12-Hydroxy stearic acid appended new amphiphilic scaffolds for selective capture of hydrogen halides through supramolecular hydrogelation

Article abstract of DOI:10.1039/c9nj05628a

12-Hydroxystearic acid (12-HSA) appended new amphiphilic scaffolds reveal excellent hydrogelation propensity in the presence of aqueous acids and vapors of HCl/HBr. This selective entrapment efficiency towards hydrogen halides demonstrates an unprecedented route for the successful removal of toxic chemicals, thus providing a safe and easy protocol for environment management. We anticipate that the halide derivative of the amphiphile plays a vital role in driving the self-assembly mechanism and eventually the hydrogelation phenomena.

Full text of DOI:10.1039/c9nj05628a

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LETTER
12-Hydroxy stearic acid appended new
amphiphilic scaffolds for selective capture
of hydrogen halides through supramolecular
hydrogelation†
Cite this: New J. Chem., 2020,
44, 3828
Received 13th November 2019,
Accepted 18th February 2020
a
b
c
Ankita Sharma,
Anita DuttKonar
Arindam Gupta,
*
Priyanka Tiwari,a Anindya Basu
and
DOI: 10.1039/c9nj05628a
ac
rsc.li/njc
12-Hydroxystearic acid (12-HSA) appended new amphiphilic scaf-
Aligned with this goal, herein we report two structurally related
folds reveal excellent hydrogelation propensity in the presence of amphiphilic peptides, 12-HSA-amino tetrazole (compound: I) and
aqueous acids and vapors of HCl/HBr. This selective entrapment 12-HSA-aniline tetrazole (compound: II) (12-HSA:12-hydroxy-
efficiency towards hydrogen halides demonstrates an unprecedented stearic acid) that display excellent hydrogelation propensity in
route for the successful removal of toxic chemicals, thus providing a safe the presence of aqueous acids and vapors of HCl/HBr thus
and easy protocol for environment management. We anticipate that the providing a simple cost effective protocol for the clean-up of
halide derivative of the amphiphile plays a vital role in driving the self- acidic effluents (Fig. 1). Being mindful of the potentiality of the
assembly mechanism and eventually the hydrogelation phenomena.
alcoholic hydroxy group of 12-HSA in undergoing nucleophilic
substitution reactions, we tethered this component at the
Stimuli responsive low molecular weight hydrogelators com- N-terminus of the compounds.7 We coupled the heterocycle tetrazole
prising peptides have witnessed remarkable growth in recent to the amphiphile due to its salt forming tendency with hydrohalic
years.1 Low production cost, benign fate and simplified synthesis acids.8 Since the design consisted of a heterocycle appended amphi-
protocol render peptides as appealing synthons for biomaterial phile, we anticipated that in the presence of hydrogen halides
design.2 In turn, the involvement of peptide self-assembly (nucleophile), there could be possibilities for two units of nucleo-
utilizing non-covalent interactions makes these constructs highly phile to participate.6,7 One for forming the halide derivative and the
promising candidates for the design of smart materials with other in salt formation.7,8 These individual properties of the respec-
diversified applicabilities.2,3
tive scaffolds might collectively contribute to the process of
Hydrogen halides are a class of toxic entities produced self-assembly by its enhanced hydrogen bonding likeliness and
during the pyrolysis of numerous substances encountered p–p correspondence employing the bottom up approach.9
during industrial transformations, and their exposure to the
environment causes detrimental effects on health.4 They
are highly corrosive in nature and cause acute injury to the
respiratory tract.5 Although researchers have dedicated signifi-
cant efforts to discovering materials pertaining to a plethora of
applications, little progression could be achieved in the arena
of halide capture, due to the inhibitory response of the anions
towards gelation.6 So the development of scaffolds for the success-
ful removal of toxic halides selectively through supramolecular
hydrogelation appears highly challenging and will be of para-
mount interest to society.
a Dept. of Applied Chemistry, Rajiv Gandhi Technological University, Bhopal, India.
E-mail: anitaduttkonar@rgtu.net
b Dept. of Chemistry, IISER, Bhopal, India
c School of Pharmaceutical Sciences, Rajiv Gandhi Technological University, Bhopal,
Fig. 1 The chemical structures of the heterocycle appended amphiphile
leading to the formation of self-supporting hydrogels in the presence of
aqueous acids and vapors of HCl/HBr for compounds I–IV and no gel
formation for compound V.
India
† Electronic supplementary information (ESI) available: Details of spectral data,
1H NMR, IR, and mass. See DOI: 10.1039/c9nj05628a
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To gain insight into the feasibility of hydroxy replacement in evidence to support the observation and first turned our atten-
the compounds, computational studies were performed where tion towards the FT-IR spectra of the compounds both in the
the heats of formation (Hf) corresponding to the heterocyclic solid state, as synthesized, and in the corresponding xerogels
salt of different halide derivatives were calculated using two (Fig. S2, S3 and Tables S2, S3, ESI†). We assumed that if the
popular semi-empirical methods, namely Austin Model 1 (AM1) predictions of the nucleophilic substitution reaction were
and Parametric Method 3 (PM3), and DFT (Table S1, ESI†).10 correct, then from the IR spectra some information about the
The Hf values obtained from all the procedures followed a formation of the C–X bond might be obtained. As evident from
similar trend and were found to be negative, suggesting that the spectra, in the xerogels, a small peak at 794/538 cmꢀ1 (HCl/
the probable scaffold could be held responsible for driving the HBr) for compound I and 662/616 cmꢀ1 (HCl/HBr) for com-
self-aggregation mechanism. Additionally the parameter Hf was pound II was noticed, with the corresponding peaks missing in
found to increase with an increase in the size of the halides the solid compounds (Fig. S2, S3 and Tables S2, S3, ESI†). This
(Table S1, ESI†). Therefore we envisioned that compounds I and peak was attributed to the formation of the C–X (X: Cl/Br) bond
II could exhibit better gelation propensities with HCl/HBr in under experimental conditions.11 However the heights of the
comparison to HI.
peaks were small, so arriving at a definitive conclusion was
To experimentally verify the above hypothesis, the com- difficult. This led us to delve deeper into the NMR spectra of the
pounds were dissolved in a methanolic water medium and compounds in d6-DMSO since the latter provides better
concentrated hydrohalic acids (HCl/HBr/HI) were added drop- insights into the self-assembly process (Fig. 3 and Table S4,
wise (MeOH : water : hydrohalic acids: 3 : 1 : 1). Initially a clear ESI†). In continuation with the previous assumption of hydroxy
solution was produced, but the gradual addition of hydrohalic replacement, we envisioned that in the NMR spectra, the
acids led to complete immobilization of the solution instanta- hydroxy peak in the solid molecule might be visible and
neously resulting in the formation of an opaque gel for disappear in the xerogels. For compound I, in the solid state,
HCl/HBr (Fig. 1). But for HI, we obtained a black suspension the chemical shifts of tetrazole and amide NHs along with
and were unable to draw a definitive conclusion from it, which 12-HSA OH appeared at 15.78, 11.95 and 4.21–4.19 ppm respec-
is in accordance with the computational analysis. However tively. On the other hand, the spectra of the xerogels reflected
none of these solvents (methanol–water–HCl/HBr) solely peaks at 15.78 and 11.97 in the case of HCl and only 11.93 in
were competent to induce the gelation protocol. To confirm the case of HBr. Similarly for compound II, the NHs, aromatic
whether any other acids were able to nucleate the phenomena, protons and 12-HSA OH depicted chemical shifts at 9.90,
the experiments were repeated with HNO3, H2SO4, HCOOH, 8.12 (Ha), 7.65–7.62 (Hb & Hd), 7.28–7.25 (Hc) and 4.23–4.22 ppm
CH3COOH, H3BO3, H3PO4, HClO4 and TFA (variation in anion respectively in the solid state and 10.29, 8.44 (Ha) & 7.78–7.74
component). But in every case for both types of organic and (Hb & Hd), 7.52–7.49 (Hc) ppm in xerogel HCl and 10.29,
inorganic acids, negative results were obtained. But gelation 8.23 (Ha), 7.74–7.73 (Hb & Hd), 7.55–7.45 (Hc) ppm in xerogel
occurred in the presence of other alcohols like ethanol and HBr. The corresponding Dd values (in ppm) were as follows:
isopropanol instead of methanol. Thus this investigation For amide NHs (a) 0.02 in compound I (xerogel HCl) and 0.39 (xerogel
allowed us to conclude the extreme selectivity of this process HCl)/0.25 (xerogel HBr) in compound II; (b) for aromatic H’s the
towards polar protic acids HCl/HBr. With this information in values correspond to 0.32 (Ha), 0.13–0.12 (Hb & Hd), and 0.24 (Hc)
hand, we decided to investigate the efficiency of the compounds in xerogel HCl and 0.11 (Ha), 0.09–0.11 (Hb & Hd), and
in trapping the corresponding halide vapors. To achieve this, 0.27–0.20 (Hc) in xerogel HBr in compound II.
gelation experiments were performed using HCl gas as shown in
Fig. 2 and Fig. S1A (ESI†).
From the change in chemical shifts we noticed that in both
the compounds neither the amide NHs nor aromatic H’s
We speculated that the methanolic solution of the com- (compound II) illustrated substantial change. Therefore their
pounds readily absorbed HCl vapors and subsequently formed involvement in nucleating the gelation phenomena was ruled
a gel upon self-assembly. The experiment was repeated with out (Fig. 3 and Table S4, ESI†).
HBr gas also, for both the compounds (Fig. S1B, ESI†). Notably
Indeed the OH peak of 12-HSA which was clearly visible in
in every case we ended up with a positive inference. Aligned to the solid state of both the compounds, was found to disappear
the investigative workflow, we started gathering experimental in the xerogel state, in line with our vision. However the NMR
spectra further revealed that the completely converted derivative
and the partially converted derivative remained in equilibrium as
has been reflected by the occasional appearance of tetrazole NH in
the NMR spectra (Fig. 3).11 Thus from the IR and NMR spectra it
was confirmed that the nucleophilic substitution reaction had
taken place leading to the replacement of the hydroxy group of the
amphiphile by the halides, in accordance with the prediction.
To strengthen our intuition and affirm whether the salt
formation in compounds I and II has occurred, mass spectro-
metry of the xerogels obtained from HBr was performed
(Fig. S4, ESI†). From the HRMS spectra, we obtained peaks
Fig. 2 The gelation phenomena occurring in the presence of HCl gas, for
compound I.
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Fig. 3 The 1H NMR spectra of the xerogels and solid compounds in d6-DMSO at 25 1C; NH of tetrazole K; amide NH %; OH of 12-HSA m.
corresponding to (a) C19H37Br2N5O obtained: 519.4918 [M + 5H]+; appeared to be broad in the xerogel state. However the wave-
calculated: 513.54 [M]+ and (b) C25H41Br2N5O obtained: 587.3876 numbers of the H-bond donors OH/NH shifted from around 3770
[M]+; calculated: 587.43 [M]+ (Fig. S4, ESI†), in agreement with the to 3500 and 3300 cmꢀ1 for all the compounds. Similarly in the
bromo derivative of the heterocyclic salt of the amphiphile. Thus xerogels for the amide I/II carbonyl, distinct peaks were observed
this experimental evidence amply manifests the formation of the in the region (a) 1688/1554 cmꢀ1 (HCl) & 1656/1550 cmꢀ1 (HBr)
halide derivative as well as the salt in the reaction medium for for compound I; (b) 1650/1548 cmꢀ1 (HCl) & 1650/1556 cmꢀ1
both the compounds.
(HBr) for compound II; (c) 1656/1516 cmꢀ1 (HCl) for compound
Next, our interest lied in determining the fundamental III and 1656/1522 cmꢀ1 (HCl) for compound IV respectively
residue responsible for driving the gelation mechanism. So (Fig. S2, S3, S6 and S7, ESI†). This could only happen if hydrogen
we synthesized compounds III–V (Fig. 1). In compounds III bonding and van der Waals interactions were engaged in inter-
and IV, the normal amino acids Trp (compound III: with connecting the molecules to form an entangled fibrous network
indole; basic heterocycle) and Tyr (compound IV: phenol; acidic leading to hydrogel formation through b-sheet conformation.12
heterocycle), devoid of the salt forming ability, were appended
To re-confirm the conformation, we carried out PXRD
with 12-HSA at the C-terminus (Fig. 1). In compound V, the analysis with the xerogels of the compounds (Fig. S8, ESI†).13
12-HSA moiety of compound II was replaced with stearic acid The wide angle PXRD patterns were as follows: (a) 2y: 19.31
(SA) (Fig. 1). Interestingly compound III & IV formed stable gels, (HCl)/19.21 (HBr) for d: 4.5 Å, (b) 2y: 22.41 (HCl)/22.01 (HBr) for
but compound V failed to do so, which highlights the impor- d: 3.7 Å, for compound I; (c) 2y: 19.41 (HCl)/19.31 (HBr) for d:
tance of the hydroxy substituent of the amphiphile in nucleat- 4.5 Å, (d) 2y: 22.81 (HCl)/22.31 (HBr) for d: 3.7 Å, for compound
ing gelation phenomena. Inspired by these results, next we II; (e) 2y: 19.11/22.91 for d: 4.5 Å /3.7 Å (HCl), for compound III;
decided to check whether 12-HSA alone (not in any derivatized (f) 2y: 19.31/22.61 for d: 4.5 Å/3.7 Å (HCl), for compound IV
form) could form gels. Surprisingly, we obtained negative respectively further supporting the presence of b-sheet like
results, indicating the importance of the maintenance of a extended structures stabilized by non-covalent interactions,
crucial balance of both the hydrophobic and p–p interactions mainly p–p correspondence.
in driving the self-assembly mechanism and subsequently the
Additionally, the formation of the parallel b-sheet structure
gelation phenomena. However, failure to attain this delicate of the compounds was further supported by our computational
cruciality leads to negative results as was reflected by the case of studies (Fig. 4 and Fig. S9, ESI†). The halide derivative was
12-HSA in the underivatized form.
found to promote van der Waals interaction amongst 12-HSA
Overall, the computation and experimental inferences
allowed us to consider the 12-HSA appended derivatives to be
a new amphiphilic scaffold for the selective entrapment of
hydrogen halides through supramolecular hydrogelation.
Next we attempted to characterise the hydrogels of compounds
I–IV using standard techniques. The minimum gelation concen-
trations (ꢀm1gc) of the compounds were as follows: (a) I & II: 4 and
6 mg ml respectively for both HCl and HBr case; (b) III & IV:
4 mg mlꢀ1 for HCl for both the compounds (Fig. S5, ESI†).9 The
gel formation time of the hydrogelators is described in Table S5
(ESI†). To determine the secondary structural aspect of the
xerogels we looked deeper into the FT-IR spectra of the
compounds (Fig. S2, S3, S6 and S7, ESI†). From the spectra it
was clearly evident that the region corresponding to OH and NH
Fig. 4 Energy optimised structures of the actual construct; chloride
derivatives of the heterocyclic salt of compound (A) I & (B) II, and their
self-assembly patterns stabilizing b-sheets. For the formation of sheets
four monomeric units have been considered. Colours of the atoms are as
follows: carbon: cyan; hydrogen: white; oxygen: red; nitrogen: blue; and
chlorine: green. H-Bondings are shown as dotted lines.
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aliphatic chains, whilst the aromatic units reinforced the p–p
In summary in this paper we report the design and synthesis
interactions in the compounds resulting in successful gelation. of a new amphiphilic scaffold containing 12-HSA at the
Thus on the basis of FT-IR, PXRD and computational data, we N-terminus, that possesses the capability to entrap hazardous
concluded that the compounds pack in b-sheet like structures.
hydrogen halides namely HCl/HBr and form hydrogels in the
To gain insight into the morphological aspect of the form of vapors or liquids. This selective anion encapsulation
xerogels, field emission scanning electron microscopic studies procedure represents an alternate route for the effective
were performed using xerogels of the same concentration. removal of these harmful chemicals from industrial effluents,
Importantly, the images of all the compounds demonstrated thus providing a safe and easy protocol for green management.
an entangled three dimensional fibrillar network of dimen- We attribute this phenomenon to be a major contribution from
sions 20–50 nm in width and several micrometers in length, a the hydroxy substituent of the amphiphile. From the synthesis
characteristic of b-sheet structures.13 Additionally, we noted perspective it involved a single step reaction and therefore is
that in compound II & III, the fibrils were more closely packed cost effective. We envision that the resultant halo-entrapped
than that in I & IV which might be reflected in their mechanical hydrogels may exhibit potential applicabilities in the develop-
strength (Fig. 5).
ment of novel materials in versatile avenues.
In continuation with the previous studies, to gain deeper
insights into the mechanical integrity of the compounds, we
performed rheological measurements, as it is one of the prime
requirements for any hydrogel to be used as a biomaterial.
In this experiment, the elastic response (G0) and viscous
response (G00) were measured as a function of strain.14 As observed
Conflicts of interest
There are no conflicts to declare.
from Fig. S10 (ESI†), throughout the viscoelastic region, the Acknowledgements
storage modulus (G0) was higher than the loss modulus (G00) in
the region 1 to 100 rad sꢀ1 (angular frequency) until the applica-
tion of strain of approximately 5% for compound I & IV and 40%
for compound II & III. This behavior demonstrated a soft gel
phase formation (Fig. S10, ESI†).13 At this corresponding limit of
maximum strain, a cross over point was noticed where the value
of loss modulus (G00) slightly exceeded the value of the storage
modulus (G0) and transformed into a solution. Increasing the
strain beyond this point, resulted in the decrease of both the
modulus since intermolecular forces had won over the applied
strain and the fibrils were unable to withstand large deforma-
tions. Thus from the rheological studies we noted the strain
bearing ability of compounds II & III to be higher than that of
I & IV, data previously supported by the morphological observation.
AS and PT thank MPCST/CSIR for research fellowships. ADK
acknowledges UGC (F.4-(55)/2014(BSR)/FRP), New Delhi, for financial
support. All the authors are grateful to Dr Sanjit Konar, IISER Bhopal
for his valuable advice.
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