(496d) Solute-Solvent-Membrane Interactions in Organic Solvent Nanofiltration

Solute-solvent-membrane interactions in
Organic Solvent Nanofiltration

In
recent years, nanofiltration (NF) has been applied in organic solvents more and
more widely [1,2,3]. In the pharmaceutical industry, for example, NF has been
proposed as an emerging technique to perform concentration, separation, and
salt/solvent exchange of peptide solutions, as a consequence of the increasing
interest in peptides as pharmaceuticals, which has been challenging the peptide
industry to develop economically competitive methods for large scale
manufacturing. Application of NF to peptide processes has permitted the
improvement of the overall peptide downstream processes.

Since
application of membrane technology in non-aqueous media is a recently emerging
field, understanding the transport mechanism of organic solvent mixtures through
NF and UF membranes is still an open research topic. Straight extension of
steric and electrostatic separation mechanisms, typical of aqueous
environments, to non-aqueous systems is complex, due to the significant differences
in the structures and properties of the solvents [1,4,5,6]. It has been
observed that the NF performance is much less predictable in the presence of
organic solvents, than in aqueous solutions [4,5] and the molecular weight
cut-off (MWCO) is an insufficient descriptor for the separation capability of
the membrane in organic solvents [4]. In comparison to well-established aqueous
processes, non-aqueous processes are characterized by the increase in the
number of solute-solvent-membrane interactions [3], which play a determining
role in the understanding of both solvent flux and solute rejection.

The
factors affecting the molecular interactions at the nanoscale can be classified
in terms of solvent-membrane and solute-membrane affinity interactions. Solvent-membrane
affinity is a function of solvent nature and composition of the solvent mixture.
Solute affinity is generally a function of four factors:

(i)
chemical nature of the molecule, in terms of steric, electrostatic,
hydrophilic/phobic and polar properties;

(ii)
electrostatic interactions between solute and membrane charge, already extensively
studied in water, as Donnan effects [6], and questioned for Organic Solvent
Nanofiltration (OSN) [1,2,5];

(iii)
composition of the solvent mixture. When a solute is dissolved in a mixture of
two or more solvents, solute-solvent interactions may differ in strength for
each solvent. This may cause the composition of the solvation shell of the
solute to be different from that of the bulk solution. In this case, the solute
is said to be preferentially (or selectively) solvated by one of the two
solvents [7].

(iv)
concentration of salts/ions, often present in a typical peptide process
solution. On one hand, ions affect the charge interaction, by affecting the
solution pH or ionic strength. On the other hand, ions can affect the solute
solubility, depending on their kosmotropic ("order-maker") or
chaotropic ("disorder-maker") nature [9], via salt formation or
water-mediated ion pairs.

The
aim of this work is to study the effect of solute-membrane vs. solvent-membrane
affinities on the OSN performance. The work is divided in three parts.

Firstly,
permeation of water, organic solvents and their mixtures is investigated through
hydrophilic nanofiltration and ultrafiltration (UF) ceramic membranes (Inopor®
Nano 450 Da, Inopor® Nano 750 Da and Sulzer 1000 Da, all composed of TiO2/Al2O3, and Inopor® Ultra 2000 Da, composed of
ZrO2/Al2O3). Experimental results clearly
indicate that the Hagen-Poiseuille viscous flow, which assumes the viscosity as
the key parameter influencing permeation, fails in describing solvent
permeation through NF membranes, whereas it is able to describe the
experimental permeability through UF membranes. This is ascribed to the
significance of surface effects against bulk effects (i.e. viscosity) for high
specific surface systems (such as NF membranes), compared to low specific
surface systems (such as UF membranes). Several correction factors are
considered in this work, to account for the surface phenomena that arise in a
nanotube due to solvent-membrane surface interactions. These correction terms
(namely interfacial tension, polarity and molecular dimension) are included
into an improved phenomenological model for solvent permeation [10]. As
expected, they are functions of the pore size, and, namely, significant for
small pores (cf. NF), and negligible for large pores (cf. UF).

Afterwards,
permeation of single salts and acids (NaCl, KCl, LiCl, NaI, NaF, HCl and trifluoroacetic
acid, TFA-H) in water and organic/water mixtures through the same NF and UF
ceramic membranes is investigated. Salts/acids are chosen for three reasons.
Firstly, salts are not affected by steric retention, and therefore electrostatic
and molecular affinity effects can be isolated and analyzed separately.
Afterwards, charge effects have been largely studied in water [6] and have been
well explained by the Donnan theory. The extension of these considerations to
organic solvents is therefore possible. Finally, preferential solvation data
for common inorganic ions are either available in the literature or easily
derivable from theoretical models. Availability of these data permits one to
look for a correlation between permeation performances and solvation
characteristics. The effects of pore dimension, nature of the organic solvent
and nature of anion/cation for different salts and acids are presented and
discussed in this paper. The effect of the type of solvent on the ion rejection
is found to be a function of the Hansen solubility parameter of the solvent,
the Hansen solubility parameter of the ion, and the preferential solubility
parameters of the ion in the aqueous mixture. The solute-solvent competition has
a more significant effect at low pore dimension and becomes more negligible for
large pore dimension (UF range). This is shown in Figure 1, by the more significant
negative rejection (i.e. enhanced solute transport vs. solvent transport) for
NaCl in acetonitrile/water mixtures through the tighter membrane (Inopor Nano
450) than through the looser one (Inopor Nano 750).

Figure 1. NaCl rejection during NaCl NF in water
and 70%v ACN/water (C_NaCl = 1 mM).

This
demonstrates that the affinity effects are more significant in the NF range,
due to the high specific surface that characterizes these membranes, and
confirms our previous findings from the investigation of pure solvent
permeation.

Finally,
rejections of one small organic molecule, Npys, and one model peptide, synthesised
by Lonza (Visp, Switzerland) and named PEP1 in this study, through the same hydrophilic
ceramic membranes, are studied as a function of solvent composition (%v
ACN/water) and ion content (Na⁺, H⁺, Cl^-, and
TFA^-,). The effects of solvent composition, ion nature (kosmotropic
or chaotropic) and ion concentration affect the solute rejection, by affecting
the solute preferential solvation, i.e. its affinity with the membrane. The
effect of ions on the composition of the solute solvation shell is explained by
the hydration/dehydration mechanism proposed by Collins [9].

In
conclusion, this work demonstrates that surface effects and molecular affinity
interactions influence permeation of solutes and solvents through NF membranes.
For solute+solvent systems, additionally to steric and electrostatic retention
mechanism, preferential solvation of organic molecules in solution affects the
membrane transport, by changing the molecule hydration degree, and in turn the
hydrophilic/hydrophobic interactions with the membrane. Solvent composition,
ion nature and concentration are therefore significant additional effects for
the pressure-driven permeation through ceramic NF membranes.

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