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Fluorescence of Hydroxyphenyl-Substituted “Click” Triazoles Quinton J. Meisner, Joseph V. Accardo, Guoxiang Hu, Ronald J Clark, De-en Jiang, and Lei Zhu J. Phys. Chem. A, Just Accepted Manuscript • DOI: 10.1021/acs.jpca.8b00577 • Publication Date (Web): 28 Feb 2018 Downloaded from http://pubs.acs.org on March 6, 2018

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The Journal of Physical Chemistry

Fluorescence of Hydroxyphenyl-Substituted “Click” Triazoles Quinton J. Meisner1, Joseph V. Accardo1, Guoxiang Hu2, Ronald J. Clark1, De-en Jiang*2 and Lei Zhu*1 1. Department of Chemistry and Biochemistry, Florida State University, 95 Chieftan Way, Tallahassee, FL 32306-4390 2. Department of Chemistry, University of California, Riverside, California 92521 [email protected]

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ABSTRACT. The structural and optical properties of hydroxyphenyl-substituted-1,2,3-triazole molecules (“click” triazoles) are described. “Click” triazoles are prepared from the copper(I)catalyzed azide-alkyne cycloaddition reactions. The alkyne-derived C4 substituent of a “click” triazole engages in electronic conjugation more effectively with the triazolyl core than the azidederived N1 substituent. Furthermore, triazolyl group exerts a stronger electron-withdrawing effect on the N1 than the C4 substituent. Therefore, the placement of an electron-donating group at either C4 or N1 position, and the presence or the absence of an intramolecular hydrogen bond (HB), have profound influences on the optical properties of these compounds. The reported “click” triazoles have fluorescence quantum yields in the range of 0.1-0.3 and large apparent Stokes shifts (8,00013,000 cm-1) in all tested solvents. Deprotonation of “click” triazoles with a C4 hydroxyphenyl group increases their Stokes shifts; while the opposite (or quenching) occurs to the triazoles with an N1 hydroxyphenyl substituent. For the triazoles that contain intramolecular HBs, neither experimental nor computational results support a model of excited state intramolecular proton transfer (ESIPT). Rather, the excited state internal (or intramolecular) charge transfer (ICT) mechanism is more suitable to explain the fluorescence properties of the hydroxyphenylsubstituted “click” triazoles; specifically, the large Stokes shifts of these compounds.


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Introduction The reported work was initiated as a search for organic dyes with both large Stokes shifts and high fluorescence quantum yields. A large Stokes shift (experimentally determined as the difference between excitation and emission maxima in wavenumbers, which is more precisely referred as “apparent Stokes shift”) diminishes the overlap between the absorption and emission spectra of a fluorescent dye, which reduces the probability of reabsorption of the emitted photons, and consequently leads to an emission output that is independent of dye concentration.1 This characteristic is particularly beneficial to the development of energy efficient light-emitting materials, in which the dye doping concentration is desired to be high for achieving maximal brightness, while keeping the photon reabsorption (the inner filter effect) at a minimum. Photon reabsorption becomes an even more vexing issue when multiple dyes are mixed together for producing a composite emission color. Energy transfer from dyes of high-frequency emission to ones with low-frequency absorption jeopardizes the purpose of color mixing using dye composites. This situation is exacerbated when the dye doping concentration is high. Therefore, a large difference between the absorption and emission profiles of a dye composite, which is characterized by the collective Stokes shifts of the participating dyes, is preferred. The frequently used dyes fluorescein,2,3 BODIPY (e.g., BODIPY-FL),2,3 and rhodamine (e.g., TMR)2,4 (Figure 1) have small Stokes shift values of a few hundred wavenumbers. The coumarin molecule in Figure 1 has a moderate Stokes shift value reaching 2,000 cm-1. 4-(N,NDimethylamino)benzonitrile (DMABN)5-7 and 2-(2’-hydroxyphenyl)benzoxazole (HBO)8-10 are examples of compounds with large Stokes shifts that could exceed 10,000 cm-1. DMABN and HBO operate through two distinct mechanisms that result in large Stokes shifts (see the next paragraph). Recently, certain polyarylated pyrazoles11,12 and pyridines13 are found to be highly


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fluorescent with large Stokes shift values comparable to those of DMABN and HBO. Two examples are shown in Figure 1. These compounds presumably also undergo complicated excited state transformations that warrant the investment in their photophysical studies.

Figure 1. Stokes shift (SS) values rounded to 2 significant figures. BODIPY = borondipyrromethene; TMR = tetramethylrhodamine; HBO = 2-(2’-hydroxyphenyl)benzoxazole; DMABN = 4-(N,N-dimethylamino)benzonitrile. Quoted solvents are the exact descriptions in the cited source. SS values close to or over 10,000 cm-1 are marked in red.

DMABN and HBO (Figure 1) have access to photophysical processes that are responsible for large Stoke shifts. DMABN is a push-pull (or donor-acceptor) type fluorophore that possesses both a normal charge transfer emission with no structural alternation from that of the ground state, and a longer wavelength emission that results from a twisted internal charge transfer (TICT) excited state.5,14 The apparent Stokes shift of the TICT emission of DMABN is almost 14,000 cm-1.6 Non-


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coplanar biaryl compounds decorated with strong electron donor and acceptor groups could exhibit similar solvent-dependent emission properties to that of DMABN, of which emission with large Stokes shifts have been observed in polar solvents with low quantum yields.15,16 HBO may exhibit a normal ‘enol’ fluorescence with a Stokes shift of a moderate magnitude (~ 3,000 cm-1). Additionally, excited state intramolecular proton transfer (ESIPT)17-20 would occur if the solvent allows HBO to maintain an intramolecular hydrogen bond (HB). The resulting excited tautomer (i.e., the ‘keto form’) emits at a longer wavelength to reach a Stokes shift of ~ 10,000 cm-1. Park and coworkers have taken advantage of the large Stokes shift values of ESIPT dyes to develop dye conjugates that give bright dual emission without inter-fluorophore energy transfer.21

Figure 2. Triazole-containing fluorophores 1-7. SS = Stokes shift (103 cm-1);  = fluorescence quantum yield. DCM = dichloromethane; ACN = acetonitrile. Quoted solvents are the exact descriptions in the cited source.

Our group22,23 has taken an interest in the chemistry and applications of copper(I)-catalyzed azide-alkyne cycloaddition reactions.24,25 This reaction can be used to conjugate two structures via an aromatic triazolyl linker to afford a so-called “click” triazole,26 a term used by many to describe


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1,2,3-triazole molecules in the context of “click chemistry”.27 Considering the following key features summarized from Figure 1 that independently contribute to large Stokes shifts ( 10,000 cm-1): (1) capable of ESIPT, (2) capable of a large degree of charge transfer or TICT, and (3) containing nitrogen heterocycles substituted with multiple aryl groups, we postulated that polyaryl-substituted “click” triazoles (‘triazoles’ in the rest of the paper) with some or all of those attributes shall be fluorophores with large Stokes shifts. There have been a growing number of reports on fluorescent triazoles with charge transfer characters. Selected examples of 1-6 are shown in Figure 2. Each of these compounds contains an electron donor and acceptor pair connected via a triazolyl linker. For the viewing convenience, the bottom parts of 1-6 are electron donors, whereas the groups on top are electron acceptors (Figure 2). Triazoles 1 and 2 have the ICT character.28,29 The excited state charge transfer of compound 1 results in a Stokes shift (SS) of over 14,000 cm-1;28 while compound 2 exhibits a ground state charge transfer absorption band.29 Compounds 3 and 4 are regioisomers in which the electron donor component is derived from either the azide (in 3) or the alkyne precursor (in 4).30 Both isomers exhibit large SS values. Similar observations were made regarding the isomeric pair of compounds 5 and 6,31 and a closely related class of compounds.32 Comparing to the polyaryl-pyrazoles and pyridines (Figure 1) that require multiple crosscoupling steps to make,33 the synthetic ease of triazoles is a draw for exploring them in more depth with the aim of developing bright fluorophores with large Stokes shifts. Inspired by the work of Turro and coworkers on the ESIPT chemistry of (2-hydroxylphenyl)benzotriazoles,34,35 we were curious whether the introduction of intramolecular HBs in “click” triazoles might afford fluorophores with large Stokes shifts that would result from the ESIPT processes. Because a 1,2,3triazole provides two different Lewis basic, HB-accepting nitrogen atoms (N2 and N3 that are


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labeled in red in 1, Figure 2),36 we incorporated hydroxyl groups in the N1- or C4-aryl substituent of a triazole to form HB with either nitrogen atom. The acid/base chemistry of these fluorescent triazoles has also provided us with observations for understanding their photophysical properties. As a structural precedent, the intramolecular HB-capable compound 7 (Figure 2) was reported by Landge and coworkers.37 This compound exhibits a Stokes shift value of 4,180 cm-1 and a fluorescence quantum yield 0.17% in acetonitrile.

Experimental and Theoretical Methods Materials and general methods. Reagents and solvents were purchased from various commercial sources and used without further purification unless otherwise stated. All reactions were carried out in oven- or flame-dried glassware in an inert atmosphere of argon. Analytical thin-layer chromatography (TLC) was performed using pre-coated TLC plates with silica gel 60 F254. Flash column chromatography was performed using silica (230-400 mesh) gel as the stationary phases. 1H and 13C NMR spectra were acquired on a 500 MHz instrument. All chemical shifts were reported in δ units relative to tetramethylsilane. CDCl3 was neutralized with alumina gel prior to use. High resolution mass spectra (HRMS) were obtained using a time-of-flight (TOF) analyzer.

2-Azidophenol,38

4-azidophenol,38

(methoxymethoxy)benzene,41

and

4-azido-N,N-dimethylaniline,39,40

ethynyl-4-(methoxymethoxy)benzene,42

were

ethynyl-2prepared

following published procedures. Synthesis and characterizations of new compounds. The synthetic procedures and structural characterization data, in addition to steady state absorption and emission spectra of compounds 813 are available in the Supporting Information.


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X-ray crystallography. Crystals were mounted on a nylon loop with the use of heavy oil. The samples were generally cooled to -170 C for data collection. No phase change on cooling was ever evident. Full data were taken on a Bruker SMART APEX II diffractometer using a detector distance of 6 cm. The number of frames taken was 2,400 using 0.3 degree omega scans with 20 seconds of frame collection time. Integration was performed using the program SAINT which is part of the Bruker suite of programs. Absorption corrections were made using SADABS. XPREP was used to obtain an indication of the space group and the structure was typically solved by direct methods and refined by SHELXTL. The non-hydrogen atoms were refined anisotropically. Typically the hydrogen atoms could be found during the least squares refinement, but in practice they are constrained as a riding model. The .cif files have been deposited in the Cambridge Crystallographic Data Centre (CCDC), referenced by the following CCDC numbers: 8: 1447881; 9: 1447880; 10: 1447882; 11: 1447883; and 13: 1531118. Computational methods. All calculations were carried out using the quantum chemistry package TURBOMOLE V6.5.43 The ground state geometries were optimized (Table 4) at the density functional level of theory (DFT) using the B3LYP functional44 and the def2-TZVP basis sets.45 The pKa values relative to that of phenol were calculated (Table S2) from geometrically optimized structures followed by single-point energy calculations using the COSMO (COnductorlike Screening MOdel) solvation model,46 where the dielectric constant was set at 78.4. The excited state geometric and electronic structural parameters listed in Table 7 were determined using timedependent DFT (TDDFT)47 with the same functional and basis sets as above. The vibrational frequencies of minimized geometries in the excited states were calculated using the NumForce module, which confirmed that all but one of the stationary points were minima. When calculating the minimal energy reaction paths (Figure 22), the smaller basis sets def-SV(P) were used to reduce


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the computational cost. The frontier molecular orbitals of 8-11 and 13 were plotted using gOpenMol.48,49 The excitation energies (Table S1) were calculated using the CC2 method50,51 with the resolution-of-the-identity (RI) approximation.52 The aug-cc-pVDZ basis sets53 were chosen for the excitation energy calculations.

Results

Figure 3. Structures of 8-13.

1. Molecular design and synthesis. The topical compounds are listed in Figure 3. Compounds 8-11 are 4 isomers that differ in the substitution pattern of the triazole ring or the ability of forming intramolecular HBs. The photophysical difference of 8-11 is the major topic of this work. Compounds 8 and 9 are capable of forming intramolecular HBs with N2 or N3 of triazole, respectively. The choice of N,N-dimethylanilinyl (DMA) substitution on triazolyl was made for increasing the (photo)basicity of the triazolyl group in a possible event of ESIPT. Compounds 10 and 11 are the analogs of 8 and 9 that are electronically similar without the ability of forming intramolecular HBs. Comparing the fluorescence properties of 8 and its methylated analog 8-Me shall inform whether the ESIPT process occurs in 8. The comparison of 11 and 12 shall reveal the effect of the DMA group on the emission. Finally, the dihydroxylated compound 1338 offers the


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possibility of stepwise deprotonation with interesting effects on fluorescence. The knowledge that is gained on compounds 8-12 helps explain the properties of 13. Compounds 8-13 were assembled via the Cu(OAc)2-catalyzed azide-alkyne cycloaddition reaction54 of substituted azidobenzenes3840

and ethynylbenzenes41,42 that have been reported previously (see the SI for details of synthesis

and characterization). The identities and purities of 8-13 were confirmed by elemental analysis. 2. Structures in solution and solid states. The hydroxy protons of 8 and 9 appear at 10.10 ppm and 10.93 ppm, respectively, in CDCl3 (Figures 4a and 4c). These are deshielded values of a hydroxyl group in CDCl3, which is consistent with the presence of intramolecular HBs. The HB in 8 involves N2 on the triazole ring, while N3 is engaged in hydrogen bonding in 9. The higher chemical shift of OH in 9 than that in 8 is attributed to the stronger Lewis basicity of N3 over N2 of a 1,2,3-triazole. Compounds 10 and 11 are unable to form intramolecular HBs. As such, the hydroxy proton of 10 appears to be a broad singlet with varying chemical shift values in the range of 5.5-6.2 ppm. The poor solubility of 11 did not permit NMR spectra to be acquired in CDCl3 with acceptable sensitivity and resolution. In DMSO-d6, the hydroxy proton of 11 resonates at 9.62 ppm, resulting from intermolecular hydrogen bonding with the solvent.55 The chemical shifts of the two OH groups in 13 in CDCl3 are 10.35 and 9.50 ppm (Figure 4e), which are assigned to the protons that are hydrogen bonded to N3 and N2 of triazole, respectively.


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Figure 4. 1H NMR spectra (500 MHz, CDCl3, > 5.5 ppm) of (from ‘a’ to ‘f’) compounds 8, 8 (anion), 9, 9 (anion), and 13, and 13 (anion). The triazolyl C5 protons are labeled in red, while the phenyl protons ortho to the triazolyl group are labeled in blue (see Ha and Hb in Scheme 1).

Upon the inclusion of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to deprotonate 8, all protons but the triazolyl hydrogen Ha were upfield shifted (Figures 4a and 4b) as a result of the increased electron density introduced by the negative charge. The downfield shift of Ha is attributed to the HB formation between Ha and the phenolate oxygen (Scheme 1a). An example of a similar type of intramolecular HB between a methoxy group and C5-H of a triazole has been reported in the solid state.56 The HB acidity of triazolyl Ha has been characterized in many molecular systems.57 Deprotonation of 9 also led to the downfield shifts of now both triazolyl Ha and the phenolate Hb (Figures 4c and 4d). As shown in Scheme 1b, Hb is in position to engage in a HB with N3 on the


11


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triazolyl ring, which would explain the downfield shift of Hb. Deprotonation of compound 13 also led to the downfield shifts of Ha and Hb, which can be explained using the same O-ꞏꞏꞏH-C HB pattern that was illustrated for compound 9 in Scheme 1b. When the phenolate moiety is unable to hydrogen bond with the C5-triazolyl Ha, such as in the deprotonated 12, deprotonation led to the upfield shifts of all protons (Figure S1).

Scheme 1. The change of hydrogen bonding patterns of 8 and 9 upon deprotonation.

Table 1. The structural data pertinent to intramolecular hydrogen bonds (HBs) and coplanarity of aryl moieties of triazoles 8-11 and 13. Compound  (OH)/ppm

d (O-N, or O-N’)/Åa

 (CCCC)/b  (CCNN)/c

8

10.10 (CDCl3)

2.629 (O-N’)

8.13

-52.84

9

10.93 (CDCl3)

2.676 (O-N)

3.58

11.21

10

9.93 (DMSO-d6)

2.857 (O-N’)

1.04

7.95

11

9.65 (DMSO-d6)

2.714 (O-N’)

-25.49

33.32

13

10.35, 9.50 (CDCl3) 2.642 (O-N); 2.787 (O-N’)

-15.38

14.39

a. O-N: intramolecular HB distance; O-N’: intermolecular HB distance; b.  (CCCC): torsion angle between triazolyl and the C4 substituent; c.  (CCNN): torsion angle between triazolyl and the N1 substituent.


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Compounds 8-11 and 13 were characterized in the solid states. The HB distances (either interor intra-) and the torsion angles between triazolyl and the N1 or C4 substituents are listed in Table 1. Different from the solution structure in CDCl3, no intramolecular HB that involves the N2 of triazole was observed in the single crystal structure of 8 (Figure 5). Rather, Intermolecular HB between the hydroxy and triazolyl N3 of the adjacent molecule was observed. The torsion angle between triazolyl and the alkyne component (CCCC, Table 1) is smaller than that between triazolyl and the azide component (CCNN). This observation is replicated in 9-11, suggesting that the triazolyl moiety is more in conjugation with the C4 substituent than with the N1 substituent.

Figure 5. ORTEP diagram of compound 8 (30% ellipsoids; CCDC 1447881). Black denotes hydrogen and carbon, blue denotes nitrogen, and red denotes oxygen.

Unlike 8, compound 9 retains the intramolecular HB involving N3 in the solid state (Figure 6), analogous to a structure reported by Flood and coworkers.58 The comparison of the structures of the isomeric 8 and 9 in both solution and solid states provides direct evidence that both N3 and N2 tend to form HBs, yet N3 is a stronger HB acceptor than N2. In the crystalline phase when the enthalpic effect is dominant in determining molecular conformations and superstructures, the OH


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chooses to form the strongest HB possible either inter- or intra-molecularly (i.e., with N3 in both compounds), as found in compounds 8 and 9, respectively.


Figure 7. ORTEP diagrams of 10 (top, 30% ellipsoids; CCDC 1447882) and 11 (bottom, 30% ellipsoids; CCDC 1447883). Black denotes hydrogen and carbon, blue denotes nitrogen, and red denotes oxygen.


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The structures of 10 and 11, which in regard to the position of OH are regioisomers of 8 and 9, respectively, do not allow the formation of intramolecular HBs. In the solid states of both, intermolecular HBs between OH and N3 of the adjacent molecules were observed (Figure 7). Without an exception, hydrogen bonds (HBs) involving N3 but not N2 of triazolyl group in 811 were observed in the solid states. In these compounds, the ratio of HB donor/acceptor is 1:2. Therefore, the HB donor has two options for bonding, between which the stronger acceptor N3 is preferred. The HB donor/acceptor ratio of the dihydroxy-substituted compound 13 is 1:1, which compels N2 to participate in hydrogen bonding. The 1H NMR data in CDCl3 suggests that both hydroxyl groups form intramolecular HBs with N2 and N3 (Table 1). In the solid state, the major species (91%) of 13 has the triazolyl N2 engage in an intramolecular HB while N3 in a geometrically more optimal (i.e., linear) intermolecular HB (Figure 8).


Before further conclusions regarding the major hydrogen bonding pattern of 13 are drawn, two points of ambiguity of the structural assignment of compound 13 should be noted. This first is


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regarding the locations of the three nitrogen atoms, as in the two structures in Figure 9. The R values are 5.35% and 6.18%, respectively, for A and B. This says that structure A is the more probable, but not necessarily the only depiction. The normal shape of the ellipsoids makes it clear that regardless of any disorder in the molecule, the 19 non-hydrogen atoms are at the same locations in the unit cell. It is possible that A and B are both present in some proportion, with structure A being the major component.

Figure 9. Two structures of 13 with subtly different electron density distributions.

Figure 10. Two structures of 13 that have inter- or intramolecular HB, respectively, with N3.

The second issue regards the Q (residue) peak that resides near carbon ‘x’ (see A in Figure 10) and represents electron density beyond that of the hydrogen atom that had been previously assigned and refined. This must represent a minor species (and an oxygen atom) of 13, in which the C4 substituent has rotated by 180 degrees (A’). The final structure is one in which the SHELXTL PART command has been used to divide the structure to two conformational isomers A and A’ (Figure 10). This brought the R value down to


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4.65%. The overall A/A’ ratio was 91:9. Compound 13 seems to have a complicated case of inter and intra hydrogen bonding as part of the packing forces. 3. Absorption and emission. The absorption and emission spectra of compounds 8-13 were acquired in three solvents that are characterized by polarity () and hydrogen bond (HB) basicity ()59 – dichloromethane (DCM,  = 6.2,  = 0.4), acetonitrile (ACN,  = 37.5,  = 0.31), and dimethylsulfoxide (DMSO,  = 46.7,  = 0.76). DCM represents a low polar solvent that permits the retention of intramolecular HBs, while DMSO is a strong HB acceptor that disrupts intramolecular HBs. ACN has intermediate  and  values. The wavelength maxima of absorption and emission, Stokes shift and quantum yield values, of these compounds in the referenced three solvents are listed in Table 2. The relevant data of their conjugate bases are listed in Table 3.

Figure 11. The normalized absorption (left) and emission (right) spectra of 8 in DCM (blue, λex = 304 nm), ACN (green, λex = 293 nm), and DMSO (orange, λex = 293 nm). The gap marked by black bars at the far-right side was occupied by second order scattering bands from the excitation.


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Compound 8 – solvent dependence. The absorption spectra of 8 in ACN (green on the left, Figure 11) and in DMSO (orange) are similar, while in DCM the maximum value is found at a longer wavelength. The emission of 8 shows the opposite solvent dependence (Figure 11, right): it peaks at a shorter wavelength in DCM than that in ACN or DMSO. The quantum yield values in all solvents are > 10%, with Stokes shift (SS) values > 10,000 cm-1 – quite large numbers comparing to the SS values of the compounds listed in Figures 1 and 2. The absorption and emission spectra of 8 in four additional solvents (1,4-dioxane, ethanol, formamide, and 2,2,2-trifluoroethanol (TFE)) were collected to establish a reliable solvent dependency (Figure S2). The solvent-dependent absorption spectrum of 8 reveals the nuances of solvatochromism. The absorption has the lowest energy (longest wavelength) in the least polar DCM, and the highest energy (shortest wavelength) in the most HB acidic TFE. These observations are consistent with a structural model in which a low polarity solvent such as DCM promotes intramolecular HBs. The enforced coplanarity of the molecule in the ground state leads to an efficient electron delocalization, which results in a relatively long absorption wavelength. On the contrary, a HB acidic (e.g., TFE) or basic (e.g., DMSO or formamide) solvent disrupts coplanarity, thus deceasing the absorption wavelength. The emission appears to be positively solvatochromic – i.e., the wavelength of maximum intensity moves from 410 nm in 1,4-dioxane ( = 2.3) to 520 nm in formamide ( = 84), suggesting that the excited state has a larger dipole moment than the ground state (see the computed data in Tables 4 and 7). The methylation of the hydroxyl group in 8 affords 8-Me, which no longer has an intramolecular HB. The absorption and emission spectra of 8-Me (Figure S3) are similar to those of 8 in terms of the wavelengths of maximum intensity. Therefore, by comparison with 8-Me, the intramolecular HB in 8 does not appear to contribute significantly to the large Stokes shifts of 8.


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The excitation spectra of 8 in DCM, ACN, and DMSO (Figure S4) reproduce the features of the absorption spectra. In DMSO, a long-wavelength shoulder of variable intensity was observed from repeating experiments. This shoulder centers at ~365 nm, which is amplified upon addition of a base such as DBU and therefore assigned to the deprotonated 8. The spectral susceptibility of hydroxylated aromatics to base in strongly HB-accepting solvents such as DMSO has been documented.34,60 The adventitious base might have been introduced during sample preparation.60

Figure 12. The absorption (a) and emission (b) spectral changes of compound 8 (15 μM in ACN) upon addition of 1-17 equiv. of DBU. λex = 285 nm. The initial and final spectra in the base titration series are labeled blue and red, respectively.

Compound 8 – acid/base dependence. The absorption and emission of 8 were not sensitive to the addition of trifluoroacetic acid (Figure S5); the opposite was true when the base DBU was added to 8 (Table 3). A longer wavelength absorption band ascribed to the anion grew at the expense of the absorption of the neutral molecule in ACN upon addition of DBU (Figure 12a). The corresponding emission spectrum however shifted to a shorter wavelength (Figure 12b).


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Figure 13. The normalized absorption (left) and emission (right) spectra of 9 in DCM (blue, λex = 311 nm), ACN (green, λex = 307 nm), DMSO (orange, λex = 304 nm). [9] = 15 μM.

Compound 9 – solvent dependence. The absorption of 9 (Figure 13, left) is slightly negatively solvatochromic, similar to that of 8. The negative solvatochromism is lost in the excitation spectra (Figure S6), likely because the emission yield is maximized at the planar conformation of 9, which absorbs at the red edge of the absorption in all three solvents. The emission (Figure 13, right) wavelength of 9 is the shortest in DCM – the least polar solvent. The fluorescence quantum yields of 9 are 10-30% in the solvents tested; while the Stokes shift is around 8,000 cm-1 (Table 2). Compound 9 – acid/base dependence. DBU (pKa = 12 in DMSO) in either ACN or DMSO did not deprotonate 9 to a significant degree, suggesting that the presence of a strong intramolecular HB might have lowered the acidity of 9. The addition of the stronger base tetrabutylammonium hydroxide (TBAOH, pKa = 31 in DMSO) to the solution of 9 in DMSO resulted in deprotonation (Table 3). The absorption of the anion appeared at a longer wavelength than the neutral compound (Figure 14a), and so did the emission (Figure 14b). This observation is in stark contrast to that of compound 8, the emission of which moved to a shorter wavelength upon deprotonation.


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Figure 14. The absorption (a) and emission (b) spectral changes of compound 9 (15 μM in ACN) upon addition of TBAOH up to 9 mM. λex = 330 nm. The initial and final spectra in the base titration series are labeled blue and red, respectively.

Figure 15. The normalized absorption (left) and emission (right) spectra of 10 in DCM (blue, λex = 294 nm), ACN (green, λex = 290 nm), DMSO (orange, λex = 294 nm). [10] = 15 μM.

Compound 10 is a regioisomer of compound 8 – the hydroxy of 10 is on the azide component without an intramolecular HB. The absorption spectra of 10 in the three solvents (DCM, ACN,


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Page 22 of 55

and DMSO) are similar (Figure 15a) to one another, while the emission wavelength of 10 in DCM is shorter than that in the other two solvents (Figure 15b). Overall the emission wavelengths of 10 are shorter than those of its intramolecular HB-capable regioisomer 8 under the same conditions (see Table 2). The excitation spectra of 10 (Figure S7) replicate almost exactly the shapes and frequencies of its absorption spectra. The deprotonation of 10 by DBU in ACN led to a reduction in both absorption and emission intensity with little frequency change (Figure S8), which differs from the observations on its isomer 8. Compound 11 is a regioisomer of 9. The solvent-dependence of the absorption/excitation and emission spectra of 11 (Figures S9-S10) is similar to that of 9. The effect of a base on 11 also mirrors that on 9: the addition of TBAOH in a solution of 11 in DMSO created the anion that emits at a longer wavelength (Figure S11). In order to determine the effect of the N,N-dimethylanilinyl (DMA) group on the emission of 11 and its conjugate base, compound 12, which has an n-octyl group in place of DMA, was studied. Both the absorption and emission of 12 (blue traces in Figure 16) appear at higher energy, shorter wavelength regions than those of 11. For example, the emission maximum of 12 in ACN is 324 nm, well within the UV region, while that of 11 is 410 nm. However, the emission wavelengths of the deprotonated 12 and 11 are relatively close – 517 vs 545 nm in DMSO, respectively.


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Figure 16. The absorption (a) and emission (b) spectral changes of 12 (20 μM in ACN) upon addition of TBAOH up to 2 mM. λex = 275 nm. The initial and final spectra are labeled blue and red, respectively.

Absorption and emission of dihydroxylated 13. Compound 13 absorbs at a longer wavelength in the non-polar solvent DCM than in ACN and DMSO, both of which are more polar and more Lewis basic than DCM (Figure 17). The emission of 13 was too weak to be recorded at 20 μM in all three solvents. Upon deprotonation using DBU in DMSO, the mono-anion absorption appeared at a longer wavelength from that of the neutral form, while the emission of the mono-anion centered at 435 nm (Figure 18) with a quantum yield of 0.16 (Table 3). Based on the presence of an isosbestic point in the absorption titration (Figure 18a), only the mono-anion was produced over the course of the titration experiment. The intramolecular HB involving the hydroxyl group on the C4 substituent is too strong to be removed by DBU from the mono-anion.


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Page 24 of 55

Figure 17. The normalized absorption spectra of 13 in DCM (blue), ACN (green), and DMSO (orange). [13] = 20 μM.

Figure 18. The absorption (a) and emission (b) spectral changes of 13 (20 μM in DMSO) upon addition of DBU up to 0.55 mM. λex = 360 nm. The initial and final spectra are labeled blue and red, respectively.


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Table 2. The maximal wavelengths of the absorption and emission, Stokes shifts, and quantum yields of compounds 8-12 in DCM, ACN, and DMSO. Compounds

Solvent

abs (nm)

em (nm)

Stokes shift (× 103ꞏcm-1)a

b

8

DCM

308

449

11

0.16

ACN

299

485

14

> 0.12c

DMSO

300

474

13

> 0.23c

DCM

301

436

10

0.06

ACN

293

473

13

> 0.07c

DMSO

302

486

13

> 0.20c

DCM

314

409

7.4

0.30

ACN

312

424

8.5

0.28

DMSO

318

428

8.1

0.13

DCM

294

426

11

0.12

ACN

291

455

12

0.14

DMSO

294

458

12

0.34

DCM

289

399

9.6

0.01

ACN

288

410

10

0.02

DMSO

291

415

10

0.04

DCM

251

325

9.1

0.06

ACN

253

324

8.7

0.04

DMSO

262

328

7.7

NDd

8-Me

9

10

11

12

a. Rounded to two significant figures; b. rounded to two digits after the decimal point; c. emission spectrum overlaps with the second-order scattering peak; d. ND: not determined because the absorption bands of 12 and DMSO overlap.


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Page 26 of 55

Table 3. Absorption and emission wavelength maxima, Stokes shifts, and fluorescence quantum yield values of the conjugated bases of compounds 8, 9, 11-13 (anions).a Compounds

Solvent

ex (nm)

em (nm)

Stokes shift (× 103ꞏcm-1)b



8 (anion)

ACN

289, 335

434

6.8

0.31

9 (anion)

DMSO

292, 353

524

9.2

0.14

11 (anion)

DMSO

308

545

14

0.06

12 (anion)

DMSO

297

517

14

0.05

13 (mono-anion)

ACN

361

435

4.7

0.16

a. The conjugate base of compound 11 was not included because the absorption profile did not change significantly upon titrating DBU into a solution of 11. Therefore, it was not reliable to selectively excite the conjugate base for the determination of its quantum yield; b. Determined to two significant numbers.

Figure 19. Selected conformers of 8, 9, 8-Me, and 9-Me (not prepared). HP – hydroxyphenyl; T – triazolyl; DMA – dimethylanilinyl; MeOP – methoxyphenyl.

4. Computational studies. The aim of the computational studies is to acquire the geometric and electronic structural information of 8-11 and 13 that is unobtainable from experiments. In addition, computation provides an explanation on the lack of ESIPT in 8 and 9. The lowest energy conformers of 8, 9, and their methylated analogs 8-Me and 9-Me (not prepared) are shown in


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Figure 19. The structures of these compounds are separated into three aromatic ring systems as indicated by three shaded frames. The computational studies answer the question whether the N1 or the C4 substituent is more in conjugation with the triazolyl ring in these compounds. Ground state geometries. All ground state geometries were optimized using DFT at the B3LYP level of theory with the def2-TZVP basis sets. The structures of 10, 11, and 13 are shown in Figures S13-15, and their excitation energies at the optimized geometries are included in Table S1. The narrative here focuses on the results from the intramolecularly hydrogen bonded 8 and 9. Both the normal and tautomeric (tau) starting structures of 8 relaxed to the normal form in which the C4 substituent dimethylanilinyl (DMA) and triazolyl (T) are coplanar (Figure 20a/b). The OH forms a HB with the N2 atom of triazolyl. The N1 substituent hydroxyphenyl (HP) ring is slighted twisted off the plane (13). The twist is attributed to the long-range interaction between the OH and the more Lewis basic N3 nitrogen. A similar twist is also seen in the structure of 13 (Figure S15). In another conformer of 8 where the OH interacts with the C-H bond of triazolyl rather than N2/N3, the optimized structure is entirely planar (8’ in Figure S12a). In order to quantitatively assess the relative stability between the normal and tau forms, the tau form was optimized after fixing the NH distance at 1 Å. A planar structure was obtained (Figure 20c/d). The lack of twist in the structure of the tau form is attributed to the loss of the secondary interaction that was between the OH and the N3 nitrogen in the normal form. The energy of the optimized tau form is 19 kcal/mol higher than that of the normal, suggesting its negligible presence in the ground state.

Table 4. Computed relatively energies, HB lengths, dipole moments, and pKa values.a molecule

Rel. energy (kcal/mol)

 (D)

OH (Å)

NH (Å)

pKae

8 (normal)

X

5.6

0.98

1.76

7.9


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Page 28 of 55

8 (tau)

X+19

9.1

1.60

1.00b

-

8-Me

-

5.2

2.45

NA

-

9 (normal)

Y

8.5

0.98

1.78

11.1

9 (tau)

Y+19

13

1.68

1.00b

-

9-Mec

-

6.7

2.38

NA

-

10

-

5.4

0.96

NA

8.0

11

-

7.1

0.96

NA

9.7

12

-

5.7

0.96

-

9.1

13d

-

4.7

0.98 (N2)

1.79 (N2)

6.4

0.98 (N3)

1.80 (N3)

a. DFT/B3LYP/def2-TZVP level of theory; b. fixed at 1.00 Å; c. 9-Me was studied computationally only; d. compound 13 has two intramolecular HBs with N2 and N3, respectively; e. values are relative to phenol (pKa = 10.0). The COSMO model was used in the calculation of pKa values.  = 78.4.

Figure 20. Computed ground state structures (DFT/B3LYP/def2-TZVP) of 8 (a, b), 8-tau (c, d), 9 (e, f), and 9-tau (g, h). In the tautomers, the NH distances are fixed at 1 Å.


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The normal and tau initial structures of 9 were also optimized in the same way (Figure 20e-h). Relaxation of both to the normal form was again observed. In the relaxed structure, T and HP of 9 are coplanar and hydrogen bonded (NH distance 1.78 Å, using def2-TZVP basis sets) through N3, which is the stronger Lewis basic nitrogen on triazolyl, while DMA was twisted out with a dihedral angle of 32 (Figure 20e/f). Again, this observation is consistent with the model that triazolyl (T) is more conjugated with the C4 substituent than the N1 substituent. A similar geometry was obtained for the tau form when the NH distance is fixed at 1 Å. The energy of the tau form is 19 kcal/mol higher than the normal structure. The ground state geometries of 8-Me and 9-Me resemble those of 8 and 9, respectively (Figure S16). Except for the intramolecular HBs involving N2 or N3 of the triazolyl component, of which 8-Me and 9-Me are incapable, other geometrical features were reproduced. For example, in 8-Me, DMA and T rings are coplanar, while the methoxyphenyl (MeOP) is off the plane. In 9-Me, DMA and MeOP are coplanar because MeOP are now the C4-subsitutent on T, while the DMA ring is off-plane. It is noteworthy that the methoxy group prefers to be in close contact with the C-H bond on triazolyl with the OH distances of 2.45 Å in 8-Me and 2.38 Å in 9-Me. This observation is consistent with the reported hydrogen bond donor ability of the triazolyl C-H bond.56,57 The pKa values of 8-13 relative to that of phenol (10.0 in water) were determined using the structures optimized under the same level of theory, and corrected with the application of the COSMO (COnductor-like Screening MOdel) solvation model46 to take the solvent into account explicitly (Table 4, also see Table S2 in the Supporting Information). Compounds 8, 10, and 13, in which the N1 of triazolyl is substituted on the hydroxyphenyl component, are 2-3 orders of magnitude more acidic than phenol. The effect of triazolyl on pKa is much less when the substitution occurs on the C4 position (compounds 9, 11, and 12). These data suggest that triazolyl


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Page 30 of 55

exerts a stronger electron-withdrawing effect on the N1 substituent than the C4 substituent. The higher pKa of 9 (11.1) than that of 11 (9.7) may be attributed to the strong intramolecular HB in 9. However, the effect of an intramolecular HB, albeit a weaker one, on pKa was absent in 8.

Table 5. The frontier molecular orbitals of compounds 8-11, 13.

Frontier molecular orbitals (FMOs) of 8-11 and 13 at optimized ground state geometries. The FMOs were calculated at the B3LYP/def2-TZVP level of theory. Similar types of DFT methods have been used in FMO calculations of triazolyl-containing charge transfer molecules in earlier works.29,31,32 The HOMOs of 8 and 10 (Table 5) primarily reside on the DMA/T portion, while the LUMOs shift to the space that HP/T occupies. Therefore, charge transfer electronic transitions of


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8 and 10 are expected upon photoexcitation. The HOMOs of 9 and 11 are more evenly distributed over the entire molecule, while the LUMOs tend to concentrate in the centers. Based on the space occupancy of the HOMOs and LUMOs of 9 and 11, the electronic excitations to the S1 states would carry less of a charge transfer character than 8 and 10. Experimentally, the Stokes shift values of 8 and 10 are larger than their isomeric counterparts 9 and 11, respectively, which is consistent with the analysis of the FMOs. Both the N1 and C4 substituents of 13 are 2-hydroxyphenyl. The HOMO is on the C4-HP/T fragment, suggesting that the C4 substituent is more in conjugation with the triazolyl group. Similar to what is witnessed in 8, LUMO resides on the HP substituent at N1. Therefore, a large Stokes shift was expected; however, it was not measured because the emission of 13 was too weak.


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Table 6. The frontier molecular orbitals of the deprotonated compounds 8-11, 13.

Deprotonation of 8-11 invariably shifts the HOMO to the anionic phenolate side of the molecule, regardless whether the phenolate is derived from the azide or the alkyne component (Table 6). For the charge-transfer compounds 8 and 10, the chromophore (i.e., the light-absorbing component) migrates upon deprotonation from the C4-DMA/T to phenolate/T. Structural changes of intramolecular hydrogen-bonded 8, 10, and 13 are also detected in the computed structures. The C-N or the C-C bond ortho to 2-phenolate chooses to rotate to engage in an attractive interaction with the triazolyl C5-H, which is known to be a HB donor.56,57 Experimental evidence for this structural change upon deprotonation was obtained in the 1H NMR data (Figure 4).


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Table 7. Computed relative (rel.) energies, dipole moments, and geometrical features of the excited states.a molecule

Rel. energy (kcal/mol)

(em) (nm)/fb

 (D)

OH (Å)

NH (Å)

True mind

8 (S1)

X

410/0.14

22

0.99

1.74

yes

8 (S2)

X+12

458/0.03

24

1.50

1.09

yes

8-Me (S1)

-

412/0.13

20

2.16c

-

yes

9 (S1)

Minimum not found

9 (S2)

Y

348/0.39

9.9

1.02

1.62

yes

9 (S2)

Y-8.5

563/< 0.01

12

1.97

1.02

noe

9-Me (S1)

-

359/0.79

13

2.40c

-

yes

10 (S1)

-

397/0.19

19

0.96

-

yes

11 (S1)

-

376/0.73

10

0.96

-

yes

13 (S1)

Minimum not found

a. DFT at B3LYP level of theory with def2-TZVP basis sets; b. the emission wavelength may be comparable with each other, however, the absolute values are less reliable – in addition to the inherent inaccuracy, only one conformer of each compound was calculated in vacuum without temperature consideration. It is known that emission frequencies can be highly sensitive to solvent properties and temperature; c. distance between O-methyl and C-H on triazolyl ring; d. whether the stationary point is a minimum; e. a stationary point with two imaginary frequencies.

Geometries of the excited states of 8 and 9. The geometrical optimizations of the first two excited states of 8 and 9 were done using TDDFT at the B3LYP level with the def2-TZVP basis sets free of constraints. On the S1 level of 8, a minimum of the normal structure (OH distance 0.99 Å) was identified (Figure 21a/b, also see Table 7), while optimization starting from a tautomer structure failed to converge, possibly approaching a conical intersection as the HOMO-LUMO gaps fell well below 1 eV at the end of the run. On the S2 level, both normal and tau starting structures relaxed to the same geometry (see Figure S17 for an overlay) of a tautomer form (NH distance


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Page 34 of 55

1.09 Å). Between the two identified excited states, the excitation at the S1(normal) geometry has a larger oscillator strength (0.14) than that of the S2(tau) (0.03). From these observations, it can be concluded that the S1 state of 8 is an emissive normal conformer, while proton transfer to the tautomer is expected to occur on the S2 state.

Figure 21. Computed structures (DFT/B3LYP/def2-TZVP) of 8 (normal, S1) (a, b), 8 (tau, S2) (c, d), 9 (normal, S2) (e, f), and 9 (tau, S2) (g, h – not a minimum).

The optimization of 9 on the S1 state starting from either a normal or a tautomer structure failed to converge, presumably approaching conical intersections. On the S2 level of 9, both normal and tautomer starting structures converged to respective stationary points, the latter of which is not a minimum as revealed from frequency calculations. The identified excited states of 8 and 9 are


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shown in Figure 21. The optimizations of the S1 states of 10, 11, and 13 were also performed, and their properties are listed together with those of 8 and 9 in Table 7. Minimal energy proton transfer path of 8 and 9. In order to identify any barrier of possible proton transfer processes on various electronic states, minimal energy reaction path calculation was carried out (DFT/B3LYP/def-SV(P)) by varying the OH distance from 0.8 Å to 2.2 Å with 0.1 Å increment. All other internal coordinates were allowed to relax during the geometrical optimization. Similar approaches have been used to study other ESIPT systems.61-67 For 8 (Figure 22a), a normal structure was identified on the ground state, while a normal minimum was located on the S1 level. As the OH distance increased, the energy of the S1 state fell after overcoming a barrier at OH distance of 1.2 Å without materializing into a minimum. After the OH distance was over 1.7 Å, the calculation failed as the structure is likely approaching a conical intersection. A shallow minimum was identified on the S2 level (Figure 22a), suggesting that the proton might oscillate between O and N on the S2 surface of 8. A similar ground state surface was identified for 9 (Figure 22b) that contains a single minimum of the normal structure. Differing from 8, no minimum was located on the S1, on which the molecule seems to slide down as the OH distance increases. A normal structure and a much shallower tautomer stationary point, which is not a minimum, were identified on the S2 surface of 9. Minimal energy reaction path calculations identified only the normal forms on the S1 surface of 8 and S2 surface of 9 with discrete geometries and relatively high oscillator strengths of electronic transitions (Table 7).


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Figure 22. Minimal energy paths of 8 (a) and 9 (b) along the O-H coordinate (0.8 – 2.2 Å). The stationary points are marked by arrows. The geometries of 8 in the S1 state when OH > 1.7 Å and in the S2 state when OH > 2.0 Å did not converge, possibly were approaching conical intersections.

Discussion (a) Solution and solid state structures. The solution and solid state structural studies of compounds 8-11 and 13 illustrate the hydrogen bonding preferences of these “click” triazoles: (1) the N3 of triazolyl nitrogen, which is a stronger HB acceptor than N2, dictates hydrogen bonding pattern in the solid states. (2) The C4 substituent, which is derived from the alkyne precursor of the triazole, is more coplanar with the triazolyl group than the N1 substituent, which is derived from the azide precursor. (3) In solutions at low concentrations (e.g., mM or M), intramolecular HBs prevail. (4) Upon deprotonation, phenolate oxygen engages in attractive interactions with triazolyl C5-H, if stereochemically positioned to do so. (b) Electronic structures of 8-11 and 13. These five compounds are 1,2,3-triazoles substituted with either N,N-dimethylanilinyl (DMA) or 2/4-hydroxyphenyl (HP). Based on the Hammett constants of N,N-dimethylamino and hydroxyl,68 the former is more electron-donating than the


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latter. Therefore, when DMA and 2/4-HP are connected through a 1,2,3-triazolyl moiety, one would presume that the HOMO resides primarily on the former. It is indeed the case in 8 and 10, in which DMA is a substituent at the C4 position of 1,2,3-triazole. While in 9 and 11 where DMA is found at the N1 position, both DMA and 2/4-HP have relatively equal contributions to the HOMO. Therefore, 1,2,3-triazolyl has uneven influences on the electronic structures of N1 and C4 substituents – it is more electron-withdrawing on the N1 than the C4 substituent. Based on this argument, compounds 9 and 11 have DMA substituted on the N1 position; therefore, the electrondonating ability of DMA is reduced by the triazolyl moiety, and consequently, it is no longer the primary occupier of the HOMO. In compounds 8 and 10, DMA is substituted on the C4 position of 1,2,3-triazole, which masks the electron-withdrawing ability of triazolyl. As a result, the HOMO is found principally on the C4/triazolyl fragment. The conclusion that triazolyl moiety exerts a more electron-withdrawing effect on the N1 than the C4 substituent is consistent with the observation that 8, which has hydroxyphenyl (HP) on the N1 position, is more easily deprotonated than 9 (corroborated by the computed pKa values in Table 4), which has HP on the C4 position. It is also consistent with the computation-supported structural assignment of the mono-anion of 13, in which the phenolate is on the more electron-withdrawing N1 position, while the C4-HP remains neutral. The C4-deprotonated mono-anion of 13 is 8 kcal/mol higher in the calculated SCF energy. The computation data also reveal that 1,2,3-triazolyl is in conjugation in the ground state with the C4 substituent, and less so with the N1 substituent (Figures 20, S16). The same conclusion was drawn via the analysis of the solid state data of compounds 8-11 (Table 1). (c) 8 vs 8-Me: Does the intramolecular hydrogen bond (HB) lead to ESIPT in 8, or 9? The absorption band of 8 with the longest maximum intensity wavelength (308 nm) was observed in


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DCM, the least polar solvent. The intramolecular HB of 8 in DCM is intact, which promotes electron delocalization over the entire molecule, thus resulting in a low energy absorption. In 8Me when the intramolecular HB is unavailable, the absorption drops back to 301 nm in DCM. In TFE, the solvent forms intermolecular HB with the triazolyl moiety in both 8 and 8-Me, which reduces the coplanarity of the chromophore and hence decreasing the absorption wavelength to 282 and 280 nm, respectively. Similar absorption blue shift in TFE was also observed in the intramolecular HB-capable chromophore 2-(2’-hydroxyphenyl)benzoxazole (HBO, Figure 1).60 The large Stokes shifts of 8 measured in all solvents (10-13 × 103 cm-1) prompted us to consider the ESIPT model. The methylated version of 8 (8-Me) that is incapable of ESIPT has a similarly large Stokes shift (13 × 103 cm-1, Figure S3), which renders the ESIPT model unconvincing. When the spectral data in more solvents were examined, a clearer solvatochromic correlation between emission wavelength and solvent polarity was observed, which is consistent with having a charge transfer excited state.69 Computationally, the normal form of 8 is the only minimum on the S1 surface, which corroborates the experimental conclusion that compound 8 is incapable of ESIPT. For compound 9, the only possible emissive excited state is the normal form on the S2 surface. One would be extremely hesitant to attribute the observed emission of 9 to the second excited state. However, the geometry and the excitation energy of the S2(normal) of 9 is, perhaps not coincidentally, similar to those of a non-hydrogen bonded conformer of 9 (9’ in Figure S12), the methylated derivative 9-Me, and 11 on their respective S1 levels (Table 7). Therefore, if the S2 emission of the intramolecularly hydrogen bonded normal form of 9 is ruled out, one may reasonably speculate that the non-hydrogen bonded populations of 9 emit strongly in the wavelength range that was observed in the experiment. The search for such emissive non-hydrogen bonded populations and


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the study on the properties of the optimized S2 state of the normal form are beyond the scope of this article. What we have concluded with confidence from computation is that only emissive normal excited states of 8 and 9 were identified, and that the observed emission of either 8 or 9 cannot be attributed to that of the proton-transferred tautomers. (d) 8 vs 10 and 9 vs 11: The effect of intramolecular HB on emission wavelength. The spectral comparison between 8 and 10, two regioisomers that differ in the position of hydroxyl on the N1 substituent of the triazole, offers clues to interpret the effect of an intramolecular HB on the electronic structure of the chromophore. An intramolecular HB in 8 engages the N2 of the triazolyl moiety, which is the electron-accepting end of the charge-transfer chromophore (C4DMA/T). The lower energy emission of 8 than that of 10 (see data in Table 2) can be explained by the stabilization effect of the intramolecular HB in 8 on the charge-transfer excited state. The structural rigidification by the intramolecular HB in 8 might also have played a role. A similar emission wavelength difference between regioisomers 9 and 11 was also recorded. The emission of the electronically similar 9 and 11 upon deprotonation is red-shifted, because deprotonation creates the strongly electron-donating phenolate moiety within the fluorophore, which strengthens the charge-transfer character of the emission. The deprotonation of 8 and 10 however leads to different outcomes – deprotonation of 8 affords an anion of a shorter emission wavelength, while deprotonation of 10 results in quenching. In both 8 and 10, HOMO is entirely shifted from the C4-DMA moiety to 2/4-phenolate upon deprotonation, whereas the LUMOs of both remain relatively unchanged. One may need to invoke the hydrogen bonding pattern differences of the anions of 8 and 10 to account for the emission difference. For the deprotonated 10 (and 8), the phenolate may act as an electron transfer donor70,71 to quench the excited state of the C4-DMA/T fluorophore. On the other hand, the phenolate moiety in deprotonated 8 is tied up


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with triazolyl via the O-ꞏꞏꞏH-C hydrogen bond (Scheme 1a), which simultaneously decreases the electron donor strength of phenolate and the electron-withdrawing character of triazolyl. The two effects contribute to the diminished quenching and the blue shift of the charge transfer emission, respectively. (e) 8 vs 9: the effect of triazolyl substitution pattern. Based on the single crystal structures of 8-11, the C4 substituent of a “click” triazole is more coplanar with the triazolyl moiety than the N1 substituent (Table 1), which shall lead to better electron delocalization between the triazolyl ring and the C4 than the N1 substituent. This conclusion agrees with the computationally optimized geometries, which reproduces the coplanarity of the C4 substituent and triazolyl (Figure 20), and the participation of both segments in the HOMO of each molecule (Table 5). When the C4 substituent is electron-richer than the N1 substituent, a push-pull chromophore is resulted that enjoys additional solvent-stabilizing effect in the excited state. The C4 substituent of compound 8 – DMA – is more electron-donating than that of 9 (2-hydroxyphenyl), which explains the longer emission wavelength of 8 than that of 9 when compared in the same solvent (Table 2). The same comparison stands with 10 and 11, two isomers that only differ in the triazolyl substitution pattern. Additionally, the S1 excited state dipole moment of 10 is larger (19 D vs. 10 D, see Table 7) than that of 11, which also explains the stronger charge transfer nature of 10. The deprotonation of 8 (computed pKa = 7.9, Table 4) using DBU (pKa = 12 in DMSO) occurs on the N1 substituent, which eliminates the HB with the triazolyl N2 and consequently reduces the charge transfer character of the excited C4-DMA/T fluorophore, hence decreasing the emission wavelength. The stronger base TBAOH (pKa = 31 in DMSO) was used to deprotonate 9 (computed pKa = 11.1, Table 4), the hydroxyl of which is on the C4 substituent – a part of the fluorophore C4-HP/T in 9. Consequently, the charge transfer character of 9 increases to result in an emission


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red shift. The contrast in the changes in emission color upon deprotonation of 8 and 9 is evident in the photographs of relevant solutions (Figure 23).

Figure 23. The emission colors of 8 (top) and 9 (bottom) and their conjugated bases in ACN.

(f) 11 vs 12: the effect of the N1 substituent on emission. Compound 11 shows bright blue and yellow emission in its neutral and anionic forms (Figure 23, top), respectively. An argument was made in earlier sections that the C4 substituent in a “click” triazole tends to conjugate better with the triazolyl than the N1 substituent. Thus, the C4 substituent and triazolyl collectively constitute the major component of the fluorophore. We were wondering how much impact the DMA group at N1 position of 11 has on its emission. When the DMA group is replaced with an n-octyl group in 12, the blue emission of 11 (410 nm in ACN) retreats to the UV region (324 nm, a difference of ~ 6,500 cm-1). However, the deprotonated 12 peaks at 517 nm (Figure 24, bottom), which is relatively close to that of the anion of 11 (545 nm, a difference of ~ 1,000 cm-1). These observations suggest that in the neutral form, an electron-rich N1 substituent contributes substantially to the


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emission of 11. This conclusion is corroborated by the FMO plots of 11 (Table 5), where both HOMO and LUMO of the neutral molecule cover the DMA group. In the deprotonated form as the phenolate takes over as the more electron-donating moiety, the contribution of the N1 substituent to the HOMO of the deprotonated 11 is diminished (Table 6). Therefore, the emission of 11 resembles that of the C4 substituent/triazolyl fluorophore alone (as in 12).

Figure 24. The emission colors of 11 (top) and 12 (bottom) and their conjugated bases in ACN.

(g) The doubly intramolecular hydrogen-bonded 13. An intramolecular HB in a “click” triazole helps bring C4 and/or N1 substituents into electronic conjugation with the triazolyl core. The effect of intramolecular HBs on the absorption spectrum is reaffirmed using compound 13,38,72 which is capable of forming two HBs. The absorption in DCM is substantially red-shifted from that in ACN and DMSO (Figure 17). In DMSO that offers the strongest disruption of an intramolecular HB, the absorption maximum is unequivocally the shortest. Compound 13 has weak emission in its neutral form, while computationally a minimum on the S1 surface was not located. Upon deprotonation to the mono-anion, the emission band centering at 435 nm intensifies


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(see photograph in Figure 25). 1H NMR of deprotonated 13 suggests that the phenolate moiety may form HB with the C5-H on the triazolyl group (Figure 4f), similar to that of deprotonated 8. Therefore, the emissive nature of the mono-anion may share the same origin with deprotonated 8. Further addition of base leads to the formation of the dianion that includes two phenolate moieties (Figure 25), one of which acts as an electron donor, similar to that in the deprotonated compound 10, to quench the emission.

Figure 25. The sequential deprotonation of compound 13.

Conclusion The structural and spectroscopic properties of four isomeric “click” triazoles (8-11) are studied. It is confirmed that N3 on the triazolyl ring is a stronger hydrogen bond acceptor than N2. The C4 substituent (the alkyne component) of a triazole is more coplanar with the triazolyl group than the N1 substituent (the azide component). Additionally, the triazolyl group exerts a stronger electronwithdrawing power on the N1 than on the C4 substituent, which is reflected in the differences of pKa values of these compounds. These two factors collectively determine that in 8-11 and 13, the C4-aryltriazolyl moiety, as opposed to the N1-aryltriazolyl, constitutes the majority of the


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chromophores in their neutral forms in the ground state. Upon deprotonation, the ground state chromophore invariably shifts to the negatively charged phenolate moiety. In compounds 8 and 9 that are capable of forming intramolecular hydrogen bonds, the phenolate moiety in the deprotonated form finds the C5-H bond to produce a new intramolecular attractive force. Both the ability to form intramolecular hydrogen bond and the triazolyl substitution pattern affect the optical properties of “click” triazoles profoundly. The effect of the former is revealed by the comparison between 8 and 10 (or 9 and 11), while that of the latter is demonstrated by comparing 8 and 9 (also 10 and 11). Both experiments and computation reach the same conclusion that the intramolecular hydrogen bonds in 8 and 9 does not lead to the emission resulting from excited state intramolecular proton transfer (ESIPT). The large Stokes shifts of these compounds are attributed to the charge transfer nature of the fluorophores. These conclusions may help produce high quantum yield fluorophores with large Stokes shifts with potential for producing multiple fluorescence (e.g., via strategic disruption of intramolecular hydrogen bonds).

ASSOCIATED CONTENT Supporting Information. Synthetic procedures and characterization data. Additional figures. This material is available free of charge via the Internet at http://pubs.acs.org. AUTHOR INFORMATION Corresponding Author * [email protected]; * [email protected]


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ACKNOWLEDGMENT. This work was supported by the National Science Foundation (CHE1213574 and CHE1566011 to L.Z.). Computation was supported by University of California, Riverside.

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