10160
J. Phys. Chem. B 2007, 111, 10160-10165
Microheterogeneous Structure of 1-Octanol in Neat and Water-Saturated State Kai Hu, Yan Zhou, Junfeng Shen, Zhenping Ji, and Gongzhen Cheng* College of Chemistry and Molecular Sciences, Wuhan UniVersity, Wuhan, Hubei 430072, China ReceiVed: April 12, 2007; In Final Form: June 13, 2007
The conformational and dynamic properties of 1-octanol in neat and in water-saturated states have been investigated by 1H NMR. It has been proved that neat 1-octanol is microheterogeneous in nature comprising regions enriched in either hydrocarbons or hydroxyl groups. A reversed micelle-like cluster model was proposed, where the octanol cluster has an inner polar core of hydrogen-bonded octanol hydroxyls and an outer shell of nonpolar alkyl chains radiating outside. It was also observed that the cluster structure of octanol experiences minor changes with the presence of water. In water-saturated octanol, water molecules associate via hydrogen bonding and reside in the innermost center of the polar region with restricted motion, whereas the octanol cluster structure is modified by loosening the compact structure. Moreover, the preferential solvations of both systems were tested and compared. It not only gives some clues about the microheterogeneity of the alcohol system and the structure of the cluster but also helps in advancing our understanding on the behavior and properties of the amphiphilic molecules system such as phospholipids.
Introduction It is generally accepted that alcohols are amphiphilic in nature. The formation of intermolecular hydrogen bonds results in the self-association of the molecules. Much work has been done on this self-association behavior of alcohol,1-4 but it was not until 2002 when the characteristics of alcohol were gradually unveiled by Dixit et al. with their milestone work.5 They observed incomplete mixing of alcohol/water at the molecular level and cluster formation. Since then, two other expressions, “microheterogeneity”6,7 and “cluster”,6,8 have been more frequently used in describing the conformational characteristics of the alcohol system. Much evidence suggests that molecules in an alcohol solution associate via hydrogen-bonding to form clusters of different sizes; and the cluster formation results in the microheterogeneity of the system. There exist two different regions, polar and nonpolar.9 The polar region consists of hydrogen-bonded hydroxyl groups, while the nonpolar is dominated by alkyl chains. Alcohols of different chain lengths have been investigated. Among them, 1-octanol with a relative long chain is one of the focuses due to its similarity to lipid molecules that comprise the biological membrane. The crystal structure data of 1-octanol show that10 molecules are linked into ribbons by hydrogen bonds, while the alkyl chains are packed side-by-side, perpendicular to the infinite hydrogen-bond ribbon. However, in liquid state, due to fast molecular motion, the structure of octanol aggregates are not as ordered as that in solid. It is generally accepted that in neat liquid 1-octanol, the aggregate has a linear or chain-like structure7,11-13 sharing some similarities to that in solid state. The existence of polymeric hydrogen-bonded aggregates14 has been suggested on the basis of the data of molecular simulation. Moreover, neat 1-octanol is believed to have fluctuating regions of preferentially polar and nonpolar character, as well as inverted micelle aggregates.9,15 Agreements have been achieved that 1-octanol molecules in the neat liquid state associate and align themselves by intermolecular hydrogen * Corresponding author. E-mail:
[email protected].
bonds between hydroxyl groups. However, to the best of our knowledge, relatively little information has been given on the arrangement of the hydrophobic part controlled by van der Waals forces. In addition to the neat 1-octanol system, water-saturated octanol is another focus of interest.16-23 The octanol-water partition coefficient is widely used to predict lipophilicity of drugs. Due to its small size and strong hydrogen-bonding ability, water can partly dissolve in 1-octanol. Although much work has been poured into the investigation of the water/octanol system, there still exist discrepancies about the influence of water on the structure of octanol. On one hand, some believe that the linear structure of octanol remains with water molecules as a “pocket” confined in the polar region of it.7 On the other hand, molecular simulation studies17,24 suggest that the structure of octanol is substantially altered upon saturation of water, with the structure changing from the linear aggregates in dry conditions to the large cylindrical micelles with water cores. To elucidate the conformational characteristics of alcohol, many experimental and theoretical methods such as IR,25,26 Raman,7 X-ray diffraction,27 Rayleigh-Brillouin,28,29 NMR spectroscopy,11 and molecular dynamic simulations17,20,23,24 have been used. Among them, NMR spectroscopy is one of the most powerful and reliable tools in establishing the structure of aggregates in solution, directly and comprehensively. The chemical shift reflects the environmental variation, the relaxation time gives some clues about dynamic behavior, while the J-coupling constant and the nuclear Overhauser effect (NOE) reveal the spatial arrangement. Especially, the NOE enhancement, which has a direct relationship with the distance ( fHb{-OH} > fHc{-OH}. Since the enhancement is inversely proportional to the distance between them, it is presumed that pyridine dissolved in octanol prefers to reorient its polar moiety into the polar center of octanol aggregate. This orientation helps the hydrogen-bond formation between pyridine nitrogen and octanol hydroxyl. The relatively small T1 values of pyridine protons with respect to that of benzene also support this assumption. p-Cresol (3) with both polar and nonpolar substituent groups on benzene was also investigated. Figure 3a presents the NOE spectra by saturating H1 and H8, respectively. It is noticed that H1 of 1-octanol has NOE mainly with protons on the polar end of solute molecules like Ha and Hb, while H8 has NOE with Hc and Hd on the -CH3 end of p-cresol. T1 values of p-cresol in 1-octanol and in CDCl3 were compared. Apparently, the T1’s were greatly reduced in the associated system. This helps in pointing out that the p-cresol migrates in the octanol cluster with the polar part positioned near the polar zone, while the nonpolar head is surrounded by the nonpolar alkyl chain. When performing an in-depth analysis on the polar region, two facts should be noticed: first, a negative NOE exists between the protons of p-cresol hydroxyl Ha and octanol hydroxyl H-OH; second, T1 of Ha is smaller compared to that of H-OH. The former is the result of slow chemical exchange between two types of hydroxyl protons, and the latter is due to the insertion of Ha into the innermost polar region of the octanol cluster. Together with the above analysis, a vivid picture of p-cresol solvated in neat octanol could be drawn. The p-cresol molecule dissolving in the 1-octanol cluster has its polar hydroxyl group preferentially migrating into the hydrogen-bonded polar core with its nonpolar moiety residing in the nonpolar slit of alkyl chain. Considering the relatively large size of the aromatic group, which may hamper the insertion of solute molecule into the associated octanol cluster, small-sized molecules such as 2,3-
Microheterogeneity of Water-Saturated 1-Octanol
J. Phys. Chem. B, Vol. 111, No. 34, 2007 10163
Figure 2. (a) Normal spectrum of dry 1-octanol and NOESY 1D spectrum after saturating H1; (b) the normal spectrum of wet 1-octanol and NOESY 1D spectrum after saturating hydroxyl group.
Figure 3. (a) Normal spectrum of p-cresol in octanol (bottom) and the selected NOE difference spectrum after saturating on H1 (middle) and H8 (top); (b) 1H NMR spectrum of 2,3-dimethylbut-2-en-1-ol in 1-octanol (bottom) and NOE difference spectrum after saturating on Hb (middle) and He (top).
dimethylbut-2-en-1-ol (4) and prop-2-yn-1-ol (5) were investigated. The NOE results in 1-octanol are shown in Figure 3b and Table 3. The intermolecular NOEs between 1-octanol and these two solutes give clues on the preferential solvation of 4
and 5 in solution. The same conclusion could be drawn that polar groups preferentially migrate into or near the hydrophilic region and less polar groups preferentially take up residence in hydrophobic region.
10164 J. Phys. Chem. B, Vol. 111, No. 34, 2007
Hu et al.
TABLE 3: NOE Enhancement (%) of Benzene (Top) and Prop-2-yn-1-ol in Octanol (Bottom) saturated proton (x) NOE (%)
H-OH
fx{-OH} fx{1} fx{8} fx{ben}
2.89
H1
H2
H3-7
3.27
1.04 1.48
0.15 0.27 0.20 0.13
0.04
0.06
H8
Hben 0.04 0.04 0.13
saturated proton (x) NOE (%)
H-OH
H1
fx{1} fx{2} fx{c} fx{b}
0.90 0.47 0.17 0.75
1.37 0.22 0.18
H2
H3-7
1.40 0.15
H8
Ha
Hb
Hc
0.27
0.42 0.20
0.11
0.11 0.37
0.09
0.10
0.17 0.14
One of the prime purposes for these preferential solvation studies is to provide microscopic insight into the solvation mechanism as well as the microheterogeneity of octanol in pure liquid. The NOEs between solvent and solute offer more convincing evidence for the existence of polar and nonpolar regions in the 1-octanol system. Solute molecules take a preferential orientation, based on the principle of “like-dissolveslike”, in the slit of alkyl chains with different extents of insertion, and our experimental results coincide very well with those from simulation. 3. The Structure of Water-Saturated 1-Octanol. Neat 1-octanol is microheterogeneous; therefore, molecules of different polarity can dissolve in it. Among all the solutes, water is the most special one. The 1-octanol/water partitioning system has been widely investigated as an analogue for studying the compartmental distribution characteristics of pharmaceutical agents and in predicting pharmacokinetic characteristics of drug compounds in biological systems. It has been proved that the microheterogeneity of 1-octanol remains with the addition of water under the saturation level and that this two-component solution is incompletely mixed at molecular level, even at the interface,22 with hydrophilic and hydrophobic regions. Sassi et al.26 carried out a comprehensive study on water-saturated octanol by different scattering spectroscopes, and the water behaving as a “pocket” has been proposed. However, the discussion on the modification of hydrophobic parts of the octanol cluster with the presence of water is rare. In this section, therefore, discussion will be carried out on water-saturated octanol at the following three levels: (1) the hydrogen-bonding character, (2) the location of water molecules, and (3) the effect of water added to the cluster structure of octanol. First, compared to those in pure liquid, proton resonances of both water and octanol hydroxyl in water-saturated octanol have upfield shifts of 0.057 ppm and 0.046 ppm, respectively. These chemical shift variations indicate a less ordered hydrogen-bond network with respect to that in pure. The same results were also obtained by Raman analysis, which suggests a reduction of the self-association of water in octanol.26 NOE measurements were performed (Figure 2b) where two spectrum characters should be noticed: (1) separate peaks belonging to water and octanol hydroxyl are observed, and the splitting of octanol hydroxyl as triplet is reserved; (2) a negative NOE exists between water and octanol hydroxyl. All these indicate a relatively slow chemical exchange between these two hydroxyl groups; the hydrogen bond formation between octanol and water is not favored. This result is in agreement with previous works7,24 that relatively little water-alcohol hydrogen bonds
exist in the mixture: water and alcohol prefer to build their own respective hydrogen-bond networks. Research by molecular simulation20,23,24 and dielectric study suggest that octanol-saturated water molecules are lodged in or near the polar core of the aggregates. It was found in Table 1 that T1 of water in this binary mixture is the smaller compared to those of an octanol hydroxyl in the same system and that of water in pure state. The same is true on the self-diffusion coefficient of water. By examining Figure 3b of NOE measurement, two noticeable features emerge, (1) both octanol hydroxyl and water protons have NOE with H1, and f1{-OHH2O} is smaller than f1{-OHoct}; (2) the proton NOE enhancements between water and the hydrocarbon chain of the aggregates are lacking. Given the above information, it appears that water molecules prefer to migrate into the polar region of the molecular aggregates; they are confined in the innermost core of the cluster with restricted motion, and no direct contact is observed between water and the nonpolar alkyl chain. Brillouin and depolarized-Rayleigh scattering data show that the addition of water does not cause any significant change on the octanol structure.7 In correspondence, the δ, T1, and the NOE data show relatively little differences between the two states (Table 1). It is believed that the primary structure of octanol is conserved with the addition of water. Meanwhile, a detailed analysis on the small variations of these parameters reveals some clues on the minor modifications of octanol reversed micellelike structure. Both δ and T1 show a tendency to vary toward the less concentrated solution: a small upfield shift of octanol protons and a small increase on T1’s. The variation of T1 which indicates a freer motion of octanol in this binary system is in agreement with that of the self-diffusion coefficient (D) by experiment and simulation. The increase of D of octanol with the addition of water is interpreted by Oliveira et al. as water increasing the diffusion ability of octanol in the solvent mixture.23 Therefore, it can be deduced that the presence of water will probably loosen the compact association of the alcohol cluster by lengthening the distances between the neighboring alkyl chains, that helps it to move and diffuse more freely, and this small modification on the alkyl chain will probably stabilize the system by reducing the repelling forces. The energy increase due to the reduced hydrogen-bonding ability of water and the octanol hydroxyl in the cluster is compensated by the energy decrease due to these reduced repelling forces. Thus, the energy of the whole system will achieve a new balance. The preferential solvations of some solutes such as benzene, p-cresol, prop-2-yn-1-ol, etc. in water-saturated 1-octanol were also investigated. Similar results have been obtained; the polar functional groups of the solute reside in the polar region, while the nonpolar groups mainly make contact with the nonpolar regions of the alcohol solution. These offer more evidence on the microheterogeneity of the solution and the loosening association structure of 1-octanol with the addition of water. In conclusion, a “core-corona-shell” model for the watersaturated octanol cluster can be drawn. The cluster consists of the inner core of hydrogen-bonded water molecules, then the corona of hydrogen-bonded octanol hydroxyls, and finally the shell of the alkyl chains radiating generally outward with a distance slightly larger than that in neat octanol. Water and octanol hydroxyls form the polar region, and the alkyl chains form the nonpolar region. The original octanol cluster structure is primarily retained with the addition of water, and a small modification by loosening the compact arrangement of the cluster has been suggested.
Microheterogeneity of Water-Saturated 1-Octanol Conclusion 1H
NMR data, especially Through comprehensive study of those of NOE measurements, a model of a reverse micelle-like structure of 1-octanol aggregate has been proposed. Different from the previous description of a chain or liner-like structure on neat octanol, this model focuses not only on the arrangement of hydrogen-bonded hydroxyls but also on that of the hydrocarbon chain. It is believed to be a more comprehensive picture of the cluster structure of dry octanol. The water molecule in water-saturated octanol prefers to migrate into the innermost core of the octanol cluster; its presence results in some minor modifications to the octanol structure, which is similar to the one proposed by Chen in their simulation work,17 where suggestions are made that wet octanol has a large cylindrical micelle with a water core. Different from their suggestions that substantial alteration takes place on octanol structure with the presence of water, we found that only small changes take place in this process. This discrepancy lies in the fact that their studies were based on a different original structure of neat octanol. Furthermore, by NOE measurements, the preferential solvation of 1-octanol demonstrates the microheterogeneity of octanol at the molecular level. References and Notes (1) Kirsch, J. L.; Coffln, D. R. J. Phys. Chem. 1976, 80, 2448-2451. (2) Baro´n, M.; Mechettl, H. J. Phys. Chem. 1982, 86, 3464-3648. (3) Wong, N. M.; Drago, R. S. J. Phys. Chem. 1991, 95, 7542-7545. (4) Nishi, N.; Takasashi, S.; Matsumoto, M.; Tanaka, A.; Muraya, K.; Tankamuku, T.; Yamaguchi, T. J. Phys. Chem. 1995, 99, 462-468. (5) Dixit, S.; Crain, J.; Poon, W. C. K.; Finnery, J. L.; Soper, A. K. Nature 2002, 416, 829-832. (6) Allison, S. K.; Fox, J. P.; Hargreaves, R.; Bates, S. P. Phys. ReV. B 2005, 71, 024201-024205. (7) Sassi, P.; Paolantoni, M.; Cataliotti, R. S.; Palombo, F.; Morres, A. J. Phys. Chem. B 2004, 108, 19557-19565.
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