Molecular rotor based on an oxidized resorcinarene

Abstract

Molecular rotors are an important class of dynamic molecules which have been studied not only for their possible uses as components of molecular machines but also because of potential applications as probes of local viscosity in biological media, especially self-assembled membranes. For the former, factors affecting rotational motility are critical while for the latter the rotor activity must be complexed with an output signal (often fluorescence) for reporting of local conditions. Molecular single stator-double rotor activity of an oxidized resorcinarene (fuchsonarene) macrocycle containing unsaturated hemiquinonoid groups at its meso positions was investigated. Fuchsonarenes contain two hemiquinonoid substituents at diagonally-opposed meso-positions with two electron rich phenol groups at the remaining meso-positions between the hemiquinonoid groups. All meso-substituents are in proximity at one side of the resorcinarene macrocycle (so-called rccc-type isomer) with rotational activity of the phenol meso-substituents. Rotation rates of the phenol moieties can be controlled by varying temperature, solvent polarity and acidity of the medium of study with rotation being thermally activated in neutral and acidic media and tunable in the range from 2 s⁻¹ to 20 000 s⁻¹. Experimental and computational data indicate that rotation of the mobile phenol meso-substituents is remotely affected by interactions with acidic solvents at the carbonyl C=O groups of macrocyclic acetyloxy groups, which occurs with the emergence of a lower energy electronic absorption band whose intensity is correlated with both the acidity of the medium and the rotation rate of the phenol substituents. Time-dependent DFT calculations suggest that the low energy band is due to a molecular conformational adjustment affecting electronic conjugation caused by strong interaction of macrocyclic acetyloxy carbonyl groups with the acid medium. The work presents a molecular mechanical model for estimating solution acidity and also gives insight into a possible method for modulating rotor activity in molecular machines.

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Introduction

Molecular rotors^1–7 are a class of molecular machine^8–13 containing two key components, the stator and the rotor, which undergo facile relative rotation.¹⁴ The operation of rotors might be an important factor in the development of synthetic molecular machines where they would be integrated with other molecular components having different operational activities.^15,16 Also, there exist several examples of biological molecular machine where a rotor molecular element operates based on chemical and physical stimuli.^17–19 These can be treated as archetypes for the development of molecular- and nanomolecular-level machine architectures. Although substantial progress has been made in the area of molecular machine synthesis,^20,21 and there have been demonstrations of important features of rotors such as unidirectional motion^22–24 or supramolecular activity,²⁵ there remains the requirement to investigate different molecular geometries and molecule-level activity in order to establish design rules for each active element of any possible molecular machine assemblies. A useful medium in this respect has been the metal–organic-frameworks (MOFs), where the rotation especially of the organic linker components presents the possibility to study substituent rotation under low density conditions.^26–28 Apart from the molecular machine aspects of rotors, there already exist several applications of molecular rotors as probes of local conditions in biological systems, or as sensors.^29–31 Rotor activity signified by variation in fluorescence output wavelength of certain molecule types can be harnessed to reveal local viscosity in biological membranes or models thereof,^32–35 while rotation rate modulation also signalled by fluorescence emission characteristics can also be used to indicate the presence of analytes.^36–38 Molecules having several proximal component moieties are suitable archetypes of rotors because of intramolecular interactions that govern the mutual motion of substituents. However, although macrocycles such as porphyrins^39–41 and calixarenes⁴² or highly-substituted hydrocarbons^43,44 have been extensively used, resorcinarenes^45–49 have hardly been studied for this purpose, and in cases where they have been used, they are usually operating only as a supramolecular host where an encapsulated guest rotates.^50,51

Resorcinarenes (Fig. 1) are an intensively studied class of macrocycles, which can be readily synthesized in high yields by the simple condensation of resorcinol with an aldehyde.⁵² They are sterically crowded molecules and can exist in many different isomeric forms due to the relative orientations of their hindered substituents.⁵³ Of the common isomers denoted rctt, rccc, rcct, rtct, the rccc forms have been studied due to their propensity to form oligo-molecular capsules with host–guest^{45–49,54,55} and catalytic properties.^56–58 However, the effect of meso-substituent identity on the chemical properties of resorcinarene macrocycles has not been investigated in any depth despite the ease of synthesis of the relevant compounds and the possibility of assessing inter- and intramolecular processes based on the isomeric structures of the compounds. This has been due to the widespread interest in the chemistry of the carcerand structures and the essential chemistry of the resorcinarene macrocycle itself has been largely neglected.^59,60 We have recently reported a class of resorcinarenes containing unsaturated meso-positions for which we have applied the term ‘Fuchsonarenes’ (Fig. 1) since these macrocycles contain components similar to fuchsone dyes.⁶¹ The compounds have so far been studied for their activity as multimodal molecular switches⁶² or as photosensitizers for singlet oxygen generation.⁶³ Synthesis of the fuchsonarenes is enabled by the introduction of several oxidizable groups at their meso-positions, i.e., anti-oxidant 3,5-di-tert-butyl-4-hydroxyphenyl groups (DtBHP), which allows hybridization at the meso-positions to be transformed to sp² following oxidation, introducing electronic conjugation between macrocycle and the resulting hemiquinonoid meso-substituents, and substantially rigidifying their structures. We had previously applied this principle to the meso-tetraphenylporphine system.^64–72 The nanometric dimensions, rigid conformations and chemical stability of the resulting fuchsonarene molecules suggest their potential as supramolecular components of functional nanostructures. This potential is enhanced by the already demonstrated possibility of synthesising different isomer forms (e.g., rctt and rccc) or by functionalisation at the macrocyclic resorcinol moieties.

Fig. 1 Chemical structures of resorcinarenes (left) and the corresponding fuchsonarenes (right) used in this work. Top: 2D and 3D line structures of the compounds. Bottom: 3D depictions of rccc-2 and rccc-2-Ox₂ derived from X-ray crystallographic data. Green arrows denote rotational activity of the phenolic meso-substituents in rccc-2-Ox₂. Antioxidant DtBHP substituents are indicated in yellow frames, while hemiquinonoid groups are denoted in red frames.

Here we describe a system that exploits not only the rigidification of the resorcinarene macrocycle but also the rccc conformer in the formation of a fuchsonarene-based double-rotor/stator where the specific configuration of its substituents allows observation and study of the rotational motility of those substituents. Rotation rates of the rotors relative to the stator can be controlled between 2 s⁻¹ and >20 000 s⁻¹ by varying the solvent, temperature or acidity. These effects were studied by ¹H NMR spectroscopy and electronic absorption (UV-vis) spectrophotometry. The latter was used to demonstrate that rotation rate can be probed optically where acidity of the solvent was applied as the controlling factor. Rotation rates and mechanisms were also investigated computationally using density functional theory (DFT), revealing good agreement between experimental and computed scenarios.

Results

The resorcinarene synthesis involving condensation between resorcinol and a benzaldehyde, the rccc isomer of 1 is the thermodynamically favoured product and is available in increasing proportion over the kinetically favoured product (rctt isomer) at depressed reaction temperatures.⁵² For 1, a 2.6 : 1 mixture of rctt : rccc was obtained when carrying out the synthesis at room temperature. Isomers were separated by per-O-acetylation (selectively at resorcinol-type hydroxyl groups) followed by fractional crystallization; rctt-2 precipitates rapidly from the acetylation reaction mixture while rccc-2 crystallizes more slowly over a period of several days with further subsequent purification performed by using column chromatography. A full description of the synthetic methods can be found in the ESI.† Oxidation of rccc-2 follows the same trend as previous studies,^62,63 where double oxidation of rccc isomers is preferred, yielding the fuchsonarene derivative rccc-2-Ox₂, whose properties as a double-rotor/stator are described here.

Significant line broadening of the resonances due to certain meso substituent t-butyl groups in ¹H NMR spectra obtained at room temperature in chloroform-d (CDCl₃) was observed (Fig. 2a and b). This is assigned as being due to restricted rotation of the remaining non-oxidized phenolic meso-substituents of rccc-2-Ox₂. This had not previously been observed in ¹H NMR spectra of other fuchsonarene molecules and is so far a unique observation for this isomer structure and oxidation state, prompting our further investigation. An assignment of the NMR spectra of rccc-2-Ox₂ in CDCl₃ (with TMS reference at room temperature) was achieved by a combination of 2D NMR spectra (at 50 °C) with ¹H NMR spectra measured at various temperatures (¹H VT-NMR) (see ESI†).

Fig. 2 Relative rotation of the meso-substituents of rccc-2-Ox₂. The model at the top depicts the oxidation of meso-substituents where hemiquinonoid groups are shown in red in the model at right. Regions of the molecule unchanged by the oxidation process are shown in yellow in the scheme at the top (DDQ: 2,3-dichloro-5,6-dicyano-1,4-benzoquinone). (a and b) High field (t-butyl) region of ¹H NMR spectra in acetone-d₆ at different temperatures of (a) rccc-2 and (b) rccc-2-Ox₂. (c and d) Log-linear plot of rotation rates in different solvents at accessible temperatures of phenolic meso substituents in (c) rccc-2 and (d) rccc-2-Ox₂. (e) Free energy profile of rotation of one of the phenolic meso substituent (the top-left one in shown structures) of rccc-2-Ox₂ as obtained from MD simulations at 25 °C. Computational snapshots of several of the structures in acetone are included. (f) Comparison of rotation rates of phenolic meso substituents in rccc-2 and rccc-2-Ox₂ in different solvents at 24 °C and 42 °C.

¹H VT-NMR spectroscopy, in conjunction with spectral line-shape analysis, allows for a detailed characterization of the rotation rate (k) of phenolic meso substituents in the compounds studied here. The broadening and coalescence of spectral lines (e.g.Fig. 2a and b) can be described by invoking a two-state symmetrical exchange between A and B states of phenolic t-butyl groups close to and remote from the centre of the macrocycle, respectively (Fig. 2, top). The spectrum can then be derived from the exchange between two non-interacting spin singlets and fitted using the spectral line shape formula S(ω) expressed in eqn (1).^70,73,74

α_A = R_2A + k − i(ω − ω_A)

α_B = R_2B + k − i(ω − ω_B)

where M₀ is equilibrium magnetization, R_2A and R_2B (in s⁻¹) are spin–spin relaxation rates of each state, k (in s⁻¹) is the rate constant of exchange (i.e. 180° rotation of phenolic meso substituent), i is the unit imaginary number, ω_A and ω_B (in rad per s) are resonance frequencies of each state when no exchange occurs (k = 0 s⁻¹), and ω (in rad per s) is an independent variable connected to chemical shift δ (in ppm) by formula ω = 2πν₀δ, where ν₀ (in MHz) is the operating frequency of the spectrometer (in the present case ν₀ = 300.4 MHz). The real part of eqn (1) (i.e., the absorption spectrum⁷⁰) is used for actual spectral fitting (see section ¹H NMR spectra fitting in ESI†).

There is a connection between the rate constant k and the Gibbs energy of activation ΔG^‡ (i.e., the barrier height) in the form of the Eyring equation (eqn (2)).⁷⁵

where k_Boltz is the Boltzmann constant, h is the Planck constant, R is the gas constant and T (in K) is the absolute temperature. The Gibbs activation energy ΔG^‡ = ΔH^‡ − TΔS^‡, where ΔH^‡ is the enthalpy of activation and ΔS^‡ is the entropy of activation of the 180° rotation process of the phenolic meso substituent. ΔH^‡ and ΔS^‡ were obtained using the analyses of temperature dependency of the rate constant k using an Eyring plot (i.e., a plot of ln(k/T) vs. 1/T with subsequent extraction of slope and intercept of the linear dependency). The results (k, ΔH^‡ and ΔS^‡) are summarized in Tables S1 and S2† for rccc-2 and Tables S3 and S4† for rccc-2-Ox₂ with groups of ¹H NMR resonances used to obtain the data defined in Fig. S1 and S2† (marked by green triangles).

¹H VT-NMR studies on rccc-2 (Fig. 2a, Table S1 and S2, Fig. S3–S6†) revealed that 180° rotation of the meso substituents is slow (13 s⁻¹) at room temperature in acetone-d₆ and that the barrier to rotation is high (ΔG^‡ = 66.5 kJ mol⁻¹) at 24.1 °C. The rate increases with temperature exponentially (i.e. straight lines in log-linear plot), and changing the solvent leads to variation in the rotation rates within a half order of magnitude, as shown in Fig. 2c. For rccc-2-Ox₂ under identical conditions (Fig. 2b, Table S3 and S4, Fig. S7–S11†), a similar pattern of rotation rate dependencies was found (Fig. 2d). However, the rotation rate of the remaining unoxidized phenol substituents in rccc-2-Ox₂ is significantly (more than one order of magnitude) greater than that of phenols in rccc-2 with, for example, a 28-fold rate increase observed at 24 °C in acetone-d₆ (compare Fig. 2c and d or see Fig. 2f). This behaviour is counterintuitive considering the highly sterically hindered environments of the substituents since the unoxidized phenol groups are apparently blocked by the hemiquinonoid groups whose rotation is prevented by the double-bound connection of these substituents to the macrocyclic meso-positions. The barrier ΔG^‡ to the rotation of the phenolic meso substituents of rccc-2-Ox₂ was determined from NMR data to be 58.3 kJ mol⁻¹ (in acetone-d₆, at 24 °C, Table S4†), which is in good agreement with the value obtained from its free energy profile (ca. 50 kJ mol⁻¹ at 25 °C, Fig. 2e) obtained using molecular dynamics (MD) simulations (see ESI section 1.3, Computational methods and Fig. S14†).^76–85 These values are similar to those found for 2-substituted biphenyls and meso-tetraarylporphyrins systems.^86,87 These results demonstrate that oxidation of two meso-substituents of resorcinarene rccc-2 to fuchsonarene rccc-2-Ox₂ has the effect of promoting the rotation of the unoxidized phenolic meso substituents over those in rccc-2 and that the rate of rotation can be controlled by varying both the solvent used and the temperature, with rotation rates ranging from <2 s⁻¹ to >20 000 s⁻¹ depending on conditions (see Fig. 2c, d and f, Fig. S15†). The promoted rotation rate caused by oxidation at the meso-substituents is an interesting feature of this system which can be assigned to variation in the conformation of the macrocycle caused by sp² hybridization at its meso positions. It is also an interesting possible design parameter when considering the preparation of rotor systems in similarly substituted molecules.

While variations in temperature and solvent can be used to control the rotation rate of meso-substituents in rccc-2-Ox₂, it was also found that exposure to trifluoroacetic acid-d (TFA-d) leads to a decrease in the rate of rotation of the unoxidized phenol meso substituents (370 s⁻¹ in acetone-d₆vs. 25 s⁻¹ in TFA-d, Fig. 3a) denoted by the appearance of two individual t-butyl resonances in the ¹H NMR spectrum. Interestingly, solutions of rccc-2-Ox₂ are orange in TFA, and the colour change is accompanied by a new absorption band centred at 517 nm in its UV-vis spectrum (Fig. 3b). ¹H VT-NMR studies revealed that the rate of rotation in the presence of TFA can again be controlled by varying temperature, where rotation is essentially arrested below 6 °C but increases to 460 s⁻¹ at 59 °C (Fig. 3c, Table S3, Fig. S10 and S15†). This suggests that a third input for controlling the phenolic meso substituents rotation rate can be used, where exposure of the compounds to an acidic environment leads to a decrease in the rate of rotation.

Fig. 3 Effect of trifluoroacetic acid on the rate of rotation of phenolic meso substituents in rccc-2-Ox₂. (a) ¹H NMR spectra of rccc-2-Ox₂ in acetone-d₆ and TFA-d at 24 °C with symbols (triangle and circle) denoting different types of meso substituents. (b) UV-vis spectra of rccc-2-Ox₂ in chloroform (yellow) and TFA (red) at 3.05 × 10⁻⁴ M in a 1 cm pathlength cell. (c) ¹H VT-NMR spectra of rccc-2-Ox₂ in TFA-d with spectra referenced to chemical shift of the first acetate resonance (2.48 ppm). Arrows indicate the coalescing resonances due to phenolic meso substituent.

The rotation rate of the unoxidized meso-substituents can be tuned under isothermal conditions by varying the composition of a binary mixture of TFA-d/acetone-d₆ (Fig. 4, Table S5, Fig. S12 and S13†). Increasing the ratio of TFA-d in the binary mixture slows the rotation rate from ca. 470 s⁻¹ to 10 s⁻¹ (Fig. 4a, Table S5†) with a concomitant gradual change in the solution colour (Fig. 4b) and variation in the UV-vis spectrum (Fig. 4c). It should be noted that the barrier to the rotation ΔG^‡ of the meso-substituent increases in pure TFA to 65.6 kJ mol⁻¹ (determined from NMR at 24 °C, Table S4†), which is again in reasonable agreement with the value of ca. 61 kJ mol⁻¹ (at 25 °C, Fig. S14†) obtained from the free energy profile using MD simulations.

Fig. 4 Effect of TFA-d volume fraction in acetone-d₆ on the rate of rotation of phenolic meso substituents in rccc-2-Ox₂. (a) ¹H NMR spectra of rccc-2-Ox₂ at 3.05 × 10⁻⁴ M in TFA-d/acetone-d₆ mixtures at 24 °C. (b) Photographs of the samples prepared for this study indicating a gradual colour change. (c) UV-vis spectra of rccc-2-Ox₂ in TFA-d/acetone-d₆ mixtures at 3.05 × 10⁻⁴ M in a 0.1 cm pathlength cell. (d) Summary of the SVD analysis indicating the presence of 3 different species (for details, see ESI, section 5†). (e) Calibration curves and formulae constructed by correlating UV-vis and ¹H NMR data (for details, see ESI, section 6†).

The presence of two isosbestic points at 401 and 427 nm (Fig. 4c) in UV-vis spectra of solutions of varying TFA-d/acetone-d₆ compositions and the results of singular value decomposition analysis (SVD)^88–94 (Fig. 4d, for details see section 5 in ESI†) indicate the presence of a third intermediate species. The spectra of second and third species qualitatively resemble those obtained by time-dependent density functional theory (TD-DFT) calculations (Fig. 5b), which indicates some degree of interaction of the acid medium with rccc-2-Ox₂ (for more details, see Discussion). The predictable variation in UV-vis profile dependent on solvent composition (in this case, acid content) presents a molecular system whose rotation rate can be indirectly estimated using UV-vis spectrophotometry, allowing for the construction of calibration curves if ¹H NMR data can be correlated with the UV-vis data (Fig. 4e). Based on the correlation, a set of calibration formulae can be generated and used to determine indirectly the rate of rotation of the phenolic meso substituents based on the absorbance data (Fig. 4e; for details see section 6 in ESI†).

Fig. 5 Calculated UV-vis spectra and related molecular conformations. TD-DFT (ωB97XD 6-311G(d)) UV-vis spectra of rccc-2-Ox₂ calculated from 20 averaged statistically-independent snapshots from MD simulations performed under various conditions: (a) Non-protonated rccc-2-Ox₂ in neat acetone and TFA solvents. (b) Spectrum of rccc-2-Ox₂ in TFA with protonation constrained at one acetyloxy group and the spectrum after removal of the proton (without structure relaxation). MD snapshots of differential excitation density (DED) of various states of rccc-2-Ox₂ in TFA. Green isodensities show the negative regions from which electrons are excited while the positive orange isodensities indicate the regions to which the electrons are excited. Transitions shown are responsible for UV-vis absorptions at wavelengths indicated below each structure. (c) DED of acetyloxy protonated (location denoted by red arrow) rccc-2-Ox₂ leading to absorption at 509 nm. (d) DED of rccc-2-Ox₂ after removal of proton from acetyloxy group in (c) (location denoted by blue arrow) shifts the absorption from 509 nm to 486 nm. (e) DED of rccc-2-Ox₂ absorbance band at 539 nm indicates no change with or without protonation of the acetyloxy group (dashed red/blue arrows). The actual structure represents a protonated form.

Discussion

There are several interesting aspects of the rccc-2-Ox₂ system presented here that have connotations for the properties of other similar molecular constructs. For example, many compounds containing multiple, especially conjugated, hemiquinonoid groups can also exist with an open shell electronic structure^95,96 with unpaired electron density present at unsaturated oxygen atoms. In this case, we have excluded this possibility based on the only weak ESR response of rccc-2-Ox₂ (due to small amounts of phenoxyl radical always present in samples of these compounds, see Fig. S16†) and the thermally induced coalescence of the relevant ¹H NMR resonances, which must be a symptom of moiety rotation. Other work^62,63 has shown that carbonyl C=O bond lengths are consistent with closed-shell forms. Also, the changes in the hue of solutions where the acetone/TFA ratio is varied is reminiscent of solvatochromism. However, the variation is merely due to increases in absorbance of the new band at 520 nm, and no shifts in absorption wavelength are observed, implying the emergence of another chemical entity with a different electronic structure.

Of the solvents employed in the present study, trifluoroacetic acid causes the most notable effects based on the emergent UV-vis band and rotation rates determined by NMR spectroscopy. Therefore, we must consider the effects of acid and possible protonation scenarios most closely. Protonation of fuchsone dyes such as 2,6-di-tert-butyl-4-(diphenylmethylene)cyclohexadien-1-one⁹⁷ initially occurs at the carbonyl oxygen atom with subsequent rearrangement to a resonance stabilized methanide carbocation that has a characteristic ¹³C NMR resonance at ∼200 ppm. However, for rccc-2-Ox₂ in TFA-d, no such low field carbocation resonance appears and the chemical shift of its hemiquinonoid carbonyl carbon atom is similar to that in CDCl₃ solution (see ESI, Fig. S17 & S30† peak at low field: 186.5 ppm in both cases) indicating that protonation does not occur at hemiquinonoid groups of rccc-2-Ox₂ (for assignments of the NMR spectra of rccc-2-Ox₂ in different media see ESI†). Resistance to protonation by rccc-2-Ox₂ is most likely due to the low electron donating power of the resorcinarene acetyloxy ester groups so that rearrangement from protonated hemiquinone to meso-carbocation (which certainly occurs in the case of simple fuchsone⁹⁷) is not supported, and the corresponding ¹³C NMR resonance at low field is not found. ¹³C NMR spectra of rccc-2-Ox₂ in TFA-d do, however, reveal significant shifts in carbonyl resonances due to acetyloxy carbonyl groups (see Fig. S17 & S30;† group of 4 peaks at 167–169 ppm (CDCl₃) shifts to 173–175 ppm (TFA-d); see Fig. S29† for the corresponding ¹H NMR spectra). There are accompanying ¹³C NMR shifts for the sp²-type meso-positions and the neighbouring cyclohexadienylidene substituent proton and carbon atoms (see section 8, ESI†) indicating that some structural change occurs close to the oxidized meso-positions, which is associated with acetyloxy/TFA interactions. These are the most important variations in the NMR spectra occurring in passing from non-polar (CDCl₃) to acidic (TFA-d) solvent. This approximately 6 ppm downfield shift of the acetyloxy C=O ¹³C resonances (and associated NMR variations of oxidized meso-substituents) suggests some interaction with the acidic medium. Therefore, we have also investigated this using time-dependent density functional theory (TD-DFT) methods.

In TD-DFT, notably, while simple H-bonding interactions were observed not to generate low energy electronic absorption in rccc-2-Ox₂ (Fig. 5a), the constrained protonation of one of its acetyloxy C=O group(s) was found to lead to the appearance of new lower energy bands in its TD-DFT calculated UV-vis spectrum similar to those observed experimentally for solutions of rccc-2-Ox₂ in TFA (compare Fig. 5b and 3b).^98–101 UV-vis spectra of rccc-2-Ox₂ in acetone or TFA without constrained protonation calculated using TD-DFT^77,102,103 are shown in Fig. 5a (for details, see section 1.3: Computational methods in ESI†). The UV-vis spectra calculated for rccc-2-Ox₂ in TFA with initial constrained protonation of an acetyloxy C=O group (Fig. 5b, red line) followed by removal of the proton without structure relaxation (Fig. 5b, blue line) show very good agreement with the experimentally obtained data (compare to Fig. 3b). The small difference between the spectra in Fig. 5b indicates that any charge located at the acetyloxy group present due to protonation makes only a minor contribution to the resulting low-energy absorbance band in UV-vis. This effect is also supported by the plots of differential excitation densities (DED) prior to and after removal of the proton from the protonated form of rccc-2-Ox₂, (Fig. 5c–e). The low energy absorption bands in the 450 to 580 nm region originate from the hemiquinone moieties of rccc-2-Ox₂. The effects of solvent environment were also tested using TD-DFT resulting in consistent significant absorptive transitions in the 410 to 580 nm region (Fig. S18†). A further assessment of the effects of acetyloxy protonation on the structure was carried out by MD simulations. The results indicate that protonation at an acetyloxy C=O group causes structural variation of the rccc-2-Ox₂ macrocycle so that planes of adjacent phenol-hemiquinone substituent pairs become almost parallel (Fig. S19a†) allowing their closer approach causing reduction in rotation rate with the resorcinarene macrocycle being concurrently increasingly skewed (Fig. S19b†). These structural changes are responsible for the emergence of the new low-energy absorption bands due to the resulting increase in π-electronic conjugation between hemiquinone and macrocycle. It should be noted that protonation on an acetyloxy group would be the first step in their acid promoted hydrolytic cleavage, although we found no evidence for decomposition of rccc-2-Ox₂ by this route under the conditions used (treatment with strong mineral acids does result in decomposition to intractable products). Therefore, while protonation of acetyloxy groups in this system can influence the molecular conformation so that new low energy bands appear in UV-vis spectra, these protonated states are not sufficiently persistent to lead to deacetylation of the macrocycle.

The calculations suggest that in TFA there is a degree of protonation or at least strong H-bonding of acetyloxy C=O groups of rccc-2-Ox₂, which influences its electronic structure, although the corresponding experimental observations suggest only incomplete or equilibrium processes. Also, the addition of stronger (than TFA) organic acids causes a further increase in the intensity of the absorption centred at 520 nm in experimentally observed spectra. Other pertinent experimental observations include infrared spectra (see ESI, Fig. S20†), where absorptions due to acetyloxy carbonyl stretching are shifted to lower frequency when exposed to TFA vapour, which can be associated with hydrogen bonding. There is also a weak ESR signal in rccc-2-Ox₂ (see ESI, Fig. S16†) although compounds containing multiple DtBHP groups usually contain small amounts of phenoxyl radical due to handling under aerobic conditions. The spectroscopic changes, including shifts in the ¹³C resonances of the acetyloxy carbonyl groups and the appearance of the low energy UV-vis absorption, suggest that there is a significant protic process occurring between TFA and the acetyloxy C=O groups. The strength of this interaction is sufficient to change the conformation of rccc-2-Ox₂, which cannot be detected directly. It also occurs in the proximity of a fuchsone moiety which is usually susceptible to protonation and rearrangement. In rccc-2-Ox₂, it seems then that two effects operate: (1) macrocyclic acetyloxy substituents are sufficiently electron-withdrawing to destabilize prospective meso-carbocations thus disfavouring protonation at the hemiquinonoid C=O, and (2) multiple acetyloxy groups of rccc-2-Ox₂ are available for interaction with the acid medium, which leads to modification of its chromophore structure and emergence of electronic absorption bands in the visible region. It is currently unclear whether or not (2) influences (1) so that protonation at hemiquinonoid is even more strongly disfavoured at higher acidities.

We note that the simple variation of macrocyclic substituent from benzyloxy (ether) to acetyloxy (ester) leads to a dramatic change in the response of the compounds to their environments. For the former (ether), meso-substituent protonation affects the properties of the compounds, while for the latter (ester) described here, interaction with the medium is limited to the macrocyclic acetyloxy (i.e., not meso) substituents. This is an important point as we learn about the factors affecting the chemistry of resorcinarenes and, in particular, the fuchsonarenes. As mentioned previously, the resorcinarenes have largely been considered for their propensity to form large nanocapsular assemblies. In this and previous work, we have found that complex chemical relationships exist, and these can occur not only intramolecularly between different types of substituents (e.g., macrocylic benzyloxy groups support meso-carbocation formation in contrast to acetyloxy) but also intermolecularly involving the solvent medium. It is interesting to note that in this case, the resistance to protonation of hemiquinonoid groups probably caused by macrocyclic acetyloxy groups is countered by a corresponding perhaps counterintuitive interaction of the acetyloxy groups with the acidic medium. Also, coincidentally, interactions of acid with fuchsonarenes at hemiquinonoid or acetyloxy groups lead to the emergence of UV-vis bands in the visible region despite the origins of these bands being very different.

Conclusions

In conclusion, we have demonstrated the activity of a fuchsonarene as a molecular single stator-double rotor. In terms of its structure, this is a rare example where rotary action can be controlled by varying solvent, temperature, or chemical inputs yielding a controllable system whose rotation rate can be tuned in the range of 2 s⁻¹ to 20 000 s⁻¹ depending upon the combination of the aforementioned inputs. Rotation speed governed by the TFA concentration can be monitored using UV-vis absorption data due to its correlation with the rotation rate determined by ¹H NMR spectroscopy, and suitable formulae for this purpose have been presented. TD-DFT was used to investigate features of this system and indicates that strong interactions of the acetyloxy groups with the solvent (most likely H-bonding) occur in acidic solution and are responsible for the emergence of new low energy bands in the UV-vis spectrum of rccc-2-Ox₂. Resorcinarenes are more often considered from the point-of-view of supramolecular capsule formation and related catalytic activities. Here, we have further expanded the chemistry of the resorcinarenes through the study of the rotor activity of their substituents – a previously unknown aspect of these well-studied compounds. The resorcinarene macrocycle presents a new scaffold for molecular machines where the orientation of rotor-active substituents can be controlled within a compact 3-dimensional space, and rotation rate is modulated according to temperature, solvent polarity and acidity. Overall, this work suggests a molecular mechanical method for indirect estimation of solution acidity by simple monitoring of UV-vis spectra, and also gives insight into a possible method for modulating rotary activity in molecular machines.

Data availability

General experimental details, description of synthetic procedures, rotation data and ¹H-NMR spectra from which they were derived, supplementary figures, description of singular value decomposition methods, calibration curves, additional characterization data, assignment of the NMR spectra of rccc-2-Ox₂ inclduing extensive 2D-NMR spectra. These items are available in the ESI.†

Author contributions

D. T. P., J. L. and J. P. H. designed the experiments, led the project and composed and wrote the manuscript with scientific discussions and contributions from all co-authors. D. T. P. performed the synthesis and chemical analyses of the compounds and collected analytical data. J. L. analysed the VT ¹H NMR data, extracted the rate constants and constructed the calibration curves. Z. F. undertook the MD and DFT computational work. V. B. and L. H. performed SVD analysis. M. K. C. undertook UV-vis measurements and data processing. All authors contributed to the writing of the manuscript.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This work was partly supported by World Premier International Research Center Initiative (WPI Initiative), MEXT, Japan. D. T. P is grateful to the Japan Society for the Promotion of Science (JSPS) for a JSPS Fellowship and to the International Center for Young Scientists (ICYS-Namiki), NIMS for continued financial support. This work was also partially supported by JSPS KAKENHI Grant No. 19K05229. Computational resources were supplied by the project “e-Infrastruktura CZ” (e-INFRA LM2018140) provided within the program Projects of Large Research, Development and Innovations Infrastructures.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/d1qo01479j

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