Excited-state Proton Transfer Research Articles

Structural Origin and Vibrational Fingerprints of the Ultrafast Excited State Proton Transfer of the Pyranine-Acetate Complex in Aqueous Solution.

The excited state proton transfer (ESPT) reaction from the photoacid 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS or pyranine) to an acetate molecule has been investigated in explicit aqueous solution via excited state ab initio molecular dynamics simulations based on hybrid quantum/molecular mechanics (QM/MM) potentials. In all the trajectories, the direct proton transfer has been observed in the excited state within 1 ps. We find that the initial structural configuration extracted from the ground state distribution strongly affects the ESPT kinetics. Indeed, the relative orientation of the proton donor-acceptor pair and the presence of a water molecule hydrogen bonded to the phenolic acid group of the pyranine are the key factors to facilitate the ESPT. Furthermore, we analyze the vibrational fingerprints of the ESPT reaction, reproducing the blue shift of the acetate CO stretching (COac), from 1666 to 1763 cm-1 testifying the transformation of acetate to acetic acid. Finally, our findings suggest that the acetate CC stretching (CCac) is also sensitive to the progress of the ESPT reaction. The CCac stretching is indeed ruled by the two vibrational modes (928 and 1426 cm-1), that in the excited state are alternately activated when the proton is shared or bound to the donor/acceptor, respectively.

In silico simulation of the excited state proton transfer reaction of 2-(2-furyl)-3-hydroxychromone (FHC) in solution by empirical valence bond (EVB) method in conjunction with classical molecular dynamics

2-(2-Furyl)-3-hydroxychromone (FHC) is a dual emitter fluorescent probe exhibiting excited state intramolecular proton transfer (ESIPT) reaction in solution and inserted in biological relevant macromolecules. Its two fluorescence bands are attributed to normal form (N*) for the short wavelength and the long-wavelength band to the tautomer form (T*), the product of the ESIPT reaction. To rationalise the mechanisms that lead to the occurrence of the ESIPT reaction and predict the fluorescence spectra, the excited and ground state dynamic of this compound was followed in acetonitrile, ethanol, methanol, N-methylformamide and formamide, by the classical molecular dynamic simulation in conjunction with the empirical valence bond (EVB) model to describe bond dissociation process. A set of transferable parameters were used to fit the EVB potential energy curve to TDDFT data. Using these parameters, the occurrence time of the ESIPT reaction was predicted to be 7, 84, 113, 98, 207ps, respectively in the considered solvents, in excellent agreement with the experimentally reported values. These values are comparatively higher than those determined for the parent flavone dye (less than 100 fs), giving FHC a higher potential for sensor development. By examining structural parameters such as the distance from the proton to acceptor, the intermolecular H-bond between FHC and the solvent molecules and proton trajectories, we found that ESIPT occured in acetonitrile and alcohols as a combination of low frequency high amplitude donor-acceptor bending motion and charge redistribution in the excited state, that were modulated by the solvent H-bond donor potency. Differently in amides ESIPT occured via tunnelling mechanism due to the close energy of N* and T*. Fluorescence spectra calculated from potential energies of the EVB model along the reaction coordinates were qualitatively in agreement with the recorded spectra.

Theoretical study on the mechanism for the excited-state double proton transfer process of an asymmetric Schiff base ligand

Excited-state double proton transfer (ESDPT) in the 1-[(2-hydroxy-3-methoxy-benzylidene)-hydrazonomethyl]-naphthalen-2-ol (HYDRAVH2) ligand was studied by the density functional theory and time-dependent density functional theory method. The analysis of frontier molecular orbitals, infrared spectra, and non-covalent interactions have cross-validated that the asymmetric structure has an influence on the proton transfer, which makes the proton transfer ability of the two hydrogen protons different. The potential energy surfaces in both S0 and S1 states were scanned with varying O–H bond lengths. The results of potential energy surface analysis adequately proved that the HYDRAVH2 can undergo the ESDPT process in the S1 state and the double proton transfer process is a stepwise proton transfer mechanism. Our work can pave the way towards the design and synthesis of new molecules.

Effects of azole rings with different chalcogen atoms on ESIPT behavior for benzochalcogenazolyl-substituted hydroxyfluorenes

ESIPT behavior has attracted a lot of eyes of researchers in recent years because of its unique optical properties. Due to its large Stokes shift and double emission fluorescence, white light can be generated in the fluorophore based on the excited state intramolecular proton transfer (ESIPT) principle. The excited state proton transfer behavior of hydroxylated benzoxazole (BO-OH), benzothiazole (BS-OH) and benzoselenazole (BSe-OH) have been investigated in heptane, chloroform and DMF solvents. By comparing the infrared vibration spectra and the variation of bond parameters from the S0 to S1 states, and analyzing the frontier molecular orbitals, the influence of hydrogen bond dynamics, the solvent polarity, charge redistribution and the effects of different proton acceptors on proton transfer were observed. The only structural difference among the three substituted hydroxyfluorenes is the heteroatom in the azole ring (oxygen, sulfur and selenium, respectively). We have scanned the potential energy curve of the ESIPT process, and compared the potential barrier, it is found that the heavier chalcogen atoms are more favorable for proton transfer. At the same time, the potential application of changing heteroatoms in the azole ring by walking down the chalcogenic group in crystal luminescence color regulation is also discussed.

Rational design of shortwave infrared (SWIR) fluorescence probe: Cooperation of ICT and ESIPT processes for sensing endogenous cysteine

Cysteine is well-known to be an important biothiol and related to many diseases. However, the in vivo detection of endogenous cysteine still suffers from lacking small-molecule fluorophores with both excitation and emission in the near-infrared (650-900 nm)/shortwave-infrared region. Herein, we report a molecular engineering strategy for shortwave infrared (SWIR, 900-1700 nm) sensing of cysteine, which integrated an excited-state intermolecular proton transfer (ESIPT) building block into the intramolecular charge transfer (ICT) scaffold. The obtained novel fluorophore SH-OH displays a maximum absorption at the NIR region, and emission at the SWIR region. We introduce the cysteine-recognition moiety to SH-OH structure, and demonstrate sensing of endogenous cysteine in living animals, using the SWIR emission as a reliable off-on fluorescence signal. This fluorophore design strategy of cooperation of ICT and ESIPT processes expands the in vivo sensing toolbox for accurate analysis in clinical applications.

Effects of Intermolecular Hydrogen Bonding and Solvation on Enol-Keto Tautomerism and Photophysics of Azomethine-BODIPY Dyads.

Boron-dipyrromethene derivatives (BODIPYs) are a category of molecules with excellent photophysical properties and can be applied to various fields. This work investigates the fluorescent properties of two azomethine-BODIPY dyads in different solvents based on the time-dependent density functional theory (TD-DFT) method. The potential energy curves (PECs) show that the polar protic solvent and the enhanced π-conjugation effect can lower the proton-transfer (PT) barriers, causing the main configuration of NA-BODIPY in methanol to be the keto form, while the main configuration of NA-BODIPY in toluene and SA-BODIPY in methanol and toluene is the enol form. The keto forms of the two compounds possess the twisted intramolecular charge transfer (TICT) decay pathway in the excited state identified by the optimized twisted configurations and the appropriate barriers of the TICT process, whereas the twisted configurations of the enol forms are nonexistent. TICT successfully competes with excited-state proton transfer (ESIPT) of the keto form, which leads to the fluorescence quenching of NA-BODIPY in methanol. This work provides new ideas for the influence of enol-keto tautomerism and the competitiveness of TICT and ESIPT on the photophysical properties of BODIPYs and is expected to provide guidance for the design of new BODIPY functional molecules.

Salicylaldehyde-based anion sensors featuring turn-on fluorescence, colorimetry, and the anti-counterfeiting application

Two simple salicylaldehyde-based sensors BDQ and BQ were developed, which had been applied in anion sensing and anti-counterfeiting. Their chemical structures were determined by the 1H, 13C NMR and mass spectra. In the anion sensing investigations, F− ions exhibited more competitive response over the others, thus the related detecting limits, anti-interference ability, stoichiometry and sensing mechanism had been carefully carried out. Impressively, once the F− ions were added, the color of the sensor solutions obviously transformed from colorless to yellow, directly recognizing by naked eyes. On the other hand, these sensors were almost non-emissive in solutions, the green fluorescence were successfully turned on after adding fluoride anions. Moreover, the F− ion detection limits achieved by these sensors were as low as 7.5 × 10−7 M, much lower than that of World Health Organization (WHO) permission level. Most importantly, the mechanism of colorimetric change and turn-on fluorescence was safely attributed to the excited-state proton transfer (ESPT) process coming from the sensor-F− complex constructed by the hydrogen bond, which had been deeply interpreted by the NMR and mass titration experiments as well as the theoretical calculations. Finally, the practical application of these sensors for fluoride ion detections in real environment were conducted as well. Meanwhile, considering the reversible fluorescence transformation from blue to green, the high-level and repeatable anti-counterfeiting patterns were developed. Based on all of the results, it's expected that this contribution could provide useful clues for design the high-performance chemo-sensors and anti-counterfeiting materials.

Nanomolar determination of nitrofurans in water via excited-state inter-ligand proton transfer

Qualification and quantification of trace organic contaminants necessitates development of highly efficient sensing system, where excited-state inter-ligand proton transfer (ESILPT) provides a feasible pathway to construct efficient chemo-sensors. Herein, a strategically synthesized lanthanide complex, Eu(DBM)3(MeOH)3 (briefly as Eu-DBM-MeOH; DBM = dibenzoylmethane), features two-step ESILPT processes, along with modification on molecular structure and energy band. As a result, Eu-DBM-MeOH exhibits excellent photophysical properties with characteristic luminescence of Eu3+ ion. Benefiting from these merits, the Eu-DBM-MeOH complex acts as ultra-sensitive chemo-sensor toward nanomolar-level nitrofuran antibiotics (nitrofurazone and nitrofurantoin) in water, by disrupting ESILPT processes. Combining the advantages on photophysical property and luminescent sensitivity, ESILPT-active compounds are expected to widen and deepen the research on complex-based luminophores, being potentially useful in trace detection and biological imaging.

Excited-State Proton Transfer Dynamics in LSSmOrange Studied by Time-Resolved Impulsive Stimulated Raman Spectroscopy.

LSSmOrange is a fluorescent protein that exhibits a large energy gap between absorption and emission, which makes it a useful tool for multicolor bioimaging. This characteristic of LSSmOrange originates from excited-state proton transfer (ESPT): The neutral chromophore is predominantly present in the ground state while the bright fluorescence is emitted from the anionic excited state after ESPT. Interestingly, it was reported that this ESPT process follows bimodal dynamics, but its origin has not clearly been understood. We investigate ESPT of LSSmOrange using time-resolved impulsive stimulated Raman spectroscopy (TR-ISRS) that provides femtosecond time-resolved Raman spectra. The results indicate that the bimodal ESPT dynamics originates from the structural heterogeneity of the chromophore. Species-associated Raman spectra obtained by spectral analysis based on singular value decomposition (SVD) suggest that cis and trans chromophores coexist in the ground state. It is considered that these two forms are photoexcited and undergo ESPT in parallel, resulting in the bimodal dynamics of ESPT in LSSmOrange.

Photophysics of Ru(II) complexes with hydroxylated diimine ligands: Photoinduced electron/proton transfer to anthraquinone

This manuscript reports the reaction of the 3MLCT excited states of two luminescent chromophores, [(bpy)2Ru(OHbpy)]2+ and [(bpy)2Ru(OMebpy)]2+ (bpy = 2,2′-bipyridine, OHbpy = 4-hydroxy-2,2′-bipyridine, OMebpy = 4-methoxy-2,2′-bipyridine), with anthraquinone (AQ). A series of luminescence, electrochemical, spectrophotometric and transient absorption studies were done in order to determine free energies for the potential reaction paths between the photoexcited complexes and AQ. For the OMebpy complex, only excited state electron transfer (ET*) from the 3MLCT state of the complex to AQ was possible. However, for the OHbpy complex, the excited state could react with AQ via a variety of pathways including excited state electron transfer, ET*, excited state proton transfer (PT*) and excited state proton coupled electron transfer (PCET*). The thermodynamic analysis revealed that, for the OHbpy complex PT* was very endergonic and not a viable reaction pathway, however both ET* and PCET* could occur. Luminescence quenching studies revealed that both the OHbpy and the OMebpy excited complexes reacted with AQ (kq ~ 109 M−1s−1 for both). Transient absorption analysis showed that, for the OMebpy complex, no photoproducts escaped the encounter complex associated with the quenching reaction. The result is consistent with strong electrostatic association of the 3+/1- encounter complex. For the OHbpy complex transient absorption results clearly show the formation of PCET* products from the encounter complex. The result represents one of a small number of examples of excited states of chromophores reacting via proton coupled electron transfer within an encounter complex.

Benzofuranyl-derived flavylium salts, chalcones and chalconates: Insights from X-ray structure, DFT calculations and spectroscopic pH response

In this contribution, we report the synthesis of benzofuranyl-derived flavylium salts whose structure have been confirmed by mass spectrometry and by NMR. Their structural and electronic properties have been studied by absorption and fluorescence spectroscopies and DFT calculations. Theoretical structural parameters of the calculated compounds were validated by the experimentally obtained X-Ray structure of 2-(2-benzofuranyl)-7-hydroxy-1-benzopyrylium perchlorate. The absorption spectra of the benzofuranyl-derived flavylium salts were simulated with good accuracy with respect to the experimental data. In equilibrated buffered solutions, the pH-driven multi-state evolution reaction of novel benzofuranyl-flavyliums afforded trans-chalcone and chalconate derivatives as the predominant species. The elusive nature of the species formed in solution was corroborated by chemical quantum calculations. The fluorescence bands of the flavylium, trans-chalcone and chalconate forms were assigned to their fluorophoric units by selective excitation of each one of the species present in solution. Fluorescence spectroscopy strongly suggests that 2-(2-benzofuranyl)-7-hydroxy-1-benzopyrylium perchlorate displays excited state proton transfer (ESPT).

Three Simultaneous Fluorescence Resonance Energy Transfer Processes and Structural Relaxation of Enhanced Yellow Fluorescent Protein Observed by Picosecond Time-Resolved Fluorescence Anisotropy.

Fluorescent proteins (FPs) have been widely used to visualize biological processes in living cells. It is essential to understand the underlying fluorescence mechanism to develop novel FPs and to interpret imaging data appropriately. Enhanced yellow fluorescent protein (eYFP) is one of the most typical FPs; however, several reports to date have been limited to individual discussion, which is insufficient to understand the full picture of the dynamics involved. In this study, we focused on the fluorescence resonance energy transfer (FRET) and dimerization behavior and performed picosecond time-resolved fluorescence measurements of eYFP and its A206K mutant, which does not form a dimer. The combination of the dissociation constant and the acid dissociation constant rationally explains the mechanism of ultrafast homo-FRET and ultrafast hetero-FRET. It is also shown that structural relaxation occurs in the dimer after excited-state proton transfer. The formation efficiencies and quaternary structures of dimers consisting of different protonation states are shown to be different. Furthermore, under high-concentration conditions, "slow" homo-FRET with tens of nanoseconds timescale occurs between monomers and dimers. The findings from this study will be applied to other fluorescent proteins such as Aequorea victoria green FP and its mutants and various red FPs with longer conjugation lengths.

Substituents effect on the methanol-assisted excited-state intermolecular proton transfer of 7-Aminoquinoline: A theoretical study

Studies have shown that changing the substituted groups applied to the amine can effectively affect the strength of the excited state hydrogen bond. However, it is not common to study the mechanism of how to effectively control the hydrogen bond strength of the excited state through the substituted group. Here, we have taken 7-Aminoquinoline and its various derivatives, the TDDFT method is used to study the influence of its R substitution on the hydrogen bond strength of the excited state and the mechanism of solvent-assisted excited-state multiple proton transfer (ESMPT) reaction. We have utilized bond length, IR vibrational spectra, atomic polar tensors (APT) charge analysis and potential energy curves to depict the relationship between hydrogen bond strength and substituted groups in excited state. We have modulated deliberately the number of methanol molecules involved in the ESMPT processes based on the site-specificity of hydrogen-bonding interactions, the potential energy curves indicate that the proton transfer process is more likely to happen in 7AQs·(MeOH)3 tetramer than in 7AQs·(MeOH)2 trimer, which is conflict with previous experimental conclusion. Meanwhile, the transition state structure during the ESMPT reaction indicates that the process is concerted. Our study demonstrates well the fluorescence behavior of 7AQs molecules regulated by different R substituents and extends the boundaries of site-specific hydrogen-bonding interactions research slightly.

Radiationless Decay Processes of an Unnatural DNA Base: Pyrrole 2-Carbaldehyde.

Pyrrole-2-carbaldehyde (Pa) forms one of the unnatural nucleic acid bases, and as a base pair with 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds), it has been known to be stable in DNA. The Ds-Pa pair is stabilized in DNA via van der Waals' interaction and shape fitting. There are some studies on the origin of its stability and reactivity in the ground state. However, for a successful unnatural base pair, it needs to be stable not only in the ground state but also upon irradiation with UV-visible light. To understand the photoinduced reactivity, we investigate the excited-state properties of the Pa base and understand the energetically feasible photoprocesses that can occur upon excitation in the UV region. Two distinct pathways are obtained. One of the pathways involves an out-of-plane mode and has some similarities with the deactivation channels in the natural pyrimidine bases. On the other hand, the second pathway involves an excited-state proton transfer.

Theoretical Insights into Excited-State Intermolecular Proton Transfers of 2,7-Diazaindole in Water Using a Microsolvation Approach.

The detailed excited-state intermolecular proton transfer (ESInterPT) mechanism of 2,7-diazaindole with water wires consisting of either one or two shells [2,7-DAI(H2O)n; n = 1-5] has been theoretically explored by time-dependent density functional theory using microsolvation with an implicit solvent model. On the basis of the excited-state potential energy surfaces along the proton transfer (PT) coordinates, among all 2,7-DAI(H2O)n, the multiple ESInterPT of 2,7-DAI(H2O)2+3 through the first hydration shell (inner circuit) is the most easy process to occur with the lowest PT barrier and a highly exothermic reaction. The lowest PT barrier resulted from the outer three waters pushing the inner circuit waters to be much closer to 2,7-DAI, leading to the enhanced intermolecular hydrogen-bonding strength of the inner two waters. Moreover, on-the-fly dynamic simulations show that the multiple ESInterPT mechanism of 2,7-DAI(H2O)2+3 is the triple PT in a stepwise mechanism with the highest PT probability. This solvation effect using microsolvation and dynamic simulation is a cost-effect approach to reveal the solvent-assisted multiple proton relay of chromophores based on excited-state proton transfer.

Minimal Optimized Effective Potentials for Density Functional Theory Studies on Excited-State Proton Dissociation.

Recently, a new method [P. Partovi-Azar and D. Sebastiani, J. Chem. Phys. 152, 064101 (2020)] was proposed to increase the efficiency of proton transfer energy calculations in density functional theory by using the T state with additional optimized effective potentials instead of calculations at S. In this work, we focus on proton transfer from six prototypical photoacids to neighboring water molecules and show that the reference proton dissociation curves obtained at S states using time-dependent density functional theory can be reproduced with a reasonable accuracy by performing T calculations at density functional theory level with only one additional effective potential for the acidic hydrogens. We also find that the extra effective potentials for the acidic hydrogens neither change the nature of the T state nor the structural properties of solvent molecules upon transfer from the acids. The presented method is not only beneficial for theoretical studies on excited state proton transfer, but we believe that it would also be useful for studying other excited state photochemical reactions.

Large Stokes shift fluorescence activation in an RNA aptamer by intermolecular proton transfer to guanine

Fluorogenic RNA aptamers are synthetic functional RNAs that specifically bind and activate conditional fluorophores. The Chili RNA aptamer mimics large Stokes shift fluorescent proteins and exhibits high affinity for 3,5-dimethoxy-4-hydroxybenzylidene imidazolone (DMHBI) derivatives to elicit green or red fluorescence emission. Here, we elucidate the structural and mechanistic basis of fluorescence activation by crystallography and time-resolved optical spectroscopy. Two co-crystal structures of the Chili RNA with positively charged DMHBO+ and DMHBI+ ligands revealed a G-quadruplex and a trans-sugar-sugar edge G:G base pair that immobilize the ligand by π-π stacking. A Watson-Crick G:C base pair in the fluorophore binding site establishes a short hydrogen bond between the N7 of guanine and the phenolic OH of the ligand. Ultrafast excited state proton transfer (ESPT) from the neutral chromophore to the RNA was found with a time constant of 130 fs and revealed the mode of action of the large Stokes shift fluorogenic RNA aptamer.

Photophysical Properties of Noncanonical Amino Acid 7-Fluorotryptophan Sharply Different from Those of Canonical Derivative Tryptophan: Spectroscopic and Quantum Chemical Calculations.

Due to the limited number of naturally existing canonical amino acids, several noncanonical amino acids have been designed to understand the diverse complex biological functions. Fluorinated amino acids are one of the important noncanonical amino acids that have been used to understand the different complex processes of proteins. In this study, the photophysical properties of the noncanonical amino acid 7-fluorotryptophan (7F-Trp) in different solvents have been investigated using extensive spectroscopic as well as quantum chemical calculation methods and compared with those of tryptophan (Trp). The spectroscopic and quantum chemical calculation data suggest that unlike Trp, 7F-Trp can be used to detect the excited-state proton transfer from solvents depending on its acidity, which makes 7F-Trp a potential candidate for sensing the excited-state proton transfer from the solvent molecules.

Luminescent excited-state intramolecular proton-transfer dyes based on 4-functionalized 6,6′-dimethyl-3,3′-dihydroxy-2,2′-bipyridine (BP(OH)2-Rs); DFT simulation study

The 4-functionalized 6,6′-dimethyl-3,3′-dihydroxy-2,2′-bipyridine dyes (BP(OH)2-Rs) have exhibited dienol and diketo emissions. The optimum geometrical structures for ground, singlet and triplet excited states are computed by DFT/B3LYP/6–31++G that showed the planarity of BP(OH)2-Rs structure. The emission spectra of the molecules are determined in the gas-phase at singlet and triplet excited states using CIS/6–31++G. The theoretical calculations are carried out for BP(OH)2-Rs to understand the impact of different substituents (R = –H (I), –Br (II), –TMS (III), –C2H (IV), –terpyridine (V) and –bodipy (diazaboraindacene) (VI)) on excited-state intramolecular proton transfer (ESIPT) in singlet and triplet excited states. Based on the calculations, the concerted diproton transfer proceeds in the triplet excited state, in which nπ* state has a significant participation in ESIPT. The spectral variation at ESIPT emission of BP(OH)2-Rs is influenced by the electron-acceptor ability of the substituents. The compound V revealed a higher spectral intensity compared to the others. From the comparison with the experimental data, the molecule V is almost planar agreed with the X-ray structure and trend variation of wavelengths. The molecule VI contains bodipy chromophore that excitation energy transfers completely from BP(OH)2 core to a bodipy substituent, leading to emission from the lowest-lying bodipy substituent, and consequently, ESIPT does not occur for this dye.

Dual mode in a metal-organic framework based mixed matrix membrane for discriminative detection of amines: Vapoluminescent and vapochromic response

The determination of amines is of great interest not only for monitoring food quality and disease state but also protecting human health from exposure to toxic amines. Herein, the utilization of the active functional site (−OH) of dht ligand based on luminescent [Cd2(dht)(idc)(H2O)4] (1) ; H2dht = 2,5-dihydroxyterephthalic acid and H2idc = 4,5-imidazoledicarboxylic acid can serve excited-state proton transfer (ESPT) together with enol-keto tautomerism for sensing amines. The sensor exhibits dual mode for detecting amines in terms of vapoluminescent process based on shifted emission and vapochromic process based on colorimetric detection. This probe not only displays dual mechanism toward methylamine through “turn-off” in low concentration and red-shifted emission in high concentration but also can sense pyridine through blue-shifted emission. Besides, it also shows discriminative color detection within the same group of amines. This material exhibits high selectivity, short response, wide range of detection in coverage of safety and danger levels for human health, good repeatability and reproducibility as well as low detection limit which is lower than the harmful level in human being. In addition, the metal-organic framework based mixed matrix membrane has been prepared and applied for quantitative analysis of amines in real time through smartphone.