1
INTRODUCTION
Saccharides and their derivatives are widely distributed in various forms of life as
essential moieties of glycoproteins, glycolipids, nucleic acids and polysaccharides. These
are found with an enormous range of complexity, from simple mono- to mega-dalton
polysaccharide structures. Because of conformational flexibility, saccharides play
significant roles in many biological processes such as signaling, cell-cell recognition,
molecular and cellular communication1-4
. To understand mechanisms of biological
processes, low molecular model compounds (e.g. alcohols, saccharides, peptides, nucleic
acid bases, nucleosides and nucleotides) have been studied due to the complexities of
biomolecules. Saccharides are important compounds due to their hydrophilic hydroxy
(–OH) rich periphery, coordinating ability, homochirality, stereospecificity, etc.
Saccharides with their well known stereochemistry are logical choices in stereo-selective
reactions for the synthesis of biologically active target molecules5-6
. The hydration
characteristics of saccharides in aqueous solutions are of direct relevance for
understanding the role of glycoproteins and glycolipids in molecular recognition7-11
.The
saccharide components of cell membranes are the receptors of biologically active
compounds (enzymes, drugs) etc. Saccharides consisting of an aliphatic moiety and polar
–OH groups are appropriate models for studying hydration properties of proteins and
nucleic acids. However, the understanding of the relationship between saccharide
structure and their biological function is still far behind that of proteins and nucleic
acids2,12
.
Saccharides act as stabilizing agents for enzymes, therapeutic proteins, hormones,
and antibodies, etc. because of their ability to enhance the structure of water, whereas
others have attributed this to the preferential hydration of proteins. Lee
&Timasheff13
studied the thermal transitions of α-chymotrypsin, chymotrypinogen and
ribonuclease in sucrose and argued that the sucrose stabilize proteins against thermal
damage. However, the mechanism by which stabilization is imparted still belongs to a
realm of speculation14-19
.
In mushroom, yeast, fungi and brine shrimp, intracellular ,-trehalose
contributes throughout its vitrification to their survival abilities against severe conditions
like freezing and desiccation. It is widely recognized that the known biological protective
2
function of trehalose has undoubtedly a close relationship with its physical features.
Although the disaccharides are structurally similar, their protective efficacies differ.
Several mechanisms for the antidesiccation properties of disaccharides have been
advanced, but their protective mechanisms are not well understood20-21
. The mechanistic
understanding of sweet taste chemoreception has been advanced by the micro- and
macro-scopic studies of sweetner-H2O interactions. The hydration characteristics of
saccharides in aqueous solutions are thus a key feature to understand their structural,
functional properties and the mechanism of taste chemoreception22-23
.
Since Angyal’s pioneering work24
, there has developed a great deal of interest in
the thermodynamic studies of saccharides in aqueous electrolyte solutions due to their
importance in several fields related to biology, medicine, catalysis and the environment.
Organisms exploit the water- structuring characteristics of the different saccharides in a
number of ways such as to modify the viscosity of cellular fluids and to protect against
freezing/dehydration25
. Trehalose forms viscous solutions and glasses at room
temperature which have proved useful in studies of protein dynamics. Trehalose coating
prevents thermal denaturation by damping large-scale fluctuations of protein-specific
motions20,21
. The presence of salts modifies important properties of aqueous saccharide
solutions related to their protective role such as viscosity, water sorption, and
crystallization rate and glass transition temperature21,26
. Due to the fact that saccharides
readily undergo isomerization and conformational changes their complexation with metal
ion result in the formation of mixture of products. In spite the weak metal-saccharide
complexes formed, their interactions are selective. Complexing abilities of different
saccharides are primarily dependent on conformation, stereochemistry and size of the
metal ion. Saccharides containing an ax-eq-ax sequence of three -OH groups in a
pyranose ring /cis-cis sequence in furanose ring (ribose isomers) have specific
interactions with some metal cations in solution. But the studies of metal ion-saccharide
interactions regarding binding preferences, structural and stereochemical features and
stabilization of the species formed are largely unexplored27-29
.
Thermodynamic and transport properties are very useful in the study of
hydration behaviour of saccharides. Many technological applications of saccharides
utilize the exotic rheological properties of their aqueous solutions, such as the control of
gelling processes, and the osmoregulation of tissues and organs in cryoprotective
3
provisions30-31
. Fundamental thermodynamic information is important to select the
reaction conditions (e.g. feasibility and optimization) of industrial processes.
Thermodynamic properties of aqueous saccharides at high temperature and pressure are
also applied in a variety of geochemical studies to assess the relative stabilities of
biomolecules at high temperature and pressure. The energetics of catabolism in
thermophiles and barophiles is one of the applications of such data32
. Saccharides have
substantial effects on tailoring phase tunable of ionic liquids (ILs) and water. These
systems are feasible to be used as extraction systems, especially in biological and
environmental engineering33
. In spite of the need, there is relatively little information
available on the enthalpy, heat capacity and volumetric properties for aqueous solutions
of saccharides as a function of temperature, pressure and concentration7,34-36
.
To understand the behaviour of saccharides in aqueous and mixed aqueous
solutions, an understanding of the structure of water, ionic and polar group hydration,
hydrophobic hydration and hydrophobic interactions, etc. is a prerequisite.
Consequently in the following sections, these aspects are being briefly discussed.
1.1 Structure of Water
Water is the most important and widely studied solvent due to its ubiquitous
in biological and industrial processes37-39
. This has evoked a lot of interest to study
the current status of the structure of water and aqueous solutions in biological
systems, particularly the manner in which a solute modifies the short-range and long-
range order existing in water40
. Considerable effort has been devoted towards an
understanding of structure of water, both by experimental and theoretical probes41-49
.
Inspite of all these efforts, the structure of water is still a matter of conjecture37,48
.
Water owes its unique and unusual personality to certain anomalous
physicochemical properties, which distinguish it from other simple fluids50-51
. The most
striking examples of its anomalous behaviour are contraction upon melting (shown
only by Germanium and Bismuth among all the known substances44
), density
maximum, negative pressure coefficient of viscosity, high melting and boiling points,
high latent heat of fusion and evaporation, high dielectric constant, and high molar
heat capacity.
4
The pioneering work on solution X-ray diffraction measurements by Bernal
and Fowler52
and later by Morgan and Warren53
reveal that water is tetrahedrally
coordinated through hydrogen bonds, similar to that in ice I (Fig.(1.1)). The
various hypothetical models put forth to depict the water structure are classified into
(i) Continuum Model ; (ii) Mixture Models.
Fig. 1.1 Schematic representation of Crystal Structure of Ice I at Low Pressure
1.1.1 Continuum Model
The continuum or uniformist model assumes that liquid water is uninterrupted,
three dimensional lattice of tetrahedrally coordinated hydrogen bonded molecules52-
57. Thermal, electrostatic and steric perturbations are thought to produce hydrogen bond
stretching and bending deformations rather than bond breakage. The recently highly
successful continuum model, also known as Random Network Model (RNM) has
5
been proposed by Rice and Sceats56
and developed by Henn and Kauzmann57
. It does
not involve changes in the number of hydrogen bonds. RNM model is not only a good
model for determining the heat capacity contribution due to water-water interactions
but also gives a good insight into the reorganization of water around the non polar and
polar solutes. This model also provides a simple mechanism for energy absorption and
variations of dielectric properties and X-ray radial distribution function with
temperature as a variable. However, in view of the restrictions placed on molecular
motions, this model fails on logic to explain the trend in entropy data and the hydration
properties of non polar molecules.
1.1.2 Mixture Models
These models visualize liquid water as collection of differently hydrogen bonded
species in which each water molecule can fluctuate through states where none, one or
both of its hydrogen atoms are engaged in hydrogen bonding58-67
. Depending on the type
of species involved, the mixture models have been classified as follows: (i) Interstitial
Model proposed by Samoilov68
and Forslind69
; (ii) Water Hydrate Model proposed by
Pauling70,71
; (iii) ‘Flickering Cluster’ Model proposed by Frank and Wen
58, and Frank
72.
The most popular and commonly used model, especially in the field of solution
chemistry is the 'Flickering Cluster' Model.
Flickering Cluster Model
Frank and Wen58
, and Frank72
viewed water as a mixture of clusters of
hydrogen bonded water molecules with voids therein (bulk water) and free
unbonded monomers (dense water) in equilibrium with each other (Fig. 1.2). The
formation of hydrogen bonds and the disruption of hydrogen bonds in such a
polymeric complex is considered to be a cooperative phenomenon. The physical basis
of this cooperativity is that hydrogen bond formation involving one bonding site of a
water molecule contributes delocalization energy to the molecule, which favours
additional bonding at other potential hydrogen bonding sites. According to this
model, the presence of flickering clusters of water molecules (Fig. 1.2) of short half-
time (10-11
to 10-10
s) reflects local energy fluctuations. The occurrence of some type of
dynamic monomer-polymer equilibrium in water allows an acceptable
explanation of the free energy of activation of transport processes in water, whether
6
calculated from self-diffusion, viscous flow, dielectric relaxation, or ultrasonic
absorption data73
.
Fig. 1.2 Frank-Wen Flickering Cluster Model of Liquid Water
Nemethy and Scheraga60
used a statistical thermodynamic treatment to calculate
the Helmholtz free energy, internal energy and entropy as a function of temperature of
liquid water, assuming that each of the hydrogen bonded molecules could be
associated to a discrete energy level in the flickering clusters. Hagler et al73
. and
Lentz et al74
. have modified this model to remove some major inconsistencies
prevalent in it as pointed out by Nemethy75
. Walrafen61
and Hartman76
provide the
strongest support for the mixture model from the Raman Spectroscopic studies of
7
HOD. These studies reveal a pronounced shoulder in the high frequency side along
with the intense low frequency band. Further these studies show that as the water is
heated, the intensity of the high frequency component increases compared to that of
low frequency component. The high frequency component was associated to the
monomeric species and the main band of the low frequency to the hydrogen bonded
species. It was further argued that the increasing intensity of the high frequency
component with increase in temperature reflects the conversion of hydrogen-bonded
molecules to the non-hydrogen bonded molecules (Fig. 1.3). The mixture model thus
appears to be consistent with the vibrational spectroscopic data.
Fig. 1.3 (a) Argon-lon-Laser-Raman spectrum from a 6.2 M solution of D2O in
H2O at 250C and
(b) Quantitative mercury-excited Raman spectra from a 6.2 M solution of
D2O in H2O at a series of temperature.
8
Recently Robinson and co-workers77-78
have also reported from the studies on
properties of pure water as a function of temperature and pressure that on average,
the water is composed of dynamically transforming microdomains of two very
different bonding types i.e. regular tetrahedral water-water bonding similar to that of
ordinary ice i.e. Ih and other is a more dense non-regular tetrahedral bonding similar
to that in ice II. Although many water models are successful in predicting selected
liquid water and ice polymorph properties, there is still a need to construct a model
of general applicability37,39
.
1.1.3 Computer Simulations
Computational techniques are often used to model protein folding, ligand
recognition and binding, partition coefficients, solubility, reaction rates, pK a, and
tautomer ratios, all of which depend crucially on the accuracy with which solvation
effects can be modelled37
. Two types of approaches have been used for computer
simulation studies of the liquid water: (i) Monte Carlo (MC) method79-82
; (ii)
Molecular Dynamics (MD) method83-84,49
. In both these methods, the partition
function and hence the equilibrium properties are generated for an ensemble of water
molecules from the positive additive intermolecular potential energies. The
molecular arrangements in the liquid water are also studied by these two methods.
In MD method, the temporal evolutions of the translational and rotational
trajectories of the individual molecules are followed under the joint influence of the
forces and torques exerted on it by all other molecules. These trajectories then yield
the time autocorrelation function and hence various kinetic properties of liquid
water.
The MC method generates an ensemble of molecular configurations
representing the thermal equilibrium. The results of both MD and MC methods
indicate that there exists a marked tendency of liquid water toward hydrogen bond
order, but with much less predictable geometry. However, the study of ice by
crystallography alone would have suggested this. The potential used in the MC or
MD calculations are all pairwise additives, i.e., the energy of a given assembly is
expressed as a sum of the interaction energies between all pairs of molecules in the
assembly. It has been stressed that none85
of these pair potentials can account for
both gas and condensed phase properties of water. It is evident from quantum
9
mechanical calculations on water trimers, tetramers and pentamers that hydrogen
bonding in these clusters is stronger than in the dimer86
, which suggests the
cooperative nature of hydrogen-bonding interactions.
Jorgensen87
has developed transferable intermolecular potential functions
(TIPS) suitable for use in liquid simulations for water. This potential has been used
by Jorgensen and Madura80
in MC simulation on liquid water to study the effect of
temperature on vaporization, hydrogen bonding, density, isothermal compressibility
and radial distribution functions. Recently Mahoney and Jorgensen88
by applying
classical MC Statistical Mechanical Simulations optimized a five-site, fixed charge
model of liquid water with emphasis on improving the computed density as a
function of temperature and the position of temperature of maximum density. The
obtained results further support a two state mixture models for the liquids.
Various workers49,84,89-90
have used the theoretical and simulation methods to
study the behaviour of water. It was reported82
that linear molar volume of relevant
inherent structures contributing to the liquid phase increases with the decrease in
temperature. Owicki and Scheraga91
observed a broad, smooth distribution of
hydrogen-bond energy for liquid water, rather than relatively discrete sets of the
bonded and unbonded interaction energies. Chu and Sposito92
started with the
relaxing cage model for the dynamic structure of an atomic liquid and finally
generalized it in the case of liquid water. Grunwald93
developed a model for the
structure of the liquid water network using the concept of the two state models. The
model is consistent with free energy and its temperature derivatives, the dielectric
constant, the probable number of hydrogen bonded nearest neighbours,
intermolecular vibration frequencies and dielectric relaxation dynamics.
Liu and Ichiye94
have presented a new one-site effective pair potential model
for water intended for modeling the solvent effect in biological systems. The present
model, based on modifications of the hard-sphere, sticky dipole potential of Bratko,
Blum and Luzar (BBL)94-95
contains an Lennard-Jones type repulsive soft-sphere, plus a
tetrahedral ‘sticky’ potential and an embedded point dipole. This model gives an
intermolecular energy, hydrogen bond energy and heat capacity in good agreement with
results from experiments and other models. Therefore, it represents an improvement
over the BBL in both structure and intermolecular energy. While most of these
10
results79,96
describe liquid water as a continuum of bent or stretched hydrogen bonds
but at the same time the MD results of Stillinger and co-workers83
do indicate the
presence of non-bonded -OH groups whose life time is much longer than the water
molecular vibrational periods. Therefore, these studies lend indirect support to both
continuum and mixture models. Nevertheless, they have been able to explain the
various properties of liquid water like high heat capacity, a density maximum and
compressibility minimum. Recently Dore97
and Gorden and Hura98
emphasized that the
simulation methods will need to the used in conjunction with experimental data for more
understanding of water and its anomalies. In spite of enormous investment in terms of
experimental and theoretical studies to explore water structures, a compact and
useful description is yet to be achieved.
Supercritical water has attracted scientist's interest in recent years due to its
peculiar physicochemical properties and industrial uses37-38,48,99
. Ohtaki et al.48
from X-ray
diffraction and also from neutron diffraction studies proposed a classification of
supercritical water into three categories: (i) low density water; (ii) medium density
water; (iii) high density water, because density is a very important
thermodynamic quantity to describe properties of sub- and super-critical water. It
has been concluded that water at high temperature and high pressure consists of
mixture of clusters and dispersed phase contains low aggregates including
monomeric water molecules. They further stressed that the knowledge of hydration of
ions and polar substances in supercritical water is important to understand ion-
water and polar molecule-water interactions which relate solubility phenomena and
decomposition of the substances. Karamertzanis et al.37
have proposed
a novel,
anisotropic rigid-body intermolecular potential model to predict the properties of water
and the hydration free energies of neutral organic solutes. The proposed water model is
found suitable for modeling the structure, and a range of properties of ordered ice
polymorphs and liquid water not included in its parametrization.
1.2 Structure of Aqueous Solutions
In view of the lack of a complete satisfactory theory of water structure, there
have been continuous efforts to know the structure of aqueous solutions. The most
popular model that has emerged in the area of solution chemistry is the 'Flickering
Cluster' model56-58
. Though like other models this model is not entirely adequate, still it
11
has been able to explain the various properties of aqueous solutions more satisfactorily
than any other model.
According to 'Flickering Cluster' model58
, water molecules can be
considered to be in dynamic equilibrium between the bulky tetrahedrally hydrogen
bonded clusters (H2O)n and monomer molecules, as represented by (H2O)n
n(H2O), where (H2O)n and n(H2O) represent 'bulky' and 'dense' states, respectively. The
statistical degree of ice-likeness (or whatever its structure in water) is considered to
be proportional to the half-life of the clusters, which is of the order of 10-11
s in pure
water, which may shift the equilibrium in either direction. The solute which causes a
shift so as to increase the average half-life of the cluster is termed as a ‘structure
maker’ and a solute, which has an effect in the opposite direction, is called a ‘structure
breaker’56
.
Although the concept of structure-making and structure-breaking effects of
solutes is not very satisfactory, but it has proved useful in discussing the effects of
solutes on water structure100
. These effects can be reflected experimentally by observing
the changes brought about by the solutes in the kinetic properties of water such as
fluidity, reorientation time, viscosity, conductance, etc. For instance, structure
makers are shown to decrease the fluidity of water by causing an increase in
reorientation time and increase in viscosity and result in positive excess partial molar
heat capacities in water. The reverse is true for structure breakers. Hydration of
different kinds of solutes, depending upon their nature is classified as: (i) Ionic and
polar group hydration; (ii) Hydrophobic hydration ; (iii) Hydrophobic interactions.
1.2.1 Ionic and Polar Group Hydration
The ionic hydration is one of the most important fundamental
physicochemical processes, which bears close connection with many research fields
in chemistry including chemical reactions and stability of biomolecules. For example,
the crystal lattice of salts like NaCl is held together by very strong electrostatic
attractions between ions. However, water readily dissolves crystalline NaCl because of
very strong electrostatic attractions between Na+/or Cl
- ions and water dipoles. This
leads to very stable hydrated Na+
and Cl- ions, ion-solvent interactions greatly exceed
the tendency of Na+ and Cl
- ions to attract each other. When an ion is introduced into
12
water, it interferes with the local ordering of the water molecules in its neighbourhood
and tends to impose a new order on them, ions of simple electrolytes such as LiF and
MgCl2 having high charge density act as net structure makers and the ions of electrolytes
like CsI and KBr with low charge density behave as net structure breakers. In order
to explain these phenomena, Frank and Wen58
visualized a picture (Fig. 1.4) in
which an ion is surrounded by three concentric regions of water molecules as
described below:
(i) An innermost structure-formed region 'A' consisting of polarized, immobilized and
electrostricted water molecules.
(ii) An intermediate structure-broken region 'B' in which water is less ice-like i.e.
more randomly ordered than the normal water;
(iii) An outer region 'C' in which water molecules have the normal liquid structure,
which is polarized in the usual way as the ionic field at this range will be
relatively weak..
Fig. 1.4 Frank-Wen multizone model of ion-hydration in aqueous solutions
In the electrostrictive region, ionic charge on the ion completely orients the
surrounding water molecules, which become immobilized and firmly packed around
the ion in comparison to bulk water. Samoilov68
has called this phenomenon as
positive hydration. The water in the second and third solvation layers is less
13
immobilized and orientation of water molecules is diminished but it is enough to interfere
with the formation of normal bulk water. The decreased structure in region 'B' is
presumably due to approximate balance of the two competing forces, namely, the normal
structure-orienting influence of the neighbouring water molecules and the radially-
orienting influence of the electric field of the ion which acts simultaneously on any water
molecule in this region. The latter ionic influence predominates in region ‘A’ and the
former in region ‘C’ and between ‘A’ and ‘C’, according to Frank and Wen58
, there is
a region of finite width in which more orientational disorder should exist than in
either ‘A’ or ‘C’. Thus, water in this region has less structure ( or there are fewer
hydrogen bonds) and ion can be classified as structure-breaking or negative
hydration ion.
The relative size of these three regions depends on the charge, size and
composition of the ion. In general, the ions with low charge density have relatively
weak electrostatic fields which makes the region ‘A’ very small thereby causing the net
decrease in the structure. On the other hand, ions of high charge density increase the
region ‘A’ and might induce additional structure (entropy loss) of some sort beyond
the first water layer, thereby causing a net structure-making effect.
Friedman and Krishnan101
have proposed a model for aqueous ionic
solutions primarily based on the ideas of Frank and Evans102
. Gurney103
and
Samoilov68
with the assumption that around each solute particle xz (z=charge on the
ion) there is a region termed as cosphere, having the thickness of one solvent
molecule in which solvent properties are effected by the presence of the solute.
These effects are characterized by the thermodynamics of the process:
n[Solvent(pure bulk liquid)] → n[Solvent (in cosphere state next to xz)] where, n is the
number of solvent molecules in the cospheres. Friedman and Krishnan101
model
emphasizes on the contribution of the various cosphere states to the thermodynamic
properties of solutions, while Frank and Wen model58
, and more recently Stillinger and
Ben-Naim model104
of ionic solutions being rather qualitative, are supported by the
experimental studies of kinetic properties, X-ray and neutron scattering105
. Friedman and
Krishnan101
have compiled the various thermodynamic properties and have given
reasonable explanation of these properties based on their cosphere model.
14
Recent computer simulation studies106
have confirmed the presence of two types of
hydration shells. Inner hydration shell has a well defined hydration number (exceptions
are with the low charge densities) and in the outer hydration shell, the water-water
correlation depicts a decrease in structure.
Aqueous solutions of simple polar non electrolytes which have proton donor or
acceptor sites are very interesting since many of them are components of
biological fluids or very similar to monomeric units of biological macromolecules107
.
Urea, amides, alcohols, polyols etc. are the few examples where hydration of these
compounds involve hydrogen bonding, dipole-dipole and dipole-induced dipole
interactions between these and water molecules108-109
. Polyfunctional solutes e.g.
carbohydrates exhibit very complex behaviour in aqueous solutions which is
difficult22-24,110
to rationalize as both hydrophilic and hydrophobic types of hydration are
contributing. As all taste effects are mediated by water, thus the solution properties of
small saccharide molecules provide necessary clues to the possible mechanisms of
taste chemoreception109
. The apparent molar volumes of saccharide molecules
depend upon the axial and equatorial arrangement of their -OH groups111
and
saccharide molecules have been thought of as polarised with respect to water
structure just as they are oriented with respect to the taste receptor. In other words,
water molecules probably cluster preferentially around the hydrophilic end of the
saccharide molecule.
1.2.2 Hydrophobic Hydration
Non polar solutes such as hydrocarbons and ions having non polar groups e.g.
substituted hydrocarbons and alkyl-ammonium salts, behave quite differently in water
as compared to the ionic solutes, as these are readily soluble in most non polar solvents,
but only sparingly soluble in water. The relatively low solubility of hydrocarbons in
water is easy to observe and determine, but unexpectedly difficult to explain112-114
. In
thermodynamic terms, the low solubility of non polar solutes means that the transfer of
the solute molecules from the pure liquid alkane to dilute aqueous solution and this
process is accompanied by large decrease in entropy which makes the free energy of
their solution positive in spite of their exothermic dissolution in water. It seems natural
to regard the insolubility as being ‘entropy controlled’113
. This behaviour of non polar
solutes is apparently uniquely characteristic of aqueous solutions. The negative entropy
15
and enthalpy change and positive change in heat capacity upon the addition of non polar
solute to water indicates that the packing of water molecules around the non polar
solutes is somewhat tighter than in pure water. This situation is called a ‘structure
increase’ or enhancement of structure of water112,115
(Fig.1.5). This region is also known
as iceberg formation or hydration of second kind or the hydrophobic hydration although
the structure is not necessarily identical with that of ice. These models assume the
formation of short-
Fig. 1.5 Diagrammatic representation of
(a) Hydrophobic hydration and (b)-(e) hydrophobic interactions;
(b) Kauzmann-Nemethy-Scheraga contact interaction;
(c) Globular protein folding;
(d) Proposed solvent-separated interaction; and
(e) Possible stabilization of helix by interaction as in (d)
16
lived aggregates of water molecules around the solutes, having more or less well
defined structure, called as ‘icebergs’116
, ‘flickering clusters’56,58
, clathration shells’,
polyhedral cages’ similar to those found in the crystalline hydrates formed by some
small non polar molecules117
. The most impressive evidence for the formation of some
kind of definite structure i.e. iceberg or cages in aqueous solution is probably the
existence of solid gas hydrates and clathrates. These models are consistent with the
view that considers, inert non polar solutes as ‘structure makers’. The formation of
polymeric aggregates involves increased or strengthened hydrogen bonding113
, which
would give negative contribution to tH. The solutes imposed structure melts away on
heating the solutions. This ‘melting’ involves breaking of some of the excess hydrogen
bonds resulting in an increase in the heat capacity118
.
Ben-Naim119
has also discussed the stabilization of water structure caused by the
addition of non electrolytes that arise from the difference in the change of the chemical
potentials of the clusters and of the monomeric water molecules. He also pointed out
that the penetration of solute molecules into the cavities of the relatively open structure
of the clusters enhances the stabilization effect, although filling up of the cavities is not
an essential requirement for the existence of a stabilizing effect. A number of hydrates
of the noble gas atoms, hydrocarbons, halogens and of many other simple molecules are
known to exist. Frank59
has pointed out that the induced ice-likeness, cannot consist of
clathrate formation in the liquid phase, although ice-like structure could be transitory
fragments of clathrate-like aggregates.
According to Privalov and Gill118
, there are two temperatures TH and TS of
universal nature that describe the thermodynamic properties for the dissolution of liquid
hydrocarbon into water. TH is the temperature at which heat of solution is zero120
, which
is around 200C for a number of liquids, TS is the other universal temperature around
1400C where entropy of transfer of non polar compounds into water is zero, and the
process of transfer is most unfavourable. Further at any temperature other than TS, the
net effect of hydration of non polar solutes favours the transfer of non polar molecules
from the compact state into water. Thus, according to their views, the hydration effect
of non polar solutes stabilizes the dissolved state and this in itself cannot be regarded as
the cause of their hydrophobicity.
17
Muller113
has given another view that at and above TS water retains though to a
lesser extent, the same capacity for structural reorganization which makes it a unique
solvent at 250C.This modified ‘hydration shell hydrogen bond model’ (HSHB)
112
assumes that the progressive breaking of hydrogen bonds on heating accounts for about
half of the observed heat capacity of bulk water, and the bond breaking process is
perturbed by the introduction of a solute that give rise to ∆C0
p,2 . Simulations confirm
Muller’s hypothesis that a larger fraction of the hydrogen bonds within the first
solvation shell are broken in comparison to the bulk solution.
According to Lumry et al.65,121
and Ben-Naim119
there is a exact compensation
for the entropy and enthalpy change that arises from change in the state of water in the
presence of non polar solutes i.e. ordering of water, and thus this effect does not
contribute to the hydration Gibbs energy. However, Privalov and Gill118
and Murphy et
al.122
have pointed out that large heat capacity change which plays the key role in
regulating the hydration free energy change and the principal feature of hydration
process.
Borisover et al.123
suggested a new method of estimating the hydrophobic effect
contribution to the thermodynamic functions (Gibbs energies and enthalpies) of
hydration of non electrolytes. Their results indicate that enthalpies of the hydrophobic
effect for alkanes are negative which are similar to that reported by Belousov and
Panov124
. However these results are contrary to Abraham’s opinion125
that this enthalpy
is positive. Borisover et al.123
from these studies also indicated that the rare gases
exhibit hydrophobic hydration.
Costas et al.126
have found that if the combinatorial contribution to the Gibbs
energy and entropy of transfer is subtracted from the experimental values, all non polar
solutes in water behave in a universal manner, i.e. all of their thermodynamic transfer
functions can be studied with their molecular surface area as the only parameter. They
have considered that the water molecules around solute undergo a relaxation process,
which lowers the Gibbs energy, enthalpy and entropy of the system and is responsible
for large heat capacity of transfer. The origin of hydrophobicity lies in high cohesive
energy of water being counteracted by relaxation of water molecules in the
neighborhood of the hydrophobic solute.
18
Madan and Sharp114
have reported that non polar solutes have a large positive
heat capacity of hydration, Cp, while polar groups have a smaller negative Cp of
hydration. The increase in heat capacity of non polar solutes can be as large as 12 JK-1
mol-1
per first shell water at 25C, a surprisingly large change when compared to the
total heat capacity of water, 75 JK-1
mol-1
. As a consequence of the large heat capacity
increase, the low solubility of apolar groups in water at higher temperatures (>90C) is
caused by unfavourable enthalpic interactions and not because of unfavourable entropy
changes. The hydration of polar groups is accompanied by a smaller but significant
decrease in Cp. Thus the solubility of polar groups in water is driven by favourable
enthalpic interactions at both higher and lower temperatures. Talukdar and Kundu127
have studied the salt effect on the hydrophobic hydration in aqueous salt solutions. They
concluded that hydrophobic cations induce more hydrophobic hydration in aqueous
NaNO3 solution than in pure water.
1.2.3. Hydrophobic Interactions
The tendency of non polar groups to aggregate in aqueous solutions in order to
minimize energetically unfavourable interactions with water is termed as the
‘hydrophobic bonding’128-129
, ‘hydrophobic interaction130-134
. These are solvent
induced interactions between a polar moieties and are an outstanding feature of aqueous
solutions. They are driven by the urge of water in overlapping hydrophobic hydration
shells to regain the properties of water in the bulk. The entities can either be parts of
independent molecules or ions, e.g., glycerides, phospholipids, surfactants, and
dyestuffs, or side chains, covalently bonded to a common backbone, e.g., polypeptides
or proteins. They play fundamental role in the stabilization of micelles, biomembranes,
and native globular protein structures41,118,129,135-136
. These interactions are generally
involved in many molecular recognition processes such as the specific binding of
substrates in the active site of enzymes, quaternary protein structure formation, protein-
DNA interactions and host-guest binding135,137
. Hydrophobic interaction is also one of
the important factor in hydrophobic column chromatography, a novel methodology for
the purification of a variety of biological and industrial materials.These subjects are
however problematic even on semantic level138-140
.
From spectroscopic measurements, Ide et al.141
have reported that non polar
substitutents bring about structuring of water surrounding these groups. NMR studies
19
carried out by Bagno et al.142
also showed that water-water bonding in the surrounding
of hydrophobic side substituents are stronger than these within bulk water. Hechte et al.
143 has also reported the increase in water clusters around alkyl side chain with increase
in alkyl side chain length.
Commonly a distinction is made between bulk and pairwise hydrophobic
interactions in water. Bulk hydrophobic interactions, which lead to surfactant
aggregates, such as micelles and lipid bilayers, are the resultant of the fact that
insufficient water is available for the formation of independent hydration shells, so that
association can not be prevented. These aggregates are formed with a high cooperativity
and London dispersion energy contributes significantly to their stabilization. Pair wise
hydrophobic interactions on the other hand do take place via destructive overlap of
independent hydration spheres. London dispersion interactions play a much less
important role, since for these direct interactions, the hydration of solute is required.
Ludemann et al144
have reported very recently that till date there is no evidence for a
qualitative difference between pair and bulk hydrophobic interactions.The association
of non polar moieties is assumed to be partial reversal of the solution process. The
thermodynamic parameters for hydrophobic interactions i.e. ΔH0
> 0, ΔS0
> 0, ΔCp0
<
0, ΔG0
< 0 have opposite signs as compared to those of hydrophobic hydration42,60
.
The hydrophobic interaction is accompanied by disordering of water structure i.e.
partial melting of the so called ‘iceberg’ or clathrate like structure that are produced
when the separate non polar species are first introduced into water42,133
. The
hydrophobic interactions are found to be unusual as compared to normal processes
because these are temperature dependent. At 250C, the transfer of non polar solutes to
water is not principally opposed by the enthalpy, rather it is due to excess
entropy41,118,120
. It arise from the water of solvation around the solute rather than from
solute-solute interactions145-147
. Computer simulation supports a molecular
interpretation that at 250C non polar solutes are surrounded by ordered water molecules.
Water surrounding the non polar solute prefer to hydrogen bond with other water
molecules rather than to ‘waste’ hydrogen bonds by pointing them towards the non
polar species145-146
. However at higher temperatures the aversion of non polar solutes
for water becomes ordinary and less entropy driven. The heat capacity change for
transfer of non polar solutes from the pure liquid to water is large and positive41,101,118
,
which implies that the enthalpic and entropic contributions are highly temperature
20
dependent. The free energy is a nonlinear function of temperature, increasing at low
temperature and decreasing at higher temperature. Hence there will be a temperature at
which solubility of non polar species in water is a minimum41,118,120,148
. The free energy
of transfer of non polar solute into water is extrapolated to be most positive in the
temperature range 130-1600C
118-119,122,149. Hydrophobic interactions are found to be at
their maximum value at 1400C and are determined entirely by enthalpic contributions.
Hence water ordering is not the principal feature of the aversion of non polar residues of
water.
1.3 Specific Molecular Hydration
The hydration effects in aqueous solutions of non polar solutes have been shown
to be largely non-specific and are characterized by microheterogeneities (reflected in
marked concentration dependence of physical properties of these solutes). The opposite
is the case for highly polar solutes where specific interactions between proton donor or
acceptor sites (e.g. -OH, -N-, -O, >C=O) on neutral molecules and water molecules
occur. However, interactions which predominate in aqueous solutions of polyfunctional
solutes are of rather different nature from those occurring in both hydrophobic and
polar solutes.
Because of large number of structures present in saccharides, these can be very
good model compounds to explore the hydration behaviour of polyfunctional
hydrophilic solutes. The hydration of a saccharide molecule depends on its
stereochemistry, but how the hydration of a saccharide depends on its hydroxy
topology is a matter of debate and controversy8,150
. Generally there are three points of
view. It has been proposed that the anomeric effect of a saccharide governs its
hydration151
. Studies of Suggett and co-workers50,152
have shown the absence of any
marked solute-solute interactions in aqueous solutions of saccharides even at
relatively high concentrations. Tait and Frank153
have proposed the 'specific
hydration model' which emphasises that, in addition to the number of potential
hydration sites, hydration interactions depend on relative distance between, and mutual
orientations of these hydration sites. Since the hydration interaction competes with
the intermolecular hydrogen bonding in water, solute molecules which are able to
interact with the solvent without major perturbations in the solvent structure are likely to
interact preferentially. In this context, Warner154
from his model building studies,
21
pointed out that in many biological molecules, the spacing of ether, ester, hydroxyl and
carbonyl oxygen atoms is about 4.8 0A, which is very close to the next-nearest
oxygen spacing in a hypothetical ice I lattice at 298 K (4.750A). This suggests that,
provided there exists in liquid water some resemblance to an ice-like structure,
molecules like biotin, 1,4-quinone, β-D-glucose and triglycerides (Fig. 1.6) could be
cooperatively hydrogen bonded into water structure without undue modification
of the existing hydrogen bonded system.
Fig. 1.6 Correlation between oxygen spacings in organic molecules and in the ice
lattice. Numbers in the formulae indicate interaction points with the
correspondingly numbered oxygens in the ice lattice.
Model - ice
Biotin
1,4-Quinone
-D-Glucose
Triglyceride
22
In addition, Franks150,155
postulated the stereospecific hydration model, which
assumes that an equatorial hydroxy group is better hydrated than an axial hydroxy group;
hence, the hydration of a saccharide was proposed to depend on the ratio of equatorial
versus axial hydroxy groups. Although this theory has found considerable support156-160
,
doubts have arisen concerning its general applicability161
.
Recently, a modified stereospecific hydration model has been proposed23,162-163
,
emphasizing that the hydration of a saccharide depends predominantly on the relative
distance of the next-nearest neighbour oxygens of a saccharide compared to the oxygen-
oxygen distances of water. The relative position of the -OH groups at C-2 and C-4
appears to be a key factor. This theory is fully consistent with quantitative studies of
kinetic medium effects23,162
and relevant thermodynamic measurements163
.
Galema et al.8 have reported that molecular dynamics (MD) study of saccharides
in aqueous solutions provides important insights into their hydration characteristics.
There has been, and still is, a lively discussion as to the way in which molecular
dynamics simulations should be performed for saccharides in aqueous solution, because
most saccharides have a hemiacetal functionality that is subject to mutarotation.
Figs. 1.1 & 1.2 – Ref. 60, Fig. 1.3 – Ref 61, Fig. 1.4 – 58, Fig. 1.5 – Ref. 42,
Fig. 1.6 – Ref. 61.
23
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