Chirality Synchronization of Hydrogen-Bonded Complexes of Achiral N-Heterocycles

Article abstract of DOI:10.1002/anie.201609252

2,4-Diamino-6-phenyl-1,3,5-triazines carrying a single oligo(ethylene oxide) (EO) chain form an optically isotropic mesophase composed of a conglomerate of macroscopic chiral domains with opposite sense of chirality even though the constituent molecules are achiral. This mesophase was proposed to result from the helical packing of hydrogen-bonded triazine aggregates, providing long-range chirality synchronization. The results provide first evidence for macroscopic achiral symmetry breaking upon conglomerate formation in an amorphous isotropic phase formed by hydrogen-bonded associates of simple N-heterocycles that are related to prebiotic molecules.

Full text of DOI:10.1002/anie.201609252

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International Edition: DOI: 10.1002/anie.201609252
German Edition: DOI: 10.1002/ange.201609252
Chirality Very Important Paper
Chirality Synchronization of Hydrogen-Bonded Complexes of Achiral
N-Heterocycles
Jens Buchs, Laura Vogel, Dietmar Janietz,* Marko Prehm, and Carsten Tschierske*
Abstract:
2,4-Diamino-6-phenyl-1,3,5-triazines
carrying
Herein, we report the first observation of spontaneous
macroscopic symmetry breaking in an isotropic mesophase of
simple hydrogen-bonding N-heterocycles functionalized with
a polar chain, which renders them compatible with aqueous
self-assembly. These molecules are based on a 4-phenyl-2,6-
diamino-1,3,5-triazine core[23] fitted with a single tetra(ethy-
lene glycol) chain, which terminates in either a methoxy
group (3a) or in a hydroxy (3b; Scheme 1). It is shown that
hydrogen bonding leads to chiral aggregates that undergo
long-range chirality synchronization in the isotropic bulk
state, which is associated with the formation of conglomerates
of chiral domains with opposite handedness.
a single oligo(ethylene oxide) (EO) chain form an optically
isotropic mesophase composed of a conglomerate of macro-
scopic chiral domains with opposite sense of chirality even
though the constituent molecules are achiral. This mesophase
was proposed to result from the helical packing of hydrogen-
bonded triazine aggregates, providing long-range chirality
synchronization. The results provide first evidence for macro-
scopic achiral symmetry breaking upon conglomerate forma-
tion in an amorphous isotropic phase formed by hydrogen-
bonded associates of simple N-heterocycles that are related to
prebiotic molecules.
The synthesis of compounds 3 is outlined in Scheme 1 (see
the Supporting Information for details). Both compounds 3a
and 3b exhibit a single-phase transition (Scheme 1, bottom
and Figure 1a), associated with significant transition enthal-
pies, between an isotropic liquid and an amorphous viscous
mesophase, which is optically isotropic and therefore appears
completely dark between crossed polarizers. It appears to be
a glassy frozen liquid with smooth phase boundaries (Fig-
ure 1b,c), and no crystallization could be detected optically
or by calorimetric investigations over several heating and
cooling cycles (see Figure 1a) even after prolonged storage.
Only during the first heating scan, a very weak and broad
exotherm (see the Supporting Information, Figure S1) could
be detected between 50 and 808C, which could be caused by
some partial crystallization of the as-synthesized sample.
C
hirality is a unique signature of living matter[1] and an
intriguing phenomenon in various biomimetic and artificial
systems.[2] Enantioselective synthesis, catalysis, and autoca-
talysis have successfully been developed in recent decades for
the synthesis of enantiopure molecules from achiral (prochi-
ral) precursors.[3] Nowadays, the focus has shifted to the
spontaneous emergence of homogeneous chirality in ordered
assemblies formed in supramolecular systems[4–7] by bulk
crystallization (e.g., Viedma ripening)[8] and the self-assembly
of achiral molecules at interfaces[9] and in helical aggre-
gates.[10–13] However, surprisingly, spontaneous symmetry
breaking was recently also observed in liquid crystalline
phases,[14,15] ranging from lamellar phases[16] to cubic,[17,18]
columnar,[14,15,19] and nematic phases,[20] and even in isotropic
liquids of achiral compounds.[14,21] This dynamic route to
macroscopic chirality in fluid systems was discussed as
a
fundamentally new source of chirality in prebiotic
fluids.[14,21,22] However, it must also be noted that all pre-
viously reported molecules forming these symmetry-broken
fluids are lipophilic (hydrophobic) molecules combining
extended aromatic units with a number of long aliphatic
chains (bent-core mesogens,[12,15–17,20] di- and oligomeso-
gens,[13,20] and polycatenar molecules),[14,18,21] which are quite
distinct from the molecules expected to have been involved in
the chirogenesis of prebiotic aqueous fluids.[22]
[*] Dr. J. Buchs, Dipl.-Chem. L. Vogel, Priv.-Doz. Dr. D. Janietz
Fraunhofer Institute for Applied Polymer Research
Geiselbergstrasse 69, 14476 Potsdam-Golm (Germany)
E-mail: dietmar.janietz@iap.fraunhofer.de
Dr. M. Prehm, Prof. C. Tschierske
Institute of Chemistry, Organic Chemistry
Martin-Luther-University Halle-Wittenberg
Kurt-Mothes-Strasse 2, 06120 Halle/Saale (Germany)
E-mail: carsten.tschierske@chemie.uni-halle.de
Scheme 1. Synthesis of compounds 3 and their phase-transition tem-
peratures (T [8C]: on heating: top lines, cooling: bottom lines; peak
temperatures were taken from DSC heating and cooling scans at
10 KminÀ1) with associated transition enthalpies [kJmolÀ1] in square
brackets. IC*=isotropic conglomerate composed of chiral domains,
Iso=isotropic liquid, Ts=para-toluenesulfonyl.
Supporting information for this article can be found under:
http://dx.doi.org/10.1002/anie.201609252.
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namically stable (enantiotropic) phase. The relatively sharp
DSC peaks exclude a glass transition and are in line with
a reversible first-order phase transition with about 20 K
hysteresis on cooling. In optical investigations, the phase
transition was only recognized by the emergence/disappear-
ance of chiral domains (see below), associated with a signifi-
cant change of viscosity. There are no indications of any
additional (birefringent) phases occurring around this tran-
sition.
In the isotropic mesophases of both compounds 3, distinct
dark and bright domains became visible upon rotating the
polarizer by a small angle (3–58) either clockwise or
anticlockwise out of the precise 908 position. When the
polarizer was rotated in the opposite direction, the brightness
of the domains was reversed (Figure 1b,c and Figure S2).
Rotation of the sample between the polarizers did not lead to
any changes. These observations unambiguously confirm that
in the distinct areas, the plane of polarized light is rotated into
opposite directions, which means that this optically isotropic
mesophase is composed of a conglomerate of macroscopic
chiral domains with opposite senses of chirality (IC*
phase).[14,15,21]
The X-ray diffraction patterns of 3 in this conglomerate
phase display a pronounced but relatively broad reflection in
the small-angle region (Figure 2 and Figure S3) correspond-
ing to distances of d = 4.92 nm for compound 3a and d =
4.63 nm for 3b. The SAXS diffractogram of methyl-termi-
nated triazine 3a reveals that the profile of the small-angle
reflection is asymmetric. The intense reflection at 2q = 1.808 is
superimposed by an additional maximum located at about
2q = 2.658, corresponding to d = 3.33 nm (Figure S4). This
value does not match a higher-order reflection of a lamellar
structure. The SAXS pattern could be regarded as a hint on
the local lamellar organization with additional modulations.
The d values are close to twice the molecular length (3a:
L
mol = 2.77 nm; 3b: Lmol = 2.60 nm) with d/(2Lmol) = 0.89 for
both compounds, confirming a bilayer organization. The small
difference is assumed to arise from chain flexibility and
partial chain interdigitation. In the wide-angle region, there is
broad scattering for both compounds 3, which could be fitted
to three maxima (Figure 2b and Table S1). The most intense
wide-angle scattering with a maximum at about 0.45 nm was
attributed to the mean distance between the oligo(ethylene
oxide) (EO) chains. The two less pronounced maxima around
0.35 nm and 0.53 nm most probably result from a crystal-like
packing of the heteroaromatic entities. The diffuse nature and
the line broadening of the wide-angle scatterings, however,
reveal crystalline microdomains with limited correlation
length.[24,25] This presumption is in line with a cluster size of
about 30 nm for compound 3a, estimated from the full width
at half-maximum of the small-angle scattering at the lowest
angle using the Scherrer equation and assuming KS = 1.[26] In
the 2D patterns of samples with attempted surface alignment,
the scatterings always form closed rings with completely
uniform density distributions (Figure 2a). This behavior was
assumed to arise from a disordered mesoscale phase structure,
leading to the isotropic optical appearance and the broad-
ening of the X-ray scatterings. It is noteworthy that above the
phase transition temperatures determined for both com-
Figure 1. a) DSC traces (second heating and cooling scans with
10 KminÀ1) of 3b. The first heating curve is shown in Figure S1; all
other heating and cooling curves are identical to those shown here.
b,c) Chiral domains (dark/bright) with opposite handedness observed
for compound 3a in the optically isotropic mesophase (IC*) at 908C
between slightly uncrossed polarizers (Æ58). The contrast in (b) and
(c) was enhanced to improve the visibility of the domains. Double-
headed arrows indicate the orientation of polarizer and analyzer;
single-headed arrows indicate the smooth phase boundaries to air.
However, if there was a crystalline state, it would have
a melting point below the isotropic mesophase range. The
isotropic mesophase is therefore considered as a thermody-
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Figure 3. Temperature-dependent FTIR spectra of 3b obtained upon
cooling from the isotropic liquid to the conglomerate phase.
IR investigations that the formation of the conglomerate is
accompanied by hydrogen-bond formation between the
amino-substituted nitrogen heterocycles of triazines 3. The
docking of an exocyclic amino function preferably proceeds at
the more accessible endocyclic N3 nitrogen atoms of the
triazine heterocycles,[28] whereas hydrogen bonding involving
the nitrogen atoms N1 and N5 in close proximity to the bulky
phenyl moiety should be less favorable for steric reasons.
Hence, primarily double-hydrogen-bonded dimeric aggre-
gates should result as shown in Figure 4a. The dense parallel
side-by-side alignment of the dimers results in a hydrogen-
bonded aromatic bilayer structure with the highly ordered
hydrogen-bonded blocks located in the center being sepa-
rated by the flexible EO chains (Figure 4b).[29] The size of the
bilayer aggregates is strongly limited to bundles (ribbon
segments) involving about six layers (as calculated from the
correlation length, see above), which are disordered and give
rise to the isotropic optical appearance. The limited size of
these nanocrystallites is likely due to the distortion of the
bulky EO chains as well as the developing helical twist.[25]
Concerning the possible origin of chirality, the formation
of additional hydrogen bonds to the N1 and N5 nitrogen
atoms between the self-assembled dimers can induce a twist
of the benzene–triazine bond. A small helical twist might also
arise from the double hydrogen bridges between the triazines
3 themselves. For example, an angle of 9.18 between the
average planes of the diaminotriazines was reported upon
association according to the hydrogen-bonding motif shown
in Figure 4a.[28] It should be noted that structurally related
diamino-1,3,5-triazines with linear and achiral hydrophobic
chains, namely either n-alkyl or semiperfluorinated n-alkyl
chains, do not manifest any macroscopic chirality.[30] It
appears that the bulkiness of the non-linear (conformation-
ally disordered or helical) EO chains at both ends of the
hydrogen-bonded cores prohibits the parallel alignment of
these cores and thus induces a small helical twist between
them.[14] The cooperative action of the distinct sources of
chirality leads to the helical deformation of the bilayer
ribbons (Figure 4c). As helical organization is incompatible
with long-range periodic order, the formation of a long-range
lattice is prohibited and restricted to the formation of
nanocrystallites whereas amorphous regions are retained
Figure 2. a) XRD pattern of the conglomerate phase of compound 3a
at 908C. b) 2q Scan over this pattern; the inset shows the wide-angle
region with splitting into three maxima.
pounds 3 by DSC, the small-angle reflections are completely
lost, and the splitting of the wide-angle scatterings is replaced
by a single diffuse halo located at about 2q = 208 (d = 0.44 nm;
see Figure S3). This indicates the melting of local structure
with formation of an achiral isotropic liquid (Iso) above the
transition temperature.
Representative FTIR transmission spectra of 2,4-di-
amino-1,3,5-triazine 3b recorded within the liquid and in the
conglomerate state are displayed in Figure 3. In the liquid
state, the triazine shows absorption bands at n = 3210, 3340,
and 3480 cmÀ1 in the region of the NH2 stretching vibra-
tions,[27] which were attributed to non-associated triazine
molecules. Upon cooling into the temperature range of the
conglomerate, the absorption at n = 3210 cmÀ1 was shifted to
3230 cmÀ1 whereas the two other bands maintained their
positions. Two new absorption bands became visible for the
triazine in the conglomerate, peaking at n = 3143 and
3424 cmÀ1. The spectral changes are reversible upon heating
and cooling and strongly correlate with the phase transition
temperatures determined by DSC. It can be deduced from the
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Figure 5. Compound 4.
expected to distort or prevent the formation of sufficiently
large aggregates.
In summary, experimental evidence for a self-sustaining
macroscopic desymmetrization event in systems composed of
achiral molecules involving a hydrogen-bond-forming nitro-
gen heterocycle has been described. The molecules are very
distinct from the previously described ones, such as rigid bent-
core,[15,16,20] polycatenar,[14,18,21] and amphiphilic molecules.[10]
The most interesting feature is that these hydrogen-bond-
forming heterocycles with a polar EO tail bear structural
similarities to the biologically relevant nucleobases, which are
also hydrogen-bond-forming N-heterocycles, but connected
by polar ribose units and with phosphate units replacing the
polar EO chains.[34] This shows that it is in principle possible
that spontaneous chiral self-assembly of simple achiral
hydrogen-bonded heterocycles could be considered as
a route for the development of homochirality in prebiotic
systems.
Acknowledgements
This work was supported by the BMBF Initiative “Spitzen-
forschung und Innovation in den neuen Lꢀndern” within the
cooperative project “Taschentuchlabor—Impulszentrum fꢁr
Integrierte Bioanalyse” (FKZ 03IS2201C).
Figure 4. a) Double hydrogen bonding between the twofold amino-
substituted N-heterocycles of the 1,3,5-triazines 3. b) CPK model
showing three dimeric hydrogen-bonded associates of 3a with parallel
alignment of the central rod-like cores and stretched conformations for
the EO chains. c) Chiral synchronization of hydrogen-bonded dimers 3
by helical deformation of bilayer ribbon segments.
Keywords: chirality · conglomerates · heterocycles ·
hydrogen bonds · self-assembly
between the nanocrystallites.[31] The transmission of chirality
over macroscopic ranges (ca. 10 mm) could be explained by
the slow formation of the primary seeds, coupled with rapid
dendritic growth,[32] transferring chirality (helicity) over
macroscopic distances, but limiting periodic order to the
nanometer range. As the size of the uniformly aligned areas is
much smaller than the wavelength of light, an amorphous
optically isotropic phase results. The tendency of the terminal
EO tails to adopt helical conformations[33] could probably
contribute to the chirality synchronization process by sup-
porting chirality transfer.
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Manuscript received: September 21, 2016
[26] A. Guinier, X-ray diffraction, Freeman, San Fransisco, 1963.
Final Article published: && &&, &&&&
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Communications
Chirality
Spontaneous symmetry breaking was
achieved with simple achiral hydrogen-
bonded heterocycles that are related to
prebiotic molecules by formation of con-
glomerates of chiral domains with oppo-
site handedness. This optically isotropic
mesophase was proposed to result from
the helical packing of the hydrogen-
bonded triazine aggregates.
J. Buchs, L. Vogel, D. Janietz,* M. Prehm,
C. Tschierske*
&&&& — &&&&
Chirality Synchronization of Hydrogen-
Bonded Complexes of Achiral N-
Heterocycles
6
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