Resonance Raman Characterization of the Different Forms of Ground

Jan 29, 2010 - To investigate the substituent effect on the distribution of the forms of the ground-state species of 8-substituted 7-hydroxyquinolines...
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Resonance Raman Characterization of the Different Forms of Ground-State 8-Substituted 7-Hydroxyquinoline Caged Acetate Compounds in Aqueous Solutions Hui-Ying An,† Chensheng Ma,† Wen Li,† Kyle T. Harris,‡ Timothy M. Dore,*,‡ and David Lee Phillips*,† Department of Chemistry, The UniVersity of Hong Kong, Pokfulam Road, Hong Kong S.A.R., P. R. China, and Department of Chemistry, UniVersity of Georgia, Athens, Georgia 30602-2556 ReceiVed: NoVember 23, 2009

To investigate the substituent effect on the distribution of the forms of the ground-state species of 8-substituted 7-hydroxyquinolines, ultraviolet-absorption and resonance Raman experiments were performed for 8-chloro7-hydroxyquinoline (CHQ-OAc) and 8-cyano-7-hydroxyquinoline (CyHQ-OAc) in acetonitrile (MeCN), in NaOH-H2O/MeCN (60:40, v/v, pH 11-12), and in H2O/MeCN (60:40, v/v, pH 6-7) solutions, and these results were compared to those previously reported for the 8-bromo-7-hydroxyquinoline (BHQ-OAc) compound. Swapping a bromine atom in BHQsOAc for a chlorine atom in CHQ-OAc causes the amount of the tautomeric species to become larger, although the neutral species is still the predominant species for both systems in water-rich solutions. The absorption spectra and the resonance Raman spectra of CyHQ-OAc suggest that, because of the strong electron-withdrawing nature of the cyano substituent, a measurable amount of the anionic species is present and the tautomeric species cannot be easily detected in water-rich solutions. The results reported here reveal large substituent effects on the distribution of the different forms of the XHQ-OAc compounds in largely aqueous solutions. The steric effect of the 8-substituted group and competitive hydrogen bonding between the 8-substituted group and water molecules hinders the formation of a cyclic BHQ-OAc-water complex, and the electron-withdrawing property of the 8-substituted group enhances the deprotonation of the phenol group while disfavoring the formation of the positively charged quinoline nitrogen. We briefly discuss the implications of the substituent effects for using these compounds as phototriggers. SCHEME 1

Introduction In several recent papers, the 8-bromo-7-hydroxyquinolinyl group (BHQ) was reported to be a good phototrigger compound with enough sensitivity for both one-photon excitation (1PE) and two-photon excitation (2PE) applications in physiological environments.1 In addition, the low level of fluorescence for the BHQ group makes this kind of phototrigger compound more attractive for utilization in biological experiments.1 Meanwhile, it is noted that the 8-bromo-7-hydroxyquinolinyl group, as a derivative of 7-hydroxyquinoline, can exist in water-containing environments in one or more of four prototropic forms: a normal neutral molecule (N) species, an imine-protonated cation (C) species, an enol-deprotonated anion (A) species, and an imineprotonated and enol-deprotonated zwitterionic tautomer (T) species, as described for the 8-bromo-7-hydroxyquinoline acetate acid (BHQ-OAc) molecule in Scheme 1a. This ability for substituted hydroxyquinoline molecules to exist in appreciable amounts in up to four distinct species in aqueous solutions complicates the investigation of the chemistry and photochemistry of BHQ in aqueous environments. Additionally, the pKa of the phenolic moiety of 7-HQ has been reported to be 9.0,2 which is much higher than the 6.8 value of BHQ-OAc, and this indicates that the distribution of the forms of BHQ-OAc existing in neutral aqueous solutions would likely change * Authors to whom correspondence should be addressed. Tel.: 852-28592160; Fax: 852-2957-1586; E-mail: [email protected] (D.L.P.) and Tel.: 1-706-583-0423; Fax: 1-706-542-9454; E-mail: [email protected] (T.M.D.). † The University of Hong Kong. ‡ University of Georgia.

appreciably because of the presence of the 8-bromo group. On the basis of these concerns, the ground states of the different forms of BHQ-OAc were characterized in two typical solvent systems (MeCN and water-rich solutions with varying pH values) to provide fundamental information regarding the particular forms of the ground states present under different environmental conditions.3 This work found substantial amounts of the neutral and anionic forms of the molecule in neutralwater-rich solutions of BHQ-OAc with a minor coexistence of the tautomeric form, and this is a very different pattern compared to 7-hydroxyquinoline in neutral water which displays a much higher contribution of the tautomeric (29%) form than of the anionic (1%) form of the molecule.4 The large substituent

10.1021/jp911143e  2010 American Chemical Society Published on Web 01/29/2010

Forms of Ground-State 8-Substituted 7-Hydroxyquinoline Caged Acetate effect found for BHQ-OAc in neutral solution could be due to the steric and/or electronic effects of the 8-bromo group and/or competitive hydrogen bonding between the 8-bromo group and water molecules that inhibit the formation and transfer process of a BH-OAc-water cyclic complex.3 A recent paper reported that newly synthesized XHQ derivatives, 8-chloro-7-hydroxyquinoline and 8-cyano-7-hydroxyquinoline, were sensitive to 1PE and 2PE and their acetate acids CHQ-OAc and CyHQ-OAc (shown in Scheme 1b) could undergo photolysis reactions similar to those previously found for the BHQ-OAc system in neutral aqueous buffer solutions.5 It is likely that changing the bromine atom to other substituents like a chlorine atom or a cyano group will cause the pKa of the phenol group to change noticeably and thus change the distribution of the protropic species present in aqueous solutions for the substituted compound. This is very likely the case for the CyHQ-OAc compound that contains the strong electronwithdrawing cyano group. To explore the effect of 8-substituted 7-hydroxquinolines on their ground-state distribution of the different protropic species and also to provide fundamental information for further studies on their excited-state photolysis reaction mechanisms, absorption and resonance Raman spectroscopy experiments were done for CHQ-OAc and CyHQOAc in acetonitrile and neutral and alkaline mixed water/ acetonitrile solutions, and these results were compared to those previously found for BHQ-OAc. The results presented here demonstrate that there are large substituent effects on the distribution of the different forms of the XHQ-OAc compounds in largely aqueous solutions, and the implications of these substituent effects for employing these compounds as phototriggers is briefly discussed. Experimental and Computational Methods CHQ-OAc and CyHQ-OAc were prepared as described previously in the literature.5 Samples for the experiments described in this work were prepared by using spectroscopic grade acetonitrile (MeCN) and deionized water. Sodium hydroxide was used as needed to obtain sample solutions under basic conditions. Solutions of phosphate buffered saline (PBS) were titrated to the desired pH by using 1 M HCl or 1 M NaOH. A. pKa Determination. The pKa of the phenolic proton of CHQ-OAc and CyHQ-OAc was determined by measuring the UV absorbance spectra of 100 µM substrate in PBS-buffered solutions (1 mL) set to pH values between 2 and 10 in quartz cuvettes. The absorbance at 369 and 363 nm (for CHQ-OAc and CyHQ-OAc, respectively), which corresponds to the phenolate/phenol ratio, was plotted against the buffer pH, and the pKa was calculated from the half-equivalence point of the resulting titration curves. B. Absorption and Resonance Raman Experiments. UVvis spectra were acquired by using a Perkin-Elmer Lambda 19 UV-vis spectrometer. UV-vis and resonance Raman experiments were performed for CHQ-OAc and CyHQ-OAc in acetonitrile (MeCN) and NaOH-H2O/MeCN (60:40 v/v, pH ) 11-12) and H2O/MeCN (60:40 v/v, pH ) 6-7) mixed solvents. The concentrations were about 2 mM for the sample solutions. The experimental apparatus and methods used for these experiments have been described elsewhere,9 and only a short description will be given here. The resonance Raman experiments were conducted by using 266 nm excitation (the fourth harmonic from a Nd:YAG laser) with about 1 mW laser power. The excitation laser beam was loosely focused to about a 0.5 mm diameter spot size onto a flowing liquid stream of sample, and a back scattering geometry was utilized for sample

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excitation and for collection of the Raman scattered light by reflective optics. The Raman signal was detected by a liquid nitrogen cooled charge coupled device (CCD) detector and acquired for 30 s before being read out to an interfaced personal computer. Twenty of these readouts were added together to obtain the resonance Raman spectrum. The Raman bands of the MeCN solvent were used to calibrate the resonance Raman spectra with an estimated accuracy of (5 cm-1 in absolute frequency, and the solvent Raman bands were subtracted from the resonance Raman spectra by using an appropriately scaled solvent spectrum. C. Density Functional Theory (DFT) Calculations. The optimized geometry, vibrational modes, and vibrational frequencies for the singlet ground states of the four different forms of CHQ-OAc and CyHQ-OAc were obtained from (U)B3LYP/ 6-311G** DFT calculations. No imaginary frequency modes were observed at any of the optimized structures shown here. A Lorentzian function with a 25 cm-1 bandwidth was employed in conjunction with the computed Raman vibrational frequencies and their relative intensities to display the (U)B3LYP/6-311G** calculated Raman spectra to compare with the corresponding experimental resonance Raman spectra. TD-DFT-RPA calculations were also performed for the species of interest to estimate their electronic-transition energies and oscillator strengths as well as to predict the relevant frontier molecular orbitals related to the electronic transitions. All of the calculations were executed by using the Gaussian 03 program suite.10 Results Similar to BHQ-OAc, the CHQ-OAc and CyHQ-OAc molecules exist almost exclusively in their neutral form in neat organic solvents, in their cationic form in acid solutions, and in their anionic form in alkaline solutions. The pKa of BHQ-OAc1 and CHQ-OAc are both 6.8, whereas the pKa of CyHQ-OAc is 4.9. The forms of the molecules present in aqueous solutions and the distribution among the different forms will be determined by the acid-base equilibrium of the two prototropic functional groups (enol and amine) in their molecules. A. Absorption Spectra in Acetonitrile and Neutral and Alkaline Mixed H2O/MeCN Solvents. UV-vis absorption spectra of CHQ-OAc and CyHQ-OAc were measured in acetonitrile, H2O/MeCN (60:40, v/v, pH ) 6-7), and NaOHH2O/MeCN (60:40, v/v, pH 11-12) mixed solvents (see Figure 1). Because the pKa of both compounds is 6.8, it is not surprising that the absorption spectra of CHQ-OAc are quite similar to the corresponding absorption bands previously reported for BHQ-OAc with a long-wavelength absorption maxima located at around 328, 330, and 375 nm, respectively, in MeCN, neutral, and alkaline mixed aqueous solutions.3 The absorption bands observed in MeCN and alkaline solutions are attributed to the neutral and anionic species of CHQ-OAc, respectively. This indicates that the neutral form is still the predominant species in the neutral mixed aqueous solution and that the anionic and tautomeric forms do not have the comparable populations if they exist in the CHQ-OAc system. However, the spectra of CyHQ-OAc obtained in the above three solutions appear somewhat different from those of BHQ-OAc and CHQ-OAc. The spectrum of CyHQ-OAc has two long-wavelength absorption maxima at 324 and 336 nm in MeCN, and the maxima of the spectrum obtained in the alkaline mixed aqueous solution is located at 366 nm, which is about 9 nm blue-shifted compared to the other two compounds. In addition, the spectrum of CyHQ-OAc obtained in a neutral mixed aqueous solution shows a strong absorption band around 330 nm and an obvious

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Figure 1. UV-vis absorption spectra of BHQ-OAc, CHQ-OAc, and CyHQ-OAc in MeCN (black), in neutral (red), and in alkaline (blue) mixed solvents.

additional absorption band near 370 nm, and these two bands are located at absorption positions similar, respectively, to those observed in MeCN and in the alkaline mixed solution attributed to the neutral and anionic forms of CyHQ-OAc. This correlates with the fact that the pKa of the phenol group of CyHQ-OAc is 4.9, whereas that of both BHQ-OAc and CHQ-OAc is 6.8, so that the amount of the anionic species of CyHQ-OAc increases substantially, and it becomes the other main species in the system coexisting with the neutral species. Dore and coworkers5 reported that the UV spectrum of CyHQ-OAc at pH 7.2 in a KMOPS buffer only displayed one band at 364 nm, and they suggested that the compound exists as the phenolate in neutral aqueous buffer. When comparing these results with the results obtained here, it can be concluded that the band observed at 364 nm in the KMOPS solution is due to the absorption of the anionic species of the CyHQ-OAc and not to the tautomeric species which also has a phenolate structure. Dore and co-workers also reported that the absorptions bands of BHQ-OAc and CHQ-OAc obtained in a KMOPS solution appear around 370 nm1,5 and indicate that the deprotonation processes of the ground-state compounds are stimulated in the buffer solutions so that the amount of the anionic species will be significantly larger than that in the neutral mixed solvent examined here. No absorption band due to the lowest electronic transition of the proton-translocated tautomeric species of BHQ-OAc, CHQ-OAc, and CyHQ-OAc could be obviously observed in the neutral mixed solutions or in the KMOPS buffer solution. The absorption bands of the tautomeric species are usually located at wavelengths longer than those observed for the anionic

Figure 2. (a) 266 nm resonance Raman spectrum of CHQ-OAc obtained in MeCN (top) and (U)B3LYP/6-311G** calculated normal Raman spectrum (bottom) of the singlet ground state of the neutral form of CHQ-OAc, the structure of which is shown to the left of the spectrum. (b) 266 nm resonance Raman spectrum of CyHQ-OAc obtained in MeCN (top) and (U)B3LYP/6-311G** calculated normal Raman spectrum (bottom) of the singlet ground state of the neutral form of CyHQ-OAc, the structure of which is shown to the left of the spectrum. The dashed lines indicate the correlation of the calculated Raman bands to the experimental resonance Raman bands. The asterisks (/) show the places of the solvent bands.

form; the tautomeric species of 7-HQ in water6 has bands at around 400 nm. B. Resonance Raman Spectra Observed in Acetonitrile and in Neutral and Alkaline Mixed H2O/MeCN Solvents. To further characterize the anionic and tautomeric species in a neutral aqueous solution, resonance Raman spectra of CHQ-OAc and CyHQ-OAc in acetonitrile, in mixed NaOH-H2O/MeCN solvent (60:40, v/v, pH 11-12), and in mixed H2O/MeCN solvent (60:40, v/v, pH 6-7) were obtained. Acetonitrile Solution. Figure 2 shows the resonance Raman spectra of CHQ-OAc and CyHQ-OAc in acetonitrile. The experimental spectra are compared to the normal Raman spectrum of the corresponding normal forms predicted from (U)B3LYP/6-311G** DFT calculations. The experimental and calculated spectra show some differences in their relative Raman intensity pattern, which can be accounted for by the experimental spectra being resonantly enhanced whereas the calculated spectra are nonresonant Raman spectra. Examination of Figure 2a,b shows that there is reasonable agreement for CHQ-OAc and CyHQ-OAc between their resonance Raman spectra and the

Forms of Ground-State 8-Substituted 7-Hydroxyquinoline Caged Acetate

Figure 3. 266 nm resonance Raman spectra are shown for BHQ-OAc (a), CHQ-OAc (b), and CyHQ-OAc (c) obtained in MeCN. The asterisks (/) mark the region where solvent bands have been subtracted.

calculated Raman spectra for the vibrational frequency pattern with the calculated frequencies being within 8 and 7 cm-1 on average for the experimental Raman bands in the region above 1000 cm-1, respectively. The characteristic carbon double-bond bands in the resonance Raman spectra of CHQ-OAc are located at 1561 cm-1 (that has contributions from the nominal CdC ring stretching, CsN stretching, and OsH bending motions) and at 1609 cm-1 (that has contributions from the nominal CdC ring stretching and CsN stretching motions). The characteristic carbon double-bond bands in the resonance Raman spectra of CyHQ-OAc are located at 1578 cm-1 (that has contributions from the nominal CdC ring stretching, CsN stretching, and OsH bending motions) and at 1605 cm-1 (that has contributions from the nominal CdC ring stretching and CsN stretching motions). Comparisons of the experimental and calculated vibrational frequencies, preliminary vibrational assignments, and qualitative descriptions of the vibrational modes in the 600-1800 cm-1 region of Figure 2a,b are given in Tables 1S and 2S in the Supporting Information. The resonance Raman spectra and comparisons to the predicted calculated Raman spectra in Figure 2 confirm the assignments of the predominant species in MeCN being the singlet ground state of the normal forms. Figure 3 presents an overview of the resonance Raman spectra of the singlet ground states of the neutral forms of BHQ-OAc, CHQ-OAc, and CyHQ-OAc. The signal-to-noise ratio is not the best for the spectra of the neutral forms of CHQ-OAc and CyHQ-OAc because of their higher levels of fluorescence.3,5 However, it is still clear that the spectra of the neutral forms of CHQ-OAc and BHQ-OAc are very similar to each other and the spectrum of the neutral form of CyHQ-OAc appears different from the other two. For example, the characteristic band with the nominal CdC ring stretching, CsN stretching, and OsH bending motions is located at 1564 cm-1 for the neutral form of BHQ-OAc, at 1561 cm-1 for the neutral form of CHQ-OAc, and at 1578 cm-1 for the neutral form of CyHQ-OAc which is about 15 cm-1 red-shifted compared to BHQ-OAc and CHQ-OAc. Alkaline Mixed Aqueous Solution. To obtain resonance Raman spectra of the ground state of the anionic forms and to investigate whether the anionic forms coexist in neutral aqueous solutions, the resonance Raman spectra of CHQ-OAc and CyHQ-OAc were obtained in a mixed NaOH-H2O/MeCN solvent (60:40, v/v, pH 11-12). Similar to BHQ-OAc, the

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resonance Raman spectrum of CHQ-OAc obtained in the alkaline mixed aqueous solution exhibits a single Raman band at 1601 cm-1 associated with the nominal CdC ring and CsN and CsO- stretching motions compared to the two bands at 1561 and 1609 cm-1 (associated with the nominal CdC ring stretching, CsN stretching, and OsH bending motions) in the resonance Raman spectrum of the neutral form of CHQ-OAc (shown at the top of Figures 2a and 4a). Because the predominant species should be the anionic form of the molecule in the alkaline mixed aqueous solution, the experimental resonance Raman spectrum obtained in the alkaline mixed aqueous solution is compared with the normal Raman spectrum of the anionic form of CHQ-OAc predicted from B3LYP/6-311G** DFT calculations (see Figure 4a). Inspection of Figure 4a shows good agreement between the experimental resonance Raman spectrum and the calculated Raman spectrum for the singlet ground state of the anionic CHQ-OAc vibrational frequency pattern with the calculated frequencies being within 12 cm-1 on average for the twelve experimental Raman bands. A comparison of the experimental and calculated vibrational frequencies, preliminary vibrational assignments, and qualitative descriptions of the vibrational modes in the 600-1800 cm-1 region of Figure 2a is given in Table 3S in the Supporting Information. The resonance Raman spectra and comparisons to the predicted Raman spectra in Figure 4a confirm the assignment of the predominant species to the singlet ground state of the anionic form of CHQ-OAc in the mixed NaOH-H2O/MeCN solvents (60:40, v/v, pH 11-12). Similar experiments and data analysis were done for CyHQ-OAc in a mixed NaOH-H2O/MeCN solvent (60:40, v/v, pH 11-12) to obtain the resonance Raman spectrum of the anionic form of CyHQ-OAc. The difference between the experimental resonance Raman spectrum and the calculated Raman spectrum for the singlet ground state of the anionic CyHQ-OAc vibrational frequency pattern with the calculated frequencies is within 12 cm-1 on average for the seven experimental Raman bands (see Figure 2b). It is interesting to note that only a single resonance Raman band is observed in the 1600 cm-1 region for the ground-state anionic forms of BHQ-OAc and CHQ-OAc, whereas the ground-state anionic form of CyHQ-OAc exhibits two resonance Raman bands at around 1569 and 1596 cm-1 associated with the nominal CdC ring and CsN and CsO- stretching motions. In addition, two resonance Raman bands at 1499 and 1531 cm-1 associated with the nominal CdC ring, CsN stretching, and CsH bending motions are substantially enhanced in the spectrum of the anionic form of CyHQ-OAc, whereas the bands in the region below 1000 cm-1 become noticeably less intense (see Figure 5). Comparison of the resonance Raman spectra for the singlet ground states of the anionic forms of the BHQ-OAc, CHQ-OAc, and CyHQ-OAc molecules suggests that the highly enhanced resonance Raman bands seem to be affected by the electron-withdrawing nature of the substituent group. Neutral Mixed Aqueous Solution. The resonance Raman spectrum of CHQ-OAc measured in a mixed H2O/MeCN solvent (60:40, v/v, pH 6-7) is displayed at the top of Figure 6. On the basis of the knowledge that CHQ-OAc could exist in its neutral, anionic, and tautomeric forms in neutral aqueous solutions, spectrum ((a) in Figure 6) may provide the overall Raman information of the different forms of CHQ-OAc. Because the information provided by the anionic CHQ-OAc is much more distinctive and clearer than that for the neutral species, the appropriately scaled spectrum shown in part (b) of Figure 6 was subtracted from the spectrum in part (a). The

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Figure 4. (a) The 266 nm resonance Raman spectrum of CHQ-OAc obtained in a NaOH-H2O/MeCN (60:40, v/v, pH 11-12) solvent (top) and the (U)B3LYP/6-311G** calculated normal Raman spectrum (bottom) of the singlet ground state of the anionic form of CHQ-OAc (the structure of which is given to the right of the spectrum) are shown. (b) The 266 nm resonance Raman spectrum of CyHQ-OAc obtained in a NaOH-H2O/ MeCN (60:40, v/v, pH 11-12) solvent (top) and the (U)B3LYP/6-311G** calculated normal Raman spectrum (bottom) of the singlet ground state of the anionic form of CyHQ-OAc (the structure of which is given to the right of the spectrum) are shown. The dashed lines indicate the correlation of the calculated Raman bands to the experimental resonance Raman bands. The asterisks (/) mark the region where solvent bands have been subtracted.

medium intensity bands existing in the resonance Raman spectrum of the anionic CHQ-OAc at 1329 and 851 cm-1 disappear after subtraction, and spectrum (c) was obtained. Comparison of spectrum (c) in Figure 6 to spectrum (d) which is attributed to the neutral form of CHQ-OAc shows that the Raman band at 1622 cm-1 in spectrum (c) is noticeably different from that at 1609 cm-1 in spectrum (d). Therefore, spectrum (e) in Figure 6 was similarly obtained by subtracting an appropriately scaled spectrum (d) from spectrum (c). The ten bands in spectrum (e) exhibit reasonable agreement with the calculated normal Raman spectrum of the singlet ground state of the tautomeric form of CHQ-OAc (see spectrum (f) in Figure 6) for the vibrational frequency pattern with the calculated frequencies being within 10 cm-1 on average. In addition, the Raman band at 1626 cm-1 in spectrum (e) is associated with the nominal CsC stretching, CsO- stretching, and NsH

bending motions in the calculation results (see Table 5S in the Supporting Information) and is characteristic of the tautomeric form of the molecule. Compared to the spectrum of the tautomeric form of the BHQ-OAc molecule obtained by using the same method, the bands in spectrum (e) obtained here are much stronger. Because the structure and absorption properties are very similar for the CHQ-OAc and BHQ-OAc molecules, this result suggests that the ratio of the tautomeric form of CHQ-OAc is larger than that of BHQ-OAc in neutral waterrich solutions. Comparison of the three experimental spectra of CyHQ-OAc shows that the spectrum obtained in the neutral mixed solution is very similar to that obtained in MeCN (see spectra (a) and (b) in Figure 7). Spectrum (c) in Figure 7 was obtained by subtracting an appropriately scaled spectrum (b) from spectrum (a). Although the bands cannot be observed very clearly because

Forms of Ground-State 8-Substituted 7-Hydroxyquinoline Caged Acetate

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Figure 5. The 266 nm resonance Raman spectra of BHQ-OAc (a), CHQ-OAc (b), and CyHQ-OAc (c) obtained in a NaOH-H2O/MeCN (60:40, v/v, pH 11-12) solvent are shown. The asterisks (/) mark the region where solvent bands have been subtracted.

of the lower signal-to-noise ratio of spectra (a) and (b) caused by the higher level of fluorescence and some possible oversubtraction cannot be completely avoided when the subtraction was conducted, examination of spectrum (c) in Figure 7 still shows that the two remaining bands at 1531 and 1596 cm-1 are exactly located at the same places as the characteristic bands of the experimental spectrum attributed to the anionic form of CyHQ-OAc obtained in the alkaline aqueous mixed solutions. This suggests that a small amount of the anionic form of CyHQ-OAc exists in the neutral mixed solution, which is also indicated in the UV absorption spectrum of CyHQ-OAc under the same conditions. The investigation of the Raman spectra and the UV absorption spectrum of CyHQ-OAc cannot provide any clear evidence for the presence of a noticeable amount of the tautomeric form of CyHQ-OAc, and this suggests there is very little tautomeric form of CyHQ-OAc present in this waterrich solution. Discussion Examination of the resonance Raman spectra and the UV spectra of CHQ-OAc and CyHQ-OAc together with the previous report of analogous results for BHQ-OAc reveals that, compared to 7-HQ in water at pH 7, the neutral forms are still the predominant species in the water-rich solutions and the amount of the anionic forms modestly increases in these aqueous solutions. The amount of the tautomeric species decreases appreciably (for BHQ-OAc and CHQ-OAc) or diminishes almost completely (for CyHQ-OAc). We have suggested that the formation of the tautomeric forms of the 7-hydroxyquinoline and its derivatives may be affected by steric and/or electronic effects of the 8-substituented group.3 The first process that may be affected is the ease of formation of the cyclic hydroxyquinoline-water complex. Whether these compact cyclic structures can be formed will favor or disfavor the ground-state proton transfer that has been reported for 7-hydroxyquinoline7 and 8-methyl-7-hydroxyquinoline.2 The second effect that can influence the formation of the tautomeric forms is that the inductively electron-withdrawing nature of the substituent group can disfavor the formation of a positively charged nitrogen atom in the system. The third process that may be affected is the competitive hydrogen bonding between the substituent group and the water molecules. The results presented

Figure 6. (a) The 266 nm resonance Raman spectrum of CHQ-OAc obtained in a mixed H2O/MeCN solvent (60:40, v/v, pH 6-7) is displayed. (b) The 266 nm resonance Raman spectrum of CHQ-OAc obtained in a mixed NaOH-H2O/MeCN solvent (60:40, v/v, pH 11-12) is shown. (c) The bands remaining after subtraction of an appropriately scaled spectrum (b) from spectrum (a) are shown. (d) The 266 nm resonance Raman spectrum of CHQ-OAc obtained in MeCN is displayed. (e) The bands remaining after subtraction of an appropriately scaled spectrum (d) from spectrum (c) are shown. (f) DFT calculated normal Raman spectrum of the singlet ground state of the tautomeric form of CHQ-OAc (the structure of which is shown to the left of the spectrum) is presented. The dashed lines indicate the correlation of two spectra compared to each other. The pound signs (#) show the places where subtraction artifacts might be noticeable.

here for CHQ-OAc and CyHQ-OAc provide more support for these explanations of the substituent effect on the distribution of the forms of the molecules in aqueous environments. On one hand, when the chlorine substituent is compared to the bromine substituent, the size is much smaller, and the nature of the electron-withdrawing and the capacity of the formation of the hydrogen bonding are much smaller than those compared to the bromine substituent. Thus, the cyclic CHQ-OAc-water complex is much easier to form, and the formation of the hydrogen bonding between the chlorine and the water molecules is less competitive. This leads to more obvious signals attributed to the tautomeric species, which can be obtained after subtraction of the spectra of the ground-state anion species and the neutral species from the overall spectrum of CHQ-OAc. On the other hand, the cyano group has a much larger size which severely hinders the formation of the cyclic complex, and the strong electron-withdrawing nature disfavors the formation of a positively charged nitrogen in the quinoline moiety; therefore,

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Figure 7. (a) The 266 nm resonance Raman spectrum of CyHQ-OAc obtained in a mixed H2O/MeCN solvent (60:40, v/v, pH 6-7) is shown. (b) The 266 nm resonance Raman spectrum of CyHQ-OAc obtained in a MeCN solvent is displayed. (c) The bands remaining after subtraction of an appropriately scaled spectrum (b) from spectrum (a) are presented. (d) The 266 nm resonance Raman spectrum of CyHQ-OAc obtained in a mixed NaOH-H2O/MeCN solvent (60:40, v/v, pH 11-12) is shown. The dashed lines indicate the correlation of two spectra compared to each other. The pound signs (#) show the places where subtraction artifacts might be noticeable.

the tautomeric species of CyHQ-OAc is very difficult to form in this system in aqueous solutions. The full experimental resonance Raman spectra of CHQ-OAc and CyHQ-OAc covering the 0-5000 cm-1 region show that, at the 266 nm excitation wavelength, no clear feature was seen below 600 cm-1 and above 1800 cm-1 in all of the resonance Raman spectra. The lack of overtones and combination bands in the spectra obtained in these solutions suggests that water may noticeably perturb the Franck-Condon region of the electronic excited state. Time-dependent DFT calculations performed by using the random phase approximation (RPA) were done to estimate the vertical-transition energies, the oscillator strengths, and the changes in the molecular orbitals involved in the electronic transitions of the neutral and anionic forms of CHQ-OAc and CyHQ-OAc that can be directly obtained in acetonitrile solvent and in the alkaline aqueous solution. Table 1 shows their strongest oscillator-strength transitions obtained from the TDDFT calculations in the 225-275 nm region. The relevant frontier molecular orbitals related to the electronic transitions

are displayed in the Supporting Information. According to the TD-DFT-RPA calculations (see Table 1), the predominant excitations are all transformations of the electron density from the large-scale conjugated π bonding orbital to the antibonding π* orbital, and these are depicted in Figure 2S in the Supporting Information. These results indicate that the predominant transitions mostly result in a substantial weakening of the π ring system localized on the phenolic moiety and lead to higher electron densities in the ring connected with the acetate group after excitation, which may favor the release of the acetate group. Although the calculated results are similar to the neutral CHQ-OAc and BHQ-OAc species, the overtone and combinations of the strong Raman bands could not be found in the spectrum of neutral CHQ-OAc as observed for that of neutral BHQ-OAc. This may be in part due to the lower signal-tonoise ratio of the neutral CHQ-OAc spectrum caused by the high fluorescence, and it could also be due in part to the heavyatom effect which may increase the intensity of the overtone and combination bands.8 From Table 1 and the results given in Figure 2S in the Supporting Information, it can be seen that almost all of the relevant frontier molecular orbitals in the calculations of the neutral and anionic forms have little contribution from the acetate leaving group. This explains the absence of obvious resonance Raman bands related to the vibration of the acetate group in both of the resonance Raman spectra. Comparison of the above experimental results for BHQ-OAc, CHQ-OAc, and CyHQ-OAc reveals that the distribution of the different forms of the XHQ-OAc compounds in largely aqueous solutions can be substantially affected by the structure and electronic properties of the 8-subsitituted chromophores. A change of the 8-subsitituted chromophore from either a bromo or a chloro substituent to a cyano substituent lowers the pKa of the phenolic group and further makes the relative population of the anionic form species increase substantially and become obviously observable in the experimental spectra reported here. Moreover, the stronger electron-withdrawing property of the 8-substituted group can substantially enhance the deprotonation of the phenol group, and any appreciable steric effect of the substituent group will help disfavor the formation of the tautomeric form. Because the XHQ-OAc molecules in the ground state are the species that are photoexcited in the photochemical applications of these compounds in aqueous environments (for example, in physiological experiments), it is important to know what forms of the molecule and their relative populations are in the ground state of the XHQ-OAc molecules, because this will determine what is photoexcited to their

TABLE 1: Electronic Transition Energies, Oscillator Strengths, and Related Molecular Orbital Transitions for the Strongest Oscillator-Strength Transitions Obtained from (U)B3LYP/6-311G** DFT Calculations for the Neutral and Anionic Forms of CHQ-OAc and CyHQ-OAc in the 225-275 nm Region CHQ-OAc normal form

CyHQ-OAc anionic form

normal form

anionic form

235.18 nm (0.12)

247.64 nm (0.53)

a

Excitation Energy 226.37 nm (0.67) 60 f 66 61 f 67 64 f 66 64 f 67 64 f 68 64 f 69 65 f 67 a

(-0.11) (-0.14) (-0.28) (0.10) (-0.15) (0.11) (0.48)

251.45 nm (0.49) 61 f 66 63 f 66 63 f 67 63 f 68 63 f 69 65 f 68 65 f 69

Molecular Orbital Changesb (0.14) 59 f 64 (0.39) 62 f 64 (-0.35) 63 f 65 (-0.11) 63 f 66 (0.11) (-0.18) (0.20)

Numbers in parentheses are oscillator strengths of the corresponding excitations. configuration coefficients for the corresponding orbital changes to the excitations.

(0.22) (0.11) (0.30) (0.55

b

59 f 64 61 f 64 61 f 65 61 f 66 63 f 66 63 f 68 63 f 69

(0.21) (0.39) (-0.16) (-0.22) (-0.22) (-0.27) (0.12)

Numbers in parentheses are contributions of the

Forms of Ground-State 8-Substituted 7-Hydroxyquinoline Caged Acetate electronic excited states and hence their subsequent photochemistry for the compound of interest under varying aqueous conditions. The results here provide a foundation for detailed time-resolved spectroscopy experiments to directly examine the reaction pathways, intermediates, and reaction mechanisms involved in the photodeprotection reactions of XHQ-OAc molecules. Conclusions UV absorption and resonance Raman experiments were performed for the 8-substituted 7-hydroxyquinolinyl derivatives CHQ-OAc and CyHQ-OAc in MeCN, in H2O/MeCN (60: 40, v/v, pH 6-7), and in NaOH-H2O/MeCN (60:40, v/v, pH 11-12) solutions in order to investigate the substituent effect on the distribution of the forms of the ground-state species existing in neutral water-rich solutions in comparison to analogous results for the previously studied BHQ-OAc system. When changing the 8-substituent from a bromine atom to a chlorine atom, the absorption spectra and the Raman spectra indicate that, although the neutral species is still the predominant species in both cases, the amount of the tautomeric species is larger for CHQ-OAc compared to that for BHQ-OAc under similar conditions. The absorption spectra and the resonance Raman spectra of CyHQ-OAc show that, whereas the neutral form of CyHQ-OAc is still one of the major species and the amount of the anionic species increases significantly and becomes measurable, no tautomeric species can be detected in a water-rich solution. The results presented here further reveal that large substituent effects such as the steric interaction of the 8-substituted group and competitive hydrogen bonding between the 8-substituted group and water molecules can significantly inhibit the formation of a cyclic BHQ-OAc-water complex, and the electron-withdrawing property of the 8-substituted group can substantially enhance the deprotonation of the phenol group while disfavoring the formation of the positively charged quinoline nitrogen atom. Synopsis The substituent effect on the distribution of the forms of the ground-state species of 8-substituted 7-hydroxyquinolines was studied. Acknowledgment. This work was supported by a grant from the Research Grants Council of Hong Kong (HKU 7039/07P), the award of a Croucher Foundation Senior Research Fellowship (2006-07) from the Croucher Foundation, an Outstanding Researcher Award (2006) from the University of Hong Kong to D.L.P., and an NSF CAREER Award (CHE-0349059) to T.M.D. Supporting Information Available: Tables 1S, 2S, 3S, 4S, and 5S present comparisons of the experimental resonance Raman spectra vibrational frequencies and the DFT calculated vibrational frequencies over the 600-1800 cm-1 region along with preliminary vibrational assignments and qualitative descriptions of the vibrational modes for the singlet ground states of the neutral form of CHQ-OAc, the neutral form of CyHQ_OAc, the anionic form of CHQ-OAc, the anionic form of CyHQ-OAc, and the tautomeric form of CHQ-OAc,

J. Phys. Chem. A, Vol. 114, No. 7, 2010 2505

respectively. Tables 6S and 7S display selected structural parameters determined for the ground states of the neutral form, the anionic form, and the tautomeric form of CHQ-OAc and the neutral form and the anionic form of CyHQ-OAc from the (U)B3LYP/6-311G** calculations. Tables 8S and 9S show selected electronic transition energies and oscillator strengths of the ground states of the neutral form, the anionic form, and the tautomeric form of CHQ-OAc and the neutral form and the anionic form of CyHQ-OAc obtained from the (U)B3LYP/6-311G** TD-DFT-RPA calculations. Tables 10S and 11S present the Cartesian coordinates, the total energies, and the vibrational zero-point energies for the optimized geometry obtained from the (U)B3LYP/6-311G** calculations for the ground states of the neutral form, the anionic form, and the tautomeric form of CHQ-OAc and the neutral form and the anionic form of CyHQ-OAc. Figure 1S shows schematic diagrams for the structures obtained from the (U)B3LYP/6-311G** DFT calculations for the ground states of the neutral form, the anionic form, and the tautomeric form of CHQ-OAc and the neutral form and the anionic form of CyHQ-OAc. Figure 2S shows a depiction of the HOMO and LUMO for the strongest oscillator-strength transition in the 225-275 nm region for the neutral forms and the anionic forms of CHQ-OAc and CyHQ-OAc. Figure 3S shows the UV spectra of CHQ-OAc and CyHQ-OAc in PBS solution at varying pH. This material is available free of charge via the Internet at http://pubs.acs.org. References and Notes (1) (a) Fedoryak, O. D.; Dore, T. M. Org. Lett. 2002, 4, 3419. (b) Zhu, Y.; Pavlos, C. M.; Toscano, J. P.; Dore, T. M. J. Am. Chem. Soc. 2006, 128, 4267. (2) Nakagawa, T.; Kohtani, S.; Itoh, M. J. Am. Chem. Soc. 1995, 117, 7952. (3) An, H. Y.; Ma, C. S.; Nganga, J. L.; Zhu, Y.; Dore, T. M.; Phillips, D. L. J. Phys. Chem. A 2009, 113, 2831. (4) Mason, S. F.; Philip, J.; Smith, B. E. J. Chem. Soc. A 1968, 3051. (5) Davis, M. J.; Kragor, C. H.; Reddie, K. G.; Wilson, H. C.; Zhu, Y.; Dore, T. M. J. Org. Chem. 2009, 74, 1721. (6) (a) Lee, S. I.; Jang, D. J. J. Phys. Chem. 1995, 99, 7537. (b) Park, H. J.; Kwon, O. H.; Ah, C. S.; Jang, D. J. J. Phys. Chem. B 2005, 109, 3938. (c) Kwon, O. H.; Kim, T. G.; Lee, Y. S.; Jang, D. J. J. Phys. Chem. B 2006, 110, 11997. (7) Bohra, A.; Lavin, A.; Collins, S. J. Phys. Chem. 1994, 98, 11424. (8) Schmidt, R.; Afshari, E. Ber. Bunsen-Ges. Phys. Chem. 1992, 96, 788. (9) (a) Li, Y. L.; Leung, K. H.; Phillips, D. L. J. Phys. Chem. A 2001, 105, 10621. (b) Zhu, P. Z.; Ong, S. Y.; Chan, P. Y.; Leung, K. H.; Phillips, D. L. J. Am. Chem. Soc. 2001, 123, 2645. (c) Zhu, P. Z.; Ong, S. Y.; Chan, P. Y.; Poon, Y. F.; Leung, K. H.; Phillips, D. L. Chem.sEur. J. 2001, 7, 4928. (d) Chan, P. Y.; Kwok, W. M.; Lam, S. K.; Chiu, P.; Phillips, D. L. J. Am. Chem. Soc. 2005, 127, 8246. (e) Xue, J. D.; Guo, Z.; Chan, P. Y.; Chu, L. M.; But, T. Y. S.; Phillips, D. L. J. Phys. Chem. A 2007, 111, 1441. (10) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A. J.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Andres, J. L.; Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A.; Gaussian 98, revision A.7 and Gaussian 03s, revision B.05; Gaussian Inc.: Pittsburgh PA, 1998 and 2003.

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