Structure-Photochemical Function Relationships in Nitrogen-Containing Heterocyclic Aromatic Photobases Derived from Quinoline
Photobases are compounds which become strong bases after electronic excitation.Recent experimental studies have highlighted the photobasicity of the 5-R quinoline compounds, demonstrating a strong substituent dependence to the 𝑝𝐾 # * . In this paper we describe our systematic study of how the photobasicity of four families of nitrogen-containing heterocyclic aromatics are tuned through substituents. We show that substituent position and identity both significantly impact the 𝑝𝐾 # * . We demonstrate that the substituent effects are additive and identify many disubstituted compounds with substantially greater photobasicity than the most photobasic 5-R quinoline compound identified previously. We show that the addition of a second fused benzene ring to quinoline, along with two electron-donating substituents, lowers the S0®SCT vertical excitation energy into the visible while still maintaining a 𝑝𝐾 # * > 14.Overall, the structure-function relationships developed in this study provide new insights to guide the development of new photocatalysts that employ photobasicity.
Introduction<!>Theoretical Methods<!>Analysis of the Photobasicity of the Monosubstituted Quinolines<!>Additionally, Figures 6 and S6 contain multiple examples of compounds which have very similar<!>Expanding the Scope of Nitrogen-Containing Aromatic Heterocyclic Photobases:<!>On the Validity of the Förster Mechanism for Nitrogen-Containing Aromatic Heterocycles Containing Strong Electron-Donating Groups<!>Conclusions<!>Supporting Information<!>Table of Contents
<p>Photocatalysts are of widespread interest to the chemistry community because of their important role in the transformation of solar light into chemical energy as well as the ability to systematically control catalyst reactivity using light. In processes like artificial photosynthesis, photocatalysts make possible redox reactions which require the overall transfer of multiple electrons and protons. This chemistry is driven by the rearrangement of charge in the photocatalyst after excitation to a state with significant charge-transfer character. This redistribution of charge in the electronic excited state allows electron or proton transfer reactions to occur which would otherwise be thermodynamically and/or kinetically unfavorable in the ground state.</p><p>Excited-state proton transfer represents a specific manifestation of photocatalysis that has also been applied to the optical control of enzymes as well as a probe of local molecular environments. [1][2][3] Previous experimental and theoretical investigations of systems which exhibit excited-state proton transfer have primarily focused on photoacids, molecules which become stronger proton donors after electronic excitation (𝑝𝐾 # * < 𝑝𝐾 # ). [4][5][6][7][8][9][10][11] The gains in acid strength with photoexcitation can be very large, with examples reported in the literature of molecules whose 𝐾 # * is 12 orders of magnitude larger than its 𝐾 # . 9 Interestingly, photobases, molecules which become stronger proton acceptors after electronic excitation, are much less well represented in the literature despite their potential application in photocatalysis. [12][13][14][15][16][17][18][19] Recent experimental studies performed in the Dawlaty lab have investigated the photochemical properties of a family of 5-R quinoline derivatives. [20][21][22][23][24][25] These compounds were all shown to be photobases, with the magnitude of the photobasicity depending strongly on the identity of the substituent. Specifically, photoexcitation results in Kb increasing by over 10 orders of magnitude when the substituent is the electron-donating NH2 group but only approximately 2 orders of magnitude when the substituent is the electron-withdrawing CN group. This behavior has been attributed to the charge-transfer character of the singlet bright state responsible for the photobasicity, SCT. Specifically, the S0®SCT transition results in an increase of electron density on the ring nitrogen atom and hence an increase in its basicity. Electron-donating substituents amplify the charge-transfer character of the transition, leading to larger 𝑝𝐾 # * .</p><p>As a further step towards practical photocatalysts employing photobasicity, a recent study reported two iridium complexes containing a pendant quinoline ligand. 23 This study demonstrated that the quinoline moiety maintained its photobasicity in the complexes and as such, represents the first rational design of a transition metal complex in which a ligand exhibits light-triggered proton removal functionality.</p><p>While these studies demonstrate the potential of applying photobasicity in photocatalyst design, only a very limited family of photobases has been systematically studied to date. In this paper, we report a computational investigation of structure-function relationships in the photobasicity of nitrogen-containing heterocyclic aromatics related to quinoline. We demonstrate that both substituent identity and position matter in determining the thermodynamic driving force for excited state protonation. We show that the substituent effects are additive, with a number of quinoline and isoquinoline derivatives with multiple electron-donating substituents identified to have 𝐾 * * that are several orders of magnitude larger than that of the strongest monosubstituted quinoline photobase identified in experiment, 5-aminoquinoline. We demonstrate that the addition of a second fused benzene ring lowers the S0®SCT excitation energy while also decreasing the extent of photobasicity; similar conclusions were recently drawn by Hunt et al. 24 However, we identify a number of acridine and 1-azaanthracene derivatives which are both strong bases in the SCT excited state and have S0®SCT excitation energies that are in the visible. Collectively, this work further refines the design principles necessary to develop new photocatalysts which employ photobasicity.</p><!><p>Figure 1 illustrates the Förster cycle used to calculate DG* and hence p𝐾 # * from a series of quantities that are readily obtained from electronic structure calculations, specifically ∆𝐺 * = ∆𝐺 + ∆𝐸 11 2 − ∆𝐸 11 24 . In this equation, the ground state DG is related to DG* through the adiabatic SCT-S0 energy gaps of the base and conjugate acid, ∆𝐸 11 2 and ∆𝐸 11 24 . More specifically, ∆𝐸 11 2 = 𝐸 5 67 8 − 𝐸 5 9 8 , where 𝐸 5 67 8 is the electronic energy of the charge-transfer SCT state at the SCT minimum energy geometry while 𝐸 5 9 8 is the S0 electronic energy at the S0 minimum energy geometry.</p><p>The first step is calculating the ground state free energies of B and BH + , GB and GBH, where the geometry optimizations and vibrational frequency evaluations are performed at the The Förster cycle used to calculate ∆𝐺 * from ∆𝐺 and the adiabatic SCT-S0 energy gap for the base and conjugate acid (∆𝐸 11 2 and ∆𝐸 11 24 ). Vibrational relaxation on SCT is denoted by the dotted black lines.</p><p>wB97XD/def2-svpd level of theory while the electronic energies are subsequently evaluated using wB97XD/def2-tzvppd. 26,27 All DFT calculations employ a (99,590) integration grid.</p><p>Solvent effects are included using a polarizable continuum model (PCM); a conductor-like PCM (CPCM) for the geometry optimizations and an integral equation formalism PCM (IEF-PCM) for the single-point calculations. 28 Both PCM models use a cavity constructed with Bondi radii and switching Gaussian surface charges. 29,30 As in the experiments, the solvent used in these calculations is water. All electronic structure calculations were performed using the Q-Chem 5.1 software package. 31 Figure 2 demonstrates that the calculated GB-GBH is very strongly correlated with the experimental pKa of BH + for the family of 5-R-quinoline derivatives considered by Dawlaty and coworkers. 20 Indeed, we take Figure 2 to provide a suitable calibration curve to convert GB-GBH into pKa for other N-containing aromatic heterocycles where the basicity involves a sp 2 hybridized lone pair on N. The desired DG is then easily calculated from the pKa using ∆𝐺 = 2.303𝑅𝑇𝑝𝐾 ? . Finally, note that 5-bromoquinoline is excluded from the linear regression analysis presented in Figure 2 because it did not follow the same trend as the other 5-R quinoline compounds.</p><p>The remaining quantities, ∆𝐸 11 2 and ∆𝐸 11 24 , are the adiabatic SCT-S0 energy gaps for the base and conjugate acid. The excited state geometry optimizations are performed at the TD-DFT/wB97XD/def2-svpd level of theory within the Tamm-Dancoff approximation (TDA) while the single-point calculations are performed using TD-DFT/wB97XD/def2-tzvppd without the TDA. TDA is used in the excited state geometry optimizations to avoid numerical singularities that can arise when full TD-DFT is used to explore potential energy surfaces. 32 All TD-DFT calculations used a (99,590) integration grid. As above, solvent effects are included using PCM, with CPCM used in the excited state geometry optimizations and state-specific IEF-PCM used for the single-point calculations. 33,34 The PCM models were parameterized for water with cavities constructed using Bondi radii and switching Gaussian surface charges. . 20 Note that 5-bromoquinoline was not included in the above analysis because it did not follow the trend formed by the other 5-R quinoline compounds.</p><p>Our choice of the wB97XD functional for this study is motivated in part because it is a long-range corrected functional. Long-range corrected functionals are known to reduce the selfinteraction error in DFT and provide an improved description of charge-transfer states in TD-DFT calculations. 35 In particular, TD-DFT calculations performed using the wB97XD functional have been shown to provide a reasonable description of the low-lying singlet states of heteroaromatics, in particular SCT. 36,37 Throughout this study, we identify SCT as the lowest-energy 𝜋 → 𝜋 * bright state of the bases for which the ring nitrogen gains charge density and hence becomes more basic. Analysis of the electronic character of the excitations is performed using natural transition orbitals and Löwdin charge differences. 38,39 The highest occupied natural transition orbitals (HONTO) and the lowest unoccupied natural transition orbital (LUNTO) associated with SCT are shown in Figure 3 for two representative compounds considered in this study; other examples can be found in the Supporting Information. In particular, Figure 3 shows that SCT is 𝜋 → 𝜋 * with charge-transfer character, with electron density on the amine groups shifting into the rest of the molecule. We further ensure that the chosen state for the acid form of the compounds has the same electronic character as the base. For the majority of the compounds considered in this study, particularly those with strongly electron-donating substituents, SCT is identified as S1. State-tracking is used during the excited state geometry optimizations to ensure that the electronic character of the excited state is preserved. 40 We additionally verify that the natural transition orbitals of the SCT state are consistent at the S0 and SCT optimized geometries.  . 20 With the exception of 5bromoquinoline, the agreement between the experimental and calculated pKa is excellent; 5bromoquinoline was not included in the analysis shown in Figure 2 because it did not follow the same trend as the other 5-R quinoline compounds. The excellent agreement between the experimental and calculated pKa reflects our use of the calibration curve developed in Figure 2.</p><!><p>While there are some discrepancies between the calculated and experimental p𝐾 # * , we clearly  20 The R 2 values for p𝐾 # * are 0.89 for experiment and 0.91 for theory whereas for pKa they are 0.76 and 0.75. capture the same overall trend as experiment. Moreover, the agreement between experiment and theory is best for the strongly photobasic compounds with electron-donating substituents, the class of compounds of interest in this study. The errors that do exist between the calculated and experimental p𝐾 # * primarily reflect errors in the calculated adiabatic energy gaps that result from our choice of using TD-DFT with a PCM solvent model to describe the electronic excited states.</p><p>Nevertheless, Figure 4 demonstrates that our chosen computational approach captures the same trend as experiment for how photobasicity is modulated by changes to the molecular structure and hence is suitable for identifying the structure-photochemical function relationships of interest in this study.  The 8-R quinoline compounds exhibit a greater variability in their p𝐾 # * than the 5-R, 6-R, and 7-R quinolines. In particular, 8-hydroxyquinoline, 8-aminoquinoline, and 8methylaminoquinoline have much lower p𝐾 # * than would be expected based on the trend in the other 8-R quinolines. These three compounds each contain a substituent that is not only a strong electron-donating group but also a hydrogen bond donor. We therefore believe that the anomalously low p𝐾 # * of these three compounds reflects the presence of intramolecular hydrogen bonding between the ring nitrogen and the neighboring -OH, -NH2, or -NHCH3 substituent.</p><p>Protonation of the base results in the loss of this intramolecular hydrogen bonding, causing a reduction of the 𝐾 * and 𝐾 * * relative to what is expected from the purely electronic effects of the substituent. Further support for this explanation comes from the fact that the syn conformer of 8hydroxyquinoline, which has the hydroxyl group oriented towards the ring nitrogen, is stabilized by 3.25 kcal/mol relative to the anti conformer. The observation that 8-methoxyquinoline has a larger p𝐾 # * than 8-dimethylaminoquinoline additionally suggests that steric repulsion between the protonated ring nitrogen and the neighboring substituent group in the conjugate acids provides an additional reduction in the thermodynamic driving force for excited state protonation; the anti conformer of 8-methoxyquinoline avoids this steric repulsion while simultaneously allowing the methoxy group to participate in π conjugation with the rings.</p><p>Figures S6-S8 in the Supporting Information show representative molecular geometries of 8-R quinoline compounds.</p><p>Figure 5 also shows the impact of substituents on the nitrogen-containing ring. The 3-R quinoline compounds (black squares) show a similar trend to the 6-R quinolines with a generally smaller photobasicity. Interestingly, the 4-R quinoline compounds (gray squares) show the opposite trend as the other monosubstituted quinolines, with p𝐾 # * decreasing as the substituent is made increasingly electron-donating. Indeed, for 4-aminoquinoline and 4methylaminoquinoline, electronic excitation results in a decrease in basicity; for example, pKa=7.28 and p𝐾 # * =5.69 for 4-aminoquinoline. In contrast to their photobasicity, Tables S1-S6</p><p>in the Supporting Information show that 4-aminoquinoline and 4-methylaminoquinoline are the strongest bases in the ground state of all of the monosubsituted quinoline compounds considered in this study. Finally, Figure S5 in the Supporting Information shows that the effect of substituents on the S0® SCT vertical excitation energy is much smaller for the 4-R quinolines than for the other monosubsituted quinolines.</p><p>As mentioned above, photobasicity in the quinoline derivatives has been attributed to the charge-transfer character of the S0® SCT transition, with the ring nitrogen gaining electron density and hence becoming more basic. 20,24 The extent of charge-transfer character in the S0® SCT transition can be quantified through the Löwdin charge difference on the ring nitrogen (Dq). 38,39 This analysis can also be performed at the excited-state optimized geometry resulting in ∆q * . Figure 6 shows the dependence of p𝐾 # * on Dq (squares) and ∆q * (triangles) for the 4-R, 5-R, and 6-R quinolines considered in this study. Figure S9 in the Supporting Information compares p𝐾 # * and Dq for all of the monosubstituted quinoline derivatives.</p><p>For the 5-R and 6-R quinolines, Figure 6 shows that the p𝐾 # * generally increases as Dq or ∆q * on the ring nitrogen becomes more negative. Indeed, linear regression analysis on the plots of p𝐾 # * versus ∆q * reveals R 2 values of 0.96 and 0.98 for the 5-R and 6-R quinolines. Figure S6 in the Supporting Information shows that the corresponding R 2 values for p𝐾 # * versus Dq are 0.89 and 0.92 for the 5-R and 6-R quinolines, respectively. This analysis demonstrates that, for a fixed substituent position, the thermodynamic driving force for excited-state protonation of the ring nitrogen is strongly correlated with the increase in the electron density on the ring nitrogen.</p><p>This suggests that the degree of charge-transfer character of the S0® SCT transition affects the strength of the photobasicity.</p><p>The 4-R quinoline compounds represent an interesting case because, as discussed above, they display the opposite trend as the other monosubstituted quinoline compounds. Figure 6 shows that many of these compounds have positive Dq and ∆q * on the ring nitrogen, suggesting that this atom loses electron density in the S0® SCT transition and hence becomes less basic.</p><p>Moreover, as shown in Table S3 in the Supporting Information, Dq and ∆q * become increasingly positive as the R group is made more electron-donating. This reflects the fact that Figure 5 shows that 4-aminoquinoline has a smaller p𝐾 # * than 4-cyanoquinoline. Finally, note that while the 4-R quinolines exhibit the same overall trend in Figure 6 as the 5-R and 6-R quinolines, the slope is markedly smaller.</p><p>Before ending our discussion of Figure 6, we consider the magnitude of the Dq and ∆q * observed in the calculations as well as the extent to which the these quantities are predictive of p𝐾 # * . For all of the compounds shown in Figure 6, as well as those analyzed in Figure S6 in the Supporting Information, the magnitudes of Dq and ∆q * are modest, with the gain or loss of charge on the ring nitrogen less than 0.15 electrons. Moreover, vibrational relaxation on SCT does not always lead to an increase in the magnitude of the charge-transfer; for the 6-R quinolines ∆q * is more negative than Dq while the opposite is true for the 5-R quinolines.</p><!><p>Dq and ∆q * and yet significantly different p𝐾 # * . This shows that, aside from the observation that all strong photobases have Dq<0, one should not use Dq or ∆q * as a proxy for p𝐾 # * when predicting the photobasicity of a new compound. Moreover, the above analysis suggests that while SCT should have some charge-transfer character, with the ring nitrogen gaining electron density in the S0® SCT transition, the thermodynamic driving force of the excited state protonation of these photobases cannot be solely attributed to the build-up of excess charge on the ring nitrogen.</p><p>Finally, we briefly describe the geometric changes that result from the vibrational relaxation on SCT. For all of the compounds, the excited-state geometry optimization causes a distortion to the aromatic rings which results in a modest elongation of the molecules. The most pronounced geometric changes occur with the amine substituents which, as much as sterically possible, undergo planarization during the vibrational relaxation. This is most pronounced for the basic forms of the compounds; the amine groups are often planar in the ground-state optimized geometries of the acidic forms. Examples of this can be seen in Figures S7 and S8 in the Supporting Information for 8-aminoquinoline and 8-dimethylaminoquinoline.</p><!><p>Disubstituted Quinolines, Isoquinolines, Acridines, and 1-Azaanthracenes Figure 7 summarizes the diversity of compounds we considered in this study which are identified to be strong bases in SCT, p𝐾 # * > 14, along with their corresponding vertical excitation energies; the complete data set generated in this study is provided in the Supporting Information.</p><p>We specifically focused on monosubstituted (squares) or disubstituted (triangles) quinoline (purple data), isoquinoline (green data), acridine (blue data), and 1-azaanthracene (red data).</p><p>Because we are interested in identifying compounds with the potential for use in photocatalysis, we focused exclusively on electron-donating substituents in developing this dataset.  Finally, note that Figure 7 demonstrates that, in addition to increasing p𝐾 # * , the presence of a second electron-donating substituent tends to result in a reduction of the vertical excitation energy. Nevertheless, all of these disubstituted quinolines are still predicted to absorb in the UV.</p><p>The isoquinoline compounds are shown in Figure 7 to follow the same overall trends as the quinoline compounds, although the isoquinoline compounds tend to have a somewhat lower p𝐾 # * than their quinoline counterparts. Electron-donating substituents in the 5 and 8 positions of isoquinoline (which are comparable to the 5 and 8 positions of quinoline) result in the largest p𝐾 # * and lowest vertical excitation energies. In particular, 8-amino-isoquinoline is the most strongly photobasic monosubstituted isoquinoline compound with p𝐾 # * = 15.12 while 5,8amino-isoquinoline has the largest p𝐾 # * of the disubstitued compounds at 17.48. Note that substituents in the 8 position of isoquinoline have a purely electronic effect on the photobasicity; because the ring nitrogen is now in position 2, there can be no hydrogen bonding or steric interactions between it and a substituent in position 8. Similar to the 4-R quinoline compounds, Table S9 in the Supporting Information shows that increasingly electron-donating substituents in  The relationship between p𝐾 # * and the extent of charge-transfer character of SCT is further explored in Figure 8 for the disubstituted quinolines, acridines, and 1-azaanthracenes. Here, we see that p𝐾 # * generally increases as ∆q * on the ring N becomes more negative. However, the relationship between p𝐾 # * and ∆q * is too noisy to allow ∆q * to definitively predict the photobasicity strength. This is especially true for the disubstituted 1-azaanthracene data where a very narrow range of relatively small ∆q * values correspond to p𝐾 # * ranging from 10.75 to 15.17.</p><p>Figure S27 in the Supporting Information demonstrates that, for the same set of compounds, the correlation between Dq and p𝐾 # * is even less clear than the correlation between ∆q * and p𝐾 # * in Figure 8. The variability present in Figures 8 and S27 reflects, as discussed above, the fact that the thermodynamics of the excited state protonation of these compounds is not fully controlled by the degree to which the S0®SCT transition builds up electron density on the ring nitrogen.</p><p>Finally, note that the correlations between Dq and p𝐾 # * for the disubstituted quinoline, isoquinoline, acridine, and 1-azaanthracene compounds considered in this study are presented in Figures S13, S18, and S26 in the Supporting Information.</p><!><p>The analysis presented in this paper assumes that the photobasicity of nitrogen-containing heterocycles containing strong electron-donating groups is well-described by the Förster mechanism. This relies on the SCT excited state having a long enough lifetime for the excited state protonation to occur prior to any non-radiative transitions to other states. Under such conditions, the trends in the photobasicity of these compounds will be well captured by the thermodynamic analysis presented above.</p><p>Using transient absorption spectroscopy, Dawlaty and coworkers identified evidence of SCT undergoing intersystem crossing into the triplet manifold for a series of 5-R quinolines. 21 In particular, for 5-aminoquinoline, the strongest photobase that was experimentally investigated,  the spectroscopic evidence points to excited state protonation occurring on a timescale of 41 ps followed by relaxation into a triplet state approximately 36 ps later. Such a process does not necessarily invalidate the applicability of the Förster mechanism to the photobasicity of 5aminoquinoline as the intersystem crossing only occurs after the excited state protonation. In contrast, for the weaker photobases quinoline, 5-chloroquinoline, 5-bromoquinoline, and 5cyanoquinoline intersystem crossing was found to be rapid, occurring on a timescale of less than 1 ps and preceding any excited state protonation.</p><p>While a complete analysis of intersystem crossing pathways is outside the scope of the present study, we did analyze the vertical energy gap between SCT and neighboring triplet states at the optimized SCT geometries for representative compounds identified as strong photobases. This data, which was calculated using the Tamm-Dancoff approximation to minimize triplet instability problems, is summarized in Tables S13-S16 in the Supporting Information. 43 For the acridine and 1-azaanthracene compounds, the average N𝐸 O PQR − 𝐸 5 67 N is 0.52 eV and 0.71 eV for the basic and acidic forms respectively, where Tmin is chosen as the triplet state closest in energy to SCT. Tmin is always uphill in energy from SCT for the base and often downhill in energy from SCT for the acid. Similar analysis performed on the quinoline derivatives shows that the average N𝐸 O PQR − 𝐸 5 67 N is 0.21 eV and 0.51 eV for the basic and acidic forms. In particular, the Tmin of 6-aminoquinoline, 6-methylaminoquinoline, 6-dimethylaminoquinoline, 3,5-aminoquinoline, and 3,5-dimethylaminoquinoline is within 0.16 eV of SCT and downhill in energy from it, suggesting a potential non-radiative relaxation pathway that could compete with excited state protonation for these five compounds. For the other quinoline derivatives, the closest triplet state is uphill in energy from SCT by 0.10-0.42 eV for the basic form, suggesting that intersystem crossing may be less important for these compounds, at least prior to protonation. We stress, though, that the analysis presented here is only preliminary and that a more complete picture of the intersystem crossing pathways in these photobases will represent an important addition to the thermodynamic trends presented in this paper. Efforts to accomplish this are currently underway.</p><p>A recent computational study by the Furche group argues for an alternative mechanism for the photobasisicity of 5-methoxyquinoline in which the SCT state undergoes internal conversion into a dark singlet state with significant intermolecular charge-transfer character from a solvent water molecule to the photobase. 44 This results in the transient photooxidation of the solvent water molecule, producing a 5-methoxyquinoline radical anion and H2O radical cation pair stabilized by the exciton binding energy. Subsequent proton transfer followed by backelectron transfer ultimately generates protonated 5-methoxyquinoline in the ground state and hydroxide. By comparing the calculated excited state electron affinity of 5-methoxyquinoline to the estimated 6.5±0.5 eV ionization potential of H2O, Furche and coworkers arrive at a lower bound to the exciton binding energy of 0.7±0.5 eV. 45 In Table 1, we report the excited state electron affinity of representative compounds considered in this study, calculated as the difference in the electronic energy of SCT and the radical anion (Eradical anion -𝐸 5 67 ) at the SCT optimized geometry. The radical anion is described using the restricted open-shell formalism to eliminate spin contamination. As shown in Table 1, in going from 5-methoxyquinoline to 5-aminoquinoline the Eradical anion -𝐸 5 67 decreases in magnitude by over 0.5 eV from -5.63 eV to -5.11 eV. The excited state electron affinity is even smaller in magnitude when a second electron-donating group is added, Eradical anion -𝐸 5 67 = -4.53 eV for 5,6-aminoquinoline, -4.53 eV for 1,2-aminoacridine, and Table 1 also reports the energy difference between SCT and the intermolecular charge transfer state involving the solvent water molecule that is hydrogen bonding with the photobase, S TO 4 U V , at optimized geometries on S0 and SCT. These calculations were performed with four explicit water molecules forming a hydrogen bonding network around the ring nitrogen, the same model as used by Furche and coworkers. At both the S0 and SCT geometries, 𝐸 5 67 W U X − 𝐸 5 67 increases as the substituent is made more electron-donating. The addition of a second amine group results in a further increase in the energy gap, raising 𝐸 5 67 W U X − 𝐸 5 67 to over 1.3 eV and 2.2 eV at the S0 and SCT optimized geometries, respectively. Finally, for all of the compounds, relaxation on SCT results in an increase in 𝐸 5 67 W U X − 𝐸 5 67 . The analysis reported in Table 1 suggests that as the strength and number of electrondonating substituents increases, the photooxidative mechanism becomes less favorable in two ways. First, the major component of the thermodynamic driving force for the solvent to solute charge-transfer, the excited state electron affinity of the photobase, is reduced by over 1 eV from 5-methoxyquinoline to the disubstituted compounds. Second, the two states involved in the photooxidation mechanism, SCT and S TO 4 U V , grow further apart in energy as the substituents are made increasingly electron-donating. This energy gap is important because the photooxidative mechanism relies on the existence of a thermally accessible conical intersection between SCT and S TO 4 U V , which becomes less likely as 𝐸 5 67 W U X − 𝐸 5 67 increases. Moreover, this energy gap significantly increases with vibrational relaxation on SCT. It is therefore reasonable to conclude that the photooxidative mechanism becomes less likely as the electron-donating strength of the substituent(s) increases.</p><!><p>Overall, the results reported in this study demonstrate the degree to which two key properties of photobases, p𝐾 # * and the excitation energy, can be tuned for quinoline and related compounds through substituents. We demonstrated that the photobasicity is affected by the identity, quantity, and position of the substituent(s). We showed that the addition of a second electron-donating substituent to quinoline can result in a significant increase in p𝐾 # * relative to the monosubstituted quinoline compounds. We identified a number of disubstituted acridine and 1-azaanthracene compounds with vertical excitation energies under 3.1 eV and p𝐾 # * > 14. The structure-function relationships uncovered in this study therefore provide insights into the design principles needed for the development of new photocatalysts which incorporate photobasicity.</p><p>Efforts to extend this analysis to more complex nitrogen-containing heterocyclic aromatics containing multiple heteroatoms as well as to more rigorously explore the impact of other photochemical pathways (e.g. intersystem crossing) on the photobasicity of the compounds considered in this study are currently underway in our lab.</p><!><p>The complete dataset analyzed in this study, images of the HONTO and LUNTO for representative compounds, plots illustrating the correlation between p𝐾 # * and Dq on the ring N, and analysis of energy differences between SCT and neighboring triplet states are provided in the Supporting Information.</p><!><p>Page(s)                        versus change in charge (Dq) on the ring nitrogen for the disubstituted 1-azaanthracene (gray squares), acridine (red squares), and quinoline (blue squares) compounds. Note that the p𝐾𝐾 # * are calculated using adiabatic energy gaps whereas the Dq on the ring N are calculated at the ground state geometry. Linear regression analysis leads to R 2 values of 0.004, 0.56, and 0.33 for the 1-azaanthracene, acridine, and quinoline compounds respectively.  S13: Calculated E SCT and E T -E SCT between S CT and the two closest triplet states for representative 5-R and 6-R quinoline compounds at the S CT optimized geometries. Because the Tamm-Dancoff approximation (TDA) is known to minimize triplet instability problems that can appear in TDDFT calculations, all of these energies were calculated using TDA. 2 The E SCT is reported relative to the ground state.</p>