Excited-state Antiaromaticity Research Articles

Excited-state antiaromaticity relief drives facile photoprotonation of carbons in aminobiphenyls.

A combined computational and experimental study reveals that ortho-, meta- and para-aminobiphenyl isomers undergo distinctly different photochemical reactions involving proton transfer. Deuterium exchange experiments show that the ortho-isomer undergoes a facile photoprotonation at a carbon atom via excited-state intramolecular proton transfer (ESIPT). The meta-isomer undergoes water-assisted excited-state proton transfer (ESPT) and a photoredox reaction via proton-coupled electron transfer (PCET). The para-isomer undergoes a water-assisted ESPT reaction. All three reactions take place in the singlet excited-state, except for the photoredox process of the meta-isomer, which involves a triplet excited-state. Computations illustrate the important role of excited-state antiaromaticity relief in these photoreactions.

Small is Beautiful: Electronic Origin and Synthetic Evolution of Single-Benzene Fluorophores.

ConspectusSingle-benzene fluorophores (SBFs) are small molecules that produce visible light by using only one benzene ring as the sole aromatic core. This Account centers around the chemistry of a new class of SBF that we accidentally discovered but rationally developed and refined afterward. In a failed experiment that took an unintended reaction pathway, we encountered the bright green fluorescence of ortho-diacetylphenylenediamine (o-DAPA). Despite its uninspiring look, reminiscent of textbook examples of simple benzene derivatives, this molecule had neither been synthesized nor isolated before. This discovery led to our studies on the larger DAPA family, including isomeric m-DAPA and p-DAPA. Remarkably, p-DAPA is the lightest red fluorophore, with a molecular weight of only 192. While o- and p-DAPA are emissive, m-DAPA rapidly undergoes internal conversion, facilitated by sequential proton transfer reactions in the excited state.Leveraging the synthetic utility of the amine group, we carried out straightforward single-step modifications to create a full-color SBF library from p-DAPA as the common precursor. During the course of the investigation, we made another fortuitous discovery. With increasing acidity of the N-H group, the excited-state intramolecular proton transfer reaction is promoted, opening up additional pathways for emission to occur at even longer wavelengths. Tipping the balance between the two excited-state tautomers enabled the first example of a single-benzene white-light emitter. We demonstrated the practical utility of these molecules in white light-emitting devices and live cell imaging.According to the particle-in-a-box model, it is difficult to expect a molecule with only one small aromatic ring to produce long-wavelength emission. SBFs rise to this challenge by exploiting electron donor-acceptor pairs around the benzene core, which lowers the energy of light absorption. However, this answers only half of the question. Where do the exceptionally large spectral shifts in the light emission of SBFs originate from? Chemists have long been curious about the molecular mechanisms underlying the dramatic spectral shifts observed in SBFs. Prevailing paradigms invoke the charge transfer (CT) between electron donor and acceptor groups in the excited state. However, without a large π-skeleton for effective charge separation, how could benzene support a CT-type excited state? Our experimental and theoretical studies have revealed that large excited-state antiaromaticity (ESAA) of the benzene core itself is responsible for this remarkable phenomenon. The core matters, not the periphery. With appropriate molecular design, large and extended π-conjugation is no longer a prerequisite for long-wavelength light emission.

Photochemical Uncaging of Aldehydes and Ketones via Photocyclization/Fragmentation Cascades of Enyne Alcohols: An Unusual Application for a Cycloaromatization Process.

We utilized a cycloaromatization reaction driven by relief of excited state antiaromaticity to photouncage aldehydes and ketones. We developed several synthetic routes towards the synthesis of photocaged carbonyls as allylically substituted 3-(2-(arylethynyl)phenyl)prop-2-en-1-ols. A library of photocaged aryl aldehydes and ketones containing donors and acceptors, as well as several photocaged fragrance aldehydes and the steroid 5α-cholestan- 3 -one, were synthesized and demonstrated photouncaging in good to excellent yields.

Single-Benzene Dual-Emitters Harness Excited-State Antiaromaticity for White Light Generation and Fluorescence Imaging.

Molecular emitters simultaneously generating light at different wavelengths have wide applications. With a small molecule, however, it is challenging to realize two independent radiative pathways. We invented the first examples of dual-emissive single-benzene fluorophores (SBFs). Two emissive tautomers are generated by synthetic modulation of the hydrogen bond acidity, which opens up pathways for excited-state proton transfer. White light is produced by a delicate balance between the energy and intensity of the emission from each tautomer. We show that the excited-state antiaromaticity of the benzene core itself dictates the proton movements driving the tautomer equilibrium. Using this simple benzene platform, a fluorinated SBF was synthesized with a record high solubility in perfluorocarbon solvents. White light-emitting devices and multicolor imaging of perfluorocarbon nanodroplets in live cells demonstrate the practical utility of these molecules.

Photochemistry Driven by Excited-State Aromaticity Gain or Antiaromaticity Relief.

Gain of aromaticity or relief of antiaromaticity along a reaction path are important factors to consider in mechanism studies. Analysis of such changes along potential energy surfaces has historically focused on reactions in the electronic ground state (S0 ), but can also be used for excited states. In the lowest ππ* states, the electron counts for aromaticity and antiaromaticity follow Baird's rule where 4n π-electrons indicate aromaticity and 4n+2 π-electrons antiaromaticity. Yet, there are also cases where Hückel's rule plays a role in the excited state. The electron count reversals of Baird's rule compared to Hückel's rule explain many altered physicochemical properties upon excitation of (hetero)annulene derivatives. Here we illustrate how the gain of excited-state aromaticity (ESA) and relief of excited-state antiaromaticity (ESAA) have an impact on photoreactivity and photostability. Emphasis is placed on recent findings supported by the results of quantum chemical calculations, and photoreactions in a wide variety of areas are covered.

Computational study on the reduction and solvolysis of triplet chlorobenzenes

AbstractIn this work we explored the excited state reactivity of triplet chlorobenzenes with density functional theory and a cluster‐continuum approach. We modeled two competing reactions: a direct abstraction of hydrogen from a solvent molecule and solvolysis via photo‐SN2Ar. Electron donating (–OMe, –CH2SiMe3, –SiMe3) and withdrawing (–CN) substituents not only have distinct effects on the triplet geometries, inducing structural distortions due to the relief of excited state antiaromaticity, but also affect the reactivity of the system. Therefore, electron‐rich chlorobenzenes favor the radical reduction, while electron deficiency opens the possibility for solvolysis. Both reactions are energetically comparable to or more favorable then the dissociation of the C‐Cl bond to form triplet or singlet aryl cations, the intermediates considered responsible for these reactivities. Our findings can be correlated with experimental results on similar systems available from the literature, deeming the proposed pathways as viable alternatives to established mechanisms involving aryl cations.

Barrier-Lowering Effects of Baird Antiaromaticity in Photoinduced Proton-Coupled Electron Transfer (PCET) Reactions.

Many popular organic chromophores that catalyze photoinduced proton-coupled electron transfer (PCET) reactions are aromatic in the ground state but become excited-state antiaromatic in the lowest ππ* state. We show that excited-state antiaromaticity makes electron transfer easier. Two representative photoinduced electron transfer processes are investigated: (1) the photolysis of phenol and (2) solar water splitting of a pyridine-water complex. In the selected reactions, the directions of electron transfer are opposite, but the net result is proton transfer following the direction of electron transfer. Nucleus-independent chemical shifts (NICS), ionization energies, electron affinities, and PCET energy profiles of selected [4n] and [4n + 2] π-systems are presented, and important mechanistic implications are discussed.

Relief of excited-state antiaromaticity enables the smallest red emitter

It is commonly accepted that a large π-conjugated system is necessary to realize low-energy electronic transitions. Contrary to this prevailing notion, we present a new class of light-emitters utilizing a simple benzene core. Among different isomeric forms of diacetylphenylenediamine (DAPA), o- and p-DAPA are fluorescent, whereas m-DAPA is not. Remarkably, p-DAPA is the lightest (FW = 192) molecule displaying red emission. A systematic modification of the DAPA system allows the construction of a library of emitters covering the entire visible color spectrum. Theoretical analysis shows that their large Stokes shifts originate from the relief of excited-state antiaromaticity, rather than the typically assumed intramolecular charge transfer or proton transfer. A delicate interplay of the excited-state antiaromaticity and hydrogen bonding defines the photophysics of this new class of single benzene fluorophores. The formulated molecular design rules suggest that an extended π-conjugation is no longer a prerequisite for a long-wavelength light emission.

Degradation of Pharmaceuticals through Sequential Photon Absorption and Photoionization in Amiloride Derivatives

Summary Haloaromatic drug molecules of the amiloride family are plagued by photodegradation with associated toxicity. Herein, we report on the photodegradation of analogs of amiloride, which are known to undergo photosubstitution in water. Model compounds built on the same scaffold undergo clean photosubstitution also in alcoholic solvent, where a certain amount of photodehalogenation is normally expected. Available evidence points to a mechanism starting with photoexcitation followed by photoionization to give a radical cation intermediate. Subsequent substitution reaction with the protic solvent is assisted by a general base, possibly strengthened by the proximal solvated electron. Recombination with the solvated electron generates the observed product. Quantum chemical computations reveal that excited state antiaromaticity is relieved when an electron is ejected from the photoexcited molecule by the second photon. The mechanism indicated here could have wide applicability to photoinduced degradation of similar heteroaromatic compounds in the environment, as well as to a class of increasingly popular synthetic photoredox methods.

Impact of Excited-State Antiaromaticity Relief in a Fundamental Benzene Photoreaction Leading to Substituted Bicyclo[3.1.0]hexenes.

Benzene exhibits a rich photochemistry which can provide access to complex molecular scaffolds that are difficult to access with reactions in the electronic ground state. While benzene is aromatic in its ground state, it is antiaromatic in its lowest ππ* excited states. Herein, we clarify to what extent relief of excited-state antiaromaticity (ESAA) triggers a fundamental benzene photoreaction: the photoinitiated nucleophilic addition of solvent to benzene in acidic media leading to substituted bicyclo[3.1.0]hex-2-enes. The reaction scope was probed experimentally, and it was found that silyl-substituted benzenes provide the most rapid access to bicyclo[3.1.0]hexene derivatives, formed as single isomers with three stereogenic centers in yields up to 75% in one step. Two major mechanism hypotheses, both involving ESAA relief, were explored through quantum chemical calculations and experiments. The first mechanism involves protonation of excited-state benzene and subsequent rearrangement to bicyclo[3.1.0]hexenium cation, trapped by a nucleophile, while the second involves photorearrangement of benzene to benzvalene followed by protonation and nucleophilic addition. Our studies reveal that the second mechanism is operative. We also clarify that similar ESAA relief leads to puckering of S1-state silabenzene and pyridinium ion, where the photorearrangement of the latter is of established synthetic utility. Finally, we identified causes for the limitations of the reaction, information that should be valuable in explorations of similar photoreactions. Taken together, we reveal how the ESAA in benzene and 6π-electron heterocycles trigger photochemical distortions that provide access to complex three-dimensional molecular scaffolds from simple reactants.

Electron-driven proton transfer relieves excited-state antiaromaticity in photoexcited DNA base pairs.

The Watson–Crick A·T and G·C base pairs are not only electronically complementary, but also photochemically complementary. Upon UV irradiation, DNA base pairs undergo efficient excited-state deactivation through electron driven proton transfer (EDPT), also known as proton-coupled electron transfer (PCET), at a rate too fast for other reactions to take place. Why this process occurs so efficiently is typically reasoned based on the oxidation and reduction potentials of the bases in their electronic ground states. Here, we show that the occurrence of EDPT can be traced to a reversal in the aromatic/antiaromatic character of the base upon photoexcitation. The Watson–Crick A·T and G·C base pairs are aromatic in the ground state, but the purines become highly antiaromatic and reactive in the first 1ππ* state, and transferring an electron and a proton to the pyrimidine relieves this excited-state antiaromaticity. Even though proton transfer proceeds along the coordinate of breaking a N–H σ-bond, the chromophore is the π-system of the base, and EDPT is driven by the strive to alleviate antiaromaticity in the π-system of the photoexcited base. The presence and absence of alternative excited-state EDPT routes in base pairs also can be explained by sudden changes in their aromatic and antiaromatic character upon photoexcitation.

How does excited-state antiaromaticity affect the acidity strengths of photoacids?

Photoacids like substituted naphthalenes (X = OH, NH3+, COOH) are aromatic in the S0 state and antiaromatic in the S1 state. Nucleus independent chemical shifts analyses reveal that deprotonation relieves antiaromaticity in the excited conjugate base, and that the degree of "antiaromaticity relief" explains why some photoacids are stronger than others.

Excited-state proton transfer relieves antiaromaticity in molecules

Baird's rule explains why and when excited-state proton transfer (ESPT) reactions happen in organic compounds. Bifunctional compounds that are [4n + 2] π-aromatic in the ground state, become [4n + 2] π-antiaromatic in the first 1ππ* states, and proton transfer (either inter- or intramolecularly) helps relieve excited-state antiaromaticity. Computed nucleus-independent chemical shifts (NICS) for several ESPT examples (including excited-state intramolecular proton transfers (ESIPT), biprotonic transfers, dynamic catalyzed transfers, and proton relay transfers) document the important role of excited-state antiaromaticity. o-Salicylic acid undergoes ESPT only in the "antiaromatic" S1 (1ππ*) state, but not in the "aromatic" S2 (1ππ*) state. Stokes' shifts of structurally related compounds [e.g., derivatives of 2-(2-hydroxyphenyl)benzoxazole and hydrogen-bonded complexes of 2-aminopyridine with protic substrates] vary depending on the antiaromaticity of the photoinduced tautomers. Remarkably, Baird's rule predicts the effect of light on hydrogen bond strengths; hydrogen bonds that enhance (and reduce) excited-state antiaromaticity in compounds become weakened (and strengthened) upon photoexcitation.

The Missing C1-C5 Cycloaromatization Reaction: Triplet State Antiaromaticity Relief and Self-Terminating Photorelease of Formaldehyde for Synthesis of Fulvenes from Enynes.

The last missing example of the four archetypical cycloaromatizations of enediynes and enynes was discovered by combining a twisted alkene excited state with a new self-terminating path for intramolecular conversion of diradicals into closed-shell products. Photoexcitation of aromatic enynes to a twisted alkene triplet state creates a unique stereoelectronic situation, which is facilitated by the relief of excited state antiaromaticity of the benzene ring. This enables the usually unfavorable 5-endo-trig cyclization and merges it with 5-exo-dig closure. The 1,4-diradical product of the C1-C5 cyclization undergoes internal H atom transfer that is coupled with the fragmentation of an exocyclic C-C bond. This sequence provides efficient access to benzofulvenes from enynes and expands the utility of self-terminating aromatizing enyne cascades to photochemical reactions. The key feature of this self-terminating reaction is that, despite the involvement of radical species in the key cyclization step, no external radical sources or quenchers are needed to provide the products. In these cascades, both radical centers are formed transiently and converted to the closed-shell products via intramolecular H-transfer and C-C bond fragmentation. Furthermore, incorporating C-C bond cleavage into the photochemical self-terminating cyclizations of enynes opens a new way for the use of alkenes as alkyne equivalents in organic synthesis.