One-pot synthesis of porphyrin-based [5]rotaxanes

Article abstract of DOI:10.1039/d0ob00906g

A one-pot reaction is used to make a series of [5]rotaxanes. The protocol involves simultaneous threading-followed-by-stoppering to trap a macrocycle (dibenzo[24]crown-8, DB24C8) on an axle to form a mechanically interlocked molecule (MIM)-in this case a

Full text of DOI:10.1039/d0ob00906g

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One-pot synthesis of porphyrin-based
[5]rotaxanes†
Cite this: DOI: 10.1039/d0ob00906g
Pablo Martinez-Bulit,
Benjamin H. Wilson
and Stephen J. Loeb
*
A one-pot reaction is used to make a series of [5]rotaxanes. The protocol involves simultaneous thread-
ing-followed-by-stoppering to trap a macrocycle (dibenzo[24]crown-8, DB24C8) on an axle to form a
mechanically interlocked molecule (MIM) – in this case a rotaxane – and the condensation of an aldehyde
with a pyrrole to form a porphyrin precursor. For each [5]rotaxane, a different combination of recognition
site and stoppering group was used; the protonation state of the [5]rotaxane can be used to generate
different co-conformational states for each [5]rotaxane making these systems potential multi-state
switches for further study in solution or the solid-state.
Received 30th April 2020,
Accepted 26th May 2020
DOI: 10.1039/d0ob00906g
rsc.li/obc
and chromophores might be used to understand and replicate
electron-transfer in photosynthetic systems.26,27 Goldup and
Introduction
The synthesis of mechanically interlocked molecules (MIMs) co-workers believe that MIMs with porphyrins can be incorpor-
with higher degrees of complexity and an increased number of ated into “smart” materials and have potential to be used in
components has gained attention in recent years. [n]Rotaxanes catalysis.3
with porphyrin moieties have been synthesized as molecular
Lindsey’s method for the preparation of meso-substituted
compressors/receptors,1 tweezers,2 mechanical picket-fences,3 porphyrins has a high tolerance for the functionalization of
scaffolds to pre-organize polyynes,4 precursors for the syn- the aldehyde precursor and the yields are higher (up to 50%
thesis of porphyrin nanorings,5 molecules for anion reco- yield) compared to other synthetic methods.28,29 Here, we
gnition,6 systems for electron-transfer,7,8 catalytic models,9 employ this method for the synthesis of symmetrical [5]rotax-
and potential molecular switches.10 Other interesting MIMs anes in a one-pot reaction. This reaction works as a multi-
with porphyrins and/or high compositional complexity have capping method, where commonly used recognition sites are
also been reported in the literature.5,11–25 Most of these employed to direct the molecular recognition in conjunction
examples require a multi-step pathway where the interlocked with simple crown ether wheels to create [5]rotaxanes. We
components are first individually assembled and then fused believe this procedure represents one of the most direct routes
together to form the final product. Also, many of the assembly for obtaining MIM architectures with a large number of
processes are driven by non-covalent interactions and/or components.
coordination bonds. If more efficient methods could be found
for covalent synthesis, the potential to explore their chemistry
and develop functional systems with these molecules would be
increased.
Results and discussion
Synthesis
The incorporation of porphyrin cores into mechanically
interlocked architectures has been of interest due to the wide
range of applications of porphyrins (e.g. artificial photosyn-
thesis, catalysis, light harvesting, molecular photonics) and
their robustness as supramolecular building blocks. Sauvage
and co-workers proposed that systems with mechanical bonds
Scheme 1 shows the general procedure followed for the syn-
thesis of [5]rotaxanes R1–R6. First, an aldehyde thread with a
recognition site is prepared and then in a one-pot reaction, it
is combined with a suitable macrocyclic ring – in this case a
24-membered crown ether – and pyrrole to form a porphyrino-
gen that can be oxidized to yield the final [5]rotaxane. Using
this method, it is possible to vary the nature of the recognition
site, the stopper groups or the macrocyclic wheel without alter-
ing the overall synthetic pathway.
Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON,
N9B 3P4, Canada. E-mail: loeb@uwindsor.ca
†Electronic supplementary information (ESI) available: Full details of all syn-
thesis and characterisation, details of SCXRD experiments. CCDC 2000087. For
ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/
d0ob00906g
Porphyrin-[5]rotaxanes R1–R6 were isolated in moderate
yields (10–30%) from the reaction between aldehyde axles 1–6,
dibenzo[24]crown-8 (DB24C8) and pyrrole in CH2Cl2 as out-
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Table 1 Associations constants for[2]pseudorotaxane formation
between precursor aldehydes 1–6 and DB24C8
Axle
Association constanta (M−1
)
1
2
3
4
5
6
2.10 × 102
1.55 × 103
2.50 × 102
1.30 × 103
>104 b
>104 b
a Measured in CD2Cl2 solution at 300 K and a concentration of 10−3
M. Error estimated to be ∼10%. b Only bound axle was observed.
gnition process, with association constants at least two orders
of magnitude higher. The substituents on the axle might also
affect the association constant by modifying the electronic pro-
perties (e.g. EWG on aldehyde 1 vs. EDG on aldehyde 4).31 It
should also be noted that the condensation reaction between
the [2]pseudorotaxane aldehydes and pyrrole does not seem to
be greatly affected by any of the modifications studied, and the
differences in yield can primarily be attributed to the
efficiency of the purification procedure.
Characterisation
The [5]rotaxanes were characterized by NMR and UV-Vis spec-
troscopy, mass spectrometry, and single-crystal X-ray diffrac-
tion for [R1-H6][BF4]6. The mass spectra of rotaxanes R1–R6 all
show a molecular ion corresponding to [M + 4H]4+ and the
isotope patterns are in good agreement with simulations (see
ESI, Fig. S34†). Additional molecular ions corresponding to [M
+ 2H]2+, [M + 3H]3+, [M + 5H]5+, and [M + 6H]6+ were observed
in some cases and provide additional evidence that the macro-
cycle, and not a polymeric chain, is the isolated product. For
R1, an additional spectrum using matrix-assisted laser desorp-
tion ionization (MALDI) was collected and the molecular ion
corresponding to [M + H]+ was observed (see ESI, Fig. S33†).
Except for R4, for which it was not possible to completely
assign all the peaks, due to aggregation effects, the rotaxanes
Scheme 1 A description of the one-pot approach to the synthesis of
porphyrin-based [5]rotaxanes.
1
were successfully characterized by H NMR spectroscopy. They
exhibit the characteristic peaks of a meso-substituted por-
lined in Scheme 1. As for most porphyrin syntheses using phyrin with D4h symmetry and integration of the peaks from
Lindsey’s method, many of the compounds produced are oli- the different components – porphyrin, axle and wheel –
gomers and polymers with the same basic units as the target further corroborates the formation of fully occupied [5]rotax-
porphyrins. Thus, attempts to estimate NMR yields were anes with the incorporation of four interlocked DB24C8 rings
thwarted by the lack of unique resonances and overlapping per porphyrin unit. Characteristic splitting due to MIM for-
peaks. The use of CH2Cl2 increases the non-covalent inter- mation is observed for both –NH– and –CH2– peaks on the
actions between the crown ether ring and the protonated axle. axle, as well as shifting and splitting of the various proton
DB24C8 was selected for this work due to its propensity to environments on the DB24C8 rings, indicating hydrogen-
induce crystallinity and is used in excess to ensure complete bonding and π-stacking interactions with the recognition site.
complexation of the axles prior to condensation. Subsequent The proton resonances of the porphyrin core (β-pyrrole and
oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone core pyrrolic) for the aniline-based rotaxanes do not change
(DDQ) makes the porphyrinogen permanently interlocked.
substantially upon rotaxane formation, however they are very
The nature of the recognition site has the most noticeable sensitive to protonation changes of both the recognition sites
impact on initial [2]pseudorotaxane formation30 and eventual and the central pyrrole units. For the benzimidazole-based
[5]rotaxane formation (Table 1). The benzimidazolium motif is MIMs, substantial shifting of the β-pyrrole and aryl protons
much more efficient than anilinium in the molecular reco- adjacent to the porphyrin core is observed.
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Fig. 2 UV-vis absorption spectra showing the titration of [R1-H6]6+
with DBU (top). Photographs of the accompanying changes in colour
upon deprotonation (bottom).
Fig. 1 A ball-and-stick representation of the single-crystal X-ray struc-
ture of [R1-H6][BF4]6. O-Atoms = red, N-atoms = blue, C-atoms = black,
H-atoms = white, porphyrin core and axle bonds = blue, DB24C8 bonds
= red. BF4− anions are omitted for clarity.
R4 was also studied by UV-Vis spectroscopy and the
addition of the electron-rich trityl groups has an effect on the
energy levels of the porphyrin. The QIV band is red shifted by
about 125 nm, and some additional bands are observed (see
ESI, Fig. S32†). This has been described as the hyper-porphyrin
effect and is caused by charge transfer transitions from the
electron-rich trityl π orbital to the porphyrin π* orbital.33,34
Finally, the titration curve for cationic R5 with DBU shows the
same type of behaviour as R1, with the benzimidazole core
π–π* transition observed in the 330–360 nm region (see ESI,
Fig. S31†).
The single-crystal X-ray structure of [R1-H6][BF4]6 was deter-
mined and is shown in Fig. 1.‡ The crown ether adopts a
C-conformation allowing π-stacking interactions with the elec-
tron-deficient isophthalic fragment (3.8 Å). Attempts to obtain
the crystal structure of neutral R1 and the other [5]rotaxanes
for comparison purposes were unsuccessful (see ESI,
Fig. S29†).
A characteristic UV-Vis-NIR spectrum for a porphyrin with
meso-substitution was observed for rotaxanes R1–R6. The por-
phyrin P1 (same core as R1 but without interlocked DB24C8)
was synthesized in order to compare the spectrum to that of
R1; the two spectra are almost identical, with only minor
changes (<5 nm) in the absorption maxima (see ESI,
Fig. S30†).
Upon protonation or metalation, the spectrum is simplified
to two Q bands instead of four, as expected.32 Titration of R1
with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) shows the
classic profile for a porphyrin, with the blue shifting of the
Soret band and the appearance of the QII and QIII bands
because of the deprotonation of the central pyrrole nitrogen
atoms and reduction in symmetry from D4h to D2h (Fig. 2). No
additional equilibria from the deprotonation of the –NH– reco-
gnition sites are observed. Analysis of the data suggests that
this is a cumulative equilibrium and no stepwise binding equi-
libria are detected.
Co-conformational changes
Previous studies of MIMs containing DB24C8 or other rings
capable of π-stacking have shown that the conformation of the
macrocycle, e.g. folded S-shape, C-shape or open for DB24C8
(Fig. 3), is dependent on the charge state of the recognition
unit and can be inferred from the J-couplings and chemical
shifts of characteristic protons.30,35 Additionally, if the macro-
cycle is desymmetrized it can be incorporated into what is
known as a flip-switch system where the two co-conformations
‡Crystallographic data for the structure reported in this paper have been de-
posited with the Cambridge Crystallographic Data Centre as supplementary pub-
lication no. CCDC 2000087.†
Fig. 3 Three possible conformations commonly adopted by DB24C8
when acting as the wheel component of a rotaxane.
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can be interconverted.36–38 If such large amplitude confor-
mational switches could be organized into arrays – e.g. four
per porphyrin platform – and could operate over a large spatial
area, this would represent a realistic starting point for their
incorporation into ordered systems where they might function
coherently.
Noting that in the solid-state structure of [R1-H6]6+ DB24C8
adopts a C-shaped conformation and π-stacks with the iso-
phthalic stopper groups, it was of interest to investigate
whether any co-conformational changes occur with variation
in pH, since the neutral aniline axle is much less likely to be
involved in π-stacking. Accordingly, [R1-H6]6+ was titrated with
DBU, and changes monitored by 1H NMR spectroscopy
(Fig. 4).
The resulting spectra show that some of the aromatic
environments on both DB24C8 and the isophthalic stopper
groups become less shielded (∼1 ppm) with addition of base.
Along with a concomitant change in the second-order coupling
constant, this provides evidence that π-stacking between the
axle and wheel is lost upon neutralization of the recognition
site. However, it is not possible to assign all the peak in the
aromatic region to π-stacking, since there are concomitant
shifts due to changes in protonation state and the influence of
one of these factors with respect to the other cannot be com-
pletely deconvoluted. The chemical shift of the glycolic crown
ether protons and the splitting patterns are also influenced by
the protonation state and upon neutralization these peaks are
shifted slightly upfield, consistent with the loss of hydrogen
bonding interactions. Thus, a pH driven structural change
occurs from the C-shaped co-conformation observed for
DB24C8 in [R1-H6]6+ to an open form in neutral [R1]
(Scheme 2).
Scheme 2 Interconversion between two co-conformations of the [5]
rotaxane R1 and [R1-H6]6+ via acid/base chemistry.
Nuclear Overhauser effect spectroscopy (NOESY) 1H NMR
experiments were conducted to determine if through space
correlations could be used as an additional probe of the MIM
co-conformation. Fig. 5 shows a comparison between 1H
NOESY spectra of [R1-H6]6+ and R1. Although no direct NOE
cross-peaks are observed between the aromatic protons of
DB24C8 and the axle – likely since these distances are >4 Å –
the intensity of the NOE correlations between the glycolic
protons and the protons near or on the recognition site infer a
tighter (i.e. folded) conformation of the ring in this region.
The absence of NOE cross-peaks between the β-pyrrole protons
and the aromatic DB24C8 and the positive cross-peaks with
the glycolic protons indicate it is likely that the DB24C8 is in
the C-conformation around the isophthalic stopper as
Fig. 4 1H NMR spectra showing the titration of cationic [R1-H6]6+ with
1 to 6 equivalents of DBU. Labelling is shown in Scheme 1.
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Fig. 6 Photograph of neutral R1 (left) and protonated [R1-H6]6+ (right)
under UV light (365 nm) radiation.
Conclusions
We have developed a synthetic pathway for the fabrication of
large multi-switchable, porphyrin-based MIMs using only a
few synthetic steps for axle formation and a one-pot reaction
for the formation of [5]rotaxanes. This methodology allows for
variation of the recognition sites, the substituent groups on
the meso position, and the macrocyclic wheels and comp-
lements other dynamic covalent chemistry approaches for
making complex MIM structures, such as Chiu’s imine tem-
plates40 and Takata’s disulfide chemistry.41 With this degree of
versatility, it should be possible to build a wide range of
mechanically interlocked architectures and fine-tune their
electronic properties for specific applications.
Fig. 5 1H–1H NOESY spectra (500 MHz, CDCl3, 298 K, mixing time
400 ms) of neutral R1 (top) and protonated [R1-H6]6+ (bottom).
Future studies will be aimed at the incorporation of [5]
rotaxanes into crystalline solids. To that end, it should be
noted that [5]rotaxanes R1–R3 and R6 presented herein are
esters that can easily be converted to carboxylic acids and used
as linkers for the synthesis of metal–organic framework (MOF)
materials. If the switching behaviour observed in solution can
be translated into a solid-state material, systems with emerging
photophysical and dynamic properties could be achievable.
observed in the X-ray structure of [R1-H6]6+. The same NOESY
experiment performed with R3, but using the peaks corres-
ponding to the methyl group stoppers produced similar corre-
lations (see ESI, Fig. S13 and S14†).
For [R5-H6]6+, protons corresponding to the benzimidazole
core and the 4,7-phenyl groups are in close spatial proximity to
those of the aromatic rings of a DB24C8 molecule if a
C-shaped conformation is adopted. On the other hand, if the
crown is in an open conformation, the same protons will have
no through-space correlations. Correlation Spectroscopy
(COSY) and Total Correlation Spectroscopy (TOCSY) were used
to fully assign the resonances of the 1H spectrum (see ESI,
Conflicts of interest
There are no conflicts to declare.
1
Fig. S20 and S21†) and then H–1H NOESY was used to deter-
mine if the selected resonances could be used as probes for
co-conformational changes. Broadening of some peaks due to
aggregation makes full the interpretation of the protonated
spectrum challenging, but overall the spectroscopic evidence
infers that acid–base conformational switching also occurs
between [R5-H6]6+ and R5.
Finally, the fluorescence of benzimidazolium cations can
be used to visually (qualitatively) identify the protonation state
of the system and thus indirectly determine the conformation
of the DB24C8 macrocycles. Fig. 6 shows a photograph of
neutral R5 and charged [R5-H6]6+ under long wavelength
(365 nm) UV light radiation. The optical switching properties
of interlocked molecules have been reported and used in the
construction of a molecular abacus39 and non-linear optic
devices.
Acknowledgements
S. J. L. acknowledges financial support for this work from the
Natural Sciences and Engineering Research Council of Canada
through their Discovery Grant and Canada Research Chair
Programs.
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