A systematic understanding of gelation self-assembly: solvophobically assisted supramolecular gelation via conformational reorientation across amide functionality on a hydrophobically modulated dipeptide based ambidextrous gelator, N-n-acyl-(l)Val-X(OBn), (X = 1,ω-amino acid)

Article abstract of DOI:10.1039/c5ra10209j

A systematic investigation on gelation self-assembly has been performed on a hydrophobically modulated dipeptide based ambidextrous gelator, N-n-acyl-(l)Val-X(OBn), (X = 1,ω-amino acid). To elucidate the effect of hydrophobic tuning on gelator architecture towards its gelation self-assembly, three sets of gelators with a common formula: C_mH_2m+1C(=O)NH(l)Val(C=O)NH-(CH₂)_n-(C=O)OBn, were synthesized, Set-I includes gelators with n = 2, m = 9, 11, 13, 15, 17, for Set-II it is n = 2, 3, 5, m = 13 and Set-III comprises of two isomeric gelators (n = 2, m = 15; n = 10, m = 7). Gelation has been critically analyzed in various apolar (aromatic and aliphatic) and polar (protic and aprotic) solvents using FESEM, CD, IR, WAXRD and rheological studies. Obtained results reveal that π-π type interaction dictates the primary molecular alignment and positioning of amide functionality across the aliphatic chain which influences the peptidic orientation in parallel (when m > n) or antiparallel (when m < n) β-sheet type organization in their self-assembly. The thermal stability, gelation number (GN), T_gel and yield stress of gel systems increases with m, but for a given m, the trend goes apparently inverse with the increasing n. Circular dichroism (CD) studies suggest an intriguing evidence of non-planarity of amide plane during self-assembly, highlighting the involvement of conformational change taking place during molecular organization towards its gelation. Despite complex nature of solvent-gelator interaction, the effect of H-bonding component of solubility parameters was found to have a significant role on self-assembly. Overall, supramolecular forces acting at specific functionalities encrypted in gelator backbone must overcome the solvation energy with synergic assistance of solvophobic effect towards stabilization of gel-network with optimum gelator backbone conformation for achieving required enthalpic contribution for self-assembly.

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A systematic understanding of gelation self-assembly: Solvophobically assisted supramolecular
gelation via conformational reorientation across amide functionality on a hydrophobically modulated
dipeptide based ambidextrous gelator, N-n-acyl-(L)Val-X(OBn), (X = 1,ω-amino acid)
Saubhik Haldar* and Koninika Karmakar
Department of Chemistry, Jadavpur University, Kolkata, West Bengal, INDIA
*Corresponding author
Email: shaldar@chemistry.jdvu.ac.in ; saubhikhaldar@gmail.com
Phone no: +91 33 2414 6223, Fax. No. +91 33 2414 6223
1

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ABSTRACT
A systematic investigation on gelation self-assembly has been performed on a hydrophobically
modulated dipeptide based ambidextrous gelator, N-n-acyl-(L)Val-X(OBn), (X = 1,ω-amino acid). To
elucidate the effect of hydrophobic tuning on gelator architecture towards its gelation self-assembly,
three sets of gelators with a common formula: CmH2m+1C(=O)NH(L)Val(C=O)NH-(CH2)n-(C=O)OBn, were
synthesized , Set- I includes gelators with n = 2, m = 9,11,13,15,17, for Set-II it is n = 2,3,5, m=13 and
Set-III comprises of two isomeric gelators (n=2, m=15; n=10, m=7). Gelation has been critically analyzed
in various apolar (aromatic and aliphatic) and polar (protic and aprotic) solvents using FESEM, CD, IR,
WAXRD and rheological studies. Obtained results reveal that π-π type interaction dictates the primary
molecular alignment and positioning of amide functionality across the aliphatic chain which influences
the peptidic orientation in parallel (when m > n) or antiparallel (when m < n) β-sheet type organization
in their self-assembly. The thermal stability, gelation number (GN), Tgel and yield stress of gel systems
increases with m, but for a given m, the trend goes apparently inverse with increasing n. Circular
dichroism (CD) studies suggest an intriguing evidence of non-planarity of amide plane during self-
assembly, highlighting the involvement of conformational change taking place during molecular
organization towards its gelation. Despite complex nature of solvent-gelator interaction, the effect of H-
bonding component of solubility parameters was found to have a significant role on self-assembly.
Overall, supramolecular forces acting at specific functionalities encrypted in gelator backbone must
overcome the solvation energy with synergic assistance of solvophobic effect towards stabilization of
gel-network with optimum gelator backbone conformation for achieving required enthalpic contribution
for self-assembly.
2

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1. Introduction
Despite ample information being available on various gel forming molecular backbones,
designing of a gelator molecule using existing models capable of gelating in a particular liquid have
limited scope as the fundamental understanding of the particularities and characteristics of molecular
self-assembly resulting in gelation is still inadequate.1 A rapid growth in the research area of
supramolecular low molecular weight organo-gelator (LMOG) has been witnessed due to their diverse
application in miscellaneous fields.2-7 Constant efforts have been directed to understand the rationale
behind the formation of such soft materials arising from spontaneous self-assembly of low molecular
weight scaffolds8 and more specific to biocompatible peptide based systems.9 Inherent chirality of
amino acids with a variety of side chain residues can impart a remarkable influence on non-covalent
molecular association with interactive amide linkages on their supramolecular properties that give rise
to anisotropic aggregation towards amyloid-like fibrillar structures10 and a subsequent non-covalent
cross linking of these fibrils leads to the formation of fibrous network that restricts flow of the
entrapped solvent, resulting in gelation. The major challenge in designing a new gelator requires
adequate understanding of relative contributions of various intermolecular interactions among the
gelator molecules,11 gelator–solvent12 and the mechanism involved13 in their gelation process. Efforts
have been made by various research groups toward this direction.14-17 Utilizing the van der Waals
interaction in long hydrophobic aliphatic chains with a short peptide H-bonding sequence, gelation has
been observed in polar solvents.18-19 A rational approach of mastering the competing dynamic
interaction and hierarchical phase organization of non-covalently bound organic moieties in the dynamic
self-assembly was employed by Barboiu et. al.20 Introduction of functional groups into an already
studied gelator skeleton could be another strategy of getting functional organogels.21 However, such
approach has a possible inconvenience towards aggregation properties being significantly altered due to
new functionalization which can compete with H-bonding or alter solubility profile.22 Another systematic
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investigation was performed by Fages and co-workers with a library of N-acyl-1,ω-amino acid derived
gelators wherein the gelation ability was remarkably influenced by the type of aromatic substituted N-
acyl pendant, amino acid chain and also the degree of ionization of the carboxylate group.23 A structure-
function relationship with the mesophases of the gels obtained from amino acid derived dimeric
dendrons was correlated with different aliphatic spacers on the gelator backbone.24 However Suzuki et.
al. showed that gelation of N-alkyl amino acid amide of valine and isoleucine with 1,ω-dicarboxylic acid
and its monoester depends very much on the nature of their terminal functionality.25 Choice of amino
acid as chiral spacer on the gelator backbone was addressed recently by Bhattacharya et. al26 and our
group.27 Amino acid derived biologically inspired gelators can self-assemble via H-bonding even in polar
solvents due to large number of donor sites available per molecule and the gelation efficiency improves
as the number of peptide unit increases.28 The past, present and future direction of molecular gel have
been nicely described in a recent review by Richard G. Weiss where it has been clearly mentioned that a
very limited scope still prevails in designing molecular gelators based on various models, rather the
major dominance exists in the serendipitous discoveries of new structural classes of gelators.29 Earlier,
we have shown that peptide sequence or even the peptide architecture can modulate the self-assembly
property in a remarkable fashion.30 In the present study, a systematic variation at the hydrophobic
substituents on the molecular backbone of gelator has been made and a rationalization towards
structure function relationship has been attempted elucidating the controlling factors behind their
gelation self-assembly. A series of low molecular weight (L)Val based dipeptidic ambidextrous gelators,
N-n-acyl-(L)Val-X(OBn), (X = 1,ω-amino acid)[more specifically, CmH2m+1C(=O)NH(L)Val(C=O)NH-(CH2)n-
(C=O)OBn], were synthesized: Set- I (n = 2, m = 9,11,13,15,17), Set-II (n = 2,3,5, m=13) and Set-III
comprises of two isomeric gelators (n=2, m=15; n=10, m=7)(shown in Fig. 1) and their gelation behavior
was carefully studied using established experimental protocols. The experimental results were carefully
analyzed to find out the rationale of structural modulation over their gelation such self-assembly.
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[Fig.1]
2. Materials and Methods
2.1. Materials
Dicyclohexylcarbodiimide (DCC), L-valine and all other 1,ω-amino acids (β-alanine, γ-
aminobutyric acid, 6-aminocaproic acid, 11-aminoundecanoic acid) were purchased from Sigma
chemicals. Long chain fatty acids, 1-hydroxybenzotriazole (HOBT) were purchased from SRL, INDIA, and
N-hydroxysuccinimide (NHS), K2CO3 were purchased from Spectrochem, India. Solvents were purchased
from SD fine chemicals, India and were freshly distilled before use. Silica gel G has been used for TLC and
iodine vapor as staining agent.
2.2.
Synthesis
The L-Val based dipeptidic gelators (4a- 4h) have been synthesized in our laboratory following
the given scheme of synthesis. The details of the synthetic procedures, 1H and 13C NMR, and mass
spectroscopic data have been provided in the supporting information.
2.3.
Determination of Critical Gelation Concentration (CGC) and Gelation number (GN)
The gelators were insoluble in almost all solvents used in this study at room temperature;
however, they get dissolved on heating, which gelates on cooling. The critical gelation concentration
(CGC) as well as gelation number (GN) has been determined by dissolving known amount of gelator in
specific volume of a solvent, gelating them in identical vials bringing them at room temperature and
taking into account of the solvents gelated by the specific gelators.
2.4.
Determination of Gel Melting Temperature
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Gel to sol transition temperature (Tgel) of the gels was determined using vial inversion method31
as well as by oscillatory temperature-sweep rheology as has been described by Menger et. al.32 In the
former method, the Tgel has been defined as the temperature at which the gel melts and begins to flow
out of the vial. Where as in case of later method, the Tgel has been taken as the temperature at which
Scheme of synthesis
the elastic modulus (G’) drops below the viscous modulus (G”) indicating the point at which gel breaks
under applied stress. The gel–sol transition temperatures (Tgel) of the organogels were determined for
various solvents at different concentrations using the vial-inversion method. The vials containing the
gels were placed upside down on a water bath fixed with a high-precision temperature regulator and
heated. The bath was warmed up at the rate of about 0.1°C per sec. The temperature, at which the gel
started to flow, was taken as Tgel of the organogels.
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2.5.
FTIR Spectroscopy.
Spectra were collected using a BRUKER ALPHA FT-IR spectrometer with ATR attachment for the
gelators in solution (in CHCl3) as well as in their gel state (in acetonitrile).
2.6.
WAXRD study of thin film of xerogel
Organogels prepared in different solvents (acetonitrile, ethanol, 80% (v/v) ethanol in water,
anisole, etc.) were spread on glass cover slips and air dried carefully. The obtained films of these air
dried gels (xerogels) were subjected to WAXRD studies using Bruker D8 Advance with a parallel beam
optics attachment. The instrument was operated at a 35 kV voltage and 30 mA current using Ni-filtered
CuKα radiation and was calibrated with a standard silicon sample. Samples were scanned from 0° to 30°
in the step scan mode (step size 0.020, preset time 2 s) and the diffraction patterns were recorded using
a scintillation scan detector.
2.7.
Circular Dichroism
CD spectra were recorded using a Jasco (model J-815) CD spectrometer with a band width of 1
nm and slit width of 100 µm in the ultraviolet region (190-350 nm) and a quartz cuvette of 1 mm path
length. Experiments were performed with a sample interval of 0.5 nm and scan speed of 200 nm/min at
a controlled temperature of 20 °C. The samples for the experiment were prepared at different
concentrations.
2.8.
Field emission scanning electron microscopy
Morphologies of the gel materials were investigated using FESEM instrument INSPECT F50 (The
Netherlands) with an acceleration voltage of 20 kV. For this study, samples of the xerogels were
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prepared on a glass slide and scratched carefully and placed on carbon tape and coated with a thin layer
of gold.
2.9.
Rheology
Rheological Frequency sweep experiment was performed at 25 °C using an MCR-102 rheometer
(Anton Paar) with a cone plate (40 mm diameter and cone angle 1 degree) at a gap setting of d = 0.080
mm, linear frequency range of 1.0 to 10.0 Hz and constant strain of 0.01%. Rheological oscillatory strain
sweep experiment was also executed with the same instrument at a strain amplitude (γ) ranging from
0.01 % to 100% and a constant angular frequency of 10 rad s−1.
3. Results and Discussion
3.1.
Designing of Gelator molecules
A schematic representation of the gelators with modified segments is shown in Fig. 2. The
design comprises of four functionally distinct regions, viz, (i) an aromatic unit (benzyl ester) placed at
one end of the molecular backbone,(ii) a dipeptidic unit arising from peptide bonds between (L)-Valine
and 1,ω-amino acid residues, (iii) a flexible hydrophobic spacer sandwiched between aromatic and
peptidic zone and (iv) n-acyl chain with different molecular length connected to the N-terminal of the
dipeptide. These give rise to three sets of gelators having a common formula of
CmH2m+1C(=O)NH(L)Val(C=O)NH-(CH2)n-(C=O)OBn with varied m and n values. The gelator architecture
comprised of these four segments exhibiting specific supramolecular interactions based on their
inherent functionalities. A π-π type interaction is presumably evident at segment (i), whereas H-bonding
interaction is expected from segment (ii), and van der Waals type interaction likely to be predominant at
segments (iii) and (iv).
[Fig.2]
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In this paper, effect of hydrophobic modulation at the backbone architecture on the gelation self-
assembly has been rationalized by systematic variation at the segment (iii) and (iv) keeping invariable
units at segment (i) and (ii) which gives rise to three sets of gelators. Set-I gelators (4a- 4e) consisting of
varied N-n-acyl chain lengths (m = 9,11,13,15,17) with a given spacer (n = 2), ostensibly addresses the
effect of systematic increment in hydrophobicity at the N-acyl region on their gelation behavior. Fine
tuning of hydrophobicity at the spacer region [segment (iii)] (with n = 2, 3, 5) has been focused in Set-II
gelators, 4c, 4f and 4g where n values are 2, 3 and 5 for a given n-acyl chain (m = 13) respectively. The
reason behind choosing m = 13 is due to the fact that it is the average acyl chain length among the all
acyl units. Interestingly, Set-III includes two isomeric gelators of identical molecular length 4d (n=2,
m=15) and 4h (n=10, m=7) with peptidic zone placed at different positions addressing the issues of how
the mutual placement of amide functionality at different depths in the gelator backbone affects the
gelation. Another possible isomer with n = 15 and m=2 was excluded for the present study on the basis
of the fact that the amide unit in this isomer would be placed almost at the other termini of the gelator
backbone and this will lead the gelator to possess two functionalities (π-π interactive unit and amide
unit) having directional non-covalent interactions at the two ends and it needs to be dealt separately.
3.2.
Morphology
Vial inversion method was employed to sight the gelation and field emission scanning electron
microscopy (FESEM) to examine the self-assembled 3D network in gel matrix. The formation of
organized nanostructures, such as nanofibers, nanoribbons, and nanosheets has been widely found in
supramolecularly interactive organogels.33-34 We have taken three representative gelators 4d, 4g and 4h
from Set-I, II and III respectively (Fig. 3) and studied their molecular network in acetonitrile. In either of
the cases, fibrillar network (a prerequisite for a gel like system) with a rod like architecture was observed
in higher resolution and the dimensions of the nanofibers look different in each of these cases. As the
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respective xerogels were obtained in the identical solvent, the variation in nano-structuring is seemingly
due to differences in molecular architecture.
[Fig.3]
3.3.
Gelation behavior
The gelators have been showing an ambidextrous type gelation behavior with very high gelation
ability in various apolar and polar solvents (both protic and aprotic) including aqueous alcoholic media
(detailed data given in in S.I Table S1). The gels were stable for weeks and do not transform into
viscoelastic fluids or crystallize on prolonged storage in stoppered vessel at room temperature in closed
vials. The critical gelation concentration (CGC) has been expressed in terms of gelation number (GN)35
which is defined as the number of solvent molecules that is entrapped in the gel matrix per gelator
molecule. The change in hydrophobicity of the gelator molecules due to structural modulation has been
compared based on their clogP values. The clogP is calculated logP where P is defined as the ratio of the
equilibrium concentration of a substance dissolved in a two-phase system formed by two immiscible
solvents, octanol and water. The effect of hydrophobic modulation on gelator backbone architecture on
their GN in various solvents has been depicted in Fig. 4 where, Panel-I describes GN vs. clogP for Set-I
gelators in solvents like, (a) aromatic, (b) apolar, (c) polar aprotic and (d) polar protic media and Panel-II
depicts the same for Set-II gelators. In general, GN increases with the increase in N-acyl chain length
attached to the amide unit but not in a linear fashion where 4d (with C(16:0) N-acyl chain) shows
exceptionally high GN values than any other system. Comparatively lower GN for 4e (with C(18:0) acyl
chain) indicates that longer acyl chain might not always help in having higher gelation number. A very
interesting observation has been encountered in case of Panel-I(b) representing the change in GN with
respect to clogP in apolar solvent like cyclohexane and n-hexane for Set-I gelators; a reverse trend, i.e.,
GN decreases with the increase in clogP, was observed in n-hexane but an usual increasing trend was
found in cyclohexane. Seemingly, the gelation self-assembly gets more and more unfavorable with the
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increase in N-acyl chain length in n-hexane than it occurs in cyclohexane. Owing to an extended and
flexible conformation compared to rigid cyclic structure of cyclohexane, n-hexane can preferably
interact with the N-acyl motif with higher van der Waals interaction and thus N-acyl chains get
solubilized more in n-hexane than in cyclohexane giving rise to lower GN with higher clogP. Although,
for Set-I gelators, the GN value increases with the increase in acyl chain length, such increasing trend is
neither linear nor of an equal extent in different media. This suggests that, increase in intergelator van
der Waals stability cannot be the sole reason behind better gelation self-assembly. An analogous
understanding was cited by Iqbal et. al. where, solvophobic interactions are expected to be important
for aliphatic chains in polar solvents, however it may not be contributing significantly to the 1D-
aggregation for long and flexible chains.36 While comparing the effect of increase in hydrophobicity at
the spacer region for Set-II gelators, GN reduces with the increase in clogP via increase in methylene
units in the spacer region (as the n-acyl chain was kept identical for all cases here). A drastic decrease in
GN takes place with increase in spacer length from (CH2)2 (4c) to (CH2)3 (4f) but it increases again in
(CH2)5 (4g), i.e., the trend is like 4c>4g>4f. This could be due to the fact that instability in molecular
packing takes place while going from (CH2)2 (4c) to (CH2)3 (4f) resulting in decrease in GN values;
however a solvophobic interaction might start occurring in case of 4g, as it can also be observed that GN
value of 4g in aprotic polar solvent is comparatively more than in apolar and aromatic solvents (Fig. 4
Panel-II). Considering the hydrophobicity and conformational flexibility exerted by aliphatic tail and the
spacer region, apparently a critical balance between mutual placement of π-π interactive aromatic units
and H-bonding zone of amide play an important role in augmenting the stability of the self-assembly in
a synergic fashion. This is demonstrated by evaluating the gelation ability of Set-III gelators, where in
one of the isomeric gelators 4h for which H-bonding zone is deeply seated with respect to π-π
interactive motif. Thus it loses its gelation ability even in hydrophobic media (e.g. pet-ether, hexane etc.)
but shows gelation in aromatic solvents. The enthalpic contribution from amide unit alone is insufficient
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to stabilize the self-assembled network because the aliphatic zone (N-acyl / spacer) offers more gelator-
solvent interaction in apolar solvents rather in aromatic ones. On the other hand a polarophobic
collapse helps in self-assembly for 4h in aprotic polar solvents. Moreover, the destruction of intergelator
H-bonding network in polar protic solvent hinders the formation of self-assembly of 4h where the
polarophobic interaction might be insufficient for the self-assembly. Thus a polarophobic interaction
must be synergistically assisted by H-bonding interaction along with suitably placed other
supramolecular units with optimum flexibility to exhibit stable self-assembly. As has been highlighted by
van Esch et. al. that the direct relation of gelation strength with the changes in solvent properties is not
possible and it is more complex in nature, like, the hydrogen bonding interactions were weaker in polar
solvents whereas the gelation occurred only where sufficient compensation was provided by
intergelator van der Waals interactions.37
[Fig.4]
3.4.
Thermal stability of Gels
Gel to sol transition temperature (Tgel) of the gels was determined by vial inversion method as
well as by temperature-sweep oscillation rheology and Tgel values obtained from either of the methods
were found concurrent with each other (see SI, Figure. S5-S7).In general, the thermal stability increases
with the increase in the N-acyl chain length as the result obtained from Tgel vs. clogP plot for Set-I (Fig.5
Panel-I). But in the case of 4d, Tgel was found to be considerably very high in aprotic polar solvents like,
DMSO, acetonitrile, acetone and moderately higher in aromatic solvents like toluene, anisole and xylene
whereas it falls within the expected range in EtOH or in MeOH. Therefore, clogP alone cannot describe
the thermal stability of the gels for Set-I. In case of Set-II (Fig. 5. Panel-II), Tgel however decreases in
general with the increase in clogP though not linearly (4c>4g>4f). Thus, the increase in aliphatic spacer
might increase the hydrophobicity (clogP) but decreases the thermal stability eventually. Interestingly,
4d and 4h (showing gelation in few solvents) of Set-III having comparable clogP values (structural
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isomers) 4h with a very high spacer length has much lower Tgel compared to 4d (see SI), presumably
higher conformational flexibility at spacer region affecting the molecular packing in case of 4h.
Therefore, hydrophobic interaction at the N-acyl chain or at the spacer region cannot solely govern the
gelation process. While correlating the gelation number (GN) with the Tgel, it was observed that data
remains invariant or scattered signifying Tgel is not strictly dependent on GN values (SI, Figure Table 1). In
other words, higher GN might not reflect in their better molecular packing. This was also corroborated
with the rheological studies.
[Fig.5]
Concentration dependence on Tgel values show (Fig. 6) that the Tgel increase with the concentration of
gelators and from this, the thermodynamic parameters (ꢀH°, ꢀS° and ꢀG°) at 298 K of gels (from
different gelators) in acetonitrile were calculated (Table 1) following the reported procedures.38-39 The
results show that the values of ꢀG° were in agreement with the trend of Tgel of the gelators in CH3CN.
Moreover, Tgel of the gelators were compared at two distinct concentrations: 0.166 mM and 0.244 mM
as the former concentration is before reaching the plateau region and the later one after achieving the
plateau of Tgel vs [Gelator] plot (Fig. 6). The difference in the trend in Tgel values indicates that
reorganization in the gelation self-assembly takes place with the increase in concentration.
[Fig.6]
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Table1 Calculated thermodynamic parameters of the gelators in acetonitrile at 298 K
GELATORS
ꢀH°(kJ/moles) ꢀS°(J/moles) ꢀG°(kJ/moles)
4a
4b
4c
4d
4e
4f
91.78
83.68
147.35
108.51
99.02
98.07
50.85
43.72
278
243
445
310
286
295
137
123
8.83
11.27
14.74
15.62
13.80
10.16
9.87
4g
4h
7.07
3.5.
Rheology.
A quantitative estimation of viscoelastic properties of the materials was performed by
oscillatory rheological experiments. From an experimental point of view a gel is composed of two
component (solvent and gelator) viscoelastic system that exhibits two distinct mechanical properties: (i)
the system should not flow under a mechanical stress lesser than a limiting value, called yield stress and
(ii) it must be more elastic than viscous.40 The viscoelastic response of the material is characterized by
two material measures, i.e, the elastic storage modulus G΄ and the viscous loss modulus G˝ and
measured by dynamic oscillatory rheological strain sweep experiments.41 This study gives an indication
of the flow behavior and rigidity of the gel. The storage modulus (G’) [the ability of the deformed
material to store energy] and the loss modulus (G”) [the flow behavior of the material under stress] are
the two main parameters for the evaluations of the mechanical strengths of the gel system. In the gel
state, G’>G” and in the sol state, G”>G’. The crossover point between G’ and G” indicates the transition
point from elastic solid to viscous liquid, whereas yield stress is defined as the minimum stress that must
be applied to a sample in order to induce flow. This is determined by strain sweep experiments and the
stress value at which G” becomes higher than G’ is measured for 4a-4h. Fig.7 depicts a representative
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plot of strain-sweep experiment (G’, G” vs. Strain) for 4a, 4c, 4g and 4h. In case of Set-I gelators, yield
stress were found to be 189 (4a), 205 (4b), 262 (4c), 392 (4d) and 260 (4e); for Set-II : 262 (4c); 215 (4f);
98 (4g), and for Set-III : 392 (4d); 625 (4h). The results seemingly demonstrate that the yield stress
increases with the increase in the acyl chain length; however it shows an opposite trend with the
increase in spacer length. Such results corroborate with the results obtained for the Tgel values.
However, in case of Set-III, for isomeric gelators, 4h shows an unusual behavior where the yield stress is
higher in comparison to 4d but Tgel of 4h is less than 4d. Shear elasticity, yield stress and melting
behaviors were correlated to the cross-sectional sizes of fibers gel networks by Terech et. al.42where the
lowering of melting point attributing to the regions of solid and liquid are large enough so that
contributions from their surfaces is negligible, however the higher yield stress can be ascribed to the
internal strength of the aggregated structure and results from the balance of structural breakdown and
recovery of rheologically active units. To discern the discrepancy for 4h, it can be endorsed that,
polarophobic interaction might help to increase entanglement of fibrous network leading to higher
junction points and contribution from surfaces increases, however self-assemblies with higher
conformational flexibility at the backbone architecture led to its lower melting point. The presence and
extent of elasticity in a fluid gel systems were also analyzed using their tan δ values which represents the
ratio of viscous modulus (G") to elastic modulus (G'). The tan δ value of less than unity indicates elastic-
dominant (i.e. solid-like) behavior and values greater than unity indicate viscous-dominant (i.e. liquid-
like) behavior. In Set-I [0.210 (4a), 0.220 (4b), 0.190 (4c), 0.104 (4d), 0.235 (4e)], tan δ values were found
to decrease with the increase in acyl chain length; however tan δ values are comparable among gelators
in case of Set-II [0.190 (4c), 0.149 (4f), 0.199 (4g)] and Set-III [0.104 (4d), 0.100 (4h)], though Set-II has
comparatively higher values than Set-III. Therefore, Set-I elasticity increases with the increase in acyl
chain length which corroborates with yield stress and Tgel data. However it was not significantly different
in case of Set-II. Interestingly, a comparable elasticity was observed for Set-III gelators. Based on the
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obtained tan δ values ranging from 0.10–0.22 in the frequency sweep measurements, the systems can
be considered as strong gels where the storage modulus G’ is on average about 6–9 times greater than
the loss modulus G”.43 The increase in the elastic modulus of an organogel, as perceived by Rogers et.
al., is due to an increase in fibre–fibre interactions which lead to the formation of greater number of
transient junction zones, in turn leading to a more ordered system. 44
[Fig.7]
3.6.FT-IR Studies
To investigate the inter-gelator interaction at the peptidic region and the ester functionality near the
aromatic substituent, FT-IR studies were performed to identify the changes on the vibrational spectra of
the non-covalently interactive functional units in gel and sol state of the gelators. Since amide-I and
amide-II bands are two most prominent vibrational bands to identify protein secondary structures,45 we
tried to analyze the H-bonding network exist in the present series of gelation self-assembly. The
accompanied band shift of non H-bonded amide in soluble state to the H-bonded amide in the gel state,
the difference in vibrational mode at two states was tried to be identified by FT- IR. Analysis of the FT-IR
spectra of gelators 4a - 4h has been performed in solution (CHCl3) as well as in gel state in acetonitrile
(shown in Table 2). The amide I vibration, (absorbing near 1640 cm−1) arises primarily from the C-O
stretching vibration along with a minor contributions from the out-of-phase C-N stretching vibration,
the C-C-N deformation and the in plane bending of NH. In the present case, all the systems show
absorption within the range of 1630-1643 cm-1 which lie within the characteristic amide-I band for
parallel β-sheet type amide network. Moreover, amide-II band within the range of 1540-1547 cm-1 also
support the parallel β-sheet type arrangement. Usually, the amide II band arises from the out-of-phase
combination of the NH in plane bend and the CN stretching vibration with smaller contributions from
the CO in plane bend and the C-C and N-C stretching vibrations. While comparing the data for 4d and 4h,
a striking difference was observed. A parallel β-sheet type arrangement was evident all the gelators
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having shorter spacer unit (m > n) but with larger spacer unit (m < n, 4h) additional absorption bands at
1697 cm-1 and 1507 cm-1 (along with 1632 and 1546 cm-1) was observed suggesting a mixed β-sheet
type peptidic network (parallel and antiparallel). The shifting of amide-A band at higher wave number
while going from solution phase to gel phase also indicates the participation of N-H unit in H-bonding
interaction. Primarily an invariant band at ~1735 cm-1 , assigned for ester C=O, across all the gelators at
their gel or sol state suggests its nonparticipation in H-bonding.44 Keeping the results in proper
perspective, two types of molecular organizations have been postulated which is depicted in the Fig. 8.
Because of the molecular structures, π-π interaction among aromatic units makes the molecule to stay
in such a way that for gelators with shorter spacer (m > n, 4a -4g) interdigitation might occur at the N-
acyl unit keeping the amide units in a parallel fashion in either orientation: along the plane and at its
orthogonal direction (between the layers). But for longer spacer (n > m, 4h) interdigitation occurs with
an antiparallel β-sheet type interaction among the amide units where the N-acyl units stabilized by van
der Waals interaction with the spacer region and a parallel β-sheet type interactions may occur between
such planes at orthogonal direction. Such molecular arrangement might suggest to have a lower d100
value for 4h which is experimentally supported by XRD data where the d100 for 4h is found to be shorter
than 4d. (see XRD discussion).
[Fig.8]
3.7. Wide Angle X-Ray Diffraction
The packing pattern in the supramolecular assembly was analyzed using wide-angle X-ray
diffraction (WAXRD) spectra of the xerogels 4a - 4h in acetonitrile and also, 4c and 4g in a set of
different solvent systems to find out the solvent effect on molecular packing with respect to structures
bearing different spacer length. The obtained results were found to be in good agreement with the
proposed parallel β –sheet arrangement with π-π type interactive aromatic moieties in the
supramolecular network. A low-angle sharp peak with respect to (1 0 0 ) plane was attributed to the
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depth of the self-assembly present in the molecular network and it lies between 20 to 26 Å which is
close to the extended length of a single gelator molecule. Considering the π-π type interactive aromatic
units forming an extended network keeping the molecule in one particular orientation with parallel beta
sheet type H-bonded peptidic zone, the (1 0 0) reflection might be coming from the next π-electron rich
aromatic layer in opposite direction with an interdigitated network architecture (Fig. 10). Such
organization is also evident in literature.47 The data corresponding to d100spacing
(firstorderreflection),interlayerspacing,π-πstackingandedgelengthofcubiclattice(a) have been presented
in Table 3. In case of XRD pattern of Set-I gelators in acetonitrile, the d-spacing increases with the
increase in chain length, however, gelators with very long hydrophobic chain, was found to have a
considerable low value in d-spacing, suggesting a self-assembly having interdigitation with higher tilt
angle. Peaks assigned to a periodic distance of 3.89 Å were found ascribing to extended two-
dimensional layers of β -sheets that stack parallel on top of each other.34 While analyzing the diffraction
pattern using the plot of 1/d vs. (h2 +k2 + l2)½ a straight line passing through the origin suggests the
gelation self- assembly presumably possesses a primitive cubical phase (Pm3m) with a comparable
lattice parameter (a), however intensities of some of the reflections were too low to detect. A
representative plot for 4d in acetonitrile and 4g in acetonitrile and ethanol is presented in Fig. 9 (for
details, see SI Figure S9-S17). The major diffraction patterns (in hkl) as obtained in acetonitrile media
from the gels have been presented below.
Set I: XRD patterns of the following gelators in acetonitrile.
4a: (1 0 0), (2 0 0), (2 1 0), (2 2 0), (3 2 2).
4b: (1 0 0), (2 0 0), (2 2 0), (4 3 2).
4c: (1 0 0), (1 1 0), (1 1 1), (2 2 0), (2 2 2), (4 0 0), (4 3 2).
4d: (1 1 0), (2 0 0), (2 1 1), (4 0 0), (4 2 2).
4e: (1 0 0), (1 1 0), (1 1 1), (2 2 0).
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Set II: XRD patterns of the following gelators in acetonitrile.
4c: (1 0 0), (1 1 0), (1 1 1), (2 2 0), (2 2 2), (4 0 0), (4 3 2).
4g: (1 0 0), (2 0 0), (2 1 0), (2 2 0), (2 2 2), (4 2 0), (5 4 2).
Set II: XRD patterns of the following gelators in Anisole.
4c: (1 0 0), (1 1 0), (1 1 1), (2 0 0), (2 1 0), (2 2 0), (2 2 2), (4 2 0), (4 2 2).
4g: (1 0 0), (1 1 0), (1 1 1), (2 0 0), (2 1 0), (2 2 0), (3 3 2).
Set II: XRD patterns of the following gelators in EtOH.
4c: (1 0 0), (1 1 0), (1 1 1), (2 2 0), (3 2 0), (3 2 2), (3 3 2).
4g: (1 0 0), (1 1 0), (2 0 0), (2 1 1), (3 0 0), (3 2 0), (3 3 2), (4 2 2), (4 3 1).
Set II: XRD patterns of the following gelators in 80% (v/v) EtOH in water.
4c: (1 0 0), (1 1 0), (1 1 1), (2 1 0), (2 2 2), (3 3 1), (4 2 2).
4g: (1 0 0), (1 1 0), (2 0 0), (2 1 0), (2 2 2), (3 3 2), (3 3 3), (4 3 2).
Set III: XRD patterns of the following gelators in acetonitrile.
4d: (1 1 0), (2 0 0), (2 1 1), (4 0 0), (4 2 2).
4h: (1 0 0), (1 1 0), (1 1 1), (2 0 0), (3 2 0), (4 2 0).
[Fig.9]
To find out the effect of solvents on the molecular packing of self-assembly, we have taken two
different gelators 4c and 4g. Since 4c being a representative of both Set-I and Set-II can give insights for
both the series. Similarly, comparison between 4c and 4g (for Set-III gelators) can give the effect of
solvents on the molecular packing for Set-II gelators. The XRD patterns as observed for both the gelators
in four different media has been presented below.
4c in
Acetonitrile: (1 0 0), (1 1 0), (1 1 1), (2 2 0), (2 2 2), (4 0 0), (4 3 2).,
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Anisole: (1 0 0), (1 1 0), (1 1 1), (2 0 0), (2 1 0), (2 2 0), (2 2 2), (4 2 0), (4 2 2).
EtOH: (1 0 0), (1 1 0), (1 1 1), (2 2 0), (3 2 0), (3 2 2), (3 3 2).
80% (v/v) EtOH in water: (1 0 0), (1 1 0), (1 1 1), (2 1 0), (2 2 2), (3 3 1), (4 2 2).
4g in
Acetonitrile: (1 0 0), (1 1 0), (2 0 0), (2 1 0), (2 2 0), (2 2 2), (4 2 0), (5 4 2).
Anisole: (1 0 0), (1 1 0), (1 1 1), (2 0 0), (2 1 0), (2 2 0), (3 3 2).
EtOH: (1 0 0), (1 1 0), (2 0 0), (2 1 1), (3 0 0), (3 2 0), (3 3 2), (4 2 2), (4 3 1).
80% (v/v) EtOH in water: (1 0 0), (1 1 0), (2 0 0), (2 1 0), (2 2 2), (3 3 2), (3 3 3), (4 3 2)
The obtained results suggest that, the d-spacing is affected while going from aromatic to aliphatic
solvents as well as, going from protic polar (EtOH and 80 % (v/v) EtOH in water) to aprotic polar
(Acetonitrile). Incorporation of more H-bonding acceptor in the solvent matrix, e.g. 80% (v/v) EtOH in
water compared to EtOH, the d spacing reduces going from aprotic to protic. But the over-all packing
does not show much alteration from primitive cubical arrangement. Such cubic gels are found to have
wide applications in pharmaceutical sciences as an efficient drug delivery system.48 More details of the
solvent effect will be discussed later but it is quite evident that an increase in polarity makes the gelator
more compact in their molecular packing. Thus, the molecular structure certainly plays a dominant role
in determining the molecular organization in the gelation self-assembly. A similar observation was also
encountered by Iqbal et. al.34 where they observed that for a given compound, there were not
important differences in the position of the diffraction peaks between different solvents: attributing to
the fact that although macroscopic properties such as solubility or gelation efficiency are strongly
solvent dependent, the solvent has a limited effect in the organization at the molecular level. Using
molecular mechanics (using CS Chem3D ultra version 7.0) the molecular length of 4d has been
calculated and a gelator self-assembly was made for molecular mechanics energy minimization which
suggests considerable interdigitation among the acyl chains with calculated d100 values to be ~46.4 Å,
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however d100 obtained by XRD measurements is 21 Å, suggesting that the interdigitated self-assembly
might have a tilt angle of ~60°. The lower d100 value of 17.0 Å for 4h compared to 21.05 Å for isomeric
gelator 4d suggest a compact molecular packing in the self-assembly for the former one. In our view,
corroborating with the IR results, an interdigitated antiparallel organization of the gelator (4h) might
take place in the β-sheet arrangement as shown in Fig. 10(c) with a similar tilt angle as that of the
others.
[Fig. 10]
3.8. Circular dichroism
Initial formation of one dimensional supramolecular network via self-assembly of gelator
molecules was found to be an important event for the generation of 3D entangled fibrils in gelation
process. To discern such event for the present set of gelators, a concentration dependent circular
dichroism experiment was performed. To avoid the scattering effect, we had to carry out the
Table 3d100 spacing corresponds to first order reflection, interlayer spacing, π-π stacking and edge length of
cubic lattice (a).
gelators
d100
(in Å)
a
(in Å)
Interlayer
spacing (in Å)
π-π stacking
distance (in Å)
4a in CH3CN
4b in CH3CN
4c in CH3CN
4c in EtOH
21.01
22.57
19.18
20.62
19.74
20.52
21.05
21.43
22.06
21.07
22.20
19.83
20.55
20.63
22.37
21.04
20.20
22.66
3.86
3.87
3.81
3.82
3.80
3.84
3.89
3.90
3.84
5.88
5.63
5.65
5.68
5.68
5.68
5.67
5.68
4c in 80%aq EtOH
4c in anisole
4d in CH3CN
4e in CH3CN
4g in CH3CN
4g in EtOH
22.00
19.18
22.24
19.83
5.66
5.63
3.83
3.81
4g in 80%aq EtOH
4g in anisole
4h in CH3CN
21.01
17.00
20.33
18.36
3.87
3.76
5.69
experiment at a concentration much lower than their corresponding CGC values to keep them at the
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soluble state. In general, all the gelators showed very much similar strong positive couplet in CD spectra
with a higher wavelength (n⟶π*) negative cotton band at ~238 nm and a positive cotton band at lower
wavelength region (π⟶π*). A considerable red shift was found in the CD spectra for n⟶π* band with
the increase in concentration of the gelator. This could be due to the deviation of the planarity of amide
functionality in the self-assembly at higher concentration. Such observation was nicely described by
Lucie et. al. in their computational studies on the spectroscopic properties of nonplanar amide groups.49
Therefore, such phenomena suggest a significant conformational change on the gelator backbone is
associated with the formation of gel network at higher concentration. Unequal amount of red-shift of
CD band at higher wavelength for different gelators also suggest that, nevertheless the amino acid is
identical in all cases, the conformational flexibility of the hydrophobic segments at the spacer and/or the
acyl chain does influence differently on the gelator self-assembly.50
[Fig.11]
3.9. Solvent effect
Solvent effect on gelation behavior at its macroscopic level has been discussed by various
research groups using different solubility parameters of the solvents related to their nonspecific and
specific intermolecular forces.51 Hanabusa and co-workers reported that the minimum gelation
concentration of cyclo-(dipeptides) in various organic solvents could be correlated with a polar solubility
parameter (δa) of the solvents.50 The general relationship between macroscopic gelation and
solvatochromic parameters based on a multi-parameter approach to solvent polarity using Kamlet-Taft
parameters were reported by Smith and co-workers.53-54 However, a linear correlation between Tgel
values and the dielectric constants of alcoholic solvents were reported by Makarevic and co-workers for
the gelation of different bis (amino acid) oxalyl amides.55 Intermolecular forces are usually classified into
two distinct categories. The first category comprises the so-called directional, induction, and dispersion
forces, which are non-specific and cannot be completely saturated whereas the other category consists
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of specific and directional forces like, hydrogen-bonding forces, charge-transfer or electron-pair donor –
acceptor forces which can be saturated and lead to stoichiometric molecular compounds. We discuss
the gelation ability of the gelators 4a-4h with respect to three different solubility parameters of
solvents,56 viz, (a) Dimroth-Reichardt ET(30) parameter, (b) Hansen-Beerbower solubility parameters
(HSP) and (c) Kamlet-Taft parameters. ET(30) parameter signifies the ionizing power (loosely polarity) of
the solvents. However, HSP comprises of three components which involves (i) energy from dispersion
bonds between the molecules (δd), (ii) energy from dipolar intermolecular forces (δp) and (iii) energy
from hydrogen bonds between molecules (δh). The δo and δa are the total solubility parameter and the
2
2
polar solubility parameter respectively. The total solubility parameter δo has been described as δo = δd +
2
2
2
2
δa where δa = δp + δh . For small molecules, (δo) is equated to the cohesive energy that is required to
overcome the intermolecular forces. Parameters of the Kamlet–Taft solvatochromic relationship which
measure the hydrogen bond donor (α), hydrogen bond acceptor (β), and dipolarity/polarizability (π*)
properties of solvents as contributing to overall solvent polarity. These usually relate to the overall
solvation ability for the solutes at the ground state and/their excited state. Although no direct
correlation between GN and ET(30) was observed, a moderate decrease in GN was observed in aromatic
solvents with the increase in ET(30) values. However, a reasonable increase in GN with ET(30) was
observed in polar protic / aprotic solvent systems. Due to a wide distribution of gelating solvents in 3D
HSP space, no significant region of solvents was found to be apparent to predict the gelation behavior.
In order to have a mutual dependence of any two of these parameters on gelation behavior, plots of, δp
vs δh, δd vs δh and δp vs δd were examined and presented in Fig. 12 Panel-I, which suggests more
clustering of data in the encircled area indicating δh has preferentially more impact on the gelation
behavior than δp or δd since in the plots without δhshows no clustering of gelating solvents was observed
in comparison to other two cases. Interestingly, this observation is applicable for all the gelators, 4a- 4h,
however, the gelating solvents for 4h apparently possess lower δh values. We also analyze HSP
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parameters in terms of Tea’s plot [see SI for details, Figure S24, S25] which also corroborates the former
observation. Finally, we tried to analyze the solvent effect using Kamlet-Taft solubility parameters (KT).
In this case as well, due to inability in identifying specific zone of gelation in 3D plots of KT parameters,
we plotted separately, π* vs. α, β vs. α and β vs. π* [Fig. 12, Panel-II] and found that H-bonding donating
ability of the solvent (i.e., α) significantly influences the gelation at its two regions, 0.0 – 0.2 and another
between 0.8 -1.0, however data was found to be more dispersed in case of β vs. π* plot signifying its
lesser effect on the gelation behavior. Moreover, 4h shows a single region of gelation in π* vs. α and β
vs. α plot with lower α value as similar to the observation in case of HSP. Comparing, the isomeric
gelators in Set-III, 4d and 4h, the increase in spacer length reduces its gelation behavior in solvents with
higher α values signifying that H-bonding network gets destabilized in case of 4h with the increase in
propensity of H-bonding donor ability of the solvents. Interestingly, 4h loses its gelation ability in hexane
or cyclohexane while 4d shows the ability to gelate. Again 4h does not give any gelation in EtOH, MeOH
or isopropanol but gives gelation in acetonitrile, EtOAc and DMSO while 4d is capable of giving gelation
in either of the solvents. The increase in spacer length helps the solvation in solvents with higher
dispersive interaction (as depicted by δd in HSP) however a polarophobic interaction with lower H-
bonding donating solvents helps in gelation for 4h. On the contrary, 4d with shorter spacer length is not
only capable of forming strong H-bonding network even in protic and aprotic solvents with high δp and
δh and with a broad range of α values in KT but also in hexane or in cyclohexane with very high δd and
very low δp and δh (in HSP) [See SI Figure S21] suggesting a synergic influence of polarophobic effect with
H-bonding interaction behind gelation behavior. Such gelation behavior is very much analogous to the
observation by Zweep et. al. in their cyclohexane based bisamide and bisurea organogelators where
they found that the H-bonding interaction were weaker in polar solvents and gelation occurred only
where sufficient compensation was provided by intergelator van der Waals interactions.33 Solvophobic
interactions towards peptide based organogelation was also addressed by Loo et. al. describingtwo
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types of interactions stabilize the self-assembled structures—solvophobic interactions with the solvent
molecules and interactions between solvophobic groups in the interior of the aggregate.57
[Fig.12]
3.10.Plausible mechanism behind the gelation self-assembly
Nevertheless, the nucleation and growth of gelation self-assembly is a complex stochastic
phenomena involving highly specific interactions that allow preferential one-dimensional growth driven
by enthalpic forces,40 both gelator backbone architecture and the nature of the solvent-solute
interactions have been found to be crucial behind such process.1, 14-17 Between the two extremes of
solute-solvent interaction of being soluble or insoluble, gelation self-assembly involves colloidal state
where the molecular organization is stabilized more by enthalpic contribution.58
[Fig.13]
A plausible rationale behind the mechanism of the present gelation self-assembly has been depicted in
Fig.13. Herein, the gelator backbone, for 4a- 4h, consists of four non-covalently interactive regions : A, B,
C and D; of which A, C region with aliphatic segment offering van der Waals interaction, whereas B
region is preferably interactive via H-bonding and π-π type supramolecular interaction is prevalent at
the region D. In a gelation self-assembly, solvent contributes itself as a major component of the matrix
where the gelator contributes ~2-3 wt% of the total mass. Being a colloidal suspension (neither a
solution nor a precipitate), solvent-solute interaction plays a major role towards self-assembly as well as
imparting strength and thermal stability to the gel matrix. The influence of gelator architecture and the
nature of gelating solvents have been correlated recently with the molecular packing within the one-
dimensional objects and the nature of the derived gels obtained from 12-hydroxystearic acid and its
isomers by Mallia et.al.59Between the two extremes of very high gelator-gelator and gelator-solvent
interactions would lead the gelator either insoluble or totally soluble respectively. Thus a critical balance
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between gelator-gelator and gelator solvent interactions is a prerequisite for gelation behavior. Herein,
the self-assembly has been analyzed in solvents of different nature, viz, aromatic, nonpolar, polar protic
and polar aprotic with respect to their interactions towards A, B, C and D regions of 4a-4h. At the
monomeric stage, gelators are expected to be surrounded by the solvent molecules which interact non-
covalently with the gelator back bone. Such solvent-gelator interaction is found to be very much
decisive towards the formation of self-assembly of the gelators. In case of aromatic solvents, being quite
apolar in nature, apolar part of the molecule (i.e., A, C and D), have favorable/stabilizing interaction
(showing by ↓) with the solvent. Wherein aromatic zone (D) is expected to have preferentially more
favorable π-π type solvent-gelator interaction in all the gelators of Set-I, II and III keeping the region B
less interactive with the solvent. Therefore, in this case, the intergelator interaction leading to self-
assembly is majorly dominated by intergelator H-bonding interaction. A very similar incident is also
prevalent in case of non-aromatic apolar solvents except in case of 4h of Set-III, where the longer spacer
at C interacts with the hydrophobic solvent to such a high extent that merely H-bonding interaction
cannot hold the self-assembly and no gelation takes place. In case of polar protic solvents, the
polarophobic interaction [i.e., unfavorable gelator-solvent interaction (shown by↑)] of the hydrophobic
parts (A, C and D) helps towards gelation self-assembly nevertheless H-bonding unit at B is capable of
interacting with protic solvents. Such interaction is clearly demonstrated in Set-III systems, 4d and 4h. In
protic polar solvents , a dominant polarophobic effect leads to gelation of 4d similar to Set-I and Set-II,
but 4h fails to show gelation in similar media. Now the question arises, why doesnot the polarophobic
effect itself helps in gelation of 4h in polar protic solvents? A plausible reason being polarophobic
interaction must be synergistically supported by H-bonding network. The thermotropic and rheological
data indicates that the conformational flexibility at the spacer region reduces the gelation process, or in
other words, the H-bonding network at amide zone (B) is augmented by the presence of aromatic unit at
a critical distance but falls apart with an increase in spacer hydrophobicity (of aliphatic methylene units)
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with more conformational flexibility. In case of polar aprotic solvents, polarophobic interaction plays a
major role for self-assembly at the region A,C and D and such solvents are not expected to interact at
the region B. Thus intermolecular H-bonding interaction is not destabilized by such solvent systems.
Thus corroborating to the obtained results , the plausible mechanism can significantly emphasizes on
the critical solvophobic/solvophilic balance across the gelator backbone architecture becomes a
prerequisite for self-assembly where supramolecular functionalities encrypted on the backbone plays an
important measure across intergelator interactions, however a solvophobic effect dominates in the
gelationprocess towards achieving required enthalpic contribution for self-assembly.
4. CONCLUSION
Exploiting a systematic tuning of hydrophobicity at two distinct regions along a simple gelator backbone,
rationalization of its effect on gelation self-assembly has been critically analyzed with a series of
ambidextrous type gelators, N-n-acyl-(L)Val-X-OBn (X = 1,ω-amino acid) by means of various well
established physicochemical investigations. Primarily π-π type interaction at the aromatic unit plays a
governing role towards the alignment of the gelator molecules. Secondly, positioning of amide unit
across the aliphatic chain is found to be crucial for the orientation of peptidic unit in parallel or
antiparallel fashion during interdigitated molecular arrangement within the self-assembly. An
antiparallel orientation results if the amide unit is deeply seated at a spacer length bigger than the N-
acyl unit, however for shorter spacer (i.e., smaller than N-acyl chain) parallel orientation is preferred.
Moreover, strength arising from peptidic unit is found to be augmented by the proximal presence of
strongly hydrophobic π-π type interactive aromatic units. Increase in methylene units in spacer or in N-
acyl unit increases solute-solvent interaction in apolar media however, a polarophobic effect operates in
polar media. Manifestation of non-planarity across the amide plane with the increase in gelation
concentration as evident from the CD studies strongly suggests an additional conformational
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reorientation of the gelator backbone that takes place during the process of self-assembly. Therefore, it
is not just the gelator-gelator and gelator-solvent interaction playing their role behind the process of
gelation self-assembly, but the conformational reorientation is also taking part during the molecular
organization. Considering the effect of solvents on this of self-assembly process, a critical balance of
dispersive and directional forces operate in the self-assembly system (including solute and solvent)
which can grossly be described as solvophilic/solvophobic interaction of gelators with the solvents. Such
interaction is therefore needed to be duly supported by the optimum conformational change at the
flexible and/or apparently rigid segments of the gelator backbone for obtaining optimum
supramolecular interaction. So far the structure-function relationships are concerned, an increase in N-
acyl length, in general, increases the thermal stability whereas the same for spacer region gives reverse
results. Molecular packing differs, though not significantly, with the gelator backbone architecture,
however, a primitive cubical Pm3m type molecular arrangement was unanimously found for either of
the xerogels. Significant contribution from intergelator H-bonding interaction was found prevalent in
apolar solvents whereas; a polarophobic interaction with a synergic assistance of H-bonding effect
becomes predominant in polar media. Solvent-gelator interaction was found to be complex in nature,
one solvent parameter system was found insufficient to analyze it, however a dominant influence of δh
of HSP and α of KT has been observed where both δh and α are grossly related to the H-bonding
parameter of the solvents of the two different systems. Nevertheless self-assembly is apparently
dominated by solvophobic effect. The obtained results significantly demonstrate that non-covalent
interaction among the gelator molecules depend on their supramolecular functionalities encrypted in
their backbone architecture, but these non-covalent interactions between the molecular backbones and
the solvents of gelation should be such that mutually they can overcome the solvation energy but can
stabilize self-assembled gel-network with optimum gelator backbone conformation for achieving
required enthalpic contribution for self-assembly.
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Page 29 of 47
RSC Advances
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DOI: 10.1039/C5RA10209J
ACKNOWLEDGMENTS
Financial support from Department of Science and Technology (DST) (Grant No. SR/S1/OC-67/2008),
Govt. of India and UPE-II, Jadavpur University has been gratefully acknowledged. Authors also thank
UPE-II for their instrumental facility in performing Rheological experiments. UPE-II is also acknowledged
by KK for her research fellowship.
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