Yasuhiro Shiraishi,Keiichiro Yomo,Takayuki Hirai
Polarity-Driven Isomerization of a Hydroxynaphthalimide-Containing Spiropyran at Room Temperature
spiropyran,isomerization,polarity,naphthalimide,merocyanine
Design of spiropyrans showing spontaneous isomerization driven by the polarity of solvents is an important consideration for the synthesis of optical sensory materials. Although some spiropyrans undergo polarity-driven isomerization, they must be heated owing to the high activation energy required for isomerization. In this study, we describe that a spiropyran containing a hydroxynaphthalimide unit (1) exhibits a polarity-driven isomerization at room temperature. It exists as a colorless spirocyclic (SP) form in less polar solvents but is isomerized to a colored merocyanine (MC) form in polar solvents. The equilibrium amount of the MC form increases with an increase in the polarity of solvents. The MC form involves two resonance structures—the quinoidal and zwitterionic forms. In polar media, the zwitterionic form dominates mainly owing to solvation by polar molecules. Solvation stabilizes the negative charge of the zwitterionic form and decreases its ground state energy, thereby enhancing SP → MC isomerization. The SP ⇌ MC isomerization terminates within barely 30 s even at room temperature because the naphthol moiety with high π-electron density lowers the activation energy for the rate-determining rotational step.
Polarity-Driven Isomerization of a Hydroxynaphthalimide-Containing Spiropyran at Room Temperature

Design of spiropyrans showing spontaneous isomerization driven by the polarity of solvents is an important consideration for the synthesis of optical sensory materials. Although some spiropyrans undergo polarity-driven isomerization, they must be heated owing to the high activation energy required for isomerization. In this study, we describe that a spiropyran containing a hydroxynaphthalimide unit (1) exhibits a polarity-driven isomerization at room temperature. It exists as a colorless spirocyclic (SP) form in less polar solvents but is isomerized to a colored merocyanine (MC) form in polar solvents. The equilibrium amount of the MC form increases with an increase in the polarity of solvents. The MC form involves two resonance structures—the quinoidal and zwitterionic forms. In polar media, the zwitterionic form dominates mainly owing to solvation by polar molecules. Solvation stabilizes the negative charge of the zwitterionic form and decreases its ground state energy, thereby enhancing SP → MC isomerization. The SP ⇌ MC isomerization terminates within barely 30 s even at room temperature because the naphthol moiety with high π-electron density lowers the activation energy for the rate-determining rotational step.

Spiropyrans are a family of photochromic dyes that have been intensively studied over 50 years (Scheme 1). They generally exist in solvents as colorless spirocyclic (SP) forms. They undergo isomerization to produce the colored merocyanine (MC) form by absorbing ultraviolet (UV) light and are reverted to the SP form by absorbing visible light. The dramatic color change with the photochromism has opened up the application of spiropyrans to several kinds of optical materials such as switches, memories, and sensors. The SP ⇌ MC isomerization can be initiated using other stimuli involving pH, temperature, cations, anions, viscosity, and mechanical forces even under the dark conditions. Creating spiropyrans that exhibit reversible isomerization by external stimuli is an important consideration for newer applications. Polarity of the solvent is one of the most familiar and easy-to-handle stimuli for promoting isomerization. Previous reports revealed that some spiropyrans (Scheme 2) containing a phenol moiety with electron-withdrawing substituents such as −COOH (2), −COOCH3 (3), −SO3H (4), and −NO2 (5), when dissolved in polar solvents, are isomerized to the MC form under dark conditions, even though they exist in the SP form in less polar solvents. In less polar media (Scheme 3a), the ground state energy of the MC form of these spiropyrans is at a level higher than that of the SP form. The positive enthalpy change (ΔisomH > 0) suppresses SP → MC isomerization. However, in polar media (Scheme 3b), the ground state energy of the MC form is decreased to below the level of the SP form (ΔisomH < 0) owing to stabilization of the negative charge by electron-withdrawing substituents. This promotes SP → MC isomerization even under dark conditions. However, for these spiropyrans, the decrease in the ground state energy of the MC form is insufficient (ΔisomH ∼ −5 kJ mol–1), where the equilibrium amounts of the MC form are at most ∼50% even in polar media. For further stabilization of the MC form in polar media, introducing multiple electron-withdrawing substituents into the phenol moiety (6,7,Scheme 2) is effective: they have more negative ΔisomH (∼−15 kJ mol–1) and achieve almost 100% of equilibrium MC amounts. Therefore, incorporating an electron-deficient phenol moiety is considered essential to synthesize the spiropyrans exhibiting polarity-driven SP → MC isomerization. A problem involving SP ⇌ MC isomerization of spiropyrans at a ground state potential surface is that, as shown in Scheme 3, spiropyrans usually have high activation energy (Eisom) for isomerization (∼100 kJ mol–1). This results in slow isomerization; the time to achieve the SP ⇌ MC equilibrium at room temperature generally requires more than 1 h. The SP → MC isomerization involves several steps such as cleavage of the spiro C1–O bond followed by cis → trans rotation around the C2=C3 and C1–C2 bonds (Scheme 1), where the rotation around the C2=C3 bond is considered the rate-determining step. Therefore, the design of spiropyrans with low Eisom is important for rapid isomerization at room temperature. A recent theoretical study based on density functional theory (DFT) calculation predicted that a fused aromatic moiety such as naphthol, when replaced with a phenol moiety of spiropyran, decreases Eisom. A fused aromatic ring with a high electron density suppresses the electron transfer from the indoline moiety and decreases the π-bond order of the C2=C3 bond in the transition state. This suggests that incorporating an electron-deficient fused aromatic moiety is a possible approach to the design of spiropyrans promoting a rapid polarity-driven isomerization. Naphthalimide is a fluorescent dye with high chemical, photochemical, and thermal stability. Its application to several functional materials such as optoelectronic devices, sensors, and DNA-targeted binders has been studied extensively. A notable feature of naphthalimide is that it contains a fused naphthalene ring and behaves as an electron acceptor owing to the electron-withdrawing imide moiety. Therefore, we hypothesized that a hydroxynaphthalimide moiety, if incorporated within the structure, would produce a spiropyran with highly stabilized MC form together with low Eisom for isomerization. In the present work, we designed a spiropyran containing a hydroxynaphthalimide moiety (1, Scheme 2). We found that it undergoes a polarity-driven rapid SP ⇌ MC isomerization even at room temperature. In less polar media, 1 is almost colorless owing to the SP form. An increase in the polarity of solvents elicits a gradual coloration owing to the formation of the MC form, where the equilibrium MC amount can be changeable from 9% in toluene to 99% in DMSO. Equilibrium analysis and DFT calculations reveal that the MC form of 1 is indeed highly stabilized in polar media, thus promoting spontaneous isomerization. In addition, the SP ⇌ MC equilibrium is achieved in less than 30 s even at room temperature. Time-dependent DFT (TD-DFT) calculations revealed that the naphthol ring with high π-electron density decreases Eisom, thus promoting rapid SP ⇌ MC isomerization.

1 was obtained by the condensation of 1,3,3-trimethyl-2-methyleneindoline and 3-formyl-4-hydroxy-N-butyl-1,8-naphthalimide with 17% yield. FAB(+)-MS analysis of 1 (Figure S1, Supporting Information) shows [1 + H]+ ion (m/z 453.2). 1H, 13C NMR, and 1H–1H COSY spectra (Figures S2–S4, Supporting Information) confirmed the purity of 1. Spiropyrans bearing a dinitrophenol moiety (6) and a naphthol moiety (8) (Scheme 2) were also used for comparison of the isomerization properties. UV–vis absorption spectra of 1 were recorded at 293 K in several organic solvents after stirring the solution for 30 min in the dark. As shown in Figure 1, 1 demonstrated a weak absorption in the visible region (500–640 nm) when dissolved in less polar solvents such as toluene, where the solution was almost colorless. This indicates that 1 mainly exists as an SP form in less polar media. However, 1 dissolved in polar solvents such as DMSO showed a purple color and increased absorbance, which might be assigned to the MC form, implying that 1 undergoes spontaneous SP → MC isomerization in polar media. 1H NMR analysis of 1 was performed in deuterated solvents to confirm the formation of the MC form (Figure 2), where the full spectra are given in Figures S2 and S5–S7 (Supporting Information). Two methyl groups on the indoline moiety of the SP form are not equivalent owing to their asymmetrical structure and exhibit two separate peaks (HSP). In contrast, the methyl groups of the MC form show a single peak (HMC) owing to their equivalent structure. The spectrum obtained in toluene-d8 showed both HSP and HMC peaks, and integration of the peaks determined the SP/MC ratio to be 91:9, indicating that less polar media favorably generate the SP form. In contrast, increasing the polarity of solvents increases the HMC peak while decreasing the HSP peak; the SP/MC ratios were 29:71 in CDCl3, 25:75 in acetone-d6, and 1:99 in DMSO-d6, respectively, clearly indicating that the MC form exists mainly in more polar media. Figure 3 (red) plots the MC ratio of 1 in different solvents against the normalized solvent polarity parameter, ETN, which is referenced to tetramethylsilane (ETN = 0) as nonpolar and water (ETN = 1) as strong polar reference solvents, where the parameters used are listed in Table S1 (Supporting Information). Increasing the solvent polarity increases the MC ratio, confirming that 1 undergoes polarity-driven SP → MC isomerization. As reported, dye 6 also exhibits a polarity-driven SP → MC isomerization; no absorption is observed in the visible region in less polar media, but the MC absorbance (460–600 nm) increases in more polar media (Figure S8, Supporting Information). As shown in Figure 3 (black), 1H NMR analysis of 6 (Figure S9, Supporting Information) reveals that the equilibrium MC ratio shows a tendency similar to that of 1 (red), indicating that these dyes show a similar polarity dependence. In contrast, as demonstrated in Figure S10 (Supporting Information), dye 8 displays almost no absorption in the visible region even in polar media. These results indicate that the electron-deficient hydroxynaphthalimide moiety of 1 triggers spontaneous SP → MC isomerization in polar solvents. Spiropyrans usually undergo SP ⇌ MC photoisomerization upon absorbing UV or visible light (Scheme 1). However, 1 does not undergo photoisomerization. As presented in Figure S11 (Supporting Information), there is no change observed in the absorption spectra for 1 in either toluene or MeCN solvents when photoirradiated by UV or visible light. In Figure S12 (Supporting Information), photoexcitation of toluene containing 1 (SP form exists mainly) at 375 nm results in an emission centered at 435 nm, which is ascribed to the fluorescence from the excited-state naphthalimide moiety. In contrast, photoexcitation of MeCN containing 1 (where the MC form predominates) at 440 and 590 nm shows emissions centered at 512 and 625 nm, both of which might be ascribed to the fluorescence from the excited-state of the entire 1 molecule. These findings indicate that photoexcitation of both SP and MC forms of 1 leads to a loss of their excited energy via the fluorescence emission, as observed for related molecules, resulting in no photochromic behavior.

The SP → MC isomerization of 1 is triggered by stabilization of the MC form in polar media, similar to the case for the related spiropyrans. To clarify this, equilibrium absorption experiments were performed. The relationship between the thermodynamic equilibrium constants (Keq) and the equilibrium concentrations of the SP and MC forms is as follows CT is the total concentration of 1, and AMC and εMC are the absorbance and molar extinction coefficient of the MC form, respectively. The εMC values in the respective solvents were determined using the Lambert–Beer equation with the path length of the cell (l) The [MC]eq was determined by the 1H NMR analysis in the respective solvents (Figure 2). The solutions containing different concentrations of 1 (CT) were stirred for 4 h at different temperatures under the dark conditions. A linear relationship was observed when plotting CT against AMC (Figure S13, Supporting Information). Keq values can be determined from the slopes and the εMC values. ΔisomH values were calculated with the Keq values using the van’t Hoff equation (eq 4), as shown in Figure S14 (Supporting Information). The obtained Keq and ΔisomH are summarized in Table 1. The value of Keq of 1 in toluene is ∼0.1, but is higher in acetone (∼4.1) and DMSO (∼23). These values agree well with the equilibrium MC ratios determined by the NMR analysis (9, 75, and 99%, respectively, Figure 2), confirming the accuracy of the equilibrium analysis. ΔisomH in toluene is −0.8 kJ mol–1, but is decreased considerably in acetone (−17 kJ mol–1), and DMSO (−20 kJ mol–1). As shown in Figure 4 (red), the ΔisomH values, when plotted against ETN, show a linear relationship. This clearly indicates that increase in the solvent polarity lowers the ground state energy of the MC form of 1 and enhance spontaneous SP → MC isomerization. It is noted that ΔisomH in DMSO (−20 kJ mol–1) is comparable to that of 6 in DMSO (−18 kJ mol–1), indicating that the incorporation of a hydroxynaphthalimide moiety is effective in stabilizing the MC form. DFT calculations were carried out to further confirm the stabilization of the MC form of 1 in polar solvents. Although several isomers of the MC form exist, the TTC form (Scheme 1 right), which has a trans–trans–cis conformation around the C1–C2, C2–C3, and C3–C4 bonds, has been considered the most stable MC structure. We calculated the ground state energies of the SP and TTC forms of 1 within the Gaussian 16 program, where the polarizable continuum model (PCM) was used to consider the polarity effect.Figure 4 (black) summarizes the calculated ground state energies of the TTC form relative to that of the SP form under different PCM conditions. The relative TTC energy decreases with an increase in polarity of the PCM parameter. This tendency agrees well with that of the ΔisomH values (red). The above equilibrium analysis and the DFT calculation results clearly indicate that the lowered ground state energy of the MC form of 1 in more polar media triggers SP → MC isomerization.

The reason for the stabilization of the MC form of 1 in more polar solvents (Figure 4) must be clarified. According to Figure 1, the MC absorption band of 1 shows a hypsochromic shift in more polar solvents, as observed for the related spiropyrans.Figure 5 plots the maximum wavelengths (λmax) of the MC absorption of 1 in different solvents against the ETN parameter, where the absorption spectra of 1 in all of the solvents used are provided in Figure S15 (Supporting Information). A linear correlation indicates that the MC form of 1 has two resonance structures (Figure 6a): the quinoidal form is dominant mainly in less polar media, while the contribution of zwitterionic form becomes larger in more polar media. This is because the zwitterionic form has a lower HOMO level: therefore, increased contribution of the zwitterionic form increases the HOMO–LUMO gap and results in the hypsochromic shift of the MC absorption band. Time-dependent DFT (TD-DFT) calculations of the TTC form of 1 were performed to clarify their electronic structures under different PCM conditions. As summarized in Table S2 (Supporting Information), the electronic excitation of the TTC form mainly consists of a HOMO → LUMO transition (S0 → S1) under all PCM conditions. As shown in Figure 6b, the LUMO levels of the TTC forms are similar under all PCM conditions, but the HOMO levels decrease with an increase in polarity of PCM. Therefore, the HOMO–LUMO gap increases with the increase in the polarity. This agrees well with the hypsochromic shift of 1 (Figure 5), indicating that the contribution of the zwitterionic form indeed becomes larger in more polar media. Notably, the hypsochromic shift (Figure 5) is consistent with the decrease in ground state energy of the TTC form (Figure 4), suggesting that the zwitterionic form has a ground state energy lower than the quinoidal form. In more polar media, solvation of the MC form by polarized solvent molecules creates the polarized zwitterionic form (Figure 6a, right). This may stabilize the negative charge of the form and lower the ground state energy, thus enhancing the SP → MC isomerization. The above findings indicate that the polarity-driven formation of the zwitterionic form lowers the ground state energy of the MC form and triggers SP → MC isomerization.

Another notable feature of 1 is the rapid isomerization even at room temperature. Figure 7a,b shows changes in absorption spectra of 1 and 6, respectively, measured at 293 K under dark conditions. Each of the respective dyes was dissolved in toluene (0.1 mL), and spectral measurement was started after the addition of DMSO (1.9 mL) to the solutions. In the case of 6 (Figure 7c), the MC absorbance increases very slowly and reaches equilibrium after ∼36 h owing to its high Eisom. Therefore, heating the solution is necessary for rapid SP → MC isomerization. In contrast, in the case of 1 (Figure 7c), the MC absorbance increases very rapidly and reaches equilibrium within 10 s, indicating that 1 facilitates rapid SP → MC isomerization even at room temperature. Figure S16 (Supporting Information) presents the change in absorption spectra of 1 in DMSO (0.1 mL) after the addition of toluene (1.9 mL). The MC absorbance decreases immediately by the addition of toluene and reaches equilibrium within 30 s. This indicates that MC → SP isomerization of 1 also occurs very rapidly, confirming a low Eisom for isomerization of 1.

The Eisom values of spiropyrans can be generally determined by kinetic measurements (see text in the Supporting Information). As shown in Figure S17 (Supporting Information), the kinetic absorption measurements of 6 for SP → MC isomerization in MeCN at different temperatures (313–333 K), and the corresponding Arrhenius plots of the obtained kinetic constants determined Eisom of 6 to be 102.5 kJ mol–1. However, in the case of 1, SP → MC isomerization at around room temperature occurs very rapidly (Figure 7c). Therefore, as shown in Figure S18 (Supporting Information), the kinetic measurements were performed at lower temperatures (268–278 K). This determined Eisom of 1 to be 50.6 kJ mol–1, which is much lower than that of 6, confirming low Eisom of 1. DFT calculations were performed to further confirm the low Eisom of 1. The SP → MC isomerization usually occurs through three steps via the CCC and CTC intermediates, as summarized in Scheme 4: (i) the cleavage of the C1–O bond for the SP form gives the CCC form through a TS1 transition state; (ii) cis → trans isomerization around the C2=C3 bond gives the CTC form through a TS2 state; and (iii) cis → trans isomerization around the C1–C2 bond generates the TTC form through a TS3 state. Step (ii) is the rate-determining reaction for isomerization. The respective ground states were optimized by the DFT calculations with DMSO as PCM, and the transition states were optimized using the TS Berny method.Figure 8 presents the optimized structures of the ground and transition states of 1, 6, and 8 and their relative energies with respect to the SP form. The results clearly indicate that, as reported, TS2 (ii) indeed requires the highest energy for isomerization. The TS2 energy of 6 (101.6 kJ mol–1) is similar to the experimental value (102.5 kJ mol–1) determined by kinetic absorption measurements (Figure S17, Supporting Information), confirming the accuracy of the calculated Eisom value. The TS2 energy of 1 (69.8 kJ mol–1) is also similar to the experimental value (50.6 kJ mol–1), and is much lower than that of 6. This clearly indicates that the lower TS2 energy of 1 facilitates rapid isomerization. The TS2 consists of the rotation around the C2=C3 bond (Scheme 4); therefore, the C2=C3 bond strength is crucial for its energy. As denoted in Figure 8, the calculated C2=C3 length of the TS2 state of 1 is 1.472 Å, while the length of 6 is 1.467 Å. This indicates that 1 indeed has a longer (weaker) C2=C3 bond and, hence, results in lower Eisom. As predicted, incorporating a fused aromatic unit decreases Eisom of spiropyrans: the high-π-electron-density unit suppresses the electron transfer from the indoline moiety and decreases the π-bond order of the C2=C3 bond in the TS2 state. Figure 8c shows the calculation results of 8 incorporating a naphthol moiety (Scheme 2). The results indicate that 8 also has a long C2=C3 bond (1.476 Å) and a low TS2 energy (58.0 kJ mol–1), similar to those of 1, confirming that introducing a fused naphthol ring decreases the TS2 energy. Table S3 (Supporting Information) summarizes the dipole moment for the ground and transition states of 1, 6, and 8. TS2 of 6 has a high dipole moment (9.524 Debye), implying that electron transfer from the indoline moiety to the dinitrophenol moiety creates a charge-transferred electronic structure. In contrast, TS2 of 1 and 8 have lower dipole moments (2.927 and 4.515 Debye, respectively), indicating that the electron transfer from the indoline moiety is suppressed by introducing a naphthol moiety with high electron density. Therefore, this weakens the C2=C3 bond and lowers the rotational TS2 energy, resulting in rapid isomerization of 1. The activation entropies (ΔS‡) for SP → MC isomerization of 1 and 6, calculated from the frequency factors obtained by the Arrhenius plots (Figures S17 and S18, Supporting Information), were −65.0 J K–1 mol–1 (298 K) and 24.9 J K–1 mol–1 (298 K), respectively (see text in the Supporting Information). The ΔS‡ values depend on the ground state conformation. The C1–O cleaved CCC intermediate of 6 may have a charge-transferred rigid structure with a low entropy, whereas the CCC intermediate of 1 may have a flexible structure with a high intrinsic entropy, as suggested by the dipole moment of the CCC intermediate of 1 lower than that of 6 (Table S3, Supporting Information). The rotation around the C2=C3 bond of 1 therefore decrease ΔS‡, while that of 6 increases ΔS‡. The results are also consistent with the C2=C3 length of the TS2 state of 1 longer than that of 6 (Figure 8a,b). As shown in Figure S10 (Supporting Information), 8 scarcely undergo SP → MC isomerization even in polar media, because it does not contain an electron-deficient moiety and its TTC form is not stabilized sufficiently, as confirmed by the shallow ground state energy (Figure 8, right). Introducing a hydroxynaphthalimide, which is an electron-deficient fused aromatic moiety, lowers Eisom for isomerization, while stabilizing the TTC form. This facilitates polarity-driven rapid isomerization even at room temperature.

We demonstrated that a hydroxynaphthalimide-containing spiropyran (1) exhibits polarity-driven rapid SP ⇌ MC isomerization at room temperature. The SP → MC isomerization is driven by the ground state energy of the MC form of 1 lowered in more polar media. The quinoidal MC form exists mainly in less polar media, while the zwitterionic MC form exists dominantly with the increase in solvent polarity. The stabilized negative charge of the zwitterionic MC form lowers the ground state energy and, as a result, promotes enhanced SP → MC isomerization. 1 exhibits rapid SP ⇌ MC isomerization when changing the polarity of solvents; it reaches equilibrium within 30 s even at room temperature. Introducing a hydroxynaphthalene moiety with high π-electron density suppresses intramolecular charge transfer in the transition state. This decreases π-bond order of the C2=C3 bond and lowers the activation energy for rotational motion. The molecular design based on the introduction of an electron-deficient, fused aromatic moiety may contribute to the development of functional spiropyrans.

All reagents were purchased from Wako and Aldrich and used without further purification. The dyes 6 and 8 were obtained according to the procedure reported previously. 3-Formyl-4-hydroxy-N-butyl-1,8-naphthalimide was synthesized according to the literature procedure. The spectral measurements were carried out under aerated conditions for the sake of data reproducibility.

1,3,3-Trimethyl-2-methyleneindoline (329 mg, 1.9 mmol) and 3-formyl-4-hydroxy-N-butyl-1,8-naphthalimide (538 mg, 1.8 mmol) were stirred in EtOH (20 mL) at 343 K for 16 h. The resulting solution was concentrated by evaporation, and the residue was purified by a silica gel column chromatography using n-hexane/ethyl acetate (1:1 v/v) as an eluent, affording 1 as a dark green solid (161 mg, 17%). 1H NMR (400 MHz, DMSO-d6, TMS) δ (ppm): 8.62 (1H, s), 8.46 (1H, d, J = 7.6 Hz), 8.30 (1H, d, J = 7.6 Hz), 7.67 (1H, d, J = 8.0 Hz), 7.56 (1H, d, J = 8.0 Hz), 7.52 (1H, m), 7.45 (1H, m), 7.34 (1H, m), 3.99 (3H, m), 3.78 (3H, s), 1.72 (6H, s), 1.51–1.60 (2H, m), 1.25–1.35 (2H, m), 1.10–1.16 (1H, m), 0.86–0.91 (3H, m). 13C NMR (400 MHz, DMSO-d6, TMS) δ (ppm): 167.5, 164.3, 163.3, 142.9, 142.6, 132.2, 132.1, 132.0, 130.8, 130.2,129.2, 129.0, 126.8, 125.2, 123.0, 122.3, 122.2, 120.5, 119.7, 113.0, 50.5, 32.6, 30.4, 30.3, 27.6, 20.3, 14.4, 14.3. FAB(+)-MS m/z: calcd for C29H29N2O3+ [1 + H]+, 453.2173; found, 453.2174.