CIS-01444; No of Pages 7

Advances in Colloid and Interface Science xxx (2014) xxx–xxx

Contents lists available at ScienceDirect

Advances in Colloid and Interface Science

journal homepage: www.elsevier.com/locate/cis

Brief overview on cellulose dissolution/regeneration interactions

and mechanisms
Bruno Medronho a,⁎, Björn Lindman b,c
a
IBB-CGB, Faculty of Sciences and Technology, Ed. 8, University of Algarve, Campus de Gambelas, Faro 8005-139, Portugal
b
Division of Physical Chemistry, Department of Chemistry, Center for Chemistry and Chemical Engineering, Lund University, Lund SE-221 00, Sweden
c
Materials Science and Engineering, Nanyang Technological University, Singapore 639798, Singapore

a r t i c l e i n f o a b s t r a c t

Available online xxxx The development of cellulose dissolution/regeneration strategies constitutes an increasingly active research field.
These are fundamental aspects of many production processes and applications. A wide variety of suitable solvents
Keywords: for cellulose is already available. Nevertheless, most solvent systems have important limitations, and there is an
Cellulose dissolution intense activity in both industrial and academic research aiming to optimize existing solvents and develop new
Cellulose regeneration ones. Cellulose solvents are of highly different nature giving great challenges in the understanding of the subtle
Hydrophobic interactions
balance between the different interactions. Here, we briefly review the cellulose dissolution and regeneration
Hydrogen bonding
Solvents
mechanisms for some selected solvents. Insolubility is often attributed to strong intermolecular hydrogen bond-
ing between cellulose molecules. However, recent work rather emphasizes the role of cellulose charge and the
concomitant ion entropy effects, as well as hydrophobic interactions.
© 2014 Published by Elsevier B.V.

Contents

1. Cellulose generalities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2. Solvents used in cellulose dissolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
3. Cellulose dissolution: on the mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
4. Cellulose regeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
5. Final remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0

1. Cellulose generalities
Cellulose is a readily available and renewable biopolymer abundant-
ly found in nature, typically combined with lignin and hemicelluloses in
the cell wall of upper parts of plants [1]. This homopolysaccharide is
formed by linearly connecting D-glucose units condensed through
β(1–4) glycosidic bonds (Fig. 1). The degree of polymerization (DP)
can vary considerably depending on the source (i.e., DP from 100 up
to 20000) [2]. From the single anhydroglucopyranose unit, AGU, up to
the micro and macro fibrils, cellulose organizes in a rather complex
fashion where an extended intra- and intermolecular network of hydro-
gen bonds is indicated as the basis of cohesion between cellulose mole-
cules (Fig. 1). It is believed that intramolecular hydrogen bonds provide
⁎ Corresponding author. Tel.: +351 289800910; fax: +351 289818419.
E-mail address: bfmedronho@ualg.pt (B. Medronho).
chain stiffness, while, on the other hand, intermolecular hydrogen bonds
allow the linear polymer molecules to assemble in sheet-like struc-
tures [3]. A more recent perspective highlights the amphiphilic nature
of cellulose (Fig. 2) [4–6]; the equatorial direction of a glucopyranose
ring has a hydrophilic character because all three hydroxyl groups are lo-
cated on the equatorial positions of the ring. On the other hand, the axial
direction of the ring is hydrophobic since the hydrogen atoms of C–H
bonds are located on the axial positions of the ring. Thus, cellulose mole-
cules have an intrinsic structural anisotropy where the rather flat ribbons
present sides with clear differences in polarity [7–9]. Such structural an-
isotropy is expected to considerably influence both the microscopic and
macroscopic properties of cellulose but has largely been neglected in
most discussions.
Cellulose can be considered as a semi-crystalline polymer with amor-
phous regions, of low order, coexisting with higher order crystalline
domains [10]. The origin and pretreatments of a cellulose sample

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Please cite this article as: Medronho B, Lindman B, Brief overview on cellulose dissolution/regeneration interactions and mechanisms, Adv Colloid
Interface Sci (2014), http://dx.doi.org/10.1016/j.cis.2014.05.004
2 B. Medronho, B. Lindman / Advances in Colloid and Interface Science xxx (2014) xxx–xxx

Fig. 1. Molecular structure of cellulose where the extended network of intra and inter-hydrogen bonding is represented. The anhydrocellobiose unit (i.e., disaccharide of two glucose
molecules) is highlighted.

determines the degree of crystallinity of cellulose, which typically is
found between 40% and 60%. Several suggestions on how these crystalline
and non-crystalline regions are intermixed have been developed over the
years, such as single crystals or uniform elementary fibrils, but nowadays,
the so-called “fringed fibrillar model” is widely accepted [11–16]. In this
model, the cellulose nanofibril is not regarded a single crystal but rather
as a less structured arrangement of non-uniform crystalline segments
accompanied by amorphous parts, both longitudinally and laterally
displaced [12].
Apart from being used in unmodified forms, such as wood or cotton,
cellulose can be extracted from its natural sources and either used in the
paper industry or, in a smaller scale, in some specific applications such
as regenerated fibers (e.g., Lyocell or viscose). In fact, it is believed
that forest-based raw materials, such as cellulose, can play a major
role in replacing fossil oil-based fibers and cotton by new ecological
man-made fibers in both woven and non-woven end applications. The
success of this replacement is intimately dependent on the develop of
new solvents and strategies for dissolution and regeneration. Cellulose
may also be modified by chemical, enzymatic or microbiological
methods to obtain new valuable derivatives and materials. Large-scale
production of cellulose derivatives (mainly ethers and esters) and
regenerated materials (i.e., fibers, films, food casing, membranes, and
sponges, among others) find applications in several important commer-
cial areas such as the membrane, polymer and paint industries [3].
A challenging issue is the fact that many important applications
of cellulose involve its dissolution. Due to the complexity of such a
biopolymeric network, the partially crystalline structure and the extend-
ed non-covalent interactions among molecules, chemical processing of
cellulose is rather difficult. Cellulose does not melt nor is it soluble in com-
mon aqueous and organic solvents [2,17]. However, this polysaccharide is
soluble in more exotic media with no apparent common properties [18].
The more consensual vision among leaders in the field has been that the
key to dissolve cellulose resides in the solvent capacity to break the above
mentioned intra- and intermolecular hydrogen bond network [19]. Other
interactions among cellulose molecules have been mostly ignored. Re-
cently, we have reanalyzed this problem and argued against this accepted
picture [4–6]. Instead, we have concluded that cellulose has clear amphi-
philic properties and a careful examination of the interactions involved
suggests that hydrophobic interactions play a significant role in governing
cellulose solubility.
2. Solvents used in cellulose dissolution
Why is cellulose dissolution so important? The following reasons
can be enumerated: preparation of regenerated and innovative mate-
rials such as fibers (e.g., textile applications) and films (e.g., packaging
applications), production of valuable cellulose derivatives in a homoge-
nous environment (note that typical solvents cannot penetrate inside
crystalline regions of cellulose and heterogeneous modification is re-
stricted only to the surface of the crystallites), and finally, to degrade
cellulose more efficiently (e.g., important for, for instance, biorefinery
purposes).
Typically, cellulose dissolution is preceded by polymer swelling,
which is defined as a process where the solvent molecules penetrate
and labilize the cellulose structure to a certain extent, leaving the vol-
ume and physical properties of the biopolymer significantly altered

Fig. 2. Hydrophilic and hydrophobic parts of the cellulose molecule: left, top view of the glucopyranose ring plane highlighting hypothetic hydrogen bonding between the hydroxyl groups
located on the equatorial positions of the intermediate ring; right, side view of the glucopyranose ring plane showing the hydrogen atoms of C–H bonds on the axial positions of the ring.

Please cite this article as: Medronho B, Lindman B, Brief overview on cellulose dissolution/regeneration interactions and mechanisms, Adv Colloid
Interface Sci (2014), http://dx.doi.org/10.1016/j.cis.2014.05.004
 B. Medronho, B. Lindman / Advances in Colloid and Interface Science xxx (2014) xxx–xxx
while the solid, or semi-solid fractions, remain practically unchanged.
On the other hand, complete dissolution is expected to fully destroy
the supramolecular structure, resulting in a solution where the polymer
is, at best, molecularly dispersed. Interestingly, the same solvent may
act as a dissolving agent or merely as a swelling agent, depending on
the conditions used in the experiment (i.e., concentrations, tempera-
ture, etc.) [6].
The dissolution of a polymer, such as cellulose, in a solvent is, of
course, governed by the free energy of mixing [20]. The mixing process
will occur spontaneously when the free energy change on mixing is
negative. Otherwise, phase separation may result from the mixing pro-
cess. The polymer molecular weight is a key parameter in dissolution;
the higher the molecular weight, the weaker is the entropic driving
force contribution for dissolution [21]. Under these conditions, the en-
thalpy term is crucial in determining the sign of the Gibbs free energy
change. One should mention that polymer dissolution is often con-
trolled by kinetics rather than by thermodynamics and cellulose is a
very clear example of this. From a thermodynamic point of view, a rea-
sonable solvent for cellulose dissolution must be able to overcome the
low entropy gain by favorable solvent/polymer interactions. In practice,
finding a non-derivatizing solvent that does not reduce the DP nor does
react with the cellulose is one the most challenging parts in cellulose
dissolution. From the traditional viscose route, which is generally a
slow process and environmentally hostile (e.g., discharge of toxic
gases), up to state-of-art ionic liquid systems, several derivatizing and
non-derivatizing (aqueous and non- aqueous) solvents, with strikingly
unrelated properties, have been developed [6]. The list is vast and
includes quite unusual combinations and experimental conditions:
simple or multicomponent mixtures, aqueous and organic media, inor-
ganic and organic salts, high and low temperatures, high and low pHs,
etc. A few classical examples of non-derivatizing solvents can be men-
tioned, such as aqueous inorganic complexes (e.g., cuprammonium hy-
droxide), concentrated salt solutions (e.g., zinc chloride, ammonium,
calcium and sodium thiocyanate solutions), salts dissolved in organic
solvents (e.g., lithium chloride/N,N-dimethylacetamide, ammonia/
ammonium salt, tetrabutylammonium fluoride/dimethyl sulfoxide),
aqueous alkali (lithium hydroxide or sodium hydroxide solutions), etc.
[22]. A more detailed and updated list can be find elsewhere [1,6,23].
What most of these solvents have in common, for different reasons, is
the fact that they are not easily scaled up. Recently, developed processes
for producing regenerated cellulose fibers are emerging as possible
alternatives to the viscose process. Among them, the non-derivatizing
N-methylmorpholine-N-oxide (NMMO) process [24,25] has been
successful on the industrial scale, even if the recovery of the NMMO sol-
vent is complicated, energy demanding, and costly. These are reasons
enough to believe that this system does not meet all the requirements
for a complete replacement of the viscose technology. Ionic liquids
(ILs) have been extensively studied in recent years since these non-
volatile organic solvents are capable of dissolving large amounts of
cellulose and other carbohydrates [26]. However, there are some im-
portant limiting factors for large-scale applications of ILs such as their
high cost of production, high viscosity, sensitivity to moisture content
and poorly developed appropriate purification processes [27,28].
3. Cellulose dissolution: on the mechanisms
Regarding the mechanism of dissolution, we already mentioned
above that the widely accepted picture considers, almost exclusively,
that cellulose dissolution results from the solvent ability to eliminate
the inter- and intramolecular hydrogen bonds among biopolymer mol-
ecules. On the other hand, cellulose can be regarded as an amphiphilic
molecule and thus research aiming in creating a basis for the develop-
ment of new solvents should focus, not only in eliminating hydrogen
bonding but, more importantly, on eliminating hydrophobic interac-
tions. There are several arguments to believe in an amphiphilicity of
Please cite this article as: Medronho B, Lindman B, Brief overview on cellulose dissolution/regeneration interactions and mechanisms, Adv Colloid
Interface Sci (2014), http://dx.doi.org/10.1016/j.cis.2014.05.004
3
cellulose and the highlighted role of hydrophobic interactions and this
has been recently discussed [4–6,29].
Let us now discuss the suggested mechanisms in literature for some
of the classical solvents used for cellulose dissolution. In the aqueous
complexing systems, such as the cuprammonium hydroxide, “cuam,”
the suggested mechanism assumes that the metal complexes dissolve
cellulose via initial deprotonation of the hydroxyls followed by a coordi-
native binding to the hydroxyl groups in the C2 and C3 positions of each
anhydroglucose unit [30].
In the case of the cold alkali, one of the leading opinions is that NaOH
forms hydrates with water capable to break the inter- and intramolecu-
lar hydrogen bonds between cellulose molecules [31]. These hydrates
would have the capacity to bond with one or two hydroxyl groups of
each AGU. On the other hand, our vision is that the charging effect, in
solvent systems such as the alkali, should not be neglected [32]; when
a neutral molecule, such as cellulose, is charged up, its solubility is ex-
pected to increase and thus cellulose tends to be more soluble/be
more penetrated at either high or low pH. This is because the dissociat-
ed counterions strongly contribute to the translational entropy of
mixing. We note that this system is limited to moderately low DPs
and actually this has been used to explain the difficulties faced in dis-
ruption of the long-range order inherent to the higher DPs. Another par-
ticularity of the cold alkali track, is that the concentration range where
NaOH works as a direct solvent is very narrow. This has been discussed
on the basis of a concentration dependent size of the above mentioned
NaOH/water hydrates [33]; at lower alkali concentrations, these hy-
drates are speculated to have hydrodynamic diameters too large to pen-
etrate and diffuse into the very densely packed crystalline regions of
cellulose. The performance of these alkali systems can be increased
when certain additives, such as zinc oxide (ZnO), urea and thiourea
are present even if their role is still unclear. ZnO has been suggested to
form strong hydrogen bonds between cellulose and Zn(OH)2− 4 , a stable
zinc hydroxide species in solution [34]. Regarding urea or thiourea,
some authors argue that urea hydrates possibly self-assemble at the
surface of the NaOH hydrogen-bonded cellulose to form an inclusion
complex (IC), which would lead to full dissolution [35–39]. Zhou et al.
state that the role of urea and thiourea is to function as hydrogen
bond donors and acceptors to prevent the reassociation of cellulose
molecules, therefore conferring stability to the solution [40]. Molecular
dynamic (MD) simulations indicate that, in contrast to water molecules,
the cellulose chain prefers to interact with urea molecules [41]. A stron-
ger and more stable interaction of cellulose with urea would decrease
the self-interaction of cellulose chains and promote dissolution of cellu-
lose in urea-containing solvent mixtures. Kunze and Fink [42] argued
that NaOH and urea hydrates work in synergy to separate the cellulose
chains from each other. They are also supposed to prevent cellulose
from regenerating its intermolecular hydrogen bonding by forming a
stable “hydrate coat” on their surface. The same conclusion is shared
by Isobe et al. [43], which have recently reanalyzed the role of urea in
NaOH solvent system. These authors have concluded that urea has no
direct interaction with cellulose but helps the alkali to penetrate into
cellulose crystalline regions, stabilizing the swollen cellulose molecules.
In addition, the authors propose that the stabilizing effect of urea de-
rives from the fact that urea hinders the hydrophobic association of cel-
lulose [43]. These ideas follow the established role of urea in protein
denaturation [44]. Recent theoretical work, based on molecular model-
ing [45] and Kirkwood–Buff solution theory [46], suggests a preferential
association of urea to the hydrophobic sites of proteins. This alternative
idea highlights the amphiphilic properties of cellulose, and therefore, it
is believed that urea may weaken the entropic effect by accumulating in
the proximity of the hydrophobic surface of cellulose leading to a higher
thermal stability of cellulose in aqueous alkali solvent [43]. These
suggestions clearly support our recent discussions, which emphasize
the role of hydrophobic interactions in cellulose insolubility [4–6,29].
Another important variable in NaOH-based solvents is the relatively
low temperature needed to efficiently dissolve cellulose in opposition to
4 B. Medronho, B. Lindman / Advances in Colloid and Interface Science xxx (2014) xxx–xxx
the standard picture of solubility, which implies that the entropic
driving force is strengthened with increasing temperature. Typically,
sub-zero temperatures are required for dissolution in soda [47]. This
phenomenon has been analyzed thermodynamically by the total en-
thalpy of cellulose dissolution [48]. It was suggested that the only endo-
thermic term is associated with breaking the hydrogen bonds in the
crystalline regions. All other terms relate to interactions between cellu-
lose hydroxyl groups and the solvent system and are exothermic. There-
fore, the conclusion is that the overall process of cellulose dissolution is
exothermic and is thus favored by a lower temperature. Additionally,
the network of solvent hydrates (i.e., Na+ and OH− ions surrounded
by a “cage” of water molecules) is suggested to be temperature depen-
dent probably due to the increasing hydrogen bonding strength [49]. As
mentioned above, some authors believe that this network of solvent
hydrates disrupts mainly the closely chain packed cellulose through
the formation of new hydrogen bonds between cellulose and NaOH
hydrates. Thus, when the temperature is raised, the hydrogen bonds
are assumed to be weaker and the network of hydrates is gradually
destroyed [49]. Regarding the temperature dependence, our description
of the phenomenon is based on temperature-dependent conformation-
al changes in the cellulose chain, which would make the polymer less
polar at higher temperatures, thus reducing the attractive interactions
with the polar solvent and vice-versa [5]. Pinkert et al. [50] offers a
different view based on the idea that the inability of NaOH-based sol-
vent systems to dissolve cellulose at increased temperatures strongly
suggests that an ordered solvent state of some kind is required to
achieve dissolution.
In the case of the NMMO solvent, the active moiety is the NO group
with its strongly dipolar character. It is believed that the oxygen in this
group is able to form one or two hydrogen bonds with AGU of cellulose.
The proposed mechanism assumes the cleavage of intermolecular hy-
drogen bonds of cellulose and the formation of a soluble complex of
stronger hydrogen bonds between the cellulosic hydroxyls and the NO
group of NMMO [18].
For mixed inorganic/organic systems such as lithium chloride/
dimethylacetamide (LiCl/DMAc), several dissolution mechanisms have
been suggested [51,52]. Generally, the dissolving mechanism is believed
to go via an intermediate involving the interaction of Cl− (due to its ba-
sicity) with cellulose in addition to an exchange of DMAc in the lithium
co-ordination sphere by cellulose hydroxyl groups (Fig. 3). Accumula-
tion of C1− along the cellulose chain produces a negatively charged
polymer with the macrocation, [Li-DMAc], as the counterion. This
process can be regarded as a polyelectrolyte effect, where polymer
molecules are forced apart due to charge repulsion. Moreover, the
high osmotic pressure drives a continuous influx of solvent resulting
in further disruption of the cellulose binding forces until the polymer
is totally solvated. A similar polyelectrolyte effect is suggested for
the tetrabutylammonium fluoride/dimethyl sulfoxide (TBAF/DMSO)
Fig. 3. Example of a hydrogen-bond breaking mechanism for the cellulose dissolution in the lithium chloride/dimethylacetamide (LiCl/DMAc) solvent system. Cellulose hydroxyl groups
interact with an intermediate (Li+-DMAC macrocation) via hydrogen bonding bridged by the chloride anion. The lithium cation interacts with the carbonyl oxygen via an ion–dipole
interaction.
Please cite this article as: Medronho B, Lindman B, Brief overview on cellulose dissolution/regeneration interactions and mechanisms, Adv Colloid
Interface Sci (2014), http://dx.doi.org/10.1016/j.cis.2014.05.004
system where the solubilization of the biopolymer is expected to be en-
hanced by the electrostatic repulsion between the negatively-charged
cellulose chains (due to the condensation of F−) [53].
Regarding ionic liquids, although great experimental and computa-
tional progress has been made, there is no clear understanding of the
role of individual ionic species in dissolution. Up to date, two main
views of the interactions between ILs and cellulose prevail: (1) the dis-
solution process is governed by the interactions between the anion and
the biopolymer, with no specific role for the cation; and (2) the major
driving force for cellulose dissolution comes from the H-bond interac-
tions of the cellulose hydroxyls with the anion and the cation of ILs. In
literature, we find several examples where either changing the cation
or the anion produces remarkable effects on dissolution efficiency. In-
terestingly, some of the good hydrogen-bond-accepting anions that
have been found to dissolve cellulose can be rendered ineffective
through pairing with certain cations [54]. One of the structural features
that makes ILs so interesting is their strong asymmetry. Typically, the cat-
ions are bulky species with amphiphilic properties. Such amphiphilicity is
normally not considered when discussing the mechanism of dissolution
of cellulose. This is particularly relevant since crystalline cellulose has an
amphipathic-like structure (Fig. 1b): hydrophobic surfaces consisting
of pyranose-ring hydrogens and hydrophilic regions arising from the
hydroxyl groups directed toward the sides of the ring. The non-polar
surfaces can be organized into hydrophobic sheets paired against one
another, rather than structuring large amounts of water in solution.
(Note that in this type of interaction, the driving force for association is
not simply van der Waals' interactions but rather hydrophobic associa-
tion driven by the liberation of structured water molecules [55].) We be-
lieve that the dissolution of an amphiphilic polymer, such as cellulose,
would be facilitated in amphiphilic solvents. Therefore, the amphiphilic
properties of all cations in ILs fit in our suggestion. In fact, this also follows
from the earlier discussion on the effect of additives such as PEG, urea,
and thiourea on dissolution in alkali solutions.
4. Cellulose regeneration
Typically, the regeneration of cellulose occurs when contacting the
cellulose solution with a coagulation bath. The polymer profile at the
point of precipitation exhibits a very high interfacial concentration,
thus favoring the formation of a dense polymer “skin.” The bulk of the
sample is at near the initial concentration and is in a fluid state. Thus,
a rapid inflow of the coagulant can take place through the weak points
at the skin interface. Rapid growth of finger-like voids in the fluid region
is expected to occur due to the moving interface created by the coagu-
lant (less viscous) and the solution (more viscous). The kinetics of
regeneration is mainly controlled by the relative velocities of the
counter-diffusion process—diffusion of the solvent from the solution
 B. Medronho, B. Lindman / Advances in Colloid and Interface Science xxx (2014) xxx–xxx
into the coagulation bath and the non-solvent from the bath into the so-
lution [56].
The exchange of solvent with non-solvent leads to a desolvation of
the cellulose molecules and to the supposed reformation of the intra-
and inter-molecular hydrogen bonds [57]. The regeneration of cellulose
from, for instance, NMMO solutions using water as the coagulation sys-
tem results from a phase separation process. Typically, two mechanisms
of phase separation can take place during liquid-liquid demixing of
polymer solutions; either nucleation and growth (i.e., the nuclei of
one phase grow in the mixture) or spinodal decomposition (i.e., a peri-
odic variation of concentration leads to the final phase separation). In
the NMMO-water system, if there is a clear difference between these
two mechanisms in their first stages (nucleation and growth shows iso-
lated entities while spinodal decomposition has a 3D network-like mor-
phology), typically both tend to the same morphology at the end due to
surface tension effects [58].
The mechanical and surface chemical properties of regenerated cel-
lulose are known to depend strongly on the type of cellulose solvent and
coagulant. For a bibliography, the reader is directed to the work of Isobe
et al. [59] and references therein. For instance, in molten salts systems,
the regenerated morphologies can vary significantly depending on the
salt used; in thiocyanate melts, fiber-like samples (similar to the raw
cellulose) have been obtained while lamellar-like samples and layered
structures were regenerated from LiClO4 · 3H2O and chlorides, respec-
tively [60].
In IL systems, the presence of water affects many of the solvent prop-
erties. To date, experimental studies on cellulose/IL/non-solvent ternary
systems have not been conclusive, and a mechanistic understanding of
the interactions between water, IL, and cellulose remains unknown.
For instance, MD results are taken to indicate that the ordered cation-
anion polar interaction network is disrupted by water that forms a
network of interactions with the anion and with the cation [61].
More specifically, the suggested mechanism assumes that while
water diffuses inside the first solvation shell of cellulose, the number
of hydrogen bonds among water molecules and the polymer in-
creases and the number of H-bonds between the anion and the
sugar decreases. Meanwhile, the cations are considered to be main-
tained in the second solvation shell of cellulose due to their strong
electrostatic interactions with the anions present. The formation of
this network displaces the cation out of the first solvation shell lead-
ing to cellulose precipitation. In this model, phase separation of the
cellulose as a function of water results from competition between
the water–anion, cellulose–anion, cellulose–water, cellulose–cation,
and anion–cation interactions [61].
The regeneration mechanism for alkali systems suggests that the in-
clusion complex associated with cellulose, NaOH, and, in some cases,
urea or thiourea hydrates is disrupted by adding a non-solvent such as
water, leading to the self-association of cellulose. The regenerated cellu-
lose film is said to be formed through a rearrangement of the hydrogen
bonds [62,63]. Moreover, in acidic non-solvents, the H+ assumes a key
role to trigger cellulose regeneration by neutralizing the alkaline con-
tent. Additionally, as in the Lenzing viscose production process, the ad-
dition of a strong electrolyte to H2SO4, such as Na2SO4 and ZnSO4, can
reduce the H+ concentration in the coagulant, leading to a counter-
diffusion rate and slower acid–alkali neutralization process than by
just H2SO4 alone. This will considerably influence the final properties
of the regenerated cellulose material [10].
Recently, a very interesting study has been presented by Isobe et al.
[59]. The regeneration of cellulose, either using a coagulant or upon
heating, was followed in an aqueous alkali-urea solvent by monitoring
the process by time-resolved synchrotron X-ray scattering. The authors
suggested that when the medium surrounding the cellulose molecules
becomes energetically unfavorable for molecular dispersion, regenera-
tion starts, and the initial process would consist in stacking the hydro-
phobic glucopyranoside rings (driven by hydrophobic interactions) to
form monomolecular sheets, which then would line up by hydrogen
Please cite this article as: Medronho B, Lindman B, Brief overview on cellulose dissolution/regeneration interactions and mechanisms, Adv Colloid
Interface Sci (2014), http://dx.doi.org/10.1016/j.cis.2014.05.004
5
bonding to form Na–cellulose type IV crystallites, a hydrate form of cel-
lulose II (Fig. 4).
This constitutes the first experimental evidence of the development
of hydrophobically stacked monomolecular sheets which was firstly hy-
pothesized by Hermans [64] and later by Hayashi et al. [65]. These au-
thors found that structural disorders lie mainly in the hydrogen-
bonded intermolecular region and assumed the primary structure as a
monomolecular sheet formed by stacking of glucopyranoside planes
by van der Waals forces. Recently, the theoretical work of Miyamoto
et al. [9] simulated the regeneration of cellulose by MD, reproducing
the hypothesis of Hermans and Hayashi. While these studies gave a con-
sistent picture of the primary structure formation of regenerated cellu-
lose, they were either inferred from the resulting structure or based on
computer simulations. Therefore, the work of Isobe et al. [59] not only
shines light into the regeneration mechanism of cellulose but also con-
stitutes an alternative vision to the typical regeneration mechanism
found in literature which, as we have seen, essentially focuses exclu-
sively on the reformation of the broken inter- and intramolecular hy-
drogen bonds among cellulose molecules.
5. Final remarks
From this brief review on cellulose dissolution and regeneration, it is
clear that quite contrasting starting points have been chosen through
the years for the analysis of the mechanisms. As can be inferred, the
nature of the solvents that can efficiently dissolve cellulose covers an
enormous range making it difficult to provide a single consistent mech-
anism. While we recognize that there may be different mechanisms for
different cases, it seems important to make a classification based on
some simple views on solubility, in general, and polymer solubility, in
particular.
Solubility is governed by entropy, notably translational and configu-
rational entropy, the enthalpy in general, being unfavorable. Regarding
translational entropy, this will be very much higher for ionic polymers
with dissociating counterions than for non-ionic polymers. This is
amply demonstrated for cellulose where protonation or deprotonation,
due to addition of simple acids and bases, offers efficient ways of swell-
ing and dissolution of cellulose. An effective ionization can be obtained
not only from changes in the state of protonation but also from associa-
tion/adsorption of an ionic species. Thus, it is well known that the solu-
bility of non-ionic polymers, such as poly(ethylene glycol) and cellulose
derivatives, can be strongly increased by association of ions. This is par-
ticularly efficient for ionic surfactants but also ions with a high polariz-
ability can act as pseudo-surfactants. Actually, this is the basis for the
lyotropic series, often referred to as the Hofmeister series. Thus, it is
found that large anions, such as iodide, can increase the solubility of
non-ionic macromolecules, whereas small ions with a high charge den-
sity, have the opposite effect. The large polarizable ions are effectively
hydrophobic and tend to have a low solubility in a polar solvent and/
or being enriched at a hydrophobic surface. Generally speaking, we
can thus expect that a highly unsymmetrical electrolyte would provide
good solubility conditions for a non-ionic polymer such as cellulose,
since the ions would be non-uniformly distributed in the solution.
This is the case for molten salt systems with small, strong polarizing cat-
ions (i.e., Li+ and Zn2+) and large polarizable anions but, from the broad
overview above, looks like a rather general trend since many of the effi-
cient solvents of cellulose follow this pattern, including many of the
ionic liquids.
As we have previously argued, cellulose manifests strong hydropho-
bic properties and is thus amphiphilic [4,5]. As arguments for amphi-
philic properties we can mention the ability of other polyglucoses,
such as cyclodextrin and amylose, to solubilize non-polar and amphi-
philic compounds in aqueous solution. It is also strongly supported by
simulations [66]. Another clear support for amphiphilic properties can
be found from studies of surfactant binding to cellulose derivatives.
Thus, surfactants bind to cellulose derivatives, soluble due to
6 B. Medronho, B. Lindman / Advances in Colloid and Interface Science xxx (2014) xxx–xxx

Complete
regeneration

Intensity (a.u.)

Time
control

q (Å-1)

Fig. 4. On top, the time evolution of synchrotron x-ray diffraction profiles of a cellulose solution under regeneration in a 5 wt% Na2SO4 aqueous solution is shown. In the control (10 wt.%
cellulose solution without coagulant) no Bragg reflections are observed. After a certain time, a first Bragg reflection (110) is observed while the second one (020) is only visible after com-
plete regeneration. On bottom, a schematic illustration of cellulose regeneration deduced from the X-ray data, where first the hydrophobic stacking of cellulose molecules occurs and then
is followed by their binding via hydrogen bonding (adapted from reference [55]).

hydrophilic groups, which do not associate with surfactants. An illustra- Acknowledgments

tive example is that of cationic hydroxyethyl cellulose, which binds an-
ionic surfactant in excess of charge stoichiometry; obviously, this can
only be due to hydrophobic interactions between the cellulose back-
bone and the alkyl chain of the surfactant [67]. In view of this, eliminat-
ing the hydrophobic interactions between cellulose molecules must be
very important for the aqueous solubility of cellulose. We note that
urea can facilitate cellulose dissolution. Urea has a much lower polarity
than water and is well known to eliminate hydrophobic association in
water. As alluded to above, it acts as protein denaturant by reducing in-
tramolecular hydrophobic association. Furthermore, it inhibits hydro-
phobic association of surfactants as can be seen from the increase in
critical micelle concentration on urea addition. Other substances of
intermediate polarity, such as urea derivatives and poly(ethylene
glycol), have similar effects and are well-known enhancers of the
aqueous solubility of cellulose. The alternative notion to hydrophobic in-
teractions as the limiting factor of dissolution of cellulose in water is
hydrogen-bonding. However, this would require that the carbohydrate-
carbohydrate hydrogen-bonding would be much stronger than water-
carbohydrate and water-water hydrogen bonding, which is not the
case; regarding a solo hydrogen–bonding mechanism, it is striking that
all these interactions are very similar in magnitude; ca. 5 kcal/mol. Fur-
thermore, a hydrogen-bonding mechanism is inconsistent with a high
aqueous solubility of polysaccharides, which have as high hydrogen-
bonding capacity as cellulose.
The authors acknowledge support from the Portuguese Foundation
for Science and Technology (FCT, project PTDC/AGR-TEC/4049/2012
and a postdoc grant assigned to B. Medronho, SFRH/BPD/74540/2010).
Financial support was also received from Södra Skogsägarnas Stiftelse,
Stiftelsen Nils och Dorthi Troëdssons forskningsfond and the CelluNova
consortium.
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