Pyrene appended bile acid conjugates: Synthesis and a structure-Gelation property study

Article abstract of DOI:10.1007/s12039-011-0100-9

A wide variety of novel compounds obtained by combining two types of known organogelators, viz., bile acid alkyl amides and pyrene alkanoic acids, were synthesized and screened for their gelation ability. The 3α esters of 1-pyrene butyric acid (PB(A) of alkylamides of deoxycholic acid (DC(A) turned out to be effective in the gel formation with many organic solvents although the gelation has to be triggered by the addition of a charge transfer (CT) agent 2,4,7-trinitrofluorenone (TN(F) . The special feature of thesemolecules is that the organogelation is achieved only after derivatizing the acid moiety of the 1-pyrenealkanoic acids. Additionally, the gelation properties can be fine-tuned by inserting different functional groups at the bile acid side chain. The gels obtained are deep red in colour and optically transparent up to 2% w/v. The SEM studies of the obtained xerogels revealed bundled rod-like morphology without specialized branching. Indian Academy of Sciences.

Full text of DOI:10.1007/s12039-011-0100-9

c
J. Chem. Sci. Vol. 123, No. 4, July 2011, pp. 379–391. ꢀ Indian Academy of Sciences.
Pyrene appended bile acid conjugates: Synthesis and a
structure–gelation property study
SHREEDHAR BHATa,b, ARTO VALKONENa, JUHA KOIVUKORPIa, ANUPAMA AMBIKAb,
ERKKI KOLEHMAINENa,∗, UDAY MAITRAb,∗ and KARI RISSANENa,∗
aDepartment of Chemistry, Nanoscience Center, University of Jyväskylä, 40014 Jyväskylä, Finland
bDepartment of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
e-mail: erkki.t.kolehmainen@jyu.fi; maitra@orgchem.iisc.ernet.in; kari.t.rissanen@jyu.fi
MS received 19 January 2011; accepted 11 March 2011
Abstract. A wide variety of novel compounds obtained by combining two types of known organogelators,
viz., bile acid alkyl amides and pyrene alkanoic acids, were synthesized and screened for their gelation ability.
The 3α esters of 1-pyrene butyric acid (PBA) of alkylamides of deoxycholic acid (DCA) turned out to be
effective in the gel formation with many organic solvents although the gelation has to be triggered by the
addition of a charge transfer (CT) agent 2,4,7-trinitrofluorenone (TNF). The special feature of these molecules
is that the organogelation is achieved only after derivatizing the acid moiety of the 1-pyrenealkanoic acids.
Additionally, the gelation properties can be fine-tuned by inserting different functional groups at the bile acid
side chain. The gels obtained are deep red in colour and optically transparent up to 2% w/v. The SEM studies
of the obtained xerogels revealed bundled rod-like morphology without specialized branching.
Keywords. Pyrene; bile acid; 2,4,7-trinitrofluorenone; two component gel; scanning electron microscopy.
1. Introduction
studies. Applications of organogels include, among
many others,7 drug delivery.8 By replacing the liquid
with a gas it is possible to prepare aerogels, materi-
als with exceptional properties including very low den-
sity, high specific surface areas, and excellent thermal
insulation properties.9
The exact mechanism of the gelation of organic sol-
vents by LMOGs is not known. Although it is gen-
erally accepted that intermolecular forces such as H-
bonding,10 electrostatic attractions and/or π–π stacking
interactions are necessary to stabilize LMOG assem-
blies. It has also been demonstrated that London disper-
sion forces alone can be sufficient.11 The large variety
of structurally different gelators show that H-bonding,
but also electrostatic, π–π or charge transfer interac-
tions may lead to self-assembling networks build up
from long often entangled fibres (whiskers).12 Further-
more, it has been shown that appropriate gelators can
physically form liquid crystalline phases.13
‘Gels’ are classified in many ways.1 An ‘organogel’ is
a poorly-crystalline, non-glassy thermoreversible solid-
like material composed of a liquid organic phase
entrapped in a structured network.2 The liquid can be
e.g., an organic solvent, a mineral oil or a vegetable
oil. Organogels can be either derived from a polymer or
from small molecules. These molecules self-assemble
into elongated fibrous structures through highly spe-
cific molecular interactions in an organic solvent. The
gelling agents, so called ‘small molecule gelling agents’
are gaining popularity in the gelling of a wide range
of organic solvents to form organogels,3 which are
attractive materials for many applications. Many of the
low molecular weight organogelators (LMOGs) display
thixotropy — they become fluid when agitated, but
resolidify when resting. During the past two decades, a
wide range of LMOGs have been discovered that range
from alkanes4 to alkanoic acids, steroids to vitamin C,5
nucleosides to DNA.6 The gelation process necessarily
creates novel fibrous supramolecular structures which
can be characterized by microscopy and scattering
The gelation properties can be modified by both
chemical and physical means. Chemically, the gelation
process can be controlled by pH, ionic strength and
additives.14 Stimuli-responsive assembly of low molec-
ular weight materials (MW < 1000) have been inten-
sively studied in gels, micelles, vesicles, and synthetic
membranes.15 Sound,16,17 light18–20 and electrochemical
∗For correspondence
379

380
Shreedhar Bhat et al.
controls21 have been explored as a means of switch- 13C NMR spectra were recorded on a JEOL 300 MHz
ing molecular aggregations without the use of chemical spectrometer. ESI-QTOF MS spectra were recorded on
stimuli. However, providing a method of control that a Micromass Q-TOF micro mass spectrometer. The
is instant, positive (i.e., converting sol to aggregate), gelation tests were carried out in pyrex test tubes with a
and reversible, while also being versatile and practical, diameter of 8 mm and a length of 70 mm.
remains a challenge.
Moreover, organogels commonly suffer from insta-
bility, for instance, due to crystallization or lack of
mechanical robustness. Furthermore, despite major
achievements in supramolecular chemistry to achieve
controlled self-assembly of organic molecules,22 until
now most low molecular weight gelators have been
found by serendipity rather than by design. Recently,
Hanabusa et al.,23 Feringa et al.24 as well as Maitra
et al.25 succeeded in the systematic design of novel
gelators for organic solvents by exploiting the self-
assembling properties of amide, urea and urethane
groups.26
Our interest on the design of new materials prompted
us to connect the existing gelator motifs into hybrid
structures and study their gelation properties in solu-
tion. We envisioned that by adding a pyrene moiety
into a bile acid derived organogelators would lead to an
interesting new type of molecules that could give rise
to novel self-assembling systems. Our previous reports
introduce CT gelation of pyrene analogues. In this arti-
cle, we describe the ‘structure–gelation’ property of a
new class of gelators designed by covalently linking
the two well-known gelator moieties (viz., derived from
pyrene and bile acid).
2.1b Gelation tests: The compound and powdered
TNF (typically 1:1, Cgelator 1% w/v) were mixed in a test
tube. The suspension in the corresponding solvent was
warmed on a water bath maintained at 90◦C until all the
solid material dissolved forming a clear solution. The
hot sol was allowed to gel at ambient temperature with-
out external disturbance. For SEM imaging, the samples
were prepared by placing 10 μL of a hot solution on
a carbon tape pasted on sample stubs, and after drying
the samples for 24 h they were subjected to gold coating
using DC sputtering (50 Å) for 38 s and examined using
a QUANTA 200 scanning electron microscope with a
single crystal of LaB6 as the emitter.
2.1c Gel melting: The gel–sol transition behaviour
was characterized by gel melting. The gel melting was
estimated by the ‘inverted test tube’ method. Briefly,
gels were made in 8 mm × 70 mm tubes, sealed at the
open end, and placed upside down in a water/oil bath
whose temperature was increased slowly (2◦C/min).
The temperature at which the gel fell was recorded as
Tgel,−sol which was usually within
measurements.
2◦C in multiple
2. Experimental
2.2 Materials
2.1 Methods
2.2a General: All the glassware were acid rinsed
2.1a Spectroscopy: Absorption spectra were recor- prior to wash with deionized water and dried in a
ded on a Shimadzu UV2100 spectrometer equipped hot oven. All the organic solvents were analytical
with a thermoelectric variable-temperature set-up. FT- grade or were distilled prior to use. Chloroform and
IR spectra were recorded on a Jasco-70 FT-IR spec- dichloromethane were distilled over CaH2, THF and
trometer or on a Perkin Elmer Spectrum GX FT-IR toluene over sodium/benzophenone ketyl, and pyridine
spectrophotometer either by making a thin film of the and Et3N over KOH, respectively. All the reagents
compounds on a NaCl plate from a chloroform solu- were purchased from Aldrich and used as received. 1-
tion or using KBr pellets. One-dimensional 1H, 13C, and Pyrene carboxylic acid and 1-aminopyrene were pre-
13C DEPT-135 NMR spectra were recorded in dilute pared starting from pyrene as reported earlier.23b 1-
CDCl3-solutions at 30◦C with Bruker Avance DRX 500 Pyrene butyric acid and 1-pyrene dodecanoic acid were
(or DPX 250) FT NMR spectrometer equipped with an prepared according to our previous reports.27 TLC was
inverse detection dual probehead (BBI) and z-gradient performed on pre-coated silica gel plates (Merck) and
accessory working at 500.13 MHz for proton and at stained with iodine vapour, or with LB (Liebermann
1
125.77 for carbon-13, respectively. The H and 13C Buchard) stain, or observed under UV light. Column
chemical shifts were referenced to the signal of internal chromatography was carried out on 100 200 mesh
TMS (δ = 0.00 ppm). Variable temperature (VT) H and silica gel on gravity columns.

Pyrene appended bile acid conjugates: Synthesis and a structure–gelation property study
381
2.2b Compound 4: 3,7,12-Triformylcholic acid 85–87◦C. Anal. Calcd. (%) for C40H73NO3 + 11/2 H2O:
(0.25, 0.50 mmol, m.p. 204–205◦C),28 hexade- C, 74.71; H, 11.92; N, 2.18. found C-74.43, H-11.95,
cyalamine (0.15 g, 0.62 mmol) and DMAP (6 mg, N-2.60. IR, v˜/cm−1 (KBr): 1044, 1378, 1467, 1643,
1
0.05 mmol) were dissolved in dry DCM. To this stirring 2850, 2621, 3400 cm−1. H NMR (250 MHz, CDCl3):
mixture was added DCC (0.124 g, 0.6 mmol) pinch δ = 0.679 (s, 3H), 0.807–0.911 (m, 6H), 0.981 (d,
by pinch for 2 minutes. The resulting mixture was J = 6.0 Hz, 3H), 1.02–1.19 (m, 4H), 1.26 (br s, 30H),
stirred further for 12 h. The dicyclohexyl urea (DCU) 1.3–1.9 (m, steroidal CH, CH2 and alkyl), 3.21(m, 2H),
precipitates were filtered and the filtrated was diluted 3.59 (m, 1H), 3.97 (br s, 1H), 5.36 (m, 1H). LRMS
with 10 mL of DCM. The DCM layer was washed (ESI): m/z found 639.02. HRMS (ESI): m/z Calcd. for
with saturated NaHCO3 solution (2 × 5 mL) and water C40H73NO3Na 638.5488; found 638.5507.
(2 × 5 mL). The organic layer was dried over anhydr.
Na2SO4 and concentrated under reduced pressure.
2.2d Compound
6: Hexadecyl
3,7,12-
The product obtained was further purified by column
chromatography over silica gel with EtOAc/DCM as
eluent. The final product was obtained as a white solid
(0.22 g, Yield 60%), m.p. 45–46◦C. IR, v˜/cm−1 (KBr):
triformylcholamide (0.20, 0.28 mmol) was stirred
over K2CO3 (0.38, 2.8 mmol) in 2.0 mL MeOH for
4–5 h. After the reaction the suspension was filtered
and the filtrate was concentrated under reduced pres-
sure. The crude material was extracted into ethyl
acetate (15 mL) and washed with saturated solution of
NaHCO3 (2 × 5 mL) and water (2 × 5 mL). The organic
layer was dried over anhydr. Na2SO4 and concentrated
under reduced pressure. The product obtained was
further purified by column chromatography over silica
gel with EtOH/DCM as eluent. The final product was
obtained as a white solid (0.15 g, Yield 85%), m.p.
81–83◦C. Anal. Calcd. (%) for C40H73NO4 + 1/2 H2O:
C, 74.95; H, 11.64; N, 2.18; found C, 75.03; H, 11.65,
1
1177, 1644, 1723, 1645, 1724, 2854, 2926, 3313. H
NMR (250 MHz, CDCl3): δ 0.75 (s, 3H), 0.83–0.90
(m, 6H), 1.25 (br s, 22 H), 1.28–2.16 (steroidal CH,
CH2, alky CH2), 3.23 (m, 1H), 4.71 (m, 1H), 5.054 (d,
J = 2.5 Hz, 1H), 5.26 (br s, 1H), 5.35 (m, 1H). 13C NMR
(63 MHz,CDCl3): δ 12.16, 14.07, 17.60, 22.33, 22.66,
22.79, 25.57, 26.91, 27.19, 28.58, 29.28, 29.33, 29.53,
29.57, 29.63, 29.67, 31.35, 31.47, 31.90, 32.77, 33.53,
34.29, 34.47, 34.53, 34.85, 37.76, 39.53, 40.83, 42.97,
45.04, 47.38, 70.69, 73.73, 76.49, 160.50, 172.95.
1
N, 1.97. H NMR (250 MHz, CDCl3): δ 0.667 (s, 3H
Me-18), 0.84–0.87 (br s, triplet merged to singlet, 6H),
0.982 (d, J = 5.75 Hz, 3H), 1.25 (br s, 22H), 1.3–2.22
(m, steroidal, CH, CH2 and alkyl CH2), 2.84 (br s,
4H), 3.22 (m, 2H), 3.43 (m, 1H), 3.82 (br s, 1H), 3.95
(br s, 1H), 5.95 (m, 1H).13C NMR (63 MHz,CDCl3): δ
12.47, 14.08, 17.45, 22.43, 22.66, 23.26, 26.39, 26.98,
27.56, 28.15, 29.34, 29.59, 29.64, 29.69, 30.42, 31.74,
33.14, 34.75, 35.32, 39.48, 39.58, 39.66, 41.54, 41.69,
46.40, 46.56, 68.48, 71.90, 73.12, 173.92. HRMS
(ESI): m/z Calcd. for C40H73NO4 + Na: 655.5471;
found 655.5519.
2.2c Compound 5: 3,12-Diformyl deoxycholic
acid (0.25 g, 0.5 mmol),29 hexadecyalamine (0.15,
0.62 mmol), and DMAP (6 mg, 0.05 mmol) were dis-
solved in dry DCM. To this stirring mixture was added
DCC (0.124 g, 0.6 mmol) pinch by pinch for 2 minutes.
The resulting mixture was stirred further for 12 h. The
DCU formed were filtered and the filtrated was diluted
with 10 mL of DCM. The DCM layer was washed with
saturated NaHCO3 (2 × 5 mL) and water (2 × 5 mL).
Dried over anhydr. Na2SO4 and concentrated under
reduced pressure (0.25 g, m.p. 61–63◦C). Then, the
crude material was directly subjected to deformylation
reaction by stirring the methanolic solution of triformyl 2.2e Compound 7: 3,7,12-Triacetyl cholic acid
amide over K2CO3 (0.40 g, 2.9 mmol) for 4–5 h. After (1.00 g, 1.85 mmol),30 DCC (0.46 g, 2.22 mmol) and
the reaction the suspension was filtered and the fil- DMAP (23 mg, 0.186 mmol) were dissolved in dry
trate was concentrated under reduced pressure. The DCM (10 mL). To this stirred mixture was added iso-
crude material was extracted into ethyl acetate (15 mL) propylamine (0.19 mL, 2.22 mmol) drop-wise for 5
and washed with saturated solution of NaHCO3 (2 × minutes. The resulting mixture was stirred for addi-
5 mL) and water (2 × 5 mL). The organic layer was tional 12 h. The DCU formed were filtered and the
dried over anhydr. Na2SO4 and concentrated under filtrate was diluted with 10 mL of DCM. The DCM
reduced pressure. The product obtained was further layer was washed with sat. NaHCO3 (2 × 5 mL) and
purified by column chromatography over silica gel water (2 × 5 mL). The DCM layer was dried over
with EtOH/DCM as eluent. The final product was anhydr. Na2SO4 and concentrated under reduced pres-
obtained as a white solid (0.185 g, Yield 85%), m.p. sure. The crude material was further purified by column

382
Shreedhar Bhat et al.
chromatography over silica gel using EtOAc/DCM as added DCC (0.062 g, 0.3 mmol) pinch by pinch
the eluent. The pure white product was obtained as a for few minutes. The resulting solution was stirred
solid powder (0.58 g, Yield 55%), m.p. 92–93◦C, Anal. for 5 h. DCU was removed by filtration and the
Calcd. (%) for C33H53NO7 + 1 H2O: C-66.75, H- 9.33, filtrate was diluted with 10 mL of DCM. DCM
N- 2.35; found C-66.67, H-9.15, N- 2.40. IR, v˜/cm−1 layer was washed with saturated NaHCO3 solution
(KBr): 1024, 1248, 1377, 1537, 1647, 1736, 2872, (2 × 5 mL) and water (2 × 5 mL). The organic layer
1
2943, 2965, 3315, 3385 cm−1. H NMR (250 MHz, was dried over anhydr. Na2SO4 and concentrated
CDCl3): δ 0.700 (s, 3H Me-18), 0.792 (d, J = 6.25 Hz, under reduced pressure. The product obtained was
3H Me-21), 0.888 (s, 3H Me-19), 1.20–1.99 (steroidal, further purified by column chromatography over sil-
CH, CH2) 2.01 (s, 3H), 2.05 (s, 3H), 2.12 (s, 3H), ica gel with EtOAc/DCM as eluent. The final prod-
4.05 (m, 1H), 4.55 (m, 1H), 4.88 (d, J = 2.75 Hz, 1H), uct was obtained as pale yellow foam (0.052 g, Yield
5.06 (br s, 1H), 5.278 (d, J = 7.75 Hz, 1H). 13C NMR 11%), m.p. 86–87◦C. IR, v˜/cm−1 (KBr): 845, 1182,
(63 MHz,CDCl3): δ 12.43, 14.38, 16.87, 21.20, 21.60, 1543, 1727, 2853, 2927, 3326, 3445. Anal. Calcd.
21.64, 21.77, 22.74, 22.97, 23.01, 25.77, 27.08, 27.43, (%) for C55H77NO4 + 1 H2O: C, 77.70; H, 9.36; N,
1
29.09, 31.45, 31.81, 33.93, 34.53, 34.83, 34.91, 34.97, 1.65; found C, 77.70; H, 9.06; N, 1.99. H NMR
37.97, 41.16, 41.39, 43.59, 46.41, 47.73, 60.54, 70.89, (250 MHz CDCl3): δ 0.67 (s, 3H Me-18), 0.88 (s,
74.27, 75.62,170.49, 170.65, 170.67, 172.51. HRMS 3H Me-19), 0.97 (d, J = 6 Hz, 3H Me-21), 1.13 (d,
(ESI): m/z Calcd. for C33H53NO7 + Na: 598.3687; J = 6.5 Hz, 6H), 1.22–2.33 (steroidal CH, CH2 and
found 598.3675.
alkyl CH2), 3.27 (t, J = 7.5 Hz, 2H), 3.81 (brs, 1H),
3.95 (br s, 1H), 4.08 (m, 1H), 4.58 (m, 1H), 5.35 (d,
J = 7.5 Hz, 1H), 7.86 (d, J = 8 Hz, 1H), 7.93–8.17 (m,
7H), 8.28 (d, J = 10 Hz). 13C NMR (63 MHz,CDCl3):
δ 12.73, 14.40, 17.66, 21.23, 22.67, 23.00, 23.37,
25.15, 25.28, 25.84, 26.88, 26.96, 27.72, 28.49, 29.37,
29.46, 29.63, 29.78, 30.02, 31.79, 32.14, 33.67, 33.81,
34.16, 34.66, 34.89, 35.05, 35.12, 35.46, 35.47, 39.69,
41.40, 42.28, 46.73, 47.15, 49.34, 60.56, 68.45, 73.19,
74.23, 123.75, 124.80, 124.95, 124.97, 125.30, 125.95,
126.65, 127.27, 127.44, 127.74, 128.82, 129.89,
131.17, 131.67, 137.58, 172.93, 173.71. LRMS (ESI):
m/z Calcd. for C55H77NO4 + Na: 854.57; found 854.40.
2.2f Compound 8: A mixture containing iso-propyl-
triacetyl cholamide (0.25 g, 0.43 mmol), KOH (0.25 g,
4.5 mmol) and MeOH (2.0 mL) were refluxed at 80◦C
for 8–10 h. After completion (monitored by TLC), the
reaction mixture was cooled in ice bath and neutral-
ized with dil. HCl. The product was extracted into chlo-
roform (15 mL) and washed with saturated solution of
NaHCO3 (2 × 5 mL) and water (2 × 5 mL), dried over
anhydr. Na2SO4 and concentrated under reduced pres-
sure. The product obtained was further purified by chro-
matography over silica gel with EtOH/DCM as eluent
(0.15 g, Yield 75%), m.p. 242–244◦C. IR, v˜/cm−1
(KBr): 732, 1078, 1464, 1547, 1646, 2866, 2929,
3410, 3432 cm−1. Anal. Calcd. (%) for C27H47NO4 + 2
1/2 H2O: C, 65.68; H, 10.41; N, 2.83; found C,
2.2h Compound 11: Iso-Propyl cholamide (0.10 g,
0.22 mmol), 12-(1-pyrene)dodecanoic acid (0.11 g,
0.28 mmol) and DMAP (3 mg, 0.02 mmol) were mixed
with dry DCM. To this stirring mixture DCC (0.055 g,
0.26 mmol) was added pinch by pinch for few min-
utes. The resulting solution was stirred for 12 h. The
precipitates of DCU was removed by filtration and
the filtrate was diluted with 10 mL of DCM. DCM
layer was washed with saturated NaHCO3 solution
(2 × 5 mL) and water (2 × 5 mL). The organic layer
was dried over anhydr. Na2SO4 and concentrated under
reduced pressure. The product obtained was further
purified by column chromatography over silica gel with
EtOAc/DCM as eluent. The final product was obtained
as pale yellow foam (0.04 g, Yield 15%), m.p. 70–
71◦C. Anal. Calcd. (%) for C83H107NO6 + 1 H2O: C,
80.87; H, 8.91; N, 1.14; found C, 80.67; H, 9.59;
N, 1.12. IR, v˜/cm−1 (KBr): 845, 1182, 1543, 1727,
2853, 2927, 3385, 3417.1H NMR (500 MHz CDCl3):
1
65.78; H, 9.70; N, 1.99. H NMR (250 MHz, CDCl3):
δ 0.671 (s, 3H Me-18), 0.876 (s, 3H Me-19), 0.984
(d, J = 6.3 Hz Me-21), 1.129 (d, J = 6.5 Hz, 6H), 1.26–
2.30 (m, steroidal, CH, CH2), 2.62 (br s, 4H). 3.43
(m, 1H), 3.823 (d, J = 2.25 Hz, 1H), 3.96 (br s, 1H),
4.07 (m, 1H), 5.57 (d, J = 7.75 Hz, 1H).13 C NMR
(63 MHz,CDCl3): δ 12.71, 17.70, 22.68, 22.99, 23.47,
26.66, 27.80, 28.43, 30.74, 31.92, 33.70, 34.97, 35.60,
35.61, 39.73, 39.89, 41.39, 41.75, 41.98, 46.68, 46.96,
68.67, 72.14, 73.30, 173.16. HRMS (ESI): m/z Calcd.
for C27H47NO4 + Na: 473.3436; found 473.3447.
2.2g Compound 10: Iso-Propyl cholamide (0.27 g,
0.60 mmol), 12-(1-pyrene) dodecanoic acid (0.12 g,
0.30 mmol) and DMAP (4 mg, 0.03 mmol) were
mixed with dry DCM. To this stirring mixture was

Pyrene appended bile acid conjugates: Synthesis and a structure–gelation property study
383
δ 0.66 (s, 3H Me-18), 0.89 (s, 3H Me-19), 0.96 (d, 131.46, 137.36, 173.43. HRMS (ESI): m/z Calcd. for
J = 6.5 Hz, 3H Me-21), 1.113 (d, J = 6.5 Hz, 6H), 1.14– C68H103NO5 + Na: 1036.7734; found 1036.7737.
2.11 (steroidal, CH, CH2), 3.28–3.35 (m, 4H), 3.95 (br
s, 1H), 4.05 (m, 1H), 4.58 (m, 1H), 4.885 (d, J = 2.5 Hz,
2.2j Compound 14: Hexadecyl deoxycholamide
1H), 5.14 (d, J = 7.5 Hz), 7.81–7.85 (m, 2 H), 7.93–
(0.20 g, 0.33 mmol), 4-(1-pyrene) butyric acid (0.112 g,
8.02 (m, 6H), 8.05–8.10 (m, 4H), 8.12–8.14 (m, 4H),
0.39 mmol) and DMAP (6 mg, 0.05 mmol) were mixed
8.24–8.27 (m, 2H).13C NMR (126 MHz,CDCl3): δ
with dry DCM. To this stirring mixture DCC (0.083 g,
12.73, 14.41, 17.72, 21.23, 22.72, 23.02, 23.24, 24.50,
0.4 mmol) was added pinch by pinch for 5 min.
24.90, 25.16, 25.25, 25.32, 25.54, 25.74, 25.96, 26.65,
The resulting solution was stirred for 5 h. DCU was
26.94, 27.54, 28.37, 28.77, 29.37, 29.39, 29.58, 29.67,
removed by filtration and the filtrate was diluted with
29.73, 29.79, 29.81, 29.84, 29.86, 30.02, 30.06, 31.06,
10 mL of DCM. DCM layer was washed with saturated
31.58, 31.85, 32.13, 32.16, 32.98, 33.80, 34.00, 34.18,
NaHCO3 solution (2 × 5 mL) and water (2 × 5 mL).
34.57, 34.99, 35.02, 35.17, 35.33, 38.38, 41.17, 41.40,
The organic layer was dried over anhydr. Na2SO4 and
42.37, 46.79, 47.50, 49.37, 60.57, 70.77, 78.01, 73.98,
concentrated under reduced pressure. The product
74.31, 123.73, 124.80, 124.95, 124.97, 125.30, 125.31,
obtained was further purified by chromatography over
125.93, 126.65, 127.27, 127.42, 127.73, 128.83,
silica gel with EtOAc/DCM as eluent. The final product
129.90, 131.07, 131.68, 137.54, 173.31, 173.55. HRMS
was obtained as pale yellow foam (0.17 g, Yield 60%),
(ESI): m/z Calcd. for C83H107NO6Na: 1236.7996; found
m.p. 65–68◦C. IR, v˜/cm−1 (KBr): 844, 1383, 1645,
1236.8005.
1
1728, 2853, 2924, 3440. H NMR (250 MHz CDCl3):
δ 0.65 (s, 3H), 0.86–0.95 (m, 6H), 0.96 (d, J = 6 Hz),
1.02–1.1.20 (m, 3H), 1.26 (br s, 30H), 1.30–2.50
2.2i Compound 13: Hexadecyl cholamide (0.15 g,
(steroidal CH, CH2 and alkyl CH2), 3.22 (m, 2H), 3.38
0.24),
12-(1-pyrene)dodecanoic
acid
(0.12 g,
(t, J = 8 Hz, 2H), 3.94 (br s, 1H), 4.75 (m, 1H), 5.46 (m,
1H), 7.86 (d, J = 8 Hz, 1H), 7.94–8.18 (m, 7H), 8.31
(d, J = 9.25 Hz, 1H).13C NMR (63 MHz,CDCl3): δ
12.93, 14.29, 17.63, 22.87, 23.28, 23.77, 26.20, 26.78,
27.13, 27.19, 27.65, 28.92, 29.51, 29.54, 29.75, 29.79,
29.89, 31.93, 32.11, 32.45, 33.04, 33.79, 33.86, 34.30,
34.62, 35.09, 35.34, 36.16, 39.76, 42.10, 46.67, 47.49,
48.48,73.28, 74.46, 123.56, 124.91, 125.01, 125.05,
125.20, 125.28, 125.98, 126.85, 127.57, 127.68,
128.94, 130.15, 131.12, 131.62, 136.02, 173.17,
173.63. LRMS (ESI): m/z found 908.76. HRMS (ESI):
m/z Calcd. for C60H87NO4 + Na: 908.6533; found
908.6570.
0.30 mmol) and DMAP (3.5 mg, 0.03 mmol) were
mixed with dry DCM (1.0 mL). To this stirred mixture
was added DCC (0.062 g, 0.3 mmol) pinch by pinch
for few minutes. The resulting solution was stirred for
5 h. DCU was removed by filtration and the filtrate was
diluted with 10 mL of DCM. DCM layer was washed
with saturated NaHCO3 solution (2 × 5 mL) and water
(2 × 5 mL). The organic layer was dried over anhydr.
Na2SO4 and concentrated under reduced pressure.
The product obtained was further purified by column
chromatography over silica gel with EtOAc/DCM as
eluent. The final product was obtained as pale yel-
low foam (0.12 g, Yield 50%), m.p. 54–55◦C. Anal.
Calcd. (%) for C68H103NO5 + 11/2 H2O: C, 78.41; H,
10.25; N, 1.34; found C, 78.18, H, 9.80; N, 0.92. IR,
v˜/cm−1 (KBr): 844, 1465, 1547, 1645, 1728, 2853,
2924, 3324, 3384, 3419.1H NMR (500 MHz CDCl3): δ
0.68 (s, 3H), 0.86–0.89 (m, 6H), 1.004–1.13 (m, 6H),
1.25–1.27 (br peak, 42 H), 1.34–2.35 (steroidal CH,
CH2, alkylCH2), 3.24 (br s, 2H), 3.33 (t, J = 8 Hz, 2H),
4.57 (m, 1H), 7.87 (d, J = 7.5 Hz), 7.97–8.16 (m, 7H),
8.282 (d, J = 9 Hz, 1H). 13C NMR (126 MHz,CDCl3): δ
12.43, 14.08, 17.65, 22.39, 22.67, 23.26, 25.08, 25.37,
25.71, 26.61, 26.84, 26.92, 27.52, 28.17, 29.19, 29.27,
29.34, 29.43, 29.57, 29.59, 29.64, 29.65, 29.69, 29.813,
31.91, 31.93, 33.60, 34.53, 34.68, 34.86, 34.90, 35.19,
35.20, 39.34, 40.03, 41.22, 42.12, 46.44, 68.33, 73.10,
73.99, 123.53, 124.59, 124.74, 124.76, 125.10, 125.72,
126.45, 127.06, 127.53, 128.62, 129.69, 130.96,
2.2k Compound 15: Hexadecyl cholamide (0.12 g,
0.195 mmol), 12-(1-pyrene) dodecanoic acid (0.1 g,
0.25 mmol) and DMAP (2.5 mg, 0.02 mmol) were
mixed with dry DCM. To this stirring mixture DCC
was added pinch by pinch for few minutes. The result-
ing solution was stirred for 5 h. DCU was removed
by filtration and the filtrate was diluted with 10 mL
of DCM. DCM layer was washed with saturated
NaHCO3 solution (2 × 5 mL) and water (2 × 5 mL).
The organic layer was dried over anhydr. Na2SO4
and concentrated under reduced pressure. The prod-
uct obtained was further purified by column chro-
matography over silica gel with EtOAc/DCM as elu-
ent. The final product was obtained as pale yellow foam
(0.11 g, Yield 55%), m.p. 52–54◦C. Anal. Calcd. (%)

384
Shreedhar Bhat et al.
for C68H103NO4 + 2 H2O: C, 78.94; H, 10.42; N, 1.37; 2.2n Compound 16: The starting compound, dode-
found C, 78.55; H, 10.02; N, 1.92. IR, v˜/cm−1 (KBr): cyl deoxycholate, was prepared by reacting deoxycholic
1
844, 1181, 1465, 1643, 1731, 2852, 2924. 3380. H acid (0.5 g, 1.27 mmol) and 1-dodecylbromide (0.375 g,
NMR (250 MHz CDCl3): δ 0.57 (s, 3H), 0.77 (s, 3H), 1.5 mmol) in the presence of DBU (0.225 g, 1.48 mmol)
0.92 (t, J = 7 Hz, 3H), 1.01 (d, J = 6 Hz, 3H), 1.26– in 3 mL DMF as the solvent. The reaction mixture was
2.01 (m, steroidal, alkyl CH, CH2), 3.06–3.25 (m, 4H), stirred at 60◦C for 12 h. After the reaction, the reac-
3.81 (br s, 1H), 4.79 (t, J = 6.25 Hz, 1H), 4.97 (m, 1H), tion mixture was poured into a beaker containing dil.
7.72–8.01 (m, 8H), 8.23 (d, J = 9.25, 1H). 13C-NMR HCl solution (20 mL) and the procuct was extracted
(C6D6, 63 MHz): δ 13.33, 14.71, 17.99, 23.46, 23.60, with DCM (20 mL × 2). The organic layer was washed
24.31, 25.75, 25.88, 26.72, 26.89, 27.55, 27.70, 29.51, with dil. HCl (10 mL × 2), sat. NaHCO3 solution
29.91, 30.05, 30.18, 30.24, 30.35, 30.49, 30.56, 30.69, (10 mL × 2), followed by water wash (10 mL × 2).
31.60, 32.51, 32.61, 32.69, 33.22, 33.30, 33.93, 34.25, The solvent was removed under reduced pressure and
34.62, 35.32, 35.61, 35.98, 36.62, 39.98, 42.52, 47.14, the product was dried under high vacuum. The yeild
47.72, 48.71, 73.29, 74.48, 124.22, 125.39, 125.56, (0.66 g, 93%) of the reaction was nearly quantitative.
125.60, 126.15, 126.20, 126.41, 127.28, 129.57, Then 1-pyrene butyric acid (0.25 g, 0.87 mmol) and
130.71, 131.89, 132.40, 137.83, 172.73, 173.07. LRMS dodecyldeoxycholate in dry DCM was stirred at 25◦C
(ESI): m/z found 1020.90. HRMS (ESI): m/z Calcd. in the presence of DCC (0.186 g, 0.9 mmol) and a cat-
C68H103NO4Na 1022.7852; found 1022.7860.
alytic amount of DMAP (0.01 g, 0.08 mmol) for 24 h.
The DCU formed was filtered. The filtrate was washed
with sat. NaHCO3 solution (10 mL), followed by water
wash (10 mL). The organic layer was concentrated after
drying over anhydr. Na2SO4. The product was chro-
matographed on a silica gel column using EtOAc/DCM
as the eluent (0.21 g, Yield 30%), Anal. Calcd. (%) for
C55H76O5 + H2O: C, 79.09; H, 9.41; found C, 78.78; H,
9.43. IR, v˜/cm−1 (KBr): 828, 1181, 1466, 1639, 1733,
2850, 2928. 3040.1H NMR (300 MHz CDCl3): δ 0.66
(s, 3H), 0.85–0.93 (m, 6H), 0.97 (d, J = 6 Hz, 3H), 1.2–
2.5 (steroidal CH, CH2, alkyl CH2), 3.96 (br s, 1H),
4.05 (t, J = 6.6 Hz, 3H), 4.75 (m, 1H), 7.85 (d, 7.8 Hz,
1H), 7.94–8.08 (m, 3H), 8.08–8.20 (m, 4H), 8.31
(d, 9.3 Hz, 1H).13C NMR (75 MHz,CDCl3): δ 12.88,
14.26, 17.42, 22.83, 23.29, 23.86, 26.12, 26.31, 26.80,
27.33, 27.66, 28.83, 29.42, 29.49, 29.80, 30.59, 31.13,
31.59, 32.07, 32.50, 33.05, 33.78, 34.29, 35.36, 35.46,
36.22, 36.61, 42.29, 46.66, 47, 45, 48.37, 64.59, 71.81,
73.25, 123.60, 124.91, 125.05, 125.22, 125.35, 126.00,
126.88, 127.61, 127.66, 128.99, 130.17, 131.19,
131.70, 131.67, 136.08, 173.19, 174.50. LRMS (ESI):
m/z found 841. HRMS (ESI): m/z Calcd. C55H76O5Na
840.1952; found 840.1947.
2.2l Compound 15 + Compound 24 (TNF): Com-
pound 15 (5.5 mM) and TNF (5.5 mM) were dissolved
in benzene [D6] and NMR spectrum was recorded. H
1
NMR (250 MHz, C6D6): δ 0.59 (s, 3H), 0.79 (s, 3H),
0.92 (t, J = 6.75 Hz, 3H), 1.019 (d, J = 6 Hz, 3H), 1.17–
2.06 (m, steroidal, alkyl, CH, CH2), 2.28 (t, J = 7.5 Hz,
2H), 3.04–3.19 (m, 4H), 3.83 (br s, 1H), 4.82 (t,
J = 6 Hz, 1H), 4.95 (m, 1H), 7.32 (d, J = 8.5 Hz, 1H),
7.42–7.67 (m, 8H), 7.902 (d, J = 2 Hz,), 7.945 (br s,
0.5 H), 8.05–8.07 (m, 2H). 13C NMR (126 MHz, C6D6):
δ 13.35, 14.73, 18.00, 23.48, 23.63, 24.34, 25.44, 25.91,
26.75, 27.22, 27.56, 27.73, 28.27, 29.54, 29.95, 30.09,
30.20, 30.28, 30.38, 30.51, 30.58, 30.70, 31.62, 32.30,
32.53, 32.70, 33.23, 33.30, 34.03, 34.10, 34.27, 34.66,
35.34, 35.64, 36.03, 36.65, 40.00, 42.56, 47.17, 47.77,
48.75, 73.33, 74.51, 119.45, 122.01, 124.08, 125.07,
125.27, 125.34, 125.49, 125.61, 126.51, 127.10,
127.44, 127.69, 127.82, 130.08, 130.11, 131.31,
131.78, 136.06, 137.83, 137.95, 138.67, 142.88,
144.46, 148.81, 150.09, 172.77, 173.13, 185.41.
2.2m TNF (Compound 24) 1H-NMR (500 MHz,
C6D6): δ 7.41 (d, J = 8.5 Hz, 1H), 7.63 (d, J = 2 Hz,
0.5H), 7.64 (d, J = 2.5 Hz, 0.5 H), 8.05 (d, J = 2.5 Hz,
1H), 8.11 (d, J = 2 Hz, 1H), 8.16 (d, J = 2.5 Hz, 1H).13C
NMR (126 MHz, C6D6): δ 119.79, 122.35, 125.24,
127.53, 129.07, 129.10, 130.38, 136.27, 138.13,
138.91, 143.11, 144.82, 149.18, 150.33, 185.69,
208.46.
2.2o Compound 17: 1-Pyrene butyric acid (0.25 g,
0.87 mmol) was dispersed in 2.5 mL dry DCM. To
this dispersion was added oxalyl chloride (0.13 g,
1.02 mmol), a catalytic amount of DMF (5 μL). The
mixture was stirred for 2 h at 25◦C. The solvents
were removed using a KOH trap connected between
the vacuum pump and the sample. The acid chlo-
ride so obtained was dissolved in 1 mL of dry DCM

Pyrene appended bile acid conjugates: Synthesis and a structure–gelation property study
385
and added to a mixture containing methyl deoxy- 7.8 Hz, 1H), 7.96 (d, 7.8 Hz, 1H), 8.00–8.05 (m, 2H),
cholate (0.3 g, 0.74 mmol) and dry pyridine (2 mL) 8.07–8.19 (m, 4H), 8.30 (d, 9.25 Hz, 1H). 13C NMR
drop by drop for 30 min. The mixture was stirred (75 MHz, CDCl3): δ 14.26, 22.83, 26.12, 26.51, 29.42,
for 2 h. After the reaction, the mixture was quenched 29.49, 29.80, 30.59, 32.07, 32.64, 33.22, 35.46, 36.61,
with 10 mL of dil.HCl. The product was extracted 64.59, 123.63, 124.89, 125.01, 125.23, 125.33, 125.97,
with DCM (20 mL × 2) and washed with dil. HCl 126.89, 127.63, 127.69, 128.97, 130.15, 131.17,
(10 mL), sat. NaHCO3 solution (10 mL), followed by 131.68, 131.71, 136.06, 173.22. LRMS (ESI): m/z
water wash (10 mL). The organic layer was concen- found 466. HRMS (ESI): m/z Calcd. for C31H38O2Na
trated after drying over anhydr. Na2SO4. The prod- 465.6313; found 465.6320.
uct was chromatographed on a silica gel column using
EtOAc/DCM as the eluent (0.08 g, Yield 14%), Anal.
3. Results and discussion
Calcd. (%) for C44H54O5 + H2O: C, 77.61; H, 8.29;
found C, 77.42; H, 7.99. IR, v˜/cm−1 (KBr): 832,
The synthesis of bile acid derivatives 4–8, pyrene bile
1
1185, 1458, 1649, 1730, 2849, 2928. 3046. H NMR
acid conjugates 10, 11, 13–17 and pyrene derivative
(300 MHz CDCl3): δ 0.67 (s, 3H), 0.91 (s, 3H), 0.97
23 was achieved using common organic synthesis tech-
(d, J = 5.7 Hz, 3H), 1.0–2.5 (m, steroidal CH, CH2),
niques (chart 1, see experimental section for details) and
3.39 (t, J = 7.2 Hz, 2H), 3.67 (s, 3H), 3.96 (br s, 1H),
the gelation tests were performed in a set of different
4.79 (m, 1H), 7.86 (d, 7.8 Hz, 1H), 7.97 (d, 7.8 Hz, 1H),
organic solvents.
8.01–8.07 (m, 2H), 8.09–8.21 (m, 4H), 8.32 (d, 9.3 Hz,
To our disappointment the compounds 9–18 either
1H). 13C NMR (75 MHz, CDCl3): δ 12.93, 17.53,
remained in solution or precipitated within 12 h of test-
23.31, 23.80, 26.22, 26.82, 27.16, 27.21, 27.58, 28.95,
ing and no sign of gelation was detected. However, an
31.12, 31.27, 32.47, 33.05, 33.90, 34.35, 34.64, 35.12,
intense red coloured charge transfer (CT) complex was
35.25, 36.20, 42.11,46.72, 47.57, 48.51, 51.67, 73.31,
formed when trinitrofluorenone, TNF (24, chart 1) was
74.45, 123.59, 124.93, 125.05, 125.23, 125.33, 125.99,
added into solutions of 9–18. The gelation tests were
126.88, 127.60, 127.68, 128.98, 130.18, 131.17,
made at 1:1% w/v of the gelator and TNF in an organic
131.69, 131.66, 136.09, 173.20, 174.94. LRMS (ESI):
solvent. The gelation was visually confirmed by turn-
m/z found 686. HRMS (ESI): m/z Calcd. C44H54O5Na
ing the test tube upside down and monitoring the flow
685.8995; found 685.8989.
of the gel. The observations were carried out at room
temperature (25◦C) in organic solvent listed in table 1.
2.2p Compound 23: 1-Pyrene butyric acid (0.25 g,
0.87 mmol) was dissolved in 2 mL DMF. To this clear
solution DBU (0.152 g, 0.99 mmol) was added drop-
wise and stirred for 15 min. 1-Dodecyl bromide (0.25,
1.0 mmol) was added to above solution maintained at
60◦C. The resulting mixture was stirred for additional
6 h. The progress of the reaction was monitored by
TLC. After the disappearance of the starting mate-
rial, DMF was distilled off under reduced pressure.
The residue was extracted into DCM (25 mL × 2).
The organic layer was washed with dil. HCl (10 mL ×
2) followed by water (10 mL) and dried over anhydr.
Na2SO4. The crude material was obtained after the sol-
vent removal was further purified over silica gel col-
umn using DCM/PE as the eluent. The final product
was isolated as pale yellow oil (0.32 g, Yield 84%),
Anal. Calcd. (%) for C31H38O2: C, 84.12; H, 8.65;
found C, 78.78; H, 9.43. IR, v˜/cm−1 (KBr): 789, 821,
3.1 Gelation studies
We have introduced a few pyrene analogues and bile
acid analogues as potent gelators of organic solvents.
As both pyrene25b and bile acid25c moieties are known
as potent structural fragments in gelling these moieties
were first tested separately in gelation. No gelation was
seen with the simplest pyrene molecule 1-pyrene car-
boxylic acid (19) or its mixture with 1-aminopyrene
(20) (prepared by heating the 1:1 mixture of the amine
and acid in an organic solvent during the test), even in
the presence of an equivalent amount of CT agent, TNF.
Similarly, no gelation was seen with the 1:1 conjugate
of deoxycholic acid or cholic acid and 1-aminopyrene
in the presence of an equivalent amount of TNF. The
mixture precipitated out in most of the organic solvents
used for the study. PBA alone (21) or in the presence
of TNF does not gel organic solvents. Both 21 and
21+TNF remain in solution when mixed in benzene,
toluene and chlorobenzene. However, when 1-decanol
or cyclohexanol was used, a gelatinous precipitate, yet
1
1211, 1458, 1649, 1741, 2849, 2925. 3048. H NMR
(300 MHz CDCl3): δ 0.85 (t, J = 6.5 Hz, 3H), 1.18–
1.35 (m, 20 H), 2.17 (m, 2H), 2.35 (t, J = 5 Hz, 2H),
3.38 (t, J = 7 Hz, 2H), 3.65 (t, J = 6 Hz, 2H), 7.85 (d,

386
Shreedhar Bhat et al.
Chart 1. Gelator molecules used in the present study.
not a gel, was observed. This finding is interesting since tested solvents. However, the PBA esters of cholates 16
when a longer alkyl chain used, viz., compound 22, and 17 do gel higher alcohols and cyclohexanol (table
strong CT gels in many organic solvents are formed as 1). Thus the gelated solvent systems can be changed by
shown by us previously.24
modifying the bile acid side chain.
Interestingly, PBA esters of bile acid conjugates
The length of the connection moiety between the
(esterification of 3α-OH) formed strong gels in a num- pyrene and bile acid part of the gelators plays an impor-
ber of organic solvents in the presence of TNF. Com- tant role (viz., compounds 14 and 15). If pyrene-1-
pounds 14, 16, and 17 formed strong organogels in a dodecanoic acid (15) is used instead of PBA, the gela-
variety of organic solvents (table 1). The PBA ester of tion properties are lost (within the tested solvent range;
a cholamide (14) formed a strong CT gel in aromatic listed in table 1), 14 does gel benzene, whereas 15 does
hydrocarbon solvents like benzene similar to reported not. This is in line with our previous observations that
cholamides (compound 5, not a CT gel).31 These the presence of pyrene moiety on the bile acid side
organogels were characterized by various physical tech- chain normally leads to loss of gelation properties.24
niques and are discussed in detail in the proceeding
At this point, the role of the bile acid backbone on the
sections. Other cholamides like iso-propyl cholamide gelation is very important. This is further highlighted by
(compound 8),32 a known gelator, do not show gelation observation that a very small variation of the bile acid
if used with the corresponding PBA amide (9) in the skeleton will influence gelation. Compound 13 with one

Pyrene appended bile acid conjugates: Synthesis and a structure–gelation property study
387
organic solvents in the presence of TNF as the acceptor
prompted us to examine the role of the bile acid moiety
in these gelators. Some of these pyrene analogues were
found to gel even when the bile portion of the molecule
was replaced by a simple alkyl chain (e.g., compound
26).
To address this question, a pyrene analogue was syn-
thesized following standard protocols in which the bile
acid moiety was replaced by simple alkyl chains con-
nected to the pyrene through an ester linkage (com-
pound 23). This compound formed a deep red CT com-
plex, which remained in solution even after 4 days, no
gel formation was observed (table 1). The above gela-
tion findings clearly indicate that pyrene-based gela-
tors need the presence of a bile unit with an ester or
amide linkages between them in order to be an efficient
gelator.
Table 1. Gelation profile of compounds 14, 16, and 17 in
different organic solvents (Cgelator 1% w/v, 1:1 TNF).
Solvent
14 + 24[a] 16 + 24[a] 17 + 24[a] 23 + 24[a]
Benzene
Toluene
G
S
S
S
S
S
S
S
Dichlorobenzene
1-Chlrobenzene
Cyclohexane
Acetonitrile
CCl4
Cyclohexanol
1-Decanol
Isopropanol
Ethanol
S
S
S
Ss
S
S
S
Ss
Ss
I
S
S
GP
S
S
GP
G
GP
Ss
I
S
S
Ss
S
S
G
G
GP
Ss
I
S
S
S
P
S
S
S
Ss
Ss
I
Water
[a] = I: Insoluble, S: Solution, Ss: Sparingly Soluble, G:
Strong Gel, GP: Gelatinous Precipitate, P: Precipitate
3.2 Absorption characteristics
OH group more than 14, does not form gel with ben-
zene as 14 does. We believe that the bile acid backbone
provides a rigid central core aggregation behaviour of
which can be modulated by the substituents on it and
linked to it. It seems that the PBA moiety attached at the
position 3 of the bile backbone facilitates the multidi-
mensional growth (when TNF is added) of the prelim-
inary aggregates formed, thus leading to gel formation.
The pyrene-1-dodecanoic acid esters of bile analogues
(compounds 13 and 15), however, failed to gel organic
solvents probably due to the lack of right hydrophobic–
hydrophilic balance. These molecules may also be too
flexible to have the needed growth of the aggregates
when compared to PBA esters.
During the gelation of the compounds 14, 16 and 17,
a clear colour change was observed with TNF, caused
by an increase in the charge-transfer interaction (CT)
during the gelation. This prompted us to study the gela-
tion of these compounds by UV-Visible spectroscopy.
Absorption spectroscopic studies were performed with
compound 23 in the presence and absence of TNF
(conc. of 23 and TNF is 10 μM). At this concentration
no CT band could be seen. However, the band was seen
at 0.5 mM of 23 and TNF.
Similar studies performed for compound 17
(0.6 mM) with TNF (0.6 mM) showed a band width
λmax 575 nm (figure 1), which is indicative of the for-
mation of a charge transfer complex. Transformation
from sol to gel or from gel to sol has a clear effect on
the intensity of the charge transfer band. The charge
transfer band intensity decreased when the gel was
converted into sol and vice versa. However, there is no
The pyrene derivatives reported here are functional-
ized at the alkyl end of the pyrene that is different from
pyrene derivatives studied in our earlier reports.25a−b
Our initial discovery of aromatic donor-substituted bile
acid derivatives, such as 25 (chart 2), gelled certain
Chart 2. Reference molecules used in this study.

388
Shreedhar Bhat et al.
the upside down test tube method. The temperature at
which the gel started flowing was taken as the tran-
sition point. The CT gel 14 (1% w/v in benzene, 1:1
TNF) melted at 55◦C and became clear solution at 70◦C.
The gels of compound 16 and 17 in 1-decanol exhib-
ited slightly lower Tgel values (42◦C and 45◦C respec-
tively) compared to benzene gels of 14. The Tgel value
observed in this class of organogels is smaller compared
to other TNF gels and close to the individual powder
melting point of the gelators. The CT gels of 14, 16 and
17 are thermoreversible.
3.4 1H NMR studies
The sol–gel transition process monitored by NMR
showed a significant difference on the proton signals.
1H NMR spectra were recorded for a benzene [D6] gel
of 16 at various temperatures. A well-ordered pattern
turned into a complex broad pattern when the sol was
allowed to gel during the NMR experiment. The transi-
tion from gel–sol was studied by plotting the chemical
shift (figure 2) and the width of the NMR signals against
temperature.
Figure 1. Absorption spectrum of compound 17 (0.6 mM)
with TNF (0.6 mM).
additional band nor change in the λmax was detected
between the cycles of sol-to-gel or gel-to-sol.
3.3 Gel melting
1
A variable temperature H NMR (figure 3) is in
accordance with the melting studies. At 60◦C, the broad
signals observed at low temperatures transformed into
sharp patterns. The broadness of the signals at low tem-
peratures is probably attributed to the poor relaxation in
the gel state that transformed into a sharp signal when
gel–sol transition took place. There was appreciable
shift in the δNH of gelator 14 on going from the sol to gel
Although the gels (table 1) were formed by the entropic
factors a small contribution from the enthalpy is always
present. To dissolve the gelator in a given solvent, heat
must be supplied to the system. Once the gel is formed,
there exists a temperature at which the gel melts back
to form a sol. The gel–sol transition was recorded by
Figure 3. A plot of variable temperature 1H NMR of com-
pound 14 (5.5 mM) + TNF (5.5 mM) in benzene [D6]. Mainly
the aromatic portion of the spectrum is shown here.
Figure 2. A plot of chemical shift of a pyrene proton
vs. experimental temperature for CT gel of compound 14
(5.5 mM) with TNF (5.5 mM) in benzene [D6].

Pyrene appended bile acid conjugates: Synthesis and a structure–gelation property study
389
Figure 4. The SEM images of xerogels. a and b: Compound 14 + TNF (1:1, 1%
w/v) in benzene; c and d: Compound 17 + TNF (1:1; 1% w/v) in 1-decanol.
phase. This indicated that the side-chain functionality 50 nm. The rods are mostly bundled and the individ-
present on the bile acid has a crucial role on the gelation ual rods are rarely seen. These rods reveal no branching
of this class of gelators. In addition, the chemical shifts and the overall structure can thus be considered as an
of methylene groups of butyric acid also shifted con- open-type network. The fractures of the network seen in
siderably during the gelation (compound 14). It appears some parts of the image are probably due to the faster
that the growth of the aggregates has a strong con- evaporation of the solvent benzene at room temperature
nection with the spacer used between pyrene and bile during sample preparation.
acid. The TNF is probably acting as an initiator that
influences the growth of the aggregates, which in turn
3.6 Chirality of the supramolecular aggregates
leads to gelation of the system. The TNF protons in the
1
gel showed a strong variation in the H NMR chemi-
The exact relation between molecular chirality and
supramolecular chirality is not very clear. In some
cases, the racemic and achiral molecules form chiral
aggregates.33 Many of the reported hydrogels derived
from deoxycholate and its conjugates have been shown
to exhibit supramolecular helicity.34 The gelators 14,
16, and 17 have been derived from homochiral bile acid
systems. However, no such supramolecular helicity or
chiral signatures could be extracted from SEM analysis.
cal shifts. It was clearly observed that the doublets of
TNF at 8.05 (d, J = 2.5 Hz, 1H), and 8.11 (d, J = 2 Hz,
1H) appears as a broad singlets when they form a gel
with compound 14. When the temperature is increased
both of the signals merge into a broad singlet at 50◦C
and finally they appear as two doublets after complete
melting (figure 3). This implies a strong change in the
chemical environment during gel–sol transition.
3.5 Gel morphology
4. Conclusions
The topography of the gels was characterized by the
electron microscopy. The SEM images of the xerogels We have synthesized different pyrene and bile acid-
of compounds 14 and 16 are shown in the figure 4. The pyrene derivatives with interest of their self-association
images revealed the presence of infinitely long intercon- properties in various organic and aqueous solvents.
nected rod-like structures with a rod diameter of about Among the compounds prepared the PBA esters of bile

390
Shreedhar Bhat et al.
acid analogues were found to gel many organic sol-
vents in the presence of TNF through the formation of
a charge transfer complex. The gels obtained are opti-
cally transparent and deep red in colour attributed to
the charge transfer band. The addition of TNF seems to
grow and strengthen the smaller aggregates ultimately
leading to the gelation of the solvents. A structure–
gelation property studies revealed that the length of
the alkyl spacer between pyrene and ester carbonyl
situated at position 3 of the bile acids is one of the lim-
iting factors for the gelation. The side chain function-
ality and the structure is the second factor which can
be available for fine tuning the gelation abilities of this
class of organogelators. The replacement of a bile acid
moiety by a simple alkyl chain highlighted the impor-
tance of bile acid backbone in this gelator class. The
gels are thermoreversible and stable to several cycles of
melting and cooling. A highly entangled rod-like struc-
tures were seen from the xerogels with no signature of
supramolecular chirality.
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Acknowledgements
Financial support from the Academy of Finland (grants
106998 and 212588) is gratefully acknowledged.
Thanks are due to special laboratory technician Reijo
Kauppinen for helping NMR measurements and to spe-
cial laboratory technician Mirja Lahtiperä for mass
spectrometry (MS). We also thank the Institute Nano
Initiative (INI) at the Indian Institute of Science (IISc),
Bangalore, India, for providing SEM facility. The IISc
group thanks the Department of Science and Technol-
ogy, New Delhi, for financial support in the form of a
J.C. Bose Fellowship to UM.
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