling correction term by the thermal rate constant (TRC) obtained by TST approach. A fingerprint of the tunneling effect is a significant curvature on the Arrhenius plot (representing the effects of temperature on the TRC) at low temperature.56,57 As in this work we consider a TST method, we first need to analyze the values of geometries, energies, and frequencies of reactants, products, and transition state species in the gas phase and with explicit methanol. The aforementioned quantities were obtained at the M062X/6-31+G* level. We located a barrier about 2 kcal/mol and with the addition of ZPE energies the internal barrier vanished; however, as awarded by the references:58,59 “The values of the ZPVE should be taken with caution since they are based on a harmonic model. It is likely that the PES contains considerable anharmonic components. Although F


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around the β-diketone group seems responsible for the increase in the entropy of the system and consequently allows the breakdown of symmetry of the intramolecular proton transfer potential energy profile in the gas phase. Our results suggest a criterion to characterize the symmetry of the intramolecular proton transfer potential energy profile with environmental dependence.

IUPAC activation energy definition,61 Ea = kBT2d ln k/dT, to recognize a significant decrease in the activation energy in the methanol medium.42,62 To the best of our knowledge, there are no experimental and theoretical data available in the literature for the curcumin intramolecular proton transfer TRC. However, the range of the TRC for systems that are similar to curcumin is between 1.0 × 102 and 1.0 × 1013 s−1.1,3 Our calculated TRC value (1.0 × 1013 s−1) is within that range, as seen in Figure 5a. Considering the inverse of the residence time in the O6 obtained by CPMD simulations, an estimative for a TRC is around 1.61 × 1013 in the gas phase and 2.27 × 1013 s−1 in explicit methanol. The CPMD simulation accounts for the dynamic process, which provides a better agreement of the inverse of the residence time with the range of the TRC presented in the literature (see SI for details of the residence time). The symmetry of the proton transfer potential energy profile is a fundamental question in intramolecular hydrogen bond systems, with several documented theoretical and experimental cases in the literature.7,8,12,63 Supported by our results, we suggest a criterion to characterize the symmetry of the intramolecular proton transfer potential energy profile in each case with environmental dependence: gas phase, crystal, and solvated medium, as shown in Table 1.

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S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jpcc.6b02393. A general table of values of bond lengths and angles. Figures with the time simulation of hydrogen bond lengths between the hydrogens of the methanols that access the curcumin solvation shell. Relative energy of the intramolecular proton transfers with two explicit nonsymmetric and symmetric methanol molecules (PDF) Special Issue Paper

This paper was originally submitted for the Piergiorgio Casavecchia and Antonio Laganà Festschrift, “Forty Years of Crossed Molecular Beams and Computational Chemical Dynamics at Perugia: A Festschrift for Piergiorgio Casavecchia and Antonio Laganà”.

Table 1. Confrontation of the Molecular Environments Where the Intramolecular Proton Transfer for Curcumin Analogues Occurs gas phase energy profile

symmetric

well type experimental techniques theoretical methods

double microwaves

main references

static electronic structure/ab initio molecular dynamics 6, 7, 10

crystal

solvent

symmetric/ asymmetric single/double X-ray/neutron diffraction static electronic structure/ab initio molecular dynamics 12, 63−65

asymmetric

ASSOCIATED CONTENT

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AUTHOR INFORMATION

Corresponding Authors

*Phone: +55 (62) 3328-1156. Fax: +55 (62) 3328-1177. Email: [email protected]. *E-mail: [email protected].

double NMR/IR

Notes

The authors declare no competing financial interest.

■ ■

this work

ACKNOWLEDGMENTS The authors are grateful for the support given from by FAPEG, CAPES, and CNPq.

8, 23, 66

REFERENCES

(1) Schowen, R. L.; Klinman, J. P.; Hynes, J. T.; Limbach, H. Hydrogen-Transfer Reactions; Wiley-VCH, 2007. (2) Steiner, T. The Hydrogen Bond in the Solid State. Angew. Chem., Int. Ed. 2002, 41, 49−76. (3) Limbach, H.-H.; Miguel Lopez, J.; Kohen, A. Arrhenius Curves of Hydrogen Transfers: Tunnel Effects, Isotope Effects and Effects of Pre-Equilibria. Philos. Trans. R. Soc., B 2006, 361, 1399−1415. (4) Graham, J. D.; Buytendyk, A. M.; Wang, D.; Bowen, K. H.; Collins, K. D. Strong, Low-Barrier Hydrogen Bonds May Be Available to Enzymes. Biochemistry 2014, 53, 344−349. (5) Ghosh, R.; Mondal, J. A.; Palit, D. K. Ultrafast Dynamics of the Excited States of Curcumin in Solution. J. Phys. Chem. B 2010, 114, 12129−12143. (6) Kawashima, Y.; Tachikawa, M. Ab Initio Path Integral Molecular Dynamics Study of the Nuclear Quantum Effect on out-of-Plane Ring Deformation of Hydrogen Maleate Anion. J. Chem. Theory Comput. 2014, 10, 153−163. (7) Perrin, C. L. Are Short, Low-Barrier Hydrogen Bonds Unusually Strong? Acc. Chem. Res. 2010, 43, 1550−1557. (8) Perrin, C. L. Symmetries of Hydrogen Bonds in Solution. Science 1994, 266, 1665−1668. (9) Yamabe, S.; Tsuchida, N.; Miyajima, K. Reaction Paths of KetoEnol Tautomerization of β-Diketones. J. Phys. Chem. A 2004, 108, 2750−2757.

4. CONCLUSIONS Herein, the curcumin molecule was investigated in the gas phase and in solvated methanol medium using ab initio molecular dynamics and static M062X/DFT methods. The presence of methanol substantially influenced the intramolecular proton mobility in the β-diketone site of the curcumin. A clear change in the curcumin properties was found when this molecule was considered in two different media: gas phase and methanol. These changes are specifically reflected in the breakdown of symmetry in the potential energy profile. The proton oscillates between O2 and O6 sites with equal distribution in the gas phase, but in methanol medium it has a preference for the O2 site. Furthermore, the π-delocalized character in the β-diketone cycle undergoes a disturbance due to significant interaction between the methanol and the O6. The tunneling effect is more pronounced in intramolecular proton transfer when the curcumin is in the presence of methanol medium. Both theoretical methods employed in this work were able to reproduce correctly the change in the potential energy profile due to the presence of the methanol. The disorganized and nonsymmetric methanol environment G


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(30) Bornemann, F. A.; Schutte, C. Numerische Mathematik A Mathematical Investigation of the Car-Parrinello Method. Numer. Math. 1998, 78, 359−376. (31) Giannozzi, P.; Baroni, S.; Bonini, N.; Calandra, M.; Car, R.; Cavazzoni, C.; Ceresoli, D.; Chiarotti, G. L.; Cococcioni, M.; Dabo, I.; et al. QUANTUM ESPRESSO: A Modular and Open-Source Software Project for Quantum Simulations of Materials. J. Phys.: Condens. Matter 2009, 21, 395502−395521. (32) Perdew, J. P.; Burke, K.; Ernzerhof, M. Generalized Gradient Approximation Made Simple. Phys. Rev. Lett. 1996, 77, 3865−3868. (33) Vanderbilt, D. Soft Self-Consistent Pseudopotentials in a Generalized Eigenvalue Formalism. Phys. Rev. B: Condens. Matter Mater. Phys. 1990, 41, 7892−7895. (34) Martyna, G. J.; Klein, M. L.; Tuckerman, M. Nose−Hoover Chains: The Canonical Ensemble via Continuous Dynamics. J. Chem. Phys. 1992, 97, 2635−2643. (35) Yanagisawa, D.; Shirai, N.; Amatsubo, T.; Taguchi, H.; Hirao, K.; Urushitani, M.; Morikawa, S.; Inubushi, T.; Kato, M.; Kato, F.; et al. Relationship Between the Tautomeric Structures of Curcumin Derivatives and Their Abeta-Binding Activities in the Context of Therapies for Alzheimer’s Disease. Biomaterials 2010, 31, 4179−4185. (36) Spezia, R.; Duvail, M.; Vitorge, P.; Cartailler, T.; Tortajada, J.; Chillemi, G.; D'Angelo, P.; Gaigeot, M.-P. A Coupled Car-Parrinello Molecular Dynamics and EXAFS Data Analysis Investigation of Aqueous Co2+. J. Phys. Chem. A 2006, 110, 13081−13088. (37) Zhao, Y.; Truhlar, D. G. The M06 Suite of Density Functionals for Main Group Thermochemistry, Thermochemical Kinetics, Noncovalent Interactions, Excited States, and Transition Elements: Two New Functionals and Systematic Testing of Four M06-Class Functionals and 12 Other Function. Theor. Chem. Acc. 2008, 120, 215−241. (38) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; et al. Gaussian 09, Revision D.01; Gaussian Inc: Wallingford CT, 2009. (39) Wigner, E. On the Quantum Correction for Thermodynamic Equilibrium. Phys. Rev. 1932, 40, 749−759. (40) Bell, R. P. The Tunnel Effect in Chemistry; Champman and Hall: London, 1980. (41) Carvalho, V. H.; Aquilanti, V.; de Oliveira, H. C. B.; Mundim, K. C. Deformed Transition State Theory: Inclusion of the Tunneling Effect by Euler Exponential, Limit of Validity and Description of ́ Bimolecular Reactions. Rev. Process. Quimicos 2015, 9, 226−228. (42) Cavalli, S.; Aquilanti, V.; Mundim, K. C.; De Fazio, D. Theoretical Reaction Kinetics Astride the Transition Between Moderate and Deep Tunneling Regimes: The F + HD Case. J. Phys. Chem. A 2014, 118, 6632−6641. (43) Carvalho, V. H.; Aquilanti, V.; Oliveira, H. C. B. de; Mundim, K. C. To Be Published. (44) Claudino, D.; Gargano, R.; Carvalho-Silva, V. H.; Silva, G. M. e; Cunha, W. F. da. Investigation of the Abstraction and Dissociation Mechanism in the Nitrogen Trifluoride Channels: Combined PostHartree−Fock and Transition State Theory Approaches. J. Phys. Chem. A 2016, 120, 5464−5473. (45) Christov, S. G. The Characteristic (Crossover) Temperature in the Theory of Thermally Activated Tunneling Processes. Mol. Eng. 1997, 7, 109−147. (46) Carvalho, V. H.; Aquilanti, V.; Oliveira, H. C. B. de; Mundim, K. C. Deformed Transition-State Theory: Deviation from Arrhenius Behavior and Application to Bimolecular Hydrogen Transfer Reaction Rates in the Tunneling. 2016, to be published. (47) Gilli, G.; Bellucci, F.; Ferretti, V.; Bertolasi, V. Evidence for Resonance-Assisted Hydrogen Bonding from Crystal-Structure Correlations on the Enol Form of the.Beta.-Diketone Fragment. J. Am. Chem. Soc. 1989, 111, 1023−1028. (48) Musin, R. N.; Mariam, Y. H. An Integrated Approach to the Study of Intramolecular Hydrogen Bonds in Malonaldehyde Enol Derivatives and Naphthazarin: Trend in Energetic Versus Geometrical Consequences. J. Phys. Org. Chem. 2006, 19, 425−444.

(10) Belova, N. V.; Girichev, G. V.; Oberhammer, H.; Hoang, T. N.; Shlykov, S. A. Tautomeric and Conformational Properties of Benzoylacetone, CH3-C(O)-CH2-C(O)-C6H5: Gas-Phase Electron Diffraction and Quantum Chemical Study. J. Phys. Chem. A 2012, 116, 3428−3435. (11) Gilli, P.; Bertolasi, V.; Ferretti, V.; Gilli, G. Covalent Nature of the Strong Homonuclear Hydrogen-Bond-Study of the O-H—O System by Crystal-Structure Correlation Methods. J. Am. Chem. Soc. 1994, 116, 909−915. (12) Durlak, P.; Latajka, Z. Car-Parrinello and Path Integral Molecular Dynamics Study of the Intramolecular Hydrogen Bonds in the Crystals of Benzoylacetone and Dideuterobenzoylacetone. Phys. Chem. Chem. Phys. 2014, 16, 23026−23037. (13) Pérez, P.; Toro-Labbé, A. Characterization of Keto-Enol Tautomerism of Acetyl Derivatives from the Analysis of Energy, Chemical Potential, and Hardness. J. Phys. Chem. A 2000, 104, 1557− 1562. (14) Sikorski, E. M.; Hock, T.; Hill-Kapturczak, N.; Agarwal, A. The Story so Far: Molecular Regulation of the Heme Oxygenase-1 Gene in Renal Injury. Am. J. Physiol. Renal Physiol. 2004, 286, 425−441. (15) Esatbeyoglu, T.; Huebbe, P.; Ernst, I. M. A.; Chin, D.; Wagner, A. E.; Rimbach, G. Curcumin-From Molecule to Biological Function. Angew. Chem., Int. Ed. 2012, 51, 5308−5332. (16) Yang, F.; Lim, G. P.; Begum, A. N.; Ubeda, O. J.; Simmons, M. R.; Ambegaokar, S. S.; Chen, P.; Kayed, R.; Glabe, C. G.; Frautschy, S. A.; et al. Curcumin Inhibits Formation of Amyloid Beta Oligomers and Fibrils, Binds Plaques, and Reduces Amyloid in Vivo. J. Biol. Chem. 2005, 280, 5892−5901. (17) Mock, C. D.; Jordan, B. C.; Selvam, C. Recent Advances of Curcumin and Its Analogues in Breast Cancer Prevention and Treatment. RSC Adv. 2015, 5, 75575−75588. (18) Maiti, D.; Saha, A.; Devi, P. S. Surface Modified Multifunctional ZnFe2O4 Nanoparticles for Hydrophobic and Hydrophilic AntiCancer Drug Molecules Loading. Phys. Chem. Chem. Phys. 2015, 18, 1439−1450. (19) Sun, D.; Zhuang, X.; Xiang, X.; Liu, Y.; Zhang, S.; Liu, C.; Barnes, S.; Grizzle, W.; Miller, D.; Zhang, H.-G. A Novel Nanoparticle Drug Delivery System: The Anti-Inflammatory Activity of Curcumin Is Enhanced When Encapsulated in Exosomes. Mol. Ther. 2010, 18, 1606−1614. (20) Mazumder, A.; Raghavan, K.; Weinstein, J.; Kohn, K. W.; Pommier, Y. Inhibition of Human Immunodeficiency Virus Type-1 Integrase by Curcumin. Biochem. Pharmacol. 1995, 49, 1165−1170. (21) Zeitlin, P. Can Curcumin Cure Cystic Fibrosis? N. Engl. J. Med. 2004, 351, 606−608. (22) Balasubramanian, K. Molecular Orbital Basis for Yellow Curry Spice Curcumin’s Prevention of Alzheimer’s Disease. J. Agric. Food Chem. 2006, 54, 3512−3520. (23) Perrin, C. L. Symmetry of Hydrogen Bonds in Solution. Pure Appl. Chem. 2009, 81, 571−583. (24) Erez, Y.; Presiado, I.; Gepshtein, R.; Huppert, D. Temperature Dependence of the Fluorescence Properties of Curcumin. J. Phys. Chem. A 2011, 115, 10962−10971. (25) Erez, Y.; Presiado, I.; Gepshtein, R.; Huppert, D. The Effect of a Mild Base on Curcumin in Methanol and Ethanol. J. Phys. Chem. A 2012, 116, 2039−2048. (26) Car, R.; Parrinello, M. Unified Approach for Molecular Dynamics and Density-Functional Theory. Phys. Rev. Lett. 1985, 55, 2471−2474. (27) Tuckerman, M. E.; Parrinello, M. Integrating the Car-Parrinello Equations. I. Basic Integration Techniques. J. Chem. Phys. 1994, 101, 1302−1315. (28) Tuckerman, M. E.; Parrinello, M. Integrating the Car − Parrinello Equations. II. Multiple Time Scale Techniques. J. Chem. Phys. 1994, 101, 1316−1329. (29) Hutter, J.; Tuckerman, M.; Parrinello, M. Integrating the Car− Parrinello Equations. III. Techniques for Ultrasoft Pseudopotentials. J. Chem. Phys. 1995, 102, 859−871. H


Article

The Journal of Physical Chemistry C (49) Sallum, L. O.; Napolitano, H. B.; Carvalho, P. de S.; Cidade, A. F.; de Aquino, G. L. B.; Coutinho, N. D.; Camargo, A. J.; Ellena, J.; de Oliveira, H. C. B.; Silva, V. H. C. Effect of the Methanol Molecule on the Stabilization of C 18 H 18 O 4 Crystal: Combined Theoretical and Structural Investigation. J. Phys. Chem. A 2014, 118, 10048−10056. (50) Xie, J.; Otto, R.; Mikosch, J.; Zhang, J.; Wester, R.; Hase, W. L. Identification of Atomic-Level Mechanisms for Gas-Phase X- + CH3Y SN2 Reactions by Combined Experiments and Simulations. Acc. Chem. Res. 2014, 47, 2960−2969. (51) Sun, L.; Song, K.; Hase, W. L. A SN2 Reaction That Avoids Its Deep Potential Energy Minimum. Science 2002, 296, 875−878. (52) Xie, J.; Hase, W. L. Rethinking the SN2 Reaction. Science 2016, 352, 32−33. (53) Szabó, I.; Czakó, G. Revealing a Double-Inversion Mechanism for the F−+CH3Cl SN2 Reaction. Nat. Commun. 2015, 6, 5972−5978. (54) Szabó, I.; Czakó, G. Double-Inversion Mechanisms of the X− + CH3Y [X,Y = F, Cl, Br, I] SN2 Reactions. J. Phys. Chem. A 2015, 119, 3134−3140. (55) de Souza, M. A. F.; Correra, T. C.; Riveros, J. M.; Longo, R. L. Selectivity and Mechanisms Driven by Reaction Dynamics: The Case of the Gas-Phase OH− + CH3ONO2 Reaction. J. Am. Chem. Soc. 2012, 134, 19004−19010. (56) Silva, V. H. C.; Aquilanti, V.; de Oliveira, H. C. B.; Mundim, K. C. Uniform Description of Non-Arrhenius Temperature Dependence of Reaction Rates, and a Heuristic Criterion for Quantum Tunneling vs Classical Non-Extensive Distribution. Chem. Phys. Lett. 2013, 590, 201−207. (57) Aquilanti, V.; Mundim, K. C.; Elango, M.; Kleijn, S.; Kasai, T. Temperature Dependence of Chemical and Biophysical Rate Processes: Phenomenological Approach to Deviations from Arrhenius Law. Chem. Phys. Lett. 2010, 498, 209−213. (58) Garcia-Viloca, M.; González-Lafont, A.; Lluch, J. M. Theoretical Study of the Low-Barrier Hydrogen Bond in the Hydrogen Maleate Anion in the Gas Phase. Comparison with Normal Hydrogen Bonds. J. Am. Chem. Soc. 1997, 119, 1081−1086. (59) Schiøtt, B.; Iversen, B. B.; Hellerup Madsen, G. K.; Bruice, T. C. Characterization of the Short Strong Hydrogen Bond in Benzoylacetone by Ab Initio Calculations and Accurate Diffraction Experiments. Implications for the Electronic Nature of Low-Barrier Hydrogen Bonds in Enzymatic Reactions. J. Am. Chem. Soc. 1998, 120, 12117− 12124. (60) Morais, S. F. de A.; Mundim, K. C.; Ferreira, D. A. C. An Alternative Interpretation of the Ultracold Methylhydroxycarbene Rearrangement Mechanism: Cooperative Effects. Phys. Chem. Chem. Phys. 2015, 17, 7443−7448. (61) Laidler, K. J. A Glossary of Terms Used in Chemical Kinetics, Including Reaction Dynamics. Pure Appl. Chem. 1996, 68, 149−192. (62) Aquilanti, V.; Mundim, K. C.; Cavalli, S.; De Fazio, D.; Aguilar, A.; Lucas, J. M. Exact Activation Energies and Phenomenological Description of Quantum Tunneling for Model Potential Energy Surfaces. The F+H2 Reaction at Low Temperature. Chem. Phys. 2012, 398, 186−191. (63) Jezierska, A.; Panek, J. J. zwitterionic Proton Sponge” Hydrogen Bonding Investigations on the Basis of Car-Parrinello Molecular Dynamics. J. Chem. Inf. Model. 2015, 55, 1148−1157. (64) Durlak, P.; Mierzwicki, K.; Latajka, Z. Investigations of the Very Short Hydrogen Bond in the Crystal of Nitromalonamide via CarParrinello and Path Integral Molecular Dynamics. J. Phys. Chem. B 2013, 117, 5430−5440. (65) Madsen, G. K. H.; McIntyre, G. J.; Schiøtt, B.; Larsen, F. K. The Low-Barrier Hydrogen Bond of Deuterated Benzoylacetone Probed by Very Low Temperature Neutron and X-Ray Diffraction Studies and Theoretical Calculations. Chem. - Eur. J. 2007, 13, 5539−5547. (66) Dopieralski, P.; Perrin, C. L.; Latajka, Z. On the Intramolecular Hydrogen Bond in Solution: Car-Parrinello and Path Integral Molecular Dynamics Perspective. J. Chem. Theory Comput. 2011, 7, 3505−3513.

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