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

Pablo Martinez-Bulit , Benjamin H. Wilson and Stephen J. Loeb *
Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON N9B 3P4, Canada. E-mail: loeb@uwindsor.ca

Received 30th April 2020 , Accepted 26th May 2020

First published on 27th May 2020


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 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.


Introduction

The synthesis of mechanically interlocked molecules (MIMs) with higher degrees of complexity and an increased number of components has gained attention in recent years. [n]Rotaxanes with porphyrin moieties have been synthesized as molecular compressors/receptors,1 tweezers,2 mechanical picket-fences,3 scaffolds to pre-organize polyynes,4 precursors for the synthesis of porphyrin nanorings,5 molecules for anion recognition,6 systems for electron-transfer,7,8 catalytic models,9 and potential molecular switches.10 Other interesting MIMs with porphyrins and/or high compositional complexity have also been reported in the literature.5,11–25 Most of these examples require a multi-step pathway where the interlocked components are first individually assembled and then fused together to form the final product. Also, many of the assembly processes are driven by non-covalent interactions and/or 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.

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 photosynthesis, catalysis, light harvesting, molecular photonics) and their robustness as supramolecular building blocks. Sauvage and co-workers proposed that systems with mechanical bonds and chromophores might be used to understand and replicate electron-transfer in photosynthetic systems.26,27 Goldup and co-workers believe that MIMs with porphyrins can be incorporated into “smart” materials and have potential to be used in catalysis.3

Lindsey's method for the preparation of meso-substituted porphyrins has a high tolerance for the functionalization of the aldehyde precursor and the yields are higher (up to 50% yield) compared to other synthetic methods.28,29 Here, we employ this method for the synthesis of symmetrical [5]rotaxanes in a one-pot reaction. This reaction works as a multi-capping method, where commonly used recognition sites are employed to direct the molecular recognition in conjunction with simple crown ether wheels to create [5]rotaxanes. We believe this procedure represents one of the most direct routes for obtaining MIM architectures with a large number of components.

Results and discussion

Synthesis

Scheme 1 shows the general procedure followed for the synthesis 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 porphyrinogen 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 altering the overall synthetic pathway.
image file: d0ob00906g-s1.tif
Scheme 1 A description of the one-pot approach to the synthesis of porphyrin-based [5]rotaxanes.

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 outlined in Scheme 1. As for most porphyrin syntheses using Lindsey's method, many of the compounds produced are oligomers and polymers with the same basic units as the target porphyrins. Thus, attempts to estimate NMR yields were thwarted by the lack of unique resonances and overlapping peaks. The use of CH2Cl2 increases the non-covalent interactions between the crown ether ring and the protonated axle. DB24C8 was selected for this work due to its propensity to induce crystallinity and is used in excess to ensure complete complexation of the axles prior to condensation. Subsequent oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) makes the porphyrinogen permanently interlocked.

The nature of the recognition site has the most noticeable impact on initial [2]pseudorotaxane formation30 and eventual [5]rotaxane formation (Table 1). The benzimidazolium motif is much more efficient than anilinium in the molecular recognition 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 properties (e.g. EWG on aldehyde 1vs. 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.

Table 1 Associations constants for[2]pseudorotaxane formation between precursor aldehydes 1–6 and DB24C8
Axle Association constanta (M−1)
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.
1 2.10 × 102
2 1.55 × 103
3 2.50 × 102
4 1.30 × 103
5 >104[thin space (1/6-em)]b
6 >104[thin space (1/6-em)]b


Characterisation

The [5]rotaxanes were characterized by NMR and UV-Vis spectroscopy, mass spectrometry, and single-crystal X-ray diffraction 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 macrocycle, and not a polymeric chain, is the isolated product. For R1, an additional spectrum using matrix-assisted laser desorption 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 were successfully characterized by 1H NMR spectroscopy. They exhibit the characteristic peaks of a meso-substituted porphyrin with D4h symmetry and integration of the peaks from the different components – porphyrin, axle and wheel – further corroborates the formation of fully occupied [5]rotaxanes with the incorporation of four interlocked DB24C8 rings per porphyrin unit. Characteristic splitting due to MIM formation is observed for both –NH– and –CH2– peaks on the axle, as well as shifting and splitting of the various proton environments on the DB24C8 rings, indicating hydrogen-bonding and π-stacking interactions with the recognition site. The proton resonances of the porphyrin core (β-pyrrole and core pyrrolic) for the aniline-based rotaxanes do not change substantially upon rotaxane formation, however they are very sensitive to protonation changes of both the recognition sites and the central pyrrole units. For the benzimidazole-based MIMs, substantial shifting of the β-pyrrole and aryl protons adjacent to the porphyrin core is observed.

The single-crystal X-ray structure of [R1-H6][BF4]6 was determined and is shown in Fig. 1. The crown ether adopts a C-conformation allowing π-stacking interactions with the electron-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).


image file: d0ob00906g-f1.tif
Fig. 1 A ball-and-stick representation of the single-crystal X-ray structure 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.

A characteristic UV-Vis-NIR spectrum for a porphyrin with meso-substitution was observed for rotaxanes R1–R6. The porphyrin 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– recognition sites are observed. Analysis of the data suggests that this is a cumulative equilibrium and no stepwise binding equilibria are detected.


image file: d0ob00906g-f2.tif
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).

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).

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 macrocycle is desymmetrized it can be incorporated into what is known as a flip-switch system where the two co-conformations can be interconverted.36–38 If such large amplitude conformational 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.
image file: d0ob00906g-f3.tif
Fig. 3 Three possible conformations commonly adopted by DB24C8 when acting as the wheel component of a rotaxane.

Noting that in the solid-state structure of [R1-H6]6+DB24C8 adopts a C-shaped conformation and π-stacks with the isophthalic 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).


image file: d0ob00906g-f4.tif
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.

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 completely 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).


image file: d0ob00906g-s2.tif
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 observed in the X-ray structure of [R1-H6]6+. The same NOESY experiment performed with R3, but using the peaks corresponding to the methyl group stoppers produced similar correlations (see ESI, Fig. S13 and S14).


image file: d0ob00906g-f5.tif
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).

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, Fig. S20 and S21) and then 1H–1H NOESY was used to determine 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.


image file: d0ob00906g-f6.tif
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 complements other dynamic covalent chemistry approaches for making complex MIM structures, such as Chiu's imine templates40 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.

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.

Conflicts of interest

There are no conflicts to declare.

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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Footnotes

Electronic supplementary information (ESI) available: Full details of all synthesis and characterisation, details of SCXRD experiments. CCDC 2000087. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/d0ob00906g
Crystallographic data for the structure reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC 2000087.

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