or Water

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New Concepts at the Interface: Novel Viewpoints and Interpretations, Theory and Computations

Nano-structures in n-octanol equilibrated with additives and/or water Gregor Cevc, Ida Berts, Stefan F. Fischer, Joachim O. Rädler, and Bert Nickel Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.8b00142 • Publication Date (Web): 24 Apr 2018 Downloaded from http://pubs.acs.org on April 24, 2018

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Langmuir

Nano-structures in

n-octanol

equilibrated with

additives and/or water Gregor Cevc,

∗,†,‡

¶

Ida Berts,

Stefan F. Fischer,

Nickel

†The

¶

Joachim O. Rädler,

¶,‡

and Bert

¶,‡

Advanced Treatments Institute, Tassilostr. 3, D-82131 Gauting, Germany, E.U.

‡Nanosystems ¶Physics

Initiative, Munich, D-80539 Munich, Germany, E.U.

Department, Ludwig-Maximillians University, Geschwister-Scholl-Platz 1, D-80539 Munich, Germany, E.U.

E-mail: [email protected]

Phone: +49 (0)89 89 355 771. Fax: +49 (0)89 903 6507 Keywords:

Mesophase, liquid crystal, interface, n-alkanols, alkanes, ketoprofen, binding, lipophilicity, drug development Abstract

Fluid fatty alcohols are believed to be nanostructured but broadly amorphous (i.e., non-crystalline) uids and solvents, including the most popular fatty tissue mimetic: hydrated n-octanol (i.e., hydro-octanol). To check this premise, we studied dry octanol and hydro-octanol, as a model of relatively short uid n-alkanols, with small angle Xrays scattering (SAXS). We also combined this alkanol with the matching alkane (i.e., octane) and with a common anti-inammatory pain-killer (ketoprofen). This revealed that (hydro-)octanol, and arguably any other short fatty alcohol, forms a mesophase.

1

ACS Paragon Plus Environment

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Its basic structural motif are regularly packed polar nanoclusters, reected in the inner peak in SAXS diractogram of (hydro-)octanol and other uid n-alkanols. The nanoclusters arguably resemble tiny, (inverse) hydrated bilayer fragments, located on a thermally smeared paracrystalline lattice. Additives to hydro-octanol can change the nanoclusters only moderately, when at all. For example, octane and the drug ketoprofen added to hydro-octanol enlarge the nanoclusters only little, due to the mixture's packing frustration. To associate with and to bring more water into hydro-octanol, an additive must hence transform the nanoclusters: it expands them into irregularly distributed aqueous lacunae that form a proto-microemulsion, reected in the previously unknown Guinier's SAXS signal. A 'weak' (i.e., a weakly polar or non-polar) additive can moreover create only size-limited lacunae. Coexistence of nanoclusters and lacunae, as well as size variability of the latter in hydro-octanol, subvert the concept of octanolwater partition coecient, which relies on the studied compartments homogeneity. In turn, it opens new possibilities for interfacial catalysis. Reinterpreting 'octanol-water partition coecient' data in terms of octanol-water association or binding constant(s) could furthermore diminish variability of molecular lipophilicity description and pave the ground toward more precise theoretical quantication and prediction of molecular properties.

Introduction Fatty alcohols (alkanols, Cn -OH) and parans (alkanes, Cn ) are immensely useful, often also as solvents. Octanol (C8-OH) is a particularly interesting 'solvent', broadly accepted as the simplest surrogate for fatty tissues. Researchers hence commonly employ C8-OH to anticipate molecular distribution between an aqueous and a fatty compartment, based on so-called octanol-water partition coecient. The latter is also included even in the shortest molecular characterisations, including the popular 'rule of ve' used to assess molecular drugability. Our discoveries presented herein have therefore multiple implications, including C

C

1

2

2


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invalidation of the notion that octanol is a simple solvent. Relatively long, ordered, dry alkanols and such alkanes have a well explored structure and temperature dependence. Above their melting transition temperature, T , which increases with the number of carbons per fatty chain, n , the chains are uid and orientationally disordered, with only a low residual long-range order. Below T , but above another characteristic temperature, T < T , the fatty chains are ordered and packed on a, potentially distorted, hexagonal (rhombohedral) lattice. The propensity for the resulting rotator (i.e., 'R') phase increases with n value and the involved alkanol hydration. At even lower temperatures, T < T , a pseudo-hexagonal (orthorhombic) lattice prevails. The fatty chains are fully extended on the lattice and tilted relative to the basal plane, if they are long. The thickness of a crystalline untilted alkanol bilayer is proportional to n . The resulting repeat distance, d , is then given by d = 2[0.192+0.127n ] nm for the alkanols with an even, intermediate number of carbons (13 ≤ n ≤ 25)and thus essentially the same as for the corresponding crystalline alkanes. Alkanes packing is also similar in the untilted rotator-, α- and β -phases: d = 2[0.195 + 0.127n ] nm. By contrast, such d vs. n relationship describes just the β -phase of alkanols with an even n value; in the α-phase, alkanol bilayer thickness generally increases solely by 0.112-0.114 nm per additional methylene in a fatty chain. This reects partial disordering of the fatty chains in the α-phase, and implies their order parameter in the phase to be S = 0.89 ± 0.01 on average. The disorder probaly involves just a chain length dependent part of the fatty chains, and entails primarily the OH-groups in the gauche conformation. Recently, the interface-induced alkane and alkanol self-ordering on top of a melt drew researchers' attention. Owing chiey to X-rays reectometry, details of the quasitwo-dimensional solid structures formed by various such long molecules are now known. For example, if T − T ≤ 3 degrees, alkanes with 16 ≤ n ≤ 50 form a surface-induced monolayer, in which the fatty chains with an even 18 ≤ n ≤ 30 are perpendicular to the surface and the longer chains are tilted (conrmed for 32 ≤ n ≤ 44). Conversely, dry 38

9,10

11

m

C

m

R

m

5

C

R

68,1114

C

r

r

14

C

C

35

0

r

10,12

C

0

r

C

C

R

35

6,13

5,19,3639

m,bulk

C

C

C

3


37

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in the T − T ≤ 1 degree range form a surface ordered bilayer, in which the fatty chains with an even 18 ≤ n ≤ 24 are likewise perpendicular to the surface and hexagonally packed, whereas the longer fatty chains are tilted relative to the surface (conrmed for n = 26 and 28). Molecular area of the n = 30 n-alkanol, with only slightly tilted chains, grown into a 2D crystal at an air-water interface is A = 0.188 ± 0.001 nm . In a typical surfaceordered alkanol bilayer molecular area is moderately bigger, A ' 0.203 nm . In an alkanol monolayer at the water-air interface equilibrated with similar alcohol in the bulk each ordered fatty chain with 10 ≤ n ≤ 16 occupies a somewhat larger molecular area, A = 0.215 nm . Alkanols with 20 ≤ n ≤ 30 layered at a hexane-water interface even occupy an area A = 0.234 nm , that essentially equals a uid fatty chain area in a monolayer, A ' 0.23 nm . Spontaneous insertion of one hexane per six alcohol molecules hence completely abrogates such ordered alkanols packing stress, and thus promotes their hydration. Hydroxyls of n-alcohols attract water and tend to H-bond in rows, packing constraints of their attached fatty chains allowing. A denite melting point hence implies that the inspected alcohol has a xed stoichiometry of hydration, which stabilises rotator phase(s) in alkanols with 12 ≤ n ≤ 26. In the maximally swollen rotator phase alkanol/water molar ratio is 2/1. Then, one water is intercalated between a pair of alcohol molecules facing each other in a bilayer, as in the surface-ordered alkanol bilayer. (See also footnote .) Relatively short, and consequently normally uid, alkanols (with or without water) are structurally far less explored than the longer alkanols. Previous researchers drew from diractometry results just two rm quantitative conclusions about the former: i) the 'main' X-ray scattering peak, detectable at q ' 1.342 Å (see gure 1), characterises the average lateral separation of uid fatty chains on a hexagonal lattice and implies rather small molecular area per uid fatty chain: A = 0.19 nm ; ii) the 'pre-peak', 'side peak', or 'inner peak' (herein: the 'mesophase peak') at 0.36 ≤ q /Å≤ 0.40 in the small angle X-ray scattering alkanols

m,bulk

C

19

C

C

2 40

c

2 32

b

C

2 39 ∗

s

C

2 32

c

f

32

2

32

15

16,17

18

C

18

19

0

∗

−1

20

f

2

0

∗ The negative dierence is arguably due to the extra cohesion mediated by the 'water-bridges', H-bonded to the nearest alcohols facing each other in the opposing bilayer halves.

4


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Langmuir

(SAXS) diractogram of uid n-alkanols (cf. gures 1 and 2) implies polar OH-groups aggregation and indicates their distribution. Any further, rm information about uid alcohols structureand its sensitivity to additivesis missing to date. Stewart and Morrow were the rst to assign the two observed SAXS signals from uid fatty alcohols to "planes containing polar groups ... not perpendicular to the direction of the parallel chain molecules". They did not elaborate on this further, however, and their inference gained no traction. In the rst quantitative scrutiny of the corresponding SAXS data known to us, Franks dealt with (hydro)octanol as if it were an amorphous uid in which the alkanols' OH-groups, and in case water, form spherical groups ('reverse micelles' with aggregation numbers of 12 for dry and 16 for wet n-octanol). Vahvaselkä et al. likewise analysed the side maxima of SAXS on C1-OH to C4-OH and C8-OH as if these uid alcohols were an amorphous material. Their conclusion was that these alcohols form linear arrays of about ten molecules each, with irregularly arranged chains of variable eective chain length. Tom²i£, Jamnik, Glatter and colleagues reported similar SAXS data for the C2-OH to C10-OH series (see ref. and gure S5 in supporting information). Guided by computer simulations and their SAXS results modelling, these scientists also described uid alcohols as ensembles of sequentially H-bonded, exible, linear aggregates (winding chains), distributed uniformly in a uid phase. Other experts then shared their view. Relying on their Monte-Carlo simulations, Chen and Siepmann posit that "water saturation substantially alters the n-octanol environment from predominantly linear aggregates in dry octanol to larger cylindrical micelles with water cores", which were recently suggested to be thinner than 1 nm. A consensus on hydro-octanol structure has thus not yet been reached. We therefore studied with SAXS dry and fully hydrated n-octanol (i.e., hydro-octanol), as a particularly relevant representative of the relatively short, uid fatty alcohols. We moreover combined this alkanol with the matching alkane (i.e., octane) and with one popular anti-inammatory pain-killer drug, ketoprofen (in its neutral as well as charged form). Our 20

21

22 †

23

23

24

25

26

† We think that such assumption is only justiable for the quasi-spherical alcohols, such as tert-butanol, 31 but not for n-alkanols.

5


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resulting experimental data and analyses strongly suggest that n-octanol is not an amorphous uid but rather a (frustrated) mesophase, which is arguably the case with other uid nalkanols, too. The octanol's nano-structure is hence typically, but not necessarily, sensitive to additives, even when they adsorb onto or are incorporated into the mesophase in just a small quantity (for ketoprofen in micromolar range). Further additive incorporation requires bigger structural changes: generation of the inverse-micellar, aqueous, spherical lacunae that are dispersed irregularly throughout the mesophase (cf. 3). This has far reaching consequences, including the need to reformulate the so-called water-oilmimicked by water-octanolpartition coecient in terms of one or several adsorption or binding (i.e., association) constants.

Materials and methods X-ray setup

The small angle X-ray scattering (SAXS) setup used in the study has a microfocus X-ray source with a molybdenum target and the corresponding 2D Goebel mirror, Genix3D (both from Xenocs, Sassenage, France). This provides a highly collimated beam of 0.71 Å Xrays with less than 0.2 mrad divergence in vertical and horizontal direction. The 84 cm long collimation path has two scatterless slits, minimising parasitic scattering. The beam is around 1 mm wide, depending on the slits setting, which aords ∼ 3.3 MPh s ux at the sample. The 1 mm thick sensor of the employed Pilatus 100k detector (Dectris, Baden, Switzerland) has 76% quantum eciency for the energy of the employed molybdenum K-α line. The Teon sample chamber (inner thickness 9 mm, optimized for such energy) has two parallel Kapton windows, each 4 mm wide. The two utilised sample to detector distances (38 cm, 1100 cm) were calibrated separately with silver behenate. These distances aord respective q-ranges between 0.02-0.36 Å and 0.07-1.9 Å , which blend seamlessly and together cover the entire mesophase peak region. −1

−1

−1

6


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Langmuir

Materials

Chloroform (99.9%) and methanol (99.95%) were from Carl Roth (Karlsruhe, Germany). Octane and n-octanol (99%, Sigma-Aldrich Chemie, Taufkirchen, Germany) were used as received, as was the nonsteroidal anti-inammatory drug, ketoprofen (pharmaceutical quality, CPM, Feldkirchen, Germany). Samples preparation

To make the sodium salt of ketoprofen, we took-up the drug in chloroform/methanol/milli-Q water mixture, made in the proportion that ensured good separation of organic and aqueous phase. Adding an excess of sodium hydroxide (C = 10 M) increased the aqueous phase alkalinity to pH ∼ 10.75, which is ∼ 6 log units above the drug's apparent dissociation / (de)protonation constant in an aqueous solution. After rapidly collecting the organic phase, we up-concentrated the latter with a stream of nitrogen and nally dried it up completely in a vacuum chamber (< 200 Pa). Dissolution of ketoprofen or its sodium salt in pure water yielded the neutral (KTO) or charged (KTO ) drug form, respectively, as conrmed by solution pH measurements. To prepare the fully hydrated octanol (herein also termed hydro-octanol), we combined equal volumes of milli-Q water (specic resistance 18.2 MΩ cm at 25 degrees Celsius) and n-octanol in a shake-ask. We rst shook the mixture manually, but vigorously, for 1 min and then mechanically, on a laboratory shaker, for 24 h, after having recorded dierent SAXS patterns with similar samples aged for shorter periods. A 2 day equilibration ensured complete separation of the water-rich, lower, and the octanol-rich, upper, phase. We used the latter for all measurements and further samples preparation. To prepare octane-containing samples, we combined an equivoluminous octanol and water mixture with such amounts of octane that yielded the nal volume concentrations ratio in the range 10/100-100/100. (To translate these concentrations into the corresponding molar concentrations, we used the published individual compound densities specied in table 1, NaOH

27

−

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Page 8 of 37

together with some other pertinent molecular information.) The specied ketoprofen molar concentration always relates to the combined uids volume (i.e., water plus n-octanol and, in case, octane). Table 1: The explored compounds characteristics Water Octane Octanol Ketoprofen (H O) (C8) (C8-OH) (KTO) MW 18.053 114.23 130.23 254.281 Density [g/mL] 0.9982 0.703 0.827 1.198 Molarity of (theoretical) 1 L 55.49 12.45 9.29 3.28 log P 4.32 ± 0.36 3.05 ± 0.15 3.19 ± 0.15 log S -7.21 -3.43 -3.34 Surface tension at 25 C [mN/m] 72 51.16 58 59.8 Minimal projection area [Å 2] 7.26 25.75 22.82 41.68 Min z-length [Å] 3.69 12.96 14.15 13.19 V [Å ] 29.91 147.06 155.64 233.68 A [Å ] 35.6 276.74 286.75 367.55 A [Å ] 25.3 0 20.23 54.37 A V 1.9 3.2 3.2 3.1 A V 1.6 0.0 0.8 1.2 V [Å ] 29.91 0 8.58 13.3 Relative electrons density, ∆ρ [Å ] 0.0334 0 0.1166 0.2257 ∆ρ vs. ∆ρ 0.148 0 0.517 0.226 Partition coecients calculated with VCCLAB, Virtual Computational Chemistry Laboratory, http://www.vcclab.org, 2005. The values printed in italic calculated at http://www.chemicalize.org, using the software developed by ChemAxon.; Octane, octanol, and ketoprofen surface tensions, respectively, from Zeppieri S. et al. J. Chem. Eng. Data 2001, 46, 1086-1088; Can S. Z. et al. J. Phys. Chem. C 2007, 111, 8739-8748; T. Messiaen, Ph. D.Thesis, University of Ghent, 2010. Other results averages based on dierent sources. Calculated by multiplying the third power of the previous two cells ratio with V . 2

a

cal

b

◦

2

total

total

polar 1/2 1/3 total total 1/2 1/3 polar total

polar,estimated rel

rel

3

2 2

c

3

3

rel,KTO

a

b

c

total

Small Angle X-ray Scattering (SAXS)

We typically repeated each SAXS experiment trice, collecting SAXS data each time for 60 min. This aorded two-dimensional scattering intensity vs. momentum transfer plots, which we stored in a local computer for further processing. 8


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Langmuir

Each SAXS diractogram analysis started with the original, two-dimensional, data set transformation into a one-dimensional data set, using the Nika software. To gain absolute intensity values, we converted such data with the formula I (q) ≡ I(q) = I (q)/(I AlT t∆Ω), wherein I A is the uence, l the sample thickness, T the sample transmission, t the measuring time, ∆Ω the detector view angle, and q the momentum transfer. Finally, we subtracted the I(q) measured with the pure octane ('Background') from the correspondingly measured I(q) of the studied sample, to extract the peak most relevant for the overall structure analysis (the 'mesophase peak'). Figure 1 exemplies the outcome for dry octanol. 28

absolute

measured

0

0

SAXS results modelling

After having tested various reasonable options, we routinely described the mesophase peak with the Lorentz formula ILoren (q) = Prefactor[1 + (q − q0 )2 B −2 ]−1

(1)

,

wherein q denes the mesophase peak position in Å and B the mesophase peak half width at half maximum (HWHM in Å ). The 'Prefactor' hence gauges the scattering electrons excess density, ∆ρ = πPrefactorB, and therefore I = V ∆ρ . Expressing the simulated SAXS diractogram as a sum of two Lorentz-curves did not improve the t signicantly, and was therefore not pursued further. Using a Gauss- rather than Lorentz-form of peak even deteriorated the ts quality. The only researchers who had published a detailed analysis of SAXS on octanol applied the Ornstein-Zernike's formalism to model and thus analyse their I(q) data. We consequently also rst attempted to model our own I(q) data, covering a broader q-range, with similar approach. Having had pre-determined that the mesophase peak is more of the Lorentz- than of the Gauss-form, we implemented the Lorentz rather than the Gauss' form −1

0

−1

Loren

0,Loren

Loren

21

9


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Figure 1: The complete small angle X-ray scattering (SAXS) diractogram measured in the present study, including the or 'main', or chains-related peak, at q = 1.342 Å , and the 'inner' or 'side' peak or 'pre-peak', here at q = 0.4 05 Å , to which we refer in the main paper body as the mesophase peak. Symbols: experimental data for pure dry octanol (blue ◦), octane (grey ◦). Bullets (•) show the dierence between SAXS on octanol and SAXS on octane, being essentially the mesophase peak. Curves: data modelling with an optimised Gauss-form of peak (red curve, which is compatible with the bilayer-like scatterers that lack a long-range order) and the Ornstein-Zernike model (lled orange curve, which is compatible with a uid-like liquid alcohol structure). The latter model was inspired by ref., but involves herein a Gauss' form factor rather than the spherical form factor of Franks and colleagues, as the former form factor ts the data better than the latter form factor. Using an optimised Lorentz-form hence ensures the best t of X-rays scattering on hydro-octanol with or without additives, and also points to the bilayer-like scatterers existence (see the curves reproducing experimental data in gure 2). 0

0

−1

−1

21

10


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Langmuir

factor into the Ornstein-Zernike's formalism, however, with unsatisfactory results (cf. gure 1). Inspired by spontaneous emergence of alkanol bilayers at an air-uid alkanol interface, we therefore re-interpreted the mesophase peak as the rst of the Bragg's peaks caused by SAXS on quasi-planar, bilayer like, scatterers. Figure 1 illustrates and compares the outcome of the two tested analytical approaches. The data-tting curve (the red curve), which infers existence of bilayer-like (nano)structures, matches the experimental mesophase peak (black dots) perfectly. By contrast, the previously advocated structural model of Franks and colleagues (the orange area), which presumes a uid-like n-octanol structure, deviates from our experimental results quite appreciably, especially in the peak anks. Limiting the SAXS data analysis to the narrower q-range, explored by Franks and colleagues, obfuscates the problem, which can explain their, in our opinion erroneous, conclusions. Justied by the fact that the new structural model describes the mesophase peak more precisely than the Ornstein-Zernike's model we analysed our complete diractometric data-set solely with the former model. We moreover needed to consider an extra, previously unrecorded contribution to the SAXS diractograms, which peaks at q = 0 Å . To this end, we added to the I (q)) the 'Guinier's contribution', described with 21

−1

Loren

(2)

IGuin (q) = I0,Guin exp (−Rg2 q 2 /3) ,

wherein R is gyration radius and I = V ∆ρ ≡ C , C is proportional to the underlying X-rays scatters (i.e., lacunae) concentration. All ts illustrated in gure 2 hence rely on the superposition g

0,Guin

Guin

L

L

I(q) = ILoren (q) + IGuin (q) + Background .

(3)

Figures 1 and 2 conrm excellent reproduction of all our SAXS results, within experimental error limit, by the superposition. 11


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Structural information extraction

Consistent with the structural model introduced hereinand with the mesophase peak identication with the rst Bragg's peak at q (in Å )we posit that −1

0

(4)

dr ≡ (2π/10q0 ) nm = dp + dCnC (nC )

gives the repeat distance of bilayer-like nanoclusters (see their schematic illustration in the right part of panel 3H). In this expression, d denotes the nanocluster's polar region thickness, including two hydroxyl radical lengths, l , any bound molecules polar (parts), and/or water layer thickness. d is the length of two fatty chains with n carbons each, which we calculated from d (n ) ≡ 2l = 2(0.127n S nm + ∆l ) , (5) 0.127 nm being the length-increment per methylene group and ∆l the 'excess length' of the terminal methyl group. We found the appropriate values for l = 0.216 nm, l , and hence l = 0.558 nm, together with the corresponding eective order parameter value, S = 0.51, by linearly tting the repeat distances of molten C2-OH to C10-OH, and identifying the n = 0 value with 2(l + ∆l ). To obtain ∆l = 0.038 nm, we similarly analysed the d values reported for C11-C100 in α- and β -phases by Broadhurst. For n-octanol we thus used p

OH

CnC

C

CnC

C

CnC

C

eff

CH3

CH3

OH

CnC

C8

eff

23

OH

CH3

C

CH3

r

10

0

(6)

dp = dr − 1.116 nm .

Taking a moderately dierent subtrahendus (e.g., twice the dierence between our own d value measured with dry C8-OH and d , being 1.1023 nm (cf. table 2), does not aect our general conclusions. To describe molecular area increase from the initial A = 0.190 nm value to the r

OH

C8,0

2

‡

Our value matches closely the cross-section of an alkane, which increases with temperature in the 0.187-0.197 nm2 range. 35 ‡

12


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Langmuir

maximum achievable A we used

C8,max

= 0.221

nm as a function of an additive concentration, C , 2

a

−1 0−1 A(Ca , Ka0 ) = AC8,0 1 + (AC8,max A−1 C8,0 − 1)/(1 + Ca Ka )

(7)

,

wherein K is an adjustable constant. Using the result of this formula and V = 0.0299 nm as water molecule volume we then calculated the number of interfacially bound water molecules n (C ) = (d − d ) ∗ A(C , K )/V (8) from the measured repeat distance as a function of C , after identifying d with the dry n-octanol's repeat distance. (To model octane addition, we used K = 0.807 mol . To model KTO binding to octanol-octane blend, we employed K = 7.240 mol .) 0 a

w

3

w

a

r

r,dry

a

0 a

w

a

r,dry

−1

0 a

−1

0 a

Solute binding

Additive binding description relied on the Langmuir's binding isotherm Observable(Ca ) = ObservableMax (1 + Ca−1 Ka−1 ) + Observable(Ca = 0),

(9)

wherein Observable identies the largest achievable Observable(C ) value at saturation, i.e., its asymptotic value. K is the corresponding binding constant. Max

a

a

Supporting information

The supporting information, available in electronic form at the journal web-site, includes graphic representations of full SAXS diractograms (i.e., always including the main and the mesophase peak) as a function of various additives concentration and a compilation of the SAXS derived repeat distances measured with uid C1-OH to C10-OH n-alkanols (i.e., a blow-up of of the corresponding part of gure 4). Also included are the precise denitions of some parameters listed in table 3. 13


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Page 14 of 37

Results and discussion Our SAXS studies of the fully hydrated n-octanol started with an equivoluminous wateroctanol combination (nominal [C8-OH] = 4.61 M), and always yielded diractograms similar to that shown in gure 1. The measured mesophase peak implies a similar repeat distance, d ≡ π/5q = 1.743 nm, for any water concentration. This is only ∼ 0.2 nm above the dry C8-OH result, d = 1.529 nm, matching within experimental error limit the corresponding previously published values, d ' 1.540 nm. Octanol's low polarity (C8-OH: log P = 3.05) is but one of the reasons for this. The peak around q = 1.5 Å is hydration insensitive (cf. table 2) and related to the (hk0) Bragg's peak measurable with solid n-alkanols and alkanes in the hexagonal rotator phase. Lack of the corresponding higher-order (namely (11) and (20)) peaks is explicable by the large positional uctuations, which magnify the Debye-Waller's factor. We explain similarly the characteristics of the mesophase peak stemming from SAXS on the polar groups, which we identify with a dierent (hk0) Bragg's peak. Its singularity and changing width point at the thermally driven positional uctuations of the bilayer-like nano-clusters, which act as X-rays scatterers on a (quasi-monoclinic?) para-crystalline lattice. This peak hence reveals the repeat distance of the underlying mesophase, d , the thickness of polar region, d , and indirectly their hydration. To gain deeper insight, we also blended hydro-octanol with several small organic molecules. Addition of the length-matched alkane (octane, C8) shifts the mesophase peak to lower qvalues, uncovering the resulting blend's better hydration (see gure 2A and table 3). Octane hence increases C8-OH/H O molar ratio to at least 1/1, notwithstanding its hydrophobicity (C8: log P = 4.32)! C8 moreover enlarges the area per OH-group to A = 0.221 nm , i.e., close to the uid C8-OH ideal area (A = 0.214 nm ), arguably by relaxing the n-octanol's packing-constraints. The initially linear shift of the mesophase peak position and the peak's width insensitivity to [C8] support the conclusion. Increasing [C8] much 14 ACS Paragon Plus Environment r

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above 0.68 M, and thus appreciably exceeding the preferred C8/C8-OH = 1/6 molar ratio for alkane insertion into a layer of alkanols, widens the mesophase peak more (cf. table 3) but increases the polar region's thickness relatively less (cf. panel 3D and table 3), due to concurrent molecular area expansion. Consequently, d approaches only asymptotically d = 0.516 nm, indicative of the nanoclusters restricting paracrystalline lattice. Octanol better accommodation to the latter in presence of suciently concentrated octane thus allows a nearly ideal hydration of the alcohol, C8-OH/H O ≥ 1.5 mol/mol, reected also in 2d ' 2R (see panels 3A, D and further text for this and other concomitant changes.) 32

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Table 2: The SAXS derived structural parameters of dry and water-saturated n-octanol (= hydro-octanol) R q HWHM d /2 q HWHM I ∆ρ [nm] [Å ] [Å ] [nm] [Å ] [Å ] [cm ] [nm ]10 Octanol, dry 0.468 1.342 0.27 0.22 0.405 0.127 0.0243 0.538 Octanol, hydrated 0.468 1.342 0.27 0.31 0.360 0.102 0.0266 0.418 chains

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By contrast, a partially hydrophilic, and hence amphipatic, nonsteroidal anti-inammatory and pain-killing drug, the neutral ketoprofen (KTO: log P = 3.19), does not shift the mesophase peak markedly (cf. panel 2C). The moderately polar KTO hence does not bind to the polar nanoclusters formed by C8-OH and thus fails to increase their hydration, unlike the completely apolar octane. Similar size and polarity of ketoprofen and C8-OH therefore do not suce for ensuring these compounds compatibility. SAXS diractograms of hydro-octanol supplemented with C8 and/or KTO are clearly asymmetric in the mesophase peak region, most obviously at high KTO concentrations (see panels 2B-D). The underlying X-rays scattering signal is centred at q = 0 Å and grows with increasing C8 and KTO concentration. Its replotting in the Guinier's fashion exposes existence of the previously undetected X-ray scatterers (spherical polar aggregates) calc

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calculated dp,asympt value actually implies C8-OH/H2 O = 1.85 mol/mol, suggesting some direct H-bonding between alkanols.

15


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Page 16 of 37

Table 3: The SAXS derived structural parameters of various combinations of fully hydrated n-octanol (hydro-octanol) and, in case, octane (C8, if xed: [C8] = 0.68 M) with or without the neutral ketoprofen (KTO) or the anionic ketoprofen sodium (KTO ) R I ∆ρ d /2 q HWHM I ∆ρ [nm] [cm ] [nm ]10 [nm] [Å ] [Å ] [cm ] [nm ]10 Hydro-octanol + Octane [M] ([v-%]) 0.00 (0) n.a. 0.31 0.360 0.098 0.0258 0.418 0.29 (10) n.a. 0.36 0.342 0.111 0.0277 0.382 0.68 (25) n.a. 0.37 0.339 0.118 0.0277 0.374 1.23 (50) 0.58 0.0088 10.8 0.41 0.325 0.126 0.0263 0.321 2.05 (75) 0.58 0.0124 15.2 0.44 0.314 0.139 0.0262 0.297 4.40 (100) 0.58 0.0154 18.8 0.47 0.305 0.148 0.0242 0.256 Asymptotic value 0.52 Hydro-octanol + Ketoprofen [M] 0.0 n.a. 0.32 0.359 0.102 0.0266 0.401 0.1 0.34 0.0098 59.5 0.32 0.356 0.108 0.0270 0.412 0.2 0.40 0.0205 76.5 0.32 0.356 0.108 0.0263 0.400 0.3 0.45 0.0290 76.0 0.32 0.356 0.116 0.0253 0.385 0.5 0.58 0.0370 45.3 0.32 0.356 0.121 0.0310 0.474 Hydro-octanol+C8 + Ketoprofen [M] 0.0 n.a. 0.37 0.359 0.098 0.0277 0.374 0.1 0.49 0.0180 36.5 0.39 0.333 0.120 0.0300 0.386 0.2 0.51 0.0340 61.2 0.40 0.326 0.124 0.0296 0.365 0.3 0.53 0.0480 77.0 0.42 0.320 0.134 0.0314 0.369 0.5 0.52 0.0440 74.7 0.41 0.326 0.133 0.0305 0.374 Asymptotic value 0.43 Hydro-octanol + Ketoprofen Na [M] 0.0 n.a. 0.33 0.359 0.098 0.359 0.401 0.1 0.39 0.0102 41.0 0.36 0.347 0.105 0.3469 0.398 0.2 0.83 0.0890 37.2 0.42 0.327 0.122 0.3275 0.420 0.25 1.13 0.3234 121.4 0.51 0.289 0.158 0.289 0.572 0.3 1.21 0.4065 54.8 0.71 0.250 0.174 0.250 0.493 0.5 2.72 0.4664 5.5 3.01 0.088 0.113 0.088 0.348 Relative to octanol or water volumes, which were identical. These values are relatively less accurate, owing to the underlying signal weakness. −

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Figure 2: The measured (symbols) and tted (curves) SAXS diractograms of equivoluminous n-octanol/water combinations supplemented with dierent organic compounds, or compound forms, as a function of the nominal concentration of the latter in the total preparation. A: octane, C8; B: ketoprofen and octane, KTO+C8; C: ketoprofen, KTO; D: sodium ketoprofen, generating ketoprofen anion, KTO ; the lowest, red, data set and curve: dry octanol. The additives' molar concentration from bottom to top (for clarity, each following curve is shifted vertically): 0, 0.29, 0.68, 1.23, 2.05, 4.40 for C8 and 0, 0.1, 0.2, (0.25 just for KTO ), 0.3, 0.5 for KTO and KTO . C8 concentration in the blends with KTO is always [C8] = 0.68 M. −

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Page 18 of 37

G

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Figure 3: Eect of various additives' concentration, C , on the structural parameters derived from the data shown in gure 2 and specied in tables 2 and 3. Abundance, C (×10, ), and the average diametre, 2R (•,•), of aqueous lacuanae derived with the Guinier's style analysis from the signal centred at q = 0 Å . (Gray symbols generally imply [C8] = 0.68 M.) The thickness of nanoclusters polar region, d , illustrated in the lower panels (•,•), is dened in the text and shown as symbols for the 2 components (black) and 3 components (grey) hydrated mixtures of n-octanol (C8-OH), octane (C8), ketoprofen (KTO) or ketoprofen anion (KTO ) equilibrated with an equivoluminous aqueous phase. The black horizontal line: dry C8-OH. Curves: ts to the data based on the Langmuir's adsorption isotherm. Grey, horizontal dotted lines: the asymptotic value resulting from such t to the d data pertaining to C8. The sketches on the right illustrate: G - polar nanoclusters comprised of C8-OH headgroups (red) and water (blue) gathered in aqueous lacunae, here created by additives (KTO or KTO ; orange) in the uid hydrocarbons (green). H right: the essentially layered and bilayer like nanoclusters, rst reported herein; H left: the previously proposed "Ornstein-Zernike's type" polar groups distribution, invoked by Franks and colleagues. a

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and their gyration radius, R . (The latter is the slope of ln[I(q)] vs. q curve at low qvalues, after exclusion of the mesophase peak contribution.) Such aggregates are relatively scarce, are therefore barely detectable, in the plain hydro-octanol-octane mixtures (cf. panel 3A). They are more copious in C8-OH combinations with KTO, especially if octanol is enriched with octane (cf. panel 3B). As in the plain hydro-octanol-octane mixtures, the polar aggregates nal diametre closely resembles the maximum double thickness of polar, bilayer like nanoclusters, 2R ' 2d (see panels 3B, E), but the asymptotic d value calculated for hydro-octanol-KTO combinations is 0.174 nm below d . This implies half a bound water dierence in absence of C8. The near constancy of R vs. the added octane concentration and the small, smooth, increase of R with the lacunae inducing KTO concentration suggests small polydispersity of R values, which we are presently unable to quantify, however. Testard and collaborators had measured SAXS on two dierent C12-C8-OH mixtures contacted with water in an investigation focussing on C8-OH enhanced solubilisation of dimethyldioctylhexylethoxymalonamide surfactant in C12 (in the putative form of reverse micelles). This revealed a side maximum at 0.32 Å for the C12 rich and at 0.40 Å for the C8-OH rich preparations, resembling directionally our own ndings with the C8C8-OH mixtures. The authors interpreted their results dierently than we, however: as indicators of four-, ve-, and six-membered cyclic oligomers of alcohol, and often used the term "solution" in their paper. The same group later measured, but did not structurally analyse, SAXS on several n-alkanol/alkane mixtures: C12-C4-OH with approximate alcohol concentrations range 0.54-1.35 M and C12-C7-OH with approximate alcohol concentrations range 0.34-0.8 M, always with primary focus on alkane. Our independent analysis of these suitably adjusted data with a focus on alcohols, along the lines illustrated in our gure 3, revealed an asymptotic d (C ) curve, too. The more polar, anionic ketoprofen form (KTO : log P ∼ 1.7) aects SAXS on hydrooctanol much more than either KTO or C8. KTO at C = 0.1 M moves the mesophase 2

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Page 20 of 37

peak to 0.327 Å , for example (cf. table 3). Such nominal concentration of KTO also causes a well resolved SAXS signal at q = 0 Å , due to the underlying Guinier's signal intensity (cf. panel 2D). Increasing C generally enlarges the zero-centred signal at the mesophase peak's expense. The latter peak is consequently nearly undetectable for C = 0.5 M (cf. panel 2D and supporting gure S4). This reveals KTO progressive incorporation into C8-OH that gradually transforms most of bilayer like nanoclusters into larger spherical polar aggregates without any apparent constraint on R vs. C (cf. 3C). The relatively long range of electrostatic repulsion between the interfaces charged by KTO , as compared with the repulsion due mainly to interfacial hydration, can explain such liberal growth. Our data reported herein conrm some earlier experimental results on uid n-alkanols and elucidate such alcohols structure, with multiple practical implications. First, our d value for n-octanol (cf. gure 4, ?) is near the 'approximate half thickness' d = 2[0.254 + 0.065n ] nm, of dry, uid n-alkanols with 2 ≤ n ≤ 10 at 25 C. Smallness of d -increment (0.065 nm/CH ) reveals extensive disorder in the uid fatty chains region and low order parameter therein (S ≡ S = 0.51). For comparison, the thickness of an untilted crystalline bilayer formed by alkanols with an even, intermediate, number of carbons (13 ≤ n ≤ 25) is d = 2[0.192 + 0.127n ] nm. This resembles alkanes repeat distance in the untilted crystalline α- and β -phases and in an untilted rotator-phase: d = 2[0.195 + 0.127n ] nm. Each CH group hence increases bilayer thickness in an alkanol α-phase by 0.112-0.114 nm, corresponding to a rather high average order parameter (e.g.: S = 0.89 ± 0.01 in the rotator phase). Although S is much smaller than S , uid alkanes and alkanols tend to order spontaneously on top of their melt, forming a quasi-two-dimensional solid. Since OH-groups are apt to engage in H-bonds, the resulting alkanols' structure is an extensive bilayer. Herein we argue that alkanols manifestly form (tiny) bilayers even in their uid bulk, likewise promoted by H-bonding. Computer models cannot replicate such structuring yet, since the total −1

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volume amenable to a typical numerical simulation is presently rather small. Present simulations can consequently only reproduce the fatty chains packing, and the resulting SAXS peak, but cannot properly mimic the mesophase peak nor address the Guinier's signal. Second, our value for the hydration caused increase of octanol repeat distance, ∆d = 0.19 · · · 0.20 nm, resembles ∆d = 0.174 ± 0.02 nm of tetradecanol in a rotator phase at maximum hydration. Two uid C8-OH molecules in a bulk hence bind just ∼1H O, like alkanols in a surface-ordered bilayer. We therefore posit that bound H O spans two adjacent headgroups in uid alkanol (nano)clusters, too, since the latter are packed too tightly to bind more water into a quasi-planar, bilayer-like, structure. Third, molecular area of hydro-octanol saturated with octane, A ' 0.221 nm , does not dier much from a uid C8-OH molecular area, A ≡ A = 0.214 nm , in an 'extrapolated C8-OH monolayer' at an air-water interface. For comparison: each crystalline alkanol (with slightly tilted n = 30 chains) occupies ' 0.188 nm in a monolayer at an air-water interface, which is a bit less than A ' 0.203 nm of alkanols in a surface-ordered bilayer. By contrast, molecular area of each ordered 10 ≤ n ≤ 16 alkanol in a monolayer at the air-water interface equilibrated with the corresponding bulk alcohol is 0.215 nm and the area of one alkanol with 20 ≤ n ≤ 30 layered at a hexane-water (C6-H O) interface is comparable to uid alkanes' area in the surface-induced monolayer, A ' 0.23 nm . This implies that C8 admixture aects hydro-octanol like insertion of one hexane per six longer chain alcohol molecules: by relieving molecular packing stress, it facilitates H-bonding between alkanols' OH-groups and/or between such groups and water (see further discussion). Fourth, the linear d (n ) dependence of uid short alkanols is related to similar n dependence of ordered longer alcohols in an untilted rotator, β -, or α-phase, which was not recognised before. Correspondingly, assuming proportionality between the average fatty 23

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theoretical, uid C8-OH monolayer at an air-water interface.

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chain order parameter in each such phase, S = S S < S = S = 1, aligns the otherwise divergent data sets (see gure 4 and the grey circles and star in it). The proportionality factor, S ' 0.58, quanties the extent of additional disordering of the fatty chains at a rotator-to-uid phase transition. Encouragingly, our S estimate is in accord with the SAXSbased conclusion that the gauche-fraction of liquid alkanes is ∼ 0.45. Excellent data ts (cf. gure 4) and good correlation between the (bilayer) repeat distance and the underlying hydrocarbon chain length give further credibility to the proposed similarity of alkanols' basic bilayer packing motif in ordered and uid phases. f

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Figure 4: Repeat distance, d , of alkanes (grey) and n-alkanols (black) as a function of carbons' number per fatty chain, n . α- and β -phase data from dierent studies (∗, ? ); half of β - (•) and α-phase (♦) from ref. ; half of R-phase ( ) from; α-phase ( ) from ref. ; melt (◦) from ref. and ( ) from ref. ; order parameter adjusted data for melt (◦); this study (?). Lines: linear ts, described in the text, with the corresponding order parameters, S ). r

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forms a mesophaseslightly dierently without or with waterits chain length and uidity resemblance to octane notwithstanding. The resulting polar nanoclusterscomprised of hydroxyls with some bound water surrounded by octyl chainsaccording to our study results, form a (quasi-monoclinic?) paracrystalline 'lattice'. Such nanoclusters' regular distribution gives rise to the mesophase peak, which we therefore identify with the rst of the corresponding Bragg's peaks, the higher orders being arguably wiped-out by thermal motions. Fluid octyls are then very tightly packed, causing their area to resemble the crystalline C8-OH area (A ' 0.19 nm < 0.214 nm ). Alkanol cross-section smallness normally limits each OH-group hydration to around 0.5 H O per uid n-octanol, merely (our value derived from SAXS data without any adjustable parameter: n = 0.60; the value derived by Karl-Fischer titration: n = 0.35 ), which matches the longer alcohols' hydration in an ordered rotator R phase. The C8-OH/H O = 2/1 molar ratio is well below the maximum water-binding capacity of a hydroxyl radical, however, which is 1.5 H O per OH-group (as determined for the least constrained n-alcohol, methanol ). Octane addition to octanol relaxes said C8-OH packing constraints, and thus geometric frustration, which increases OH-groups hydration, as occurs to C6-OH at a hexane-water interface. It stands to reason that improved OHgroups accessibility to water and greater interfacial uctuations and softness play a rôle in this. Both also contribute to mesophase peak widening (cf. table 3). Nanoclusters enriched with octane consequently swell more than pure n-octanol nanoclusters, despite the alkane's complete hydrophobicity (compare grey and black symbols in gures 3 and 5). C8-OH packing stress diminishment by octane facilitates binding of other molecules, too (see the grey symbols and curves in panels 3B, 3E and in gure 5). Similarity of the extrapolated 2d values and of gyration radius, 2R (cf. panels 3A, B, D, and E) supports the notion. With just some nonconsequential earlier exceptions, most experts in the eld now view the uid fatty alcohols as nanostructured but otherwise amorphous uids comprised of linear or circular, sequentially H-bonded, exible arrays, or cylinders, of n-alkanol molecules. 2

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Figure 5: Relative intensity of X-rays scattering on freely diusing, spherical polar aggregates, or lacunae (the 'Guinier's scatterers', xx = Guin), and on water (and organic additive(s)) containing nanodroplets (the 'Lorentz scatterers', xx = Loren), as a function of additive concentration, C . Each contribution is expressed as the product of an individual density of the X-rays scattering electrons, ∆ρ , and the corresponding scattering volume, V (the latter being calculated assuming spherical geometry of the scatterers). The dotted curves were calculated by tting the Langmuir's binding isotherm to SAXS data. The dotted line should solely guide the eye. The horizontal dashed line identies the cross-over from nanodroplets to lacunae prevalence. Left panel: n-octanol-water-octane combination. Right panel: octanol-water-ketoprofen combination (black symbols and curve) and n-octanol-water-ketoprofen-octane combination (grey symbols and curve). a

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In such molecular picture, the inner peak of SAXS diractogram is traceable back to the radial distribution function of X-rays scattering oxygens. According to ref., for example: "the inner alcohol scattering peaks ... are mainly the consequence of the OO correlations". To support such structural interpretation computer simulations are typically quoted, despite their present unsuitability for dealing with relatively large and/or slowly forming structures. Herein we modify and extend the presently prevailing structural picture of uid n-alkanols and simultaneously describe as well as explain their intrinsic geometric frustration with or without water. We posit that uid n-alkanols (with possible exception of the shortest) self-aggregate into tiny, reverse bilayer-like and also transversely H-bonded, quasi-lamellar, nanoclusters on a para-crystalline lattice, which yields a thermally disordered mesophase. Correspondingly, we interpret the inner peak as the rst (hk0) Bragg's peak of SAXS on such three-dimensionally 'ordered' nanoclusters. The clusters are comprised of OH-groups and water, locally quasi-two-dimensional, and sensitive to additives. Figures 3 and 5 conrm the structural sensitivity of hydro-octanol even to dilute additives. Quite concentrated and/or polar molecules moreover seek, or help create, in hydro-octanol locations other than nanoclusters (compare both panels of gure 5). The SAXS signal starting at q = 0 Å is diagnostic of such locations (cf. gure 2 and supporting gures S1S4). They have the form of inverse-micellar lacunae comprised of octanol hydroxyls, water, and the additive's polar groups (see panel 4G for their schematic illustration). The lacunae grow in number (∝ C ) and size (2R ) with the additive's polarity and concentration (C ), but are typically bigger than nanoclusters (see panels 3A, B and table 3). The lacunae hence neither t into nor are they conned to the nanoclusters' paracrystalline lattice. They are rather distributed randomly in or move quasi-freely through the hydrated n-octanol bulk. Ternary solutions containing one hydrotrope (such as C2-OH) and two uids that are mutually immiscible but soluble in the hydrotrope at any proportion permit activity of en23

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6 of ref. 23 exemplies the present range and conclusions limitations of computer simulations: Monte-Carlo simulations match closely the SAXS peak pertaining to hydrocarbon chains (with characteristic distance 2.10±0.18 Å) but mimic the inner peak only qualitatively, at best (due to much larger characteristic distances corresponding to this peak).

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zymes that normally operate at interfaces. Similar ('pre-Ouzo') structures were recently detected and characterized in ternary mixtures of one hydrotropic co-solvent (such as C2-OH) and two partly miscible solvents (such as C8-OH and water). Testard and collaborators had shown that the related mixtures of C12 and, for example, C2-OH or C3-OH or C4-OH or C7-OH can accommodate an unusually large relative water quantity as the third component in some kind of aggregates. Zemb and colleagues explained the energetics and conrmed existence of octanol-rich domains, with radius around 2 nm, in related microemulsions comprised of C8-OH, C2-OH and water. It is tempting to view the hydro-octanol enriched with KTO and especially KTO , addressed in panels 3B, 3C and 3G, as yet another 'pre-Ouzo' microemulsion type. Furthermore, it would be interesting to check performance of interfacially active enzymes in such preparations as well as in the maximally hydrated C8-C8-OH mixtures (see panel 3A), which according to our data interpretation oer interfaces, too. Zemb and colleagues, citing Dixit et al., have stated that all alcohols in binary solutions with water form loose networks that can be seen as living polymers, the 3D mesh of which creates the specic signature in small-angle scattering; such solutions were also described as "random dynamic network in organized solvent". According to Chen and Spielmann, the polymers have the form of cylindrical micelles. Neither spherical nor cylindrical n-alkanol micelles would yield a linear n -dependence of the characteristic SAXS peak position, however. Keeping the polar headgroup area small enough to maintain the essential, cohesive intermolecular H-bonds and in parallel increasing n namely creates an increasing packing diculty, i.e., an inherent geometric frustration. The ever larger 'voids' between micelles growing in 2- or 3-dimensions are energetically progressively costly, as they diminish the short-ranged van der Waals attraction that holds the fatty chains and micelles together; gure 4 of ref. or gure 1 of ref. manifest the problem. The presently common structural description of uid n-alkanols hence betokens nonlinearity of, if not a tipping-point in, d (n ) functionwhich might be abolished if an added corresponding alkane would ll the voids. (This was actually our original motivation for supplementing C8-OH with C8.) 49

50

24

51

−

51

52

53

25

C

C

21

r

54

C

54

26


Page 27 of 37 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Figure 4 shows none of this and Table 3 implies that alkanes insert themselves along alkanol chains rather than near their ends. This strongly supports our new, bilayer-based, structural picture of (hydro)alkanols. Unlike the presently preferred one, the new structural picture is i) fully compatible with d (n ) function linearity; ii) can rationalise the limited swelling of bilayer clusters promoted by alkanes and other 'weak additives', i.e., the asymptotic form of d (C ) function; and iii) can explain why in the uid n-alkanol bulk each polar headgroup area is not signicantly bigger than in a 2D- or 3D n-alkanol crystal, is ∼ 20 % below the corresponding uid n-alkane area in a 2D monolayer, and is even smaller than in a monolayer of ordered n-alkanol molecules. Unlike the previous interpretation of SAXS on n-alkanols, our new structural picture moreover ts seamlessly into the wider picture of alkanols' and alkanes' molecular organisation in dierent phases, in the bulk as well as at interfaces. The qualitative conclusions presented herein do not rely on any model or mechanism presumption. Their correctness depends solely on our underlying SAXS data accuracy. Good agreement between the previously published and our own SAXS results on pure dry and wet n-octanol vindicates the latter. Observations arming our quantitative conclusions include: i) good agreement between the modelled and the measured mesophase peak forms (cf. gure 1); ii) co-linearity of adjusted d (n ) (cf. gure 4, pointing at underlying paracrystalline lattice of bilayers or bilayer like nanoclusters); iii) the limited thickness of bilayer like nanoclusters' polar region (cf. panels 3D, E); iv) closeness of our SAXS-derived estimate of n-octanol minimum hydration and the corresponding Karl-Fisher titration result: C8OH/H O ∼ 2/1; v) identity of the C8-OH maximum hydration value derived herein with the relevant previous result: C8-OH/H O ∼ 2/3; vi) similarity of the fully hydrated n-octanol area in the herein postulated, bilayer like, nanoclusters enriched with octane (A ' 0.221 nm ) and the ideal area of a uid octanol (theoretical) 'surface monolayer' (A = 0.214 nm ) or the alkanol area in an interfacial (bi)layer (0.203 ≤ A /nm ≤ 0.215); vii) last but not least, the fact that uid alkanols always spontaneously form a bilayer at a planar interface. r

p

C

a

r

C

42

2

43

2

OH

2

f

2 5

b

27


2

32,39

Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 28 of 37

It is hence safe to conclude that hydro-octanol is not a uid structured on (supra)molecular scale merelyas is required for a solventbut rather a variable mesophase or two such mesophases, if one also counts lacunae / the proto microemulsion; linearity of all d (n ) data-sets (cf. 4) justies generalisation of this conclusion to other n-alkanols. Saturation of various additives incorporation into hydro-octanol corroborates the former conclusion, as the total dissolved additive amount otherwise ought to increase linearly with the additive's total concentration. Hydro-octanol is moreover sensitive to additives' polarity and concentration, which is likewise incompatible with such alcohol's present picture, and current use, as a solvent. For example, octanol-water partition coecient is the most popular proxy for molecular lipophilicity characterisation. Its simplest denition, P = C /C ≡ C /C , requires fullment of specic conditions to be valid, but the general presumption is that an additive behaves like a solute and hence distributes itself uniformly between two amorphous and hence broadly homogeneous compartments (water, octanol). Whereas the additive concentration may (and typically does) dier between the compartments, the additive concentration within each compartment should be the same everywhere, independent of the additive kind. Our ndings with three kind of molecules (C8, KTO, KTO ) invalidate this postulate and imply that experimental P data are apt to depend on additive (relative) concentration. Our results moreover dictate use of binding rather than partitioning concept for analysing an additive concentration and distribution in hydro-octanol (see gure 5). r

2

O/W

S,O

S,W

a,O

C

a,W

47

46

−

O/W

47

Conclusion Contrary to the wide-spread belief, n-octanoland arguably any other molten n-alkanol (with possible exception of the shortest ones)is not an amorphous uid. We conclude herein that C8-OH and other uid n-alkanols rather gather into nanoclusters that broadly 28


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Langmuir

resemble tiny 'inverse bilayers' spaced on a thermally distorted lattice (cf. panel 3H, right half). In such hydrated nano-'bilayers', at least one water molecule connects two nearest OH-groups in the opposing bilayer halves, as in a bilayer that forms spontaneously at a uid alkanol-air interface. Additives can, but need not, promote H O association with the nano'bilayers' in a C8-OH bulk. Provision of alkane (ideally at C8-OH/C8 = 6/1 molar ratio), relieves alkanol's packing-stress, improves alkanol hydration (H O/C8-OH ∼ 1.5 mol/mol), and can support H O binding to the associated amphipats (cf. grey and black symbols in gures 3 and 5). Due to polar nanoclusters formation by alcohol headgroups on a conning paracrystalline lattice, even octane cannot completely overcome limitations of amphipat binding to hydro-octanol, however. To achieve adequate hydration in an octanol-water mesophase, amphipatic additives must enlarge a requisite proportion of said nanoclusters into the amphipats-containing, spherical, inverse-micellar aqueous lacunae, detached from the paracrystalline lattice occupied by the nanoclusters. C8 incorporation supports emersion and liberation of such proto-microemulsion from the newly discovered lattice. The lacunae can exceed nanoclusters in size several orders of magnitude. The more polar and concentrated are the binding amphipats, the more likely is nanoclusters expansion into lacunae. Octanol equilibrated with water and additives thus evidently does not behave like an amorphous uid or solvent, structured only on a nano-scale, but rather as a responsive mixture of several mesophases, with distinct, if small, surfaces and a thermally smeared, relatively long-range 'inner structure'. This challenges the present notion of partition and distribution coecient and suggests that hydro-alkanol(-alkane) nanodroplets or lacunae could be useful for interfacial catalysis. 2

2

2

Acknowledgements This work was supported by the Bundesminesterium für Bildung und Forschung (contract nr. 05K13WM1), the Deutsche Forschungsgemeinschaft (SFB 1032), and Pamet AG. 29


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References (1) Smith R. N.; Hansch C.; Ames M. M. Selection of a reference partitioning system for drug design work. J. Pharm. Sci. 1975, 64, 599-606. (2) Lipinski C. A.; Lombardo F.; Dominy B. W.; Feeney P. J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 2001 46 (1-3), 3-26. (3) Watanabe A. The Synthesis and the Physical Properties of Normal Higher Primary Alcohols. V. Thermal and X-Ray Studies of the Polymorphism of Alcohols of Odd Carbon Numbers from Undecanol to Heptatriacontanol. Bull. Chem. Soc. Japan 1963, 36, 336-340. (4) Watanabe A. Synthesis and Physical Properties of Normal Higher Primary Alcohols. IV. Thermal and X-Ray Studies on the Polymorphism of the Alcohols of Even Carbon Numbers from Dodecanol to Tetratriacontanol. Bull. Chem. Soc. Japan 1961, 34, 17281734. (5) Berge B.; Konovalov O.; Lajzerowicz J.; Renault A.; Rieu J. P.; Vallade M. Melting of Short 1-Alcohol Monolayers on Water: Thermodynamics and X-Ray Scattering Studies. Phys. Rev. Lett. 1994, 73, 1652-1655. (6) Ventola L.; Ramírez M.; Calvet T.; Solans X.; Cuevas-Diarte M. A.; Negrier P.; Mondieig D.; van Miltenburg J. C.; Oonk H. A. J. Polymorphism of N-Alkanols: 1Heptadecanol, 1-Octadecanol, 1-Nonadecanol, and 1-Eicosanol. Chem. Mater. 2002, 14, 508-517. (7) Ramírez-Cardoná M.; Ventola L.; Calvet T.; Cuevas-Diarte M. A.; Rius J.; Amigó J. M.; Reventós M. M. Crystal structure determination of 1-pentanol from low-temperature powder diraction data by Patterson search methods. Powder Dir. 2005, 20, 311-315. 30


Page 30 of 37

Page 31 of 37 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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(8) Shallard-Brown H. A.; Watkin D. J.; Cowley A. R. n-Octanol. Acta Cryst. 2005, E61, o213.-o214. (9) Ohlberg S. M. J. Phys. Chem. The Stable Crystal Structures of Pure n-Parans Containing an Even Number of Carbon Atoms in the Range C to C . 1959, 63, 248-250. (10) Broadhurst M. G. An Analysis of the Solid Phase Behavior of the Normal Parans. J. Res. Natl. Bur. Stand. A 1962, 66, 241-249. (11) Dirand M.; Bouroukba M.; Chevallier V.; Petitjean D.; Behar E.; Ruer-Meray V. Normal Alkanes, Multialkane Synthetic Model Mixtures, and Real Petroleum Waxes: Crystallographic Structures, Thermodynamic Properties, and Crystallization. J. Chem. Engin. Data 2002, 47, 115-143. (12) Craig S. R.; Hastie G. P.; Roberts K. J.; Shenvood J. N. Investigation into the Structures of Some Normal Alkanes within the Homologous Series C H to C H using Highresolution Synchrotron X-Ray Powder Diraction. Mater. Chem. 1994, 4, 977-981. (13) Michaud F.; Ventolá L.; Calvet M. T.; Cuevas-Diarte M. A.; Solans X.; Font-Bardía M. The c-form of n-eicosanol. Acta Crystal. C 2000, 56, 219-221. (14) Sirota E. B.; Singer D. M. Phase transitions among the rotator phases of the normal alkanes. J. Chem. Phys. 1994, 101, 10873-10882. (15) Böhmer R.; Gainaru C.; Richert R. Structure and dynamics of monohydroxy alcohols Milestones towards their microscopic understanding, 100 years after Debye. Phys. Rep. 2014, 545, 125-195. (16) Brooks J. H.; Alexander E. A. Spreading and Collapse Phenomena in the Fatty Alcohol series. J. Phys.Chem. 1962, 66, 1851-1853. (17) Lawrence A. S. C.; Al-Mamun M. A.; McDonald M. P. Investigation of Lipid-Water 30

13

31


36

28

60

122

Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Systems. Part 2. Eect of Water on the Polymorphism of Long Chain Alcohols and Acids. Trans. Faraday Soc. 1967, 63, 2789-2795. (18) Sirota E. B.; Wu X. Z. The rotator phases of neat and hydrated 1-alcohols. J. Chem. Phys. 1996, 105, 7763-7773. (19) Gang O.; Ocko B. M.; Wu X. Z.; Sirota E. B.; Deutsch M. Surface Freezing in Hydrated Alcohol Melts. Phys. Rev. Lett. 1998, 80, 1264-1967. (20) Stewart G. W.; Morrow R. M. X-Ray Diraction in Liquids: Primary Normal Alcohols. Phys. Rev. 1927, 30, 232-244. (21) Franks N. P.; Abraham M. H.; Lieb W. R. Molecular organization of liquid n-octanol: An X-ray diraction analysis. J. Pharm. Sci. 1993, 82, 466-470. We could not reconcile the C8-OH/H O = 2/1 mol/mol binding stoichiometry and the small area per uid chain (A ' 0.19 nm ) with the spherical polar nanodroplets proposed by Franks et al. Spherical scatterers moreover t the observed SAXS peak form less well than the bilayer-like structures advocated herein (see gure 1). (22) Vahvaselkä K. S.; Serimaa R.; Torkkeli M. Determination of Liquid Structures of the Primary Alcohols Methanol, Ethanol, 1-Propanol, 1-Butanol and 1-Octanol by X-Ray Scattering. J. Appl. Cryst. 1995, 28, 189-195. (23) Tom²i£ M.; Jamnik A.; Fritz-Popovski G.; Glatter O.; Vl£ek L. Structural Properties of Pure Simple Alcohols from Ethanol, Propanol, Butanol, Pentanol, to Hexanol: Comparing Monte Carlo Simulations with Experimental SAXS Data. J. Phys. Chem. B 2007, 111, 1738-1751. (24) Bauduin P.; Testard F.; Zemb, T. Solubilization in alkanes by alcohols as reverse hydrotropes or "lipotropes". J. Phys. Chem. B 2008, 112(39), 12354-12360. 2

f

2

32


Page 32 of 37

Page 33 of 37 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

(25) Chen B.; Siepmann J. I. Microscopic structure and solvation in dry and wet octanol. J. Phys. Chem. B 2006, 110(8), 3555-3563. (26) Ferru G.; Gomes Rodrigues D.; Berthon L.; Diat O.; Bauduin P.; Guilbaud P. Elucidation of the Structure of Organic Solutions in Solvent Extraction by Combining Molecular Dynamics and Xâray Scattering. Ang. Chem. Int. Ed. 2014 53(21), 5346-5350. (27) Elsayed M. M.; Vierl U.; Cevc G. Accurate potentiometric determination of lipid membrane-water partition coecients and apparent dissociation constants of ionizable drugs: electrostatic corrections. Pharm. Res. 2009 26, 1332-1343. (28) Ilavsky J. Nika: software for two-dimensional data reduction. J. Appl. Cryst. 2012, 45, 324-328. (29) Renault A.; Legrand J. F.; Goldmann M.; Berge B. Surface diraction studies of 2D crystals of short fatty alcohols at the air-water interface. J. de Phys. II 1993, 3(6), 761-766. (30) Legrand J. F.; Renault A.; Konovalov O.; Chevigny E.; Als-Nielsen J.; Grübel G.; Berge B. X-ray grazing incidence studies of the 2D crystallization of monolayers of 1-alcohols at the air-water interface. Thin Solid Films 1994, 248(1), 95-99. (31) Narten A. H.; Sandler S. I. X-ray diraction study of liquid tertiary butyl alcohol at 26 C. J. Chem. Phys. 1979, 71(5), 2069-2073. (32) Tikhonov A. M.; Pingali S. V.; Schlossmann M. L. Molecular ordering and phase transitions in alkanol monolayers at the water-hexane interface. J. Chem. Phys. 2004, 120, 11822-11838. (33) Abécassis B.; Testard F.; Zemb T.; Berthon L.; Madic C. Eect of n-octanol on the structure at the supramolecular scale of concentrated dimethyldioctylhexylethoxymalonamide extractant solutions. Langmuir 2003, 19(17), 6638-6644. ◦

33


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(34) Reimer J.; Nilsson M.; Álvarez Chamorro M.; Söderman O. The water/n-octane/octylβ -d-glucoside/1-octanol system: Phase diagrams and phase properties. J. Colloid Interf. Sci. 2005, 287, 326-332. (35) Craievich A. F.; Denicolo I.; Doucet J. Molecular motion and informational defects in odd-numbered parans. Phys. Rev. B 1984,30, 4782. (36) Aratono M.; Takiue T.; Ikeda N.; Nakamura A.; Motomura K. Thermodynamic study on the interface formation of water-long-chain alcohol systems. J. Phys. Chem., 1992, 96, 9422-9424. (37) Wu X. Z.; Ocko B. M.; Sirota E. B.; Sinha S. K.; Deutsch M.; Cao B. H.; Kim M. W. Surface Tension Measurements of Surface Freezing in Liquid Normal Alkanes. Science 1993, 261, 1018-1021. (38) Ocko B. M.; Wu X. Z.; Sirota E. B.; Sinha S. K.; Gang O.; Deutsch M. Surface freezing in chain molecules: Normal alkanes. Physical Review E 1997, 55, 3164-3182. (39) Gang O.; Wu X. Z.; Ocko B. M.; Sirota E. B.; Deutsch M. Surface freezing in chain molecules. II. Neat and hydrated alcohols. Phys. Rev. E 1998, 58, 6086-6100. (40) Wang J.-L.; Leveiller F.; Jacquemain D.; Kjaer K.; Als-Nielsen J.; Lahav M.; Leiserowitz L. Two-Dimensional Structures of Crystalline Self-Aggregates of Amphiphilic Alcohols at the Air-Water Interface As Studied by Grazing Incidence Synchrotron X-ray Diraction and Lattice Energy Calculations. J. Am. Chem. Soc. 1994, 116, 1192-1204. (41) Habenschuss A.; Narten A. H. X-ray diraction study of some liquid alkanes. J. Chem. Phys. 1990, 92, 5692-5699. (42) Lang B. E. Solubility of Water in Octan-1-ol from (275 to 369) K. J. Chem. Eng. Data 2012, 57, 2221-2226. 34


Page 34 of 37

Page 35 of 37 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

(43) Dixit S.; Poon W. C. K.; Crain J.; Hydration of methanol in aqueous solutions: A Raman spectroscopic study. J. Phys.: Condens. Matter 2000, 12, L323-L328). (44) Cevc G. Molecular-force theory of solvation of the polar solutes-the mean eld solvation model, its implications and examples from lipid water mixtures Chem. Scripta 1985, 25, 96-107. (45) Cevc G.; Hauser M.; Kornyshev A. A. Eects of the interfacial structure on the hydration forces between laterally uniform surfaces. Langmuir 1995, 11, 3103-3110. (46) Sangster J. Octanol-water partition coecients: Fundamentals and physical chemistry; John Wiley & Sons, New York, 1997. (47) Cevc G. Partition coecient vs. binding constant: How best to assess molecular lipophilicity. Eur. J. Pharm. Biopharm. 2015, 92, 204-215. (48) Kunz W.; Holmberg K.; Zemb T. Hydrotropes. Cur. Opin. Colloid Interface Sci. 2016, 22, 99-107. (49) Khmelnitsky Y. L.; Hilhorst R.; Veeger C. Detergentless microemulsions as media for enzymatic reactions. The FEBS Journal 1988, 176(2), 265-271. (50) Diat O.; Klossek M. L.; Touraud D.; Deme B.; Grillo I.; Kunz W.; Zemb T. Octanolrich and water-rich domains in dynamic equilibrium in the pre-ouzo region of ternary systems containing a hydrotrope. J. Appl. Crystal. 2013, 46(6), 1665-1669. (51) Zemb T. N.; Klossek M.; Lopian T.; Marcus J.; Schäettl S.; Horinek D.; Prevost S. F.; Touraud D.; Diat O.; Mar£elja S.; Kunz W. How to explain microemulsions formed by solvent mixtures without conventional surfactants. Proc. Nat. Acad. Sci. (USA) 2016, 113(16), 4260-4265. (52) Dixit S.; Crain J.; Poon W. C. K.; Finney J. L.; Soper A. K. Molecular segregation observed in a concentrated alcohol-water solution. Nature 2002, 416(6883), 829-832. 35 ACS Paragon Plus Environment

Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(53) Testard F.; Berthon L.; Zemb T. Liquid-liquid extraction: An adsorption isotherm at divided interface? Comptes Rendus Chimie 2007, 10(10-11), 1034-1041. (54) Chen Z.; Rand R. P. Comparative study of the eects of several n-alkanes on phospholipid hexagonal phases. Biophys. J. 1998, 74(2), 944-952.

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Graphical TOC Entry Additive

OHgroup

.

Water

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

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Additive concentration

37


or Water

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