Assessing the solvation mechanism of C-60(OH)(24) in aqueous solution

Assessing the solvation mechanism of C

60

(OH)

24

in aqueous solution

Cleiton Maciel

, Eudes E. Fileti

_{, Roberto Rivelino}

a_{Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, 09210-270 Santo André, SP, Brazil} b_{Instituto de Ciência e Tecnologia da UNIFESP, 12231-280 São José dos Campos, SP, Brazil}

c_{Instituto de Física, Universidade Federal da Bahia, 40210-340 Salvador, BA, Brazil}

a r t i c l e

i n f o

Article history:

Received 19 November 2010 In final form 24 March 2011 Available online 12 April 2011

a b s t r a c t

Using molecular dynamics simulations, combined with the thermodynamic integration algorithm, we examine the hydration mechanism of C60(OH)24under ambient conditions. We analyze its structural

fea-tures, dynamics, and hydration free energy. Our results have been compared with a pristine fullerene aqueous system. Despite the number of hydroxyl groups in the fullerenol, its hydration entropy is rather similar to that calculated for C60. On the other hand, we have calculated a dramatically negative free

energy of about 354 kJ/mol for the fullerenol, whereas pure fullerene presents a positive value of about 59 kJ/mol. On this basis, our study indicates that the hydration of C60(OH)24is guided by an

enthalpy-dri-ven process.

Ó2011 Elsevier B.V.

1. Introduction

Understanding hydration and dispersion of C60and other

fuller-ene derivatives is of great value for both practical and fundamental

studies[1–7]. Aqueous systems of these carbon cages have been

proposed for use in molecular sensing devices, biomedical, and

environmental applications [8–11]. Although several properties

of these ‘solutions’ appear to be well understood, the intermolecu-lar interactions between the medium and the solute are still

un-known. Also, the room-temperature predicted solubility [12] of

C60in water is very low, but not as low as recent estimates[13].

In principle, the specific solute–solvent interactions in this case are dominated by van der Waals forces. On the other hand, Labille et al.[14]have recently demonstrated that pristine fullerene can acquire hydrophilic character because of the surface hydroxylation occurring in aqueous environment. They provided spectroscopic evidences for the fullerene hydroxylation under mild chemical conditions. However, the solubility mechanisms of fullerenes and their hydroxylated derivatives continue to be a controversial issue

[15–17].

While the study of the biological properties of bare fullerene is

greatly hampered by its poor solubility in water [18], highly

hydroxylated cages, [C60(OH)n] or fullerenols, should present good

solubility in aqueous medium. Fullerenols are of great interest and they have been tested as biocompatible materials[19–21]. These molecules exhibit different degrees of solubility, depending on the number and distribution of hydroxyl groups on the fullerene surface[18,22]. Notwithstanding, the good solubility of some ful-lerenol structures can be hampered by certain ionic contamination

resulting from the synthetic methods[17]. Indeed, studies on the solubility of fullerenols are scarce and the interaction free energy of the solute with the solvent has not yet been reported in the literature.

As mentioned above, aqueous solutions of fullerenols are espe-cially important in biological applications. Thus, quantifying the solubility of fullerenols under ambient conditions is extremely useful to understand the impact of these species in several aqueous systems. Indeed, this can be investigated experimentally from the

Gibbs energy of solution [12]. Although the knowledge of the

thermodynamic properties are essential to understand the nature of the solute–solvent interactions, the structural and dynamic information is also indispensable. These latter aspects can be addressed by means of molecular dynamics (MD) simulations, and the hydration free energy with the thermodynamic integration (TI) technique[7,23].

We report in this work an atomistic MD/TI simulation study of a room-temperature aqueous solution of C60(OH)24, which has been

by far one of the most exploited molecular speciesin vitroand

in vivo[20,24,25]. Then, making use of proper atomistic parameters we analyze the thermodynamics of a C60(OH)24aqueous solution

under ambient conditions. Our study is systematically compared to the hydration properties of pristine C60, for which we have

suc-cessfully determined the free energy of transfer at different ther-modynamic conditions via MD/TI simulations[7,23].

2. Simulation details

The aqueous solutions of C60(OH)24and C60have been studied

using isothermal–isobaric (NPT) ensembles with MD simulations

atT= 298 K and P = 1 atm. Each solution was prepared with 1000 water molecules and one solute (fullerenol or fullerene) molecule

0009-2614Ó2011 Elsevier B.V. doi:10.1016/j.cplett.2011.03.080

⇑Corresponding authors. Fax: +55 11 4496 0196.

E-mail addresses:fileti@unifesp.br(E.E. Fileti),rivelino@ufba.br(R. Rivelino).

Chemical Physics Letters 507 (2011) 244–247

Contents lists available atScienceDirect

Chemical Physics Letters

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / c p l e t t

Open access under the Elsevier OA license.

in cubic boxes with periodic boundary conditions. Technical details

are given in our previous works[7,23,26]and in theSupporting

material (Tables S1–S4, Figs. S1–S4). The extended simple point charge (SPC/E)[27]potential was used to describe the potential

interaction of the water molecules. In the case of C60 we have

adopted a 60-site model[5]. The potential for C60(OH)24was

gen-erated on the basis of the OPLS force field (see parameters in Table S1). The atomic charges of this solute were obtained using the ChelpG scheme also discussed inSupporting material. As usual, the solute–solvent interactions were described by means of the Lennard–Jones and Coulomb potentials. These simulations were carried out by using the GROMACS code (version 4.0)[28].

From theNPTconditions, we have analyzed the structural and

dynamic properties of the fullerene and fullerenol aqueous solu-tions after 10 ns simulasolu-tions. To obtain information on the dy-namic properties of these systems, we have calculated the time correlation functions. The translational mobility of the solutes (ful-lerenol or fullerene) in water was obtained from the velocity auto-correlation function (VACF) and mean square displacements (MSD). With VACF we can measure the effects of the local environ-ment of the solutes. The MSD gives a good measure of the transla-tional diffusivity of both solutes in aqueous environment, and from its long time behavior we can extract the Einstein diffusion con-stants (D).

Also, to assess the hydration free energy, and consequently the water solubility, of C60(OH)24or C60stochastic dynamics

simula-tions associated with the TI method were employed within the NPTensembles[23]. We have performed a series of 26 simulations for C60 and 36 for C60(OH)24, varying the value of the coupling

parameter according to Tables S3 and S4. The detailed calculations of the free energy are discussed inSupporting material. All stochas-tic and molecular dynamics simulations have been performed with the GROMACS 4.0.

3. Results and discussion

3.1. Structural features

We present the results for the structural properties of the aque-ous solutions of C60(OH)24in comparison with the aqueous

solu-tion of C60. Because of the large molecular surface area and

volume of these solutes, the hydrogen bonding network of water is disrupted, creating a large cavity in the liquid. For pure fullerene, new hydrogen bonds are not expected to be formed with the sol-vent under ordinary conditions[29]. On the other hand, in the case of C60(OH)24, the solubility will be determined not only by the

geo-metric features but also by the hydrogen bonding interactions

be-tween the solute and solvent (Fig. S2 and S3). A hydration shell around these solutes is well defined as a spherical layer of water (Figure 1), determined by the center-of-mass radial distribution functions (RDFs).

InFigure 2a we show a comparison of the RDFs for C60(OH)24

and C60. The heights of the peaks indicate a stronger densification

of the solvent around C60than around C60(OH)24. This is because

the water molecules near the fullerene surface tend to form hydro-gen bonds between themselves avoiding the solute. Therefore, in the case of fullerene the number of water molecules in the hydra-tion shells increase, giving 63, 183, and 418 molecules on average. In the case of the fullerenol, because of the amount of hydroxyl groups in C60(OH)24, the water molecules tend to rebuild some

hydrogen bonds that were broken in the solvation process. Also, we notice three hydration shells forming structures with 48, 121, and 229 molecules on average (see additional details in Table S1 and Fig. S1).

For a polyhydroxylated fullerene, it is more interesting to exam-ine the RDFs of (i) the water oxygen atom with the solute hydrogen atoms (OW. . .HF); and (ii) the fullerenol oxygen atoms with the water hydrogen atoms (OF. . .HW). These calculated RDFs are shown inFigure 2b, where the height difference between the peaks shows a steric hindrance effect on the solute–solvent interaction. This means that C60(OH)24works as a better proton-donor than a

pro-ton-acceptor species in aqueous solution. This result is consistent with the proton conductivity of low hydroxylated fullerenes, which is a function of the amount of hydroxyl groups[30,31].

Because of the hydrophilic groups in C60(OH)24, one could

ex-pect that this fullerenol should be much more water-soluble than C60. Indeed, low hydroxylated fullerenes are less water-soluble

species, whereas the highly hydroxylated cages present a good sol-ubility in aqueous environment[17]. However, as a consequence of the steric hindrance, few water molecules can approach their hydrogen atoms to the fullerenol surface, avoiding a formation of an extended hydrogen bonding network around the solute. A de-tailed analysis of the hydrogen bonds is given inSupporting mate-rial (see Figs. S2–S4).

3.2. Dynamic properties

Figure 3shows the time correlation function for the average hydrogen bonds life time of C60(OH)24aqueous solution and in bulk

water. As discussed in Supporting material, the correlation func-tion describes the probability that a particular hydrogen bond keeps intact at a small time interval. FromFigure 3, we note that the correlation function decays faster for the hydrogen bonds in bulk water than at the fullerenol surface. This indicates that the

Figure 1.The first hydration shells of C60(left) and C60(OH)24(right) in ordinary aqueous solutions. The big atom model is only used to represent the carbon cages and the covalently bound hydroxyl groups in the fullerenol structure. Green, red, and white spheres represent carbon, oxygen, and hydrogen atoms, respectively. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

hydrogen bonds formed with the fullerenol are longer-lived than those formed in bulk water. Also, it suggests that hydrogen bond formation at the interface plays a key role in the adsorption of water on hydrophilic surfaces. As a consequence of the number and specific arrangements of the hydroxyl groups attached on the fullerene surface, which may lead to long-lived hydrophilic re-gions around this solute, it presents a relatively higher solubility in water in comparison with pristine C60.

Now we consider the differences between the dynamical behavior of C60(OH)24and C60in water. Translational diffusivities

of C60(OH)24and C60have been determined from MSD and VACFs

(Figure 4). From the MSD it is evident that the hydrogen bonds formed between C60(OH)24and water decreases significantly the

diffusion constant of the fullerenol. Our calculated diffusion

con-stants in the linear regime are of 1.91 nm2_{/ns for C}

60 and

0.37 nm2_{/ns for C}

60(OH)24. An interesting behavior is noticed in

the VACF profiles of both solutes. The normalized VACFs of C60

and C60(OH)24exhibit a different time scale behavior. In the first

case there is a mild negative region around 1.0 ps, indicating col-lisions of C60 with the nearest water molecules. This behavior,

however, is not noticed for the rapid VACF decay of C60(OH)24,

which exhibits no effect of local structures on the translational diffusion.

3.3. Hydration free energy

Using the stochastic dynamics associated with the TI method, we examine the hydration free energy of C60(OH)24in comparison

with bare fullerene. However, we cannot access directly the solu-bility of this species. As is known in thermochemistry, the solubil-ity of these compounds can be properly related to their solution free energies[12]. On the other hand, the hydration structures of the solutes have a direct impact on their solubilities. Thus, we ex-pect that C60has a lower solubility in water since it causes a

dis-continuity of the hydrogen bonding network in the solvent structure. Furthermore, this nonpolar solute does not participate in the formation of new hydrogen bonds with the surrounding water molecules. As a consequence, the hydration process of fuller-ene is exothermic, but does not proceed spontaneously. On the contrary, C60(OH)24 interacts directly with the water molecules

increasing significantly its hydration enthalpy and, consequently, favoring a spontaneous hydration process.

InTable 1we give the calculated hydration enthalpies, entro-pies, and free energies of the fullerenol compared with fullerene. Consistent with our previous analysis[23], as well as experimental predictions, the hydration entropy of C60is expected to be a

nega-tive quantity. As we have calculated, the entropic contribution (TDS) is 198.1 kJ/mol in the solvation of C60and 186.2 kJ/mol

in the solvation of C60(OH)24. Indeed, many water molecules are

spherically reordered around these solutes leading to similar hydration entropy changes. Hence, the solvation mechanism of ful-lerene and fullerenols in solvents that organize themselves through polar or hydrogen bonding interactions appears to be an enthalpy-driven process.

As should be expected, the hydration mechanism for a poly-hydroxylated cage is related to the number and specific arrange-ments of the hydroxyl groups attached on the fullerene surface. As discussed in the structural analysis, this may lead to hydrophilic regions around the solute increasing the solute–solvent enthalpy. Figure 2.Calculated RDFs between the center of mass of the solute (C60 or

C60(OH)24) and water (a); and between the O and H atoms of C60(OH)24and water (b). OW...HFindicates the curve for O of water with H of the fullerenol and OF...HW indicates the curve for H of water with O of the fullerenol.

Figure 3.Decay profile of the average hydrogen bonds life time correlation functions,C(t), for the hydrogen bonds (HB) near the fullerenol surface and in bulk water.

Figure 4.Mean-square displacement (top) and velocity autocorrelation functions (bottom) of the center of mass of the solutes in water. The value of the diffusion constant (D) was obtained from the linear fit from 40 to 400 ps.

Table 1

Calculated*_{Standard hydration entropy, enthalpy and free energy (in kJ/mol) of C}

60 and C60(OH)24. –TDSwas obtained directly fromDG=DH TDS.

DH TDS DG

C60 139.5 198.1 58.6

C60(OH)24 540.0 186.2 353.8

In fact, we have calculated a dramatically negative hydration free energy of about 354 kJ/mol for C60(OH)24, and a positive value

of about 59 kJ/mol for pure fullerene[23]. Note that our calculated hydration free energy is larger than the value of 2.9 kJ/mol, ob-tained by Stukalin et al.[32]; using the polarizable continuum model carried out within the Hartree–Fock level of theory. In fact, a good estimate of the solvation free energy will depend on the accuracy in the description of the solute–solvent dispersion inter-actions. However, comparing the hydration properties of C60and

C60(OH)24obtained via MD/TI simulations, we find a clear effect

of the hydroxyl number in the fullerenol. Although many hydrogen bonds are disrupted because of the solvation of a large solute, the behavior of the fullerenol in aqueous solution is strongly exother-mic, leading to a much more spontaneous hydration process than in the case of fullerene.

4. Conclusions

In this work, we have investigated the solvation mechanism of C60(OH)24, a stable isomer of fullerenol, in water under ambient

conditions. To allow a detailed microscopic description of the hydration, our study was based on MD simulations using fully-atomistic parameters. Combining these simulations with the TI scheme, we have demonstrated that the solvation process of the polyhydroxylated carbon cage in water is dominated by its hydra-tion enthalpy. Thus, we have obtained a very negative free energy of hydration ( 354 kJ/mol) for this species. Although the solubility is influenced by distinct solvent properties, the hydrogen bonding structure of the solvent is also a noticeable factor in the solvation mechanism. Polyhydroxylated fullerenes, such as C60(OH)24, can

form hydrogen bonds with the surrounding water molecules, which can increase dramatically their hydration energy. On the other hand, in real systems even highly hydroxylated fullerenols are also able to form colloidal particles [33]. In these cases it is known that the intermolecular interactions play an important role in the solubility of fullerenols. In this direction, our simulations can guide future investigation involving small aggregates of fullerenols in aqueous environment.

Acknowledgements

This work was supported by the funding agencies FAPESP (São Paulo), FAPESB (Bahia), and the Brazilian Research Council (CNPq). The authors thank Denis Anjos for the technical support and main-tenance of the computational facilities.

Appendix A. Supplementary data

Supplementary data associated with this article can be found, in the online version, atdoi:10.1016/j.cplett.2011.03.080.

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