DOI 10.1140/epje/i2013-13129-5

Regular Article

Eur. Phys. J. E (2013) 36: 129 THE EUROPEANPHYSICAL JOURNAL E

Structural investigations of N-methylformamide-water mixturesat various concentrations

Ferid Hammami1,2, Abir Chebaane1, Mohamed Bahri3, and Salah Nasr1,a

1 Laboratoire Physico-Chimie des Materiaux, Departement de Physique, Faculte des Sciences de Monastir, Universitede Monastir, 5000 Monastir, Tunisie

2 Department of Physics, Faculty of Sciences, Jazan University, KSA3 Laboratoire de Spectroscopie Atomique, Moleculaire et Applications, Departement de Physique, Faculte des Sciences,

Universite de Tunis-El Manar, 1060 Tunis, Tunisie

Received 15 May 2013 and Received in final form 9 September 2013Published online: 21 November 2013 – c© EDP Sciences / Societa Italiana di Fisica / Springer-Verlag 2013

Abstract. Structural investigations of N-methylformamide-water mixtures (NMF-water) are performed atroom temperature and atmospheric pressure for two water molar fractions xw = 0.66 and xw = 0.75.This paper extends our recent study on the equimolar system. H-bond networks are preferentially formedbetween NMF and water molecules. Among a large variety of DFT optimized models, X-ray scatteringdata shows that the local order of each mixture is better described by a tetramer where one NMF moleculeis connected to three water molecules. No self-association is observed in the considered systems. The effectof hydration is compared to the temperature and pressure effects in some hydrogen-bonded liquids.

1 Introduction

Hydrogen bonding has held particular interest in recentyears due to the central role it plays with regard to molecu-lar recognition in both biological and artificial systems [1–4]. It represents the fundamental force ruling the influenceof solvents on molecular structures and their reactivities.A deeper study of hydrogen bonding interactions is a pre-requisite for the proper understanding of chemical activityin aqueous solutions. To get a deeper insight into the struc-tural properties and biological functions of proteins [5–7],it is important to know how they interact with an aqueousenvironment through hydrogen bonding. Therefore, un-derstanding how these groups can interact with each otherand with the surrounding water molecules can give infor-mation about the formation of native protein structures.

Amides provide a simplified example of peptide link-ages and represent an excellent model system to studyboth hydrophobic and hydrophilic interactions. The pep-tide group is a basic recurrent unit of polypeptides andproteins [8–12]. Molecular interactions of this functionalgroup play an essential role in determining the structuresand the properties of biological systems, in particular,amide-water mixtures are very important systems exhibit-ing properties that are of great interest in physics, chem-istry and biology. Most of these intriguing systems resultfrom water’s and amide’s great abilities to form hydro-

a e-mail: salah nasr1@yahoo.fr

gen bonds. Such systems have been subject to numeroustheoretical [13–25] and experimental studies [26–37].

Both N-methylformamide (NMF) [13,14,38] and wa-ter [39,40] form continuum random networks of hydrogenbonds which determine the special physical structures ofeach liquid and are in a relation with their physical prop-erties. NMF is one of the simplest models of a biolog-ical molecule’s backbone formed from peptide linkages.Its behavior in aqueous solution provides details aboutthe important peptide-peptide and peptide-water hydro-gen bonds which arise in protein hydration.

The NMF-water mixture has been investigated the-oretically [41–43]. Xiaolan et al. [41] and Cordeiro etal. [42] have respectively performed ab initio and MonteCarlo simulations. The latter study showed that, in anequal stoechiometric system, two types of hydrogen bonds,N–H . . . O–H and C=O . . . H–O, can be formed. In the Xi-aolan et al. study [41], it has been shown that both the cisand trans forms of NMF can be linked by a linear hydro-gen bond with water. The thermodynamic measurementresults, obtained by Zaichikov et al. [43], show that thestructure of the system varies in accordance with the watermolar fraction (xw). In the region where 0.95 < xw < 1,the complex NMF-3H2O is the most stable. In the region(0.55 < xw < 0.95), NMF-2H2O and NMF-H2O exist. Inthe region (0.37 < xw < 0.55), clusters of self-associationof NMF and water exist together with NMF-2H2O andNMF-H2O. When xw < 0.37, the complexes 2NMF-H2Oand NMF-H2O prevail.

Page 2 of 8 Eur. Phys. J. E (2013) 36: 129

To our knowledge, the first experimental investigationson the NMF-water mixture were published in our recentpaper [44]. In this paper, the intermolecular associations ina system with equal stoichiometry were studied by X-rayscattering and DFT calculations. We were able to demon-strate that associations involving a single H-bond wererare in this mixture. By considering the presence of twoH-bond associations, it was found that an NMF moleculelinked by two O-H . . . O bonds to water molecules bet-ter reproduces the experimental data than the case whereO-H . . . O and N-H . . . O bonds are considered. It is worthnoting here that only the latter model has been observedby Cordeiro et al. [42] in their study. In our published pa-per [44], we have also considered the fact that more thantwo H-bonds can be established between NMF and watermolecules. Among all examined models, we have foundthat a tetramer involving one NH . . . O and two OH . . . Obonds is a more probable cluster describing the local orderin the system. To get a deeper insight into the NMF-waterinteractions, we present in this paper structural investiga-tions of 0.66 and 0.75 xw water molar fractions. X-rayscattering measurements in combination with DFT calcu-lations were used to study hydrogen-bond interactions intwo NMF-water mixtures where the water molar fractionxw was, respectively, equal to 0.66 and 0.75. First, we an-alyzed the scattering data to deduce the total structurefactor of each mixture and the corresponding pair cor-relation function. Then, DFT optimized conformation ofmonomers was taken into account to generate the molec-ular form factor. After that, to examine the intermolecu-lar interactions in the two mixtures, a series of molecularmodels were considered. The computed structure factorsand the pair correlation functions for these models werethen compared with those extracted, for each mixture,from experimental data. Moreover, Infra-red (IR) spectrafor pure NMF as well as for 0.5, 0.66 and 0.75 xw NMF-water mixtures were analyzed.

2 Experimental details

For the sample preparation, deionized water was usedand the liquid NMF was purchased from Aldrich Chemi-cal (State purity 99+%) and used without further purifi-cation. X-ray scattering measurements were carried outat room temperature on a standard (θ-2θ) diffractome-ter operating in Transmission Mode with MoKα radia-tion (λ = 0.7093 A) monochromated by bent asymmetricquartz. The scattered intensity was measured in steps of0.25◦ (2θ) from 3◦ to 120◦. The liquid was contained in aflat sample holder (4mm thick) equipped with Mylar win-dows. Several scans were accumulated until about 80000counts were obtained at each angle.

3 Theoretical considerations

3.1 X-ray diffraction formalism

The basic theory of studying X-ray scattering from molec-ular systems is well known [45], and only the essen-

tial details will be reported here. For an assembly of Nmolecules, each with m atoms, the structure factor SM (q)is defined as

SM (q) =(dσ/dΩ) coh

[∑m

α=1 fα(q)]2=

1

N [∑m

α=1 fα(q)]2

×⟨

N∑

j,k=1

m∑

α,β=1

fjα(q)fkβ(q)sin q(rαβ)

q(rαβ)

⟩

, (1)

where (rαβ) represents the distance separating the α andβ atoms in the molecules j and k, q = 4π sin θ/λ is themodulus of the scattering wave vector and fjα(q) is theatomic scattering factor of atom α in the j-th molecule and(dσ/dΩ)coh is the coherent contribution of the differentialcross section [46–48].

At large q-values, SM (q) asymptotically approachesSM (∞) =

Pmα=1 fα2

[Pm

α=1 fα(q)]2 .

For q → 0, limq→0 SM (q) = ρKBTχT , where ρ is themolecular number density, KB is Boltzmann’s constant,T is the absolute temperature and χT is the isothermalcompressibility.

For molecular liquids, it is convenient to remove theintramolecular contribution by subtracting the molecularform factor F1(q) from SM (q) to obtain the distinct struc-ture factor DM (q) [49],

DM (q) = SM (q) − F1(q), (2)

where the molecular form factor F1(q) is given by

F1(q) =m∑

α,β=1

fα(q)fβ(q)J0(qrαβ) exp

×[

−〈Δr2αβ〉

q22

]/ (m∑

α=1

fα(q)

)2

, (3)

where J0(x) = sin xx is the zero-order spherical Bessel func-

tion and 〈Δr2αβ〉1/2 = μαβ is the root mean-square (r.m.s)

vibrational amplitude for the α-β atom pair. The distinctstructure factor DM (q), which contains the information onthe intermolecular structure of the liquid, usually decaysto zero very rapidly at large q-values. However, when hy-drogen bonds exist between molecules, this function con-tinues to oscillate in the high q-range [50]; therefore, it canbe split into two parts:

DM (q) = DHBM (q) + DNHB

M (q), (4)

where DHBM (q) is the H-bond structure function [44] and

DNHBM (q) contains the intermolecular correlations other

than the H-bonded interactions.The pair correlation function of intermolecular terms

only, gL(r), which is expressed by the relation

gL(r) = 1 +1

2π2ρr

∫ qmax

qmin

qDM (q) sin(qr)dq, (5)

Eur. Phys. J. E (2013) 36: 129 Page 3 of 8

gives the probability of finding another atom lying in an-other molecule at a distance r from a given atom. Byanalogy to eq. (4), gL(r) may be written as

gL(r) = gHBL (r) + gNHB

L (r), (6)

where gHBL (r) and gNHB

L (r) are, respectively, the Fouriertransformations of DHB

M (q) and DNHBM (q). We should also

use a weighted function, independent of molecular densityand given by

dL(r) = 4πρ r [gL(r) − 1] . (7)

3.2 DFT calculation

To study the relative stability of all possible intermolecu-lar (dimers, trimers, and tetramers) arrangements of theNMF-water mixtures in the liquid state, we have per-formed a density functional theory (DFT) calculation us-ing the standard TZV basis set [51] augmented by onediffuse (d) function for C, N and O atoms and one po-larization (p) function for all H atoms with HONDO7polarization exponents. All DFT calculations were donewith the GAMESS2002 series of programs [52]. Becke’shybrid three-parameter functional B3LYP [53] was used.The optimization of each structure was considered con-verged with a maximum gradient less than 0.0001. Nofrozen coordinates and no symmetry restriction were used.

4 Results and discussions

Before eq. (1) can be used to evaluate the coherent dif-ferential cross section, the measured intensity data hasto be corrected for polarization, absorption and incoher-ent scattering. Therefore the corrected intensity is normal-ized according to the standard procedure described else-where [50]. Figure 1 shows the structure factors SM (q)(dotted, solid and dashed lines) as deduced from the X-ray data for the considered NMF-water mixtures (watermolar fraction xw = 0.5, xw = 0.66 and xw = 0.75, re-spectively). We see great similarity between the curves. Athigh q-values, the structure factors are well superimposed,which demonstrates that there is no significant variationof the intramolecular structure when the molar fractionof water xw varies from 0.5 to 0.75. With increasing xw,the first peak moves slightly toward high q-values and de-creases in amplitude, which is due to the density variation(see inset). This phenomenon is similar to the pressureeffect on some hydrogen-bonded liquids [27,54].

The first step in the data reduction is to construct themolecular form factor F1(q). This could be achieved byleast-squares fitting of eq. (3) to the experimental data inthe large q-range. However, for hydrogen-bonded liquids,the intermolecular contributions can be observed at highq-values [55]. In this case, it is difficult to define the lowlimit of q from which F1(q) will be superimposed to SM (q).Since no intermolecular contributions are expected in thegL(r) function beyond 2.6 A, it is convenient to reconsider

1.5 2.0

0.00

0.05

4 8 12 16

-0.05

0.00

0.05

0.10

q (Å-1)

S M(q

)

Fig. 1. The X-ray structure factors SM (q) of xw = 0.5, 0.66and 0.75 of N-methylformamide-water (NMF-water) mixtures(dotted, solid and dashed lines, respectively). As xw increases,the first peak of the SM (q) curves decreases in amplitude andmoves toward high q-values (see inset).

Fig. 2. Optimized geometries of trans NMF and water mole-cules.

the previous procedure by minimizing, in real space, theoscillations in the Fourier transformation of DM (q) in thelow r-range i.e.,

∑r=2.6r=0 (gL(r))2. To minimize the number

of variables, the intramolecular distances are kept equal tothe values deduced from the optimized geometry of NMFand water molecules (fig. 2). Only the Debye-Waller (D-W) parameters are then fitted. Moreover, the contributionof X-H correlations (with X = H, C, N and O) to the X-rayscattered intensity are weak at high q-values and some-times neglected [15], hence we have omitted these corre-lations from the expression of the molecular form factorF1(q).

Figure 3 (a, b and c) shows, respectively, the X-raystructure factors (solid line) for xw = 0.5, 0.66 and 0.75compared to the corresponding molecular form factors(dotted line). The analysis of the figure invokes two funda-mental points. Firstly, and as has been mentioned above,there is a large similarity between the intramolecular con-formations in all mixtures. Secondly, the significant con-tributions of the intramolecular form factors are due tothe interactions inside the NMF molecule since O-H andH-H water correlations are weak in the X-ray analysis,

Page 4 of 8 Eur. Phys. J. E (2013) 36: 129

-0.1

0.0

0.1(a)

4 8 12 16-0.05

0.00

0.05

q (Å-1)

(c)-0.1

0.0

(b)

2 4 6 8 100

1

2

r (Å)

(f)

0

1

(e)

0

1

2(d)

Fig. 3. (a, b and c) The total structure factor SM (q) (solidline) with the molecular form factor F1(q) (dotted line) forxw = 0.5, 0.66 and 0.75 NMF-water mixtures, respectively.(d, e and f) The experimental pair correlation function g(r)(solid line) of each system is respectively compared to the in-tramolecular pair correlation function gintra(r) (dotted line).

particularly at high q-values. These conclusions are high-lighted by analyzing the curves in real space. In fact, fig. 3(d, e and f) shows, respectively, the experimental pair cor-relation functions g(r) (solid line) and the intramolecu-lar gintra ones (dotted line) obtained respectively by theFourier transformation of the structure factors SM (q) andthe molecular form F1(q) for the three mixtures (xw = 0.5,0.66 and 0.75). It is clearly seen that the first peaks ap-proximately at 1.25, 2.3 and 2.9 A are well accounted forby the intramolecular correlations in each case. The firstpeak corresponds to the C3=O and C1-N bonds, the sec-ond one is ascribed to the N . . . O and C1 . . . C3 interac-tions and the third peak is attributed to the C1 . . . O cor-relation within an NMF molecule. The observed peaks athigh r-values are assigned to the intermolecular correla-tions as it will be seen below.

Figure 4 shows the weighted intermolecular pair cor-relations functions dL(r) defined in sect. 3 and deducedfrom experimental data (dotted, dashed and solid lines,respectively for xw = 0.5, 0.66 and 0.75). The curves areoffset for more clarity. Two interesting points should beaddressed here. Firstly, the curves show a first peak atabout 2.85 A which is assigned to the H-bond interactions

0 2 4 6 8 10

-0.30

-0.15

0.00

DL(r

)

r (Å)

Fig. 4. The weighted intermolecular pair correlation functions,dL(r), as deduced from X-ray data for the considered mixtures(dotted, dashed and solid lines for xw = 0.5, 0.66, 0.75, respec-tively).

Fig. 5. Optimized geometry of the considered tetramer involv-ing three hydrogen bonds.

and which grows more pronounced when going from lowerto higher water molar fraction xw. Secondly, by increasingthe latter ratio, the second, third and fourth peaks moveslightly toward lower r-values. Note that the last peakclearly decreases in amplitude when xw increases. As areminder, the dL(r) curves are offset for more visibility.

In our previous study [44] related to the equimolarNMF-water mixture, it was found that, among several in-termolecular associations inducing one, two and three H-

Eur. Phys. J. E (2013) 36: 129 Page 5 of 8

bonds, the tetramer (fig. 5) involving one NH . . . O andtwo OH . . . O bonds between one NMF and three wa-ter molecules reproduces the experimental data better.We are interested here in studying the competitivenessof the formation of the H-bonds between the two liquidswith the variation of the water molar fraction. The the-oretical structure factors deduced from dimers, trimersand a tetramer described in our recent paper [44] arethen compared to those deduced from X-ray scatteringfor xw = 0.66 and for xw = 0.75. In this procedure,the intermolecular distances for each model are fixed tothe DFT optimized values. Only the D-W parameters arefitted to reduce the difference between theoretical andexperimental SM (q) functions beyond q ≥ 2 A−1. Simi-larly to the case of the equimolar mixture, our investi-gations show that dimers and trimers are less commonspecies in the higher xw solutions than the tetramer. Infact, the computed SM (q) function (not represented), re-lated to the latter model, exhibits much less discrepancywith the experimental data than theoretical curves de-duced from dimers or trimers. This conclusion is similar tothat observed in N-methylacetamide-water (NMA-water)mixtures. Indeed, computational chemical study of NMA-water complexes has shown that a trans NMA interactspreferentially with three water molecules [56]. Moreover,neutron scattering measurements [57] lead to the conclu-sion that in liquid NMA-water, hydrogen bonds give riseto the formation of a tetramer structure made up of onetrans NMA with three D2O molecules.

The residual difference between experimental structurefactors of 0.66 and 0.75 solutions and theoretical ones de-duced from this model largely decreases by reconsideringthe fitting procedure, where the intermolecular distancesare fitted in the range of 5% from the DFT optimizedvalues together with the corresponding D-W parameters.Figure 6 (a, b and c) shows the X-ray scattering structurefactors (solid line) of 0.5, 0.66 and 0.75 mixtures com-pared to theoretical ones (dashed line) deduced from thetetramer. The dotted curve represents the contribution ofthe intramolecular and the hydrogen bonded correlationsi.e. [F1(q) + DHB

M (q)]. It is easy to see that the computedcurves match the experimental ones from 2.4 A−1. As anindication, we have reported in table 1 the values of somefitted intermolecular parameters deduced from the anal-ysis of 0.66 and 0.75 NMF-water mixtures. Figure 6 (d,e and f) representing, for the three mixtures, the experi-mental pair correlation functions (solid line 1), the theo-retical ones (dotted line) and the Fourier transformationof [F1(q)+DHB

M (q)] functions (dashed line) shed more lighton the local order in these solutions. In fact, it is notice-able that all the features of experimental g(r) curves arewell accounted for by the retained model, i.e. theoreti-cal g(r) ones (dotted line); more precisely, the three firstwell-pronounced peaks in the experimental g(r) curves aswell as the series of humps at higher distances are repro-duced by the intra and inter-molecular interactions insidethe tetramer. Otherwise, it is important to notice thatthe third peak appearing in the Fourier transformationof [F1(q) + DHB

M (q)] is partially due to the H-bonding in-

1

2

2

1

12

2 4 6 8 10

0

1

2

r (Å)

(f)

0.0

0.2

0.4

2 4

gHB L

(g)

r (Å)

0

1

2(d)

4 8 12 160.05

0.10

0.15(c)

q (Å-1)

0.1

0.2

(a)

0.10

0.15

0.20

(b)

1

2(e)

Fig. 6. (a, b and c) The experimental structure function SM (q)(solid line), compared to the calculated one (dashed line) de-duced from the retained model and to the molecular form fac-tor computed by taking into account the hydrogen-bond corre-lations inside this tetramer, i.e. the [F1(q) + DHB

M (q)] function(dotted line) for xw = 0.5, 0.66 and 0.75 mixtures, respec-tively. (d, e and f) The experimental pair correlation functiong(r) (solid line 1), compared to the theoretical one (dotted line)and to the Fourier transformation of [F1(q)+DHB

M (q)] (dashedline) deduced from the retained model. The intermolecular paircorrelation function gL(r) (solid line 2) is also plotted. (g)The gHB

L (r) (solid, dashed and dotted lines) respectively forxw = 0.5, xw = 0.66 and xw = 0.75 mixtures.

teractions as is clearly shown by the intermolecular paircorrelation function gL(r) (solid line 2). Our investigationalso shows that by increasing the water molecular fraction,the main peak of gHB

L (r) (fig. 6 (g)) moves slightly towardshigh r-values. This phenomenon contrasts with the tem-perature effect in some hydrogen-bonded liquids [58].

We have also focused on the question of the preferentialformation of hydrogen bonds between water molecules.For this purpose, we have reconsidered our previous anal-ysis by admitting that each water molecule may interactwith m (m = 0–4 at 2.81 A) and n (n = 0–6 at 4.6 A)other water molecules as is found in the pure liquid. Our

Page 6 of 8 Eur. Phys. J. E (2013) 36: 129

Table 1. Some of the fitted intermolecular parameters of the retained model of NMF-water mixtures, deduced according to thefitting procedure (see text).

xw = 0.66 O4 · ·O5 O4 · ·O6 O16 · ·N2 O6 · ·C1 O5 · ·C1 O5 · ·N2 O6 · ·O5 O5 · ·O16

rαβ (A) 2.727 2.982 3.105 3.387 5.988 4.682 4.944 6.782

μαβ (A−1) 0.124 0.125 0.258 0.255 0.320 0.201 0.200 0.407

xw = 0.75 O4 · ·O5 O4 · ·O6 O16 · ·N2 O6 · ·C1 O5 · ·C1 O5 · ·N2 O6 · ·O5 O5 · ·O16

rαβ (A) 2.980 2.690 2.973 3.386 5.972 4.677 4.884 6.552

μαβ (A−1) 0.146 0.164 0.170 0.218 0.150 0.167 0.152 0.151

Fig. 7. The experimental IR spectra of pure liquid NMFand water (considered as references) and the three consideredNMF-Water mixtures.

fitting procedure clearly shows that the two numbers mand n tend to zero. Similarly to that observed in the0.5 NMF-water mixture, it seems then that no significantoxygen-oxygen interactions occur in 0.66 and 0.75 NMF-water systems. It is obvious that NMF self-association isalso improbable in xw = 0.66 and 0.75 mixtures, sincesuch association has not been observed in the equimo-lar system [44]. This result may corroborate the study ofZaichikov et al. [43] which has shown that self-associationsof each compound are improbable for xw > 0.55. In fact,the oxygen atom of the C=O group is a better acceptor

than the oxygen atom of water. Thus, the hydrogen atomsof water prefer the C=O groups in NMF as acceptors tothe oxygen atoms of water. Moreover, the hydrogen atomsof N-H groups are not good donors, unlike those of watermolecules. Therefore, the oxygen atoms of NMF preferthe water-hydrogen atoms as acceptors rather than thehydrogen atoms of N-H groups.

To have a better understanding of the formation of H-bonds between NMF and water, we have also recorded theIR spectrum of pure liquid NMF and for 0.5, 0.66 and 0.75NMF-water mixtures; the spectrum of pure water is alsogiven (fig. 7). When compared to the spectrum of pureNMF, two interesting points should be addressed. Firstly,in the 1663-1669 cm−1 region corresponding to the bondedC=O vibration (νC=O), we are unable to find any clearvariation. Hydrogen bonds between amide and carbonylgroups in pure NMF occur between C=O and H-Owater

in the mixtures. Secondly, the most prominent spectralchange takes place in the high frequency region. A net shiftfrom 3280 cm−1 to 3401 cm−1 is observed with increasingwater molar fraction. It is worth noting that this region isthe overlap of bonded νN-H and νO-H, which demonstratesthe formation of H-bond networks between NMF and wa-ter as is clearly shown above by analyzing X-ray data. Theobserved difference between pure water and mixture spec-tra can be principally explained by the absence of N-Hbonding.

5 Conclusion

X-ray studies and DFT calculations have been performedon NMF-water mixtures with xw = 0.66 and xw = 0.75.This study extends our recent investigation on the equimo-lar system. According to the bibliography research that wehave performed, this is the first time structural informa-tion on such system is provided. The main results of thisstudy may be summarized as follows:

– The computed intramolecular X-Y correlations in theoptimized geometry of the NMF molecule reproducewell the experimental structure factor at high q-values;the contribution of X-H correlations in water and NMFmolecules is very weak in the X-ray studies.

Eur. Phys. J. E (2013) 36: 129 Page 7 of 8

– In all considered mixtures, it seems that an associa-tion between one NMF molecule and three water onesinvolving one NH . . . O and two OH . . . O bonds is themore probable model describing the local order in thesesystems. By admitting a variation of 5% from the in-termolecular distances of the optimized tetramer’s ge-ometry, the local order of all mixtures is reproducedby this model.

– Two fundamental effects of hydration should be ad-dressed: by increasing the water molar fraction xw,similarly to the observed effect of pressure on someH-bonded liquids, the first peak of the structure fac-tors SM (q) decreases in amplitude and increases in po-sition. Furthermore, the first observed peak in dL(r)curves, assigned to H-bond interactions, is progres-sively more pronounced and moves to high r-values.This phenomenon stands in contrast to the tempera-ture effect on some hydrogen bonded liquids.

– Our investigations show that H-bond networks arepreferentially formed between one NMF and three wa-ter molecules and no self-association is observed. Thisconclusion is supported by X-ray results.

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