Excited-state proton transfer relieves antiaromaticity in molecules Chia-Hua Wua, Lucas José Karasa, Henrik Ottossonb, and Judy I-Chia Wua,1 aDepartment of Chemistry, University of Houston, Houston, TX 77004; and bDepartment of Chemistry, Ångström Laboratory, Uppsala University, 751 20 Uppsala, Sweden Edited by Kendall N. Houk, University of California, Los Angeles, CA, and approved August 28, 2019 (received for review May 20, 2019) Baird’s rule explains why and when excited-state proton transfer reverse at the lowest ππ* triplet state (25). In the ground state, (ESPT) reactions happen in organic compounds. Bifunctional com- compounds with cyclic [4n + 2] π-electron delocalizations display pounds that are [4n + 2] π-aromatic in the ground state, become enhanced thermochemical stability, have low reactivity, and are [4n + 2] π-antiaromatic in the first 1ππ* states, and proton trans- aromatic. Those with [4n] π-electron delocalizations are less viable, fer (either inter- or intramolecularly) helps relieve excited-state anti- chemically reactive, and are antiaromatic. In the excited state, the aromaticity. Computed nucleus-independent chemical shifts (NICS) opposite is true (26–29). Compounds with cyclic [4n] π-electron for several ESPT examples (including excited-state intramolecular delocalizations become aromatic; those with [4n + 2] π-electron proton transfers (ESIPT), biprotonic transfers, dynamic catalyzed delocalizations become antiaromatic. It was suggested that Baird’s transfers, and proton relay transfers) document the important role rule extends also to the lowest ππ* singlet states (26, 28, 29), to of excited-state antiaromaticity. o-Salicylic acid undergoes ESPT only macrocycles (30, 31), and that the concept has much interpretive “ ” 1ππ “ ” in the antiaromatic S1 ( *) state, but not in the aromatic S2 merit for photochemistry (32, 33). Benzene, for example, is [4n + 1 ( ππ*) state. Stokes’ shifts of structurally related compounds [e.g., 2] π-electron antiaromatic in its lowest 1ππ*and3ππ* states (34); it derivatives of 2-(2-hydroxyphenyl)benzoxazole and hydrogen- becomes highly reactive and does what it can to relieve excited- bonded complexes of 2-aminopyridine with protic substrates] vary state antiaromaticity. We show here that bifunctional molecules, depending on the antiaromaticity of the photoinduced tauto- i.e., compounds that have both proton donating and accepting ’ mers. Remarkably, Baird s rule predicts the effect of light on hydro- groups, like the o-salicylic acid, can relieve excited-state anti- CHEMISTRY gen bond strengths; hydrogen bonds that enhance (and reduce) aromaticity through ESPT. In the ground state, the dominant excited-state antiaromaticity in compounds become weakened tautomer of o-salicylic acid (Fig. 1A, A form) is aromatic and (and strengthened) upon photoexcitation. displays a cyclic delocalization of [4n + 2] π-electrons. But this tautomeric form becomes antiaromatic in the first 1ππ* state, and excited-state proton transfer | Baird’srule| aromaticity | antiaromaticity | one way for it to get rid of antiaromaticity is to transfer a proton hydrogen bonding from the hydroxyl to the carboxyl group, and form Q—aquinoidal tautomer preclude of cyclic [4n + 2] π-electron delocalization. In hen light strikes a molecule, protons and electrons can this way, ESPT can relieve excited-state antiaromaticity in cyclic, Wsometimes rearrange to form rare tautomers in ratios far π-conjugated, bifunctional compounds. from equilibrium. Weller discovered the first example of such Depending on how a migrating proton moves from one site to excited-state proton transfer (ESPT) in the o-salicylic acid—alarge another, ESPT reactions are categorized into 4 types (35): ESIPT Stokes’ shift in the spectrum suggested the appearance of an odd (type I), biprotonic transfers (type II), dynamic catalyzed proton tautomer (1, 2). At first, Weller and others (3) assumed that a zwitterionic tautomer had formed, but Nagaoka et al. (4, 5) later Significance proposed that an H atom migrated from the hydroxyl to the car- boxyl group, giving a quinoid-looking tautomer (Fig. 1A, Q form). − Excited-state proton transfer (ESPT) is universally recognized as Similar prominent Stokes’ shifts (up to 10,000 cm 1)andas- − a reaction that relaxes the energy of a photoexcited organic tonishing proton transfer rates (up to 1012 s 1) were reported compound. It is commonly found in many light-driven pro- for the dimers of 7-azaindole (6, 7), 1-carbazole (8, 9), and cesses. Here we identify decisive principles underlying why and protic solvent complexes of 2-aminopyridine (10–12), and when ESPT happens. Our computational investigation of pro- even more reported examples of ESPT in organic compounds totypical ESPT reactions finds that the occurrence of ESPT can emerged in the next 30 y (13). Compounds like the 3- be explained by an electron-counting rule—Baird’s rule, which hydroxyflavone (14, 15), 2-(2-hydroxyphenyl)benzoxazole remains largely ignored despite having a near–50-y-old history. (HBO) (16), and 10-hydroxybenzo[h]quinolone (HBQ) (17) We emphasize that this surprising connection not only explains undergo excited-state intramolecular proton transfer (ESIPT) ’ the mechanistic principle of ESPT reactions, but it also predicts (18, 19) at the picosecond scale, display large Stokes shifts, and whether hydrogen bonding interactions that form within and find myriad applications as dyes and fluorescent sensors. When between organic compounds might strengthen or weaken ESPT happens, only bare protons are displaced, but what prompts when irradiated by light. Recognizing this relationship has them to move is enormous change in the electronic structure of tremendous interpretive merit for organic photochemistry. the molecule. Chemists have called this change “an increase in the acidity of the proton donor and basicity of the proton acceptor Author contributions: C.-H.W. and J.I.W. designed research; C.-H.W. and L.J.K. performed (pKa change),” (19, 20) “a difference in the character of the research; C.-H.W., L.J.K., H.O., and J.I.W. analyzed data and made intellectual contribu- wavefunction (Nagaoka’s nodal plane model),” (4, 5) or “a tions to the development of the paper; and J.I.W. wrote the paper. change in aromatic character.” (21–24) In this paper, we show The authors declare no conflict of interest. that when an organic compound is: cyclic, π-conjugated, and This article is a PNAS Direct Submission. exhibits prominent [4n + 2] π-aromatic character in the ground Published under the PNAS license. state, that change is the rise of [4n + 2] π-antiaromaticity in its 1To whom correspondence may be addressed. Email: [email protected]. photoexcited state. This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. Baird first proposed a set of rules describing that the Hückel 1073/pnas.1908516116/-/DCSupplemental. π-electron counting rules of aromaticity and antiaromaticity www.pnas.org/cgi/doi/10.1073/pnas.1908516116 PNAS Latest Articles | 1of6 Downloaded by guest on September 23, 2021 AB “breached” π-electron delocalizations) become energetically competitive. Tautomeric free energies computed in implicit sol- vation at 298 K are provided in SI Appendix,TableS1,andshow 1 the same trend. Unless noted otherwise, all S1 states refer to ππ* 3 states and all T1 states refer to ππ* states (for comparison, tran- sition energies for the closest energy 1nπ* states are provided in SI Appendix, Tables S2 and S3). Dissected nucleus-independent chemical shifts (40, 41), C D NICS(1)zz, analyses suggest that the tautomeric trends shown in Table 1 are the result of reversed aromaticity vs. antiaromaticity in A,intheS0 vs. S1 (and T1) states. In the S0 state, the computed NICS(1)zz values for all A forms are large and negative, indicating strong aromatic character. But, in the S1 (and T1) state, these values become large and positive, indicating strong antiaromatic character. In contrast, the Q forms display less-negative NICS(1)zz values in E F the S0 state, and less-positive NICS(1)zz values [modestly negative NICS(1)zz value for HBO] in the S1 (and T1) states. Direct com- parisons of computed NICS(1)zz values for the A vs. Q tautomers, in the S1 (and T1) state, suggest that ESPT helps to relieve excited- state antiaromaticity. Computed Harmonic Oscillator Model of Electron Delocalization analyses (a geometric criterion of aroma- ticity and antiaromaticity) are supportive and show the same trends (see results in SI Appendix,TablesS5–S8). Similar findings have been reported for ESIPT compounds, based on magnetic (42), Fig. 1. Examples of type I (A–C), type II (D), type III (E), and type IV (F)ESPT geometric (21, 23), and energetic (24) indices of aromaticity. reactions. Tautomers having complete cyclic [4n + 2] π-electron delocalizations Remarkably, Baird’s rule helps to explain when and why are labeled “A.” Tautomers having breached cyclic π-electron delocalizations π-conjugated organic compounds undergo ESPT. Below we are labeled “Q.” elucidate the important role of Baird’s rule for explaining the mechanisms of: 1) ESIPT, 2) solvent-catalyzed phototautomerizations, as well as 3) the effects of photoexcitation on hydrogen bond transfers (type III), and proton relay transfers involving multiple strengths. proton bridges (type IV). In dynamic catalyzed proton transfers, ESIPT reactions. ESIPT in systems like the o-salicylic acid, HBO, the catalyzing substrate shifts its position during ESPT. For ex- and HBQ, (Fig. 1 A–C), have been viewed as a consequence of ample, flavin, a photoactive cofactor in enzymes, can form 1:1 “a redistribution of electron density,”“a change in acidity and complexes with pyridine and undergo dynamic catalyzed ESPT; basicity,” or “a change in the wavefunction,” in molecules at pyridine extracts a proton from the N1 site of flavin and rotates photoexcited states. We show here that these interpretations its position to donate that same proton to the N10 site (Fig. 1E) differ in choice of words but describe the same phenomena— (36, 37).