Thermotropic liquid-crystalline folic acid derivatives: Supramolecular discotic and smectic aggregation

Article abstract of DOI:10.1039/b004815l

Thermotropic discotic and smectic liquid crystallinity can be induced for folic acid derivatives having octadecyl and undecyl substituents in wide temperatures ranges, respectively; the addition of sodium triflate to smectic liquid-crystalline folic acid

Full text of DOI:10.1039/b004815l

Thermotropic liquid-crystalline folic acid derivatives: supramolecular discotic
and smectic aggregation†
Kiyoshi Kanie,a Takayasu Yasuda,a Seiji Ujiieb and Takashi Kato*a
a Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Hongo,
Bunkyo-ku, Tokyo 113-8656, Japan. E-mail: kato@chiral.t.u-tokyo.ac.jp
b Department of Material Science, Shimane University, Matsue, Shimane 690-8504, Japan
Received (in Cambridge, UK) 15th June 2000, Accepted 29th August 2000
First published as an Advance Article on the web 18th September 2000
Table 1 Phase transition temperatures of 1a
Thermotropic discotic and smectic liquid crystallinity can be
induced for folic acid derivatives having octadecyl and
Compound
Phase transition temp./°C
undecyl substituents in wide temperatures ranges, re-
spectively; the addition of sodium triflate to smectic liquid-
crystalline folic acid leads to a change of the assembled
structures from smectic to columnar phases.
1a (n = 6)
1b (n = 11)
1c (n = 18)
S
S
M
238
240
223
Iso
Iso
Iso
Cr
Dhd
213
207
Dho
62
a Cr: crystalline; S: smectic; Dho: ordered discotic hexagonal columnar;
hd: disordered discotic hexagonal columnar; M: mesomorphic with low
viscosity; Iso: isotropic.
Nanoscale molecular architectures formed by non-covalent
interactions have been intensively studied because highly
functional molecular materials can be obtained by self-
organization processes.1–4 For liquid-crystalline (LC) materials,
the utilization of the molecular interactions such as hydrogen
bonding has been shown to be quite useful.4 The control of the
patterns and the reversible self-assembling nature of hydrogen-
bonded liquid crystals would lead to the preparation of a novel
dynamically functional material. Our intention is to use self-
organization behavior of biomolecules, which in many cases
show lyotropic behavior, for the formation of new thermotropic
LC materials.
In the present study, we have focused on the pterin ring of
folic acid. Thermotropic LC folic acids have not yet been
developed although the lyotropic mesomorphism through
discotic tetramer formation of sodium folate in aqueous solution
has been reported.5 The induction of the thermotropic liquid
crystallinity of this molecule may lead to the development of
dynamically functional anisotropic systems.
D
supported the difference of the phase structures.6 The formation
of the smectic and discotic phases can be attributed to the
ribbon- and disk-like aggregation of pterin rings of 1,
respectively, as shown in Fig. 1.7,8 The IR spectra of 1b and 1c
also indicated the existence of the two types of the hydrogen-
bonded structures.¶ The layer structure for 1a and 1b should be
induced by the ribbon-like aggregation of the pterin ring (Fig.
1A).7 In contrast, the induction of the discotic hexagonal
columnar phase of 1c was based on the disk-like aggregation of
the pterin ring of 1c (Fig. 1B).8 For 1c, the disordered alkyl
chains can be closely packed in the discotic arrangement. The
difference of these aggregated structures was due to the
dynamic nature of the hydrogen bonding.
The formation of columnar molecular assemblies has been a
recent topic for the development of functional materials.9,10 We
were able to change the LC phase of 1b from smectic to
columnar by the addition of sodium triflate (NaOTf). The
isotropization temperatures and the mesomorphic temperature
We succeeded in inducing thermotropic liquid crystallinity
for folic acid derivatives 1a–c by incorporating 2-(3,4-dialkyl-
oxyphenyl)ethyl groups into the glutamic acid moiety. Com-
pound 1c exhibited columnar mesophases, while smectic phases
were seen for compounds 1a and 1b containing shorter alkyl
chains.‡ The phase transition behavior of 1a–c is summarized in
Table 1.§
X-Ray diffraction measurements showed that 1c exhibited
ordered and disordered discotic hexagonal columnar (Dho and
Dhd) phases (Dho phase at 25 °C: d100 = 50.5, d110 = 29.2,
d200 = 25.3, and the distance between disks = 4.1 Å; Dhd phase
at 100 °C: d100 = 50.6, d110 = 29.2, and d200 = 25.3 Å). Only
one sharp peak (small angle) and a broad halo were observed for
the smectic phases of 1a and 1b. The layer spacings for 1a and
1b were 37.6 and 41.2 Å at 25 °C, respectively. It is noteworthy
that the phase behavior of 1 was greatly dependent on the length
of the alkyl chains. The textures observed for these compounds
Fig. 1 Hydrogen-bonded self-assembled structures of the pterin rings of
folic acid. (A) Linear ribbon-like aggregation style, (B) cyclic disk-like
aggregation style.
† Electronic supplementary information (ESI) available: synthesis details
and IR data. See http://www.rsc.org/suppdata/cc/b0/b004815l/
DOI: 10.1039/b004815l
Chem. Commun., 2000, 1899–1900
This journal is © The Royal Society of Chemistry 2000
1899

in a yield of 40% as a pale yellow waxy oil. Rf = 0.40 (CH2Cl2/ethanol/
benzene = 13/1/1); 1H NMR (400 MHz, CDCl3) d 8.81 (s, 1 H), 7.87 (d, J
= 8 Hz, 2 H), 7.42 (d, J = 8 Hz, 2 H), 6.81–6.69 (m, 6 H), 5.16 (s, 2 H),
4.77–4.72 (m, 1 H), 4.36–4.21 (m, 4 H), 3.99–3.93 (m, 8 H), 2.88 (t, J = 7
Hz, 2 H), 2.83 (t, J = 7 Hz, 2 H), 2.47–2.35 (m, 2 H), 2.26–2.20 (m, 1 H),
2.11–2.04 (m, 1 H), 1.80–1.76 (m, 8 H), 1.43–1.24 (m, 64 H), 0.86 (t, J =
7 Hz, 12 H); Maldi-TOF MAS (matrix, IAA): m/z 1427.65. Experimental
details for the preparation of 2b as well as 1b are summarized in the
ESI.†
§ A differential scanning calorimetric apparatus (Mettler DSC 30) and a
polarizing microscope (Olympus BH2) equipped with a Mettler FP82HT
hot stage were used for characterization of 1. X-Ray diffraction measure-
ments were carried out on a Rigaku X-ray Rad 2B system with a heating
stage using Ni-filtered Cu-Ka radiation. IR spectra were recorded on a
JASCO FT/IR-8900m at room temperature using a thin pellet of KBr as the
substrate.
¶ Similar patterns were observed for the N–H stretching band of 1a and 1b
in IR spectra (3351 and 3341 cm21, respectively), whereas the peaks were
split to 3304 and 3251 cm21 for 1c. See ESI† for the IR spectra.
Fig. 2 Isotropization temperatures of the complexes of NaOTf and 1b.
ranges of the resulting mixtures of 1b and NaOTf on heating are
summarized in Fig. 2.
The temperatures decrease drastically with the increase of the
molar ratio of NaOTf to 1b from 0 to 0.3. Further addition of
NaOTf results in the increase of the clearing points. Fan-like
textures characteristic of a hexagonal columnar phase (Colh)
were observed for the mixtures in the ratio of NaOTf to 1b from
0.5 to 2.0. The addition of more than 2.5 mol of NaOTf led to
the phase separation of the sodium salt from the mixture. The X-
ray diffraction pattern of an equimolar complex of NaOTf and
1b at 200 °C showed a sharp inner peak at 45.2 Å (d100), small
peaks at 26.0 and 22.6 Å (d110 and d200, respectively), and a
diffuse halo at 4.1 Å, which confirmed the formation of a
disordered Colh phase.
This phase transition behavior of the complexes can be
explained as follows. The initial decrease of the temperatures
was caused by the co-existence of hydrogen-bonded forms A
and B (Fig. 1) in the smectic order. Further addition of NaOTf
resulted in the formation of discotic aggregates leading to the
induction of a hexagonal columnar order by ion–dipole
interaction through sodium salts and the carbonyl oxygen of the
pterin rings. These aggregates were further stabilized by the
increase of the ion–dipole interactions. The formation of
columnar phases by the complexation of covalently bonded
cyclic molecules with metal salts has been reported.11 However,
to our knowledge, there has been no example of liquid crystals
changing from smectic to columnar phases due to the change of
hydrogen-bonding patterns by the effect of metals.
1 J.-H. Fuhrhop and J. Köning, Membranes and Molecular Assembles:
The Synkinetic Approach, The Royal Society of Chemistry, Cambridge,
1994; J.-M. Lehn, Supramolecular Chemistry, VCH, Weinheim,
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2 Molecular Self-Assembly Organic Versus Inorganic Approaches,
Structure and Bonding, Vol. 96, ed. M. Fujita, Springer, Berlin, 2000.
3 S. D. Hudson, H.-T. Jung, V. Percec, W.-D. Cho, G. Johansson, G.
Ungar and V. S. K. Balagurusamy, Science, 1997, 278, 449; V. Percec,
G. Johansson, G. Ungar and J. Zhou, J. Am. Chem. Soc., 1996, 118,
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4 T. Kato, in Handbook of Liquid Crystals, Vol. 2B. ed. D. Demus, J. W.
Goodby, G. W. Gray, H. W. Spiess and V. Vill, Wiley-VCH, Weinheim,
1998, p. 969; C. M. Paleos and D. Tsiourvas, Angew. Chem., Int. Ed.
Engl., 1995, 34, 1696; T. Kato, Struct. Bonding, 2000, 96, 95; T. Kato
and J. M. J. Fréchet, Macromol. Symp., 1995, 98, 311; N. Zimmerman,
J. S. Moore and S. C. Zimmerman, Chem. Ind., 1998, 604.
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Bossi and G. P. Spada, J. Am. Chem. Soc., 1994, 116, 7064.
6 G. W. Gray and J. W. Goodby, Smectic Liquid Crystals, Leonard Hill,
Glasgow, 1984.
7 The layered self-organized structures of guanine bases were reported,
see: K. Araki, M. Abe, A. Ishizaki and T. Ohya, Chem. Lett., 1995, 359;
G. Gottarelli, S. Masiero, E. Mezzina, S. Pieraccini, G. P. Spada and P.
Mariani, Liq. Cryst., 1999, 26, 965.
8 The cyclic tetramer formation of guanosine derivatives by complexation
with alkaline metals was reported, see: G. Gottarelli, S. Masiero and
G. P. Spada, J. Chem. Soc., Chem. Commun., 1995, 2555.
9 D. Guillon, Struct. Bonding, 1999, 95, 41; R. Kleppinger, C. P. Lillya
and C. Yang, Angew. Chem., Int. Ed. Engl., 1995, 34, 1637; M. Suárez,
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Schmidt and J. H. Wendorff, Liq. Cryst., 1996, 21, 619.
10 The tetramer formation of guanine base was applied for ionophore
formation and enantioselective extraction of amino acid derivatives,
see: S. Tirumala and J. T. Davis, J. Am. Chem. Soc., 1997, 119, 2769; V.
Andrisano, G. Gottarelli, S. Masiero, E. H. Heijne, S. Pieraccini and
G. P. Spada, Angew. Chem., Int. Ed., 1999, 38, 2386.
11 See, for example: A. Liebmann, C. Mertesdorf, T. Plesnivy, H.
Ringsdorf and J. H. Wendorff, Angew. Chem., Int. Ed. Engl., 1991, 30,
1375; V. Percec, D. Tomazos, J. Heck, H. Blackwell and G. Ungar,
J. Chem. Soc., Perkin Trans. 2, 1994, 31.
In summary, we have prepared, for the first time, thermo-
tropic LC folic acid derivatives. In particular, for compound 1b,
the smectic phase can be changed to hexagonal columnar phases
by the ion–dipole interactions. We are further exploring nano-
structures formed by hydrogen-bonded aggregation of folic acid
derivatives.
This work was financially supported by the Shiseido Fund for
Science and Technology and by the Ministry of Education,
Science, Sports, and Culture (Grant-in-Aid No. 12650864).
Notes and references
‡ Compound 1b was prepared by amidation12 of N10-trifluoroacetylpteroic
12 H. A. Godwin, I. H. Rosenberg, C. R. Ferenz, P. M. Jacobs and J.
Meienhofer, J. Biol. Chem., 1972, 247, 2266.
acid with bis[2-(3,4-diundecyloxyphenyl)ethyl] L-glutamate (2b) resulting
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Chem. Commun., 2000, 1899–1900