7-azaindole Dimer Research Articles

Selectively probing ferric ions in aqueous environments using protonated and neutral forms of 7-azaindole as a multiparametric chemosensor.

7-azaindole (7AI) dimer is a model molecule for DNA study and understanding the mutagenic behavior based on the excited-state proton transfer process in hydrogen-bonded networks. The neutral and protonated forms of 7AI monomer with significant fluorescence (FL) intensity fit the fluorescent sensor strategy to recognize selective metal ions. Out of several metal ions (Fe3+, Al3+, Fe2+, Pb2+, Ba2+, Ni2+, Zn2+, Mg2+, Ca2+, Cu2+, Hg2+ and Cd2+), the absorption, fluorescence and fluorescence lifetime of 7AI in the aqueous medium are selectively sensitive to the ferric (Fe3+) ions. The absolute value of absorption intensity increases linearly with concentration of a particular metal ions. FL intensity of both the forms of 7AI decreases gradually with Fe3+ ions and trails the linear Stern-Volmer relation. The formation of non-fluorescent complexes was confirmed with Benesi-Hildebrand and Job plots, along with FL and FL decays. The FL lifetime of the protonated form of 7AI, which is 0.83 ± 0.01ns, is nearly constant with Fe3+ ions concentrations, confirming the static quenching mechanism. The limit of detection (LoD) of Fe3+ ions over the long range of 16-363µM for the neutral and protonated forms of 7AI is 0.46 ± 0.02 and 0.49 ± 0.02µM, respectively, estimated using FL spectra. Additionally, the linear plot of absorbance with Fe3+ ions of both the forms of 7AI can also act as a calibration curve with very close LoDs, as obtained by FL spectra. Thus, the multi-parameters-based probe for detecting the Fe3+ ions over long-range in real aqueous environments with operational, high sensitivity, fast response (< 5s), and good selectivity (over 12 metal ions) is undoubtedly a superior approach over other methods.

7-Azaindole breaks carboxylic acid dimers and simplifies VCD spectra analyses of natural products.

The determination of absolute configurations of carboxylic acids by vibrational circular dichroism (VCD) spectroscopy is often complicated by self-aggregation and the subsequent need to compute the spectra of the aggregates. We show that 7-azaindole effectively breaks up these aggregates by stronger complemental hydrogen bonding to the COOH moiety, enabling drastic simplification and acceleration of VCD spectra calculations.

The Cyclic Hydrogen-Bonded 6-Azaindole Trimer and its Prominent Excited-State Triple-Proton-Transfer Reaction.

The compound 6-azaindole undergoes self-assembly by formation of N(1)-H⋅⋅⋅N(6) hydrogen bonds (H bonds), forming a cyclic, triply H-bonded trimer. The formation phenomenon is visualized by scanning tunneling microscopy. Remarkably, the H-bonded trimer undergoes excited-state triple proton transfer (ESTPT), resulting in a proton-transfer tautomer emission maximized at 435 nm (325 nm of the normal emission) in cyclohexane. Computational approaches affirm the thermodynamically favorable H-bonded trimer formation and the associated ESTPT reaction. Thus, nearly half a century after Michael Kasha discovered the double H-bonded dimer of 7-azaindole and its associated excited-state double-proton-transfer reaction, the triply H-bonded trimer formation of 6-azaindole and its ESTPT reaction are demonstrated.

A theoretical and optical spectroscopic study of the mechanism of a tautomeric transformation in the 7-azaindole dimer and the 7-azaindole complex with a water molecule

Electronic, vibrational, and electronic vibrational spectra of the 7-azaindole dimer, the 7-azaindole complex with a water molecule, and their tautomers are calculated. Transition states are considered based on the analysis of frequencies and shapes of low-frequency vibrations and the Mulliken charge redistribution. The performed quantum chemical calculation of chemical reactions enabled the determination of the structure of transition states and proton transfer conditions. It is shown that in the 7-AzI dimer the proton transfer has a character consistent with the formation of a zwitterionic form. The structure of excited states is calculated and the fluorescence spectra of the first electronic transitions that can be used as a criterion of the formation of 7-AzI tautomers as a result of chemical reactions proceeding through a proton transfer in the 7-azaindole dimer and the 7-azaindole complex with a water molecule, are interpreted.

Solvent effects on the excited-state double proton transfer mechanism in the 7-azaindole dimer: a TDDFT study with the polarizable continuum model.

Solvent effects on the excited-state double proton transfer (ESDPT) mechanism in the 7-azaindole (7AI) dimer were investigated using the time-dependent density functional theory (TDDFT) method. Excited-state potential energy profiles along the reaction paths in a locally excited (LE) state and a charge transfer (CT) state were calculated using the polarizable continuum model (PCM) to include the solvent effect. A series of non-polar and polar solvents with different dielectric constants were used to examine the polarity effect on the ESDPT mechanism. The present results suggest that in a non-polar solvent and a polar solvent with a small dielectric constant, ESDPT follows a concerted mechanism, similar to the case in the gas phase. In a polar solvent with a relatively large dielectric constant, however, ESDPT is likely to follow a stepwise mechanism via a stable zwitterionic intermediate in the LE state on the adiabatic potential energy surface, although inclusion of zero-point vibrational energy (ZPE) corrections again suggests the concerted mechanism. In the meantime, the stepwise reaction path involving the CT state with neutral intermediates is also examined, and is found to be less competitive than the concerted or stepwise path in the LE state in both non-polar and polar solvents. The present study provides a new insight into the experimental controversy of the ESDPT mechanism of the 7AI dimer in a solution.

A theoretical study of the potential energy surfaces for the double proton transfer reaction of model DNA base pairs.

The excited-state double proton transfer (ESDPT) mechanism in a model DNA base pair, 7-azaindole (7AI) dimer, has been debated over the years. Recently, Otero and coworkers concluded that the stepwise mechanism is not possible and the concerted mechanism dominates the dynamics (Chem. Sci., 2015, 6, 5762). In this work, the potential energy surfaces of the 7AI dimer in the ground state (S0) and the lowest energy excited singlet state (S1) were constructed. After vertical excitation to the S1 state, the single proton transfer can occur. The second proton transfer process in the stepwise mechanism is blocked by a high potential barrier (36.4 kcal mol-1), which is consistent with the result proposed by Otero and coworkers. However, the single proton transfer process is compatible with the concerted mechanism and we show that the single proton transfer process rather than the concerted mechanism dominates the dynamics. The concerted process is unfavorable in the S1 state compared with the barrierless single proton transfer process. In addition, the proton transfer process in the S0 state is revealed. The single proton transfer tautomer in the S1 state returns to the S0 state and transfers the second proton via a barrierless process. Finally, the double proton transfer tautomer in the S0 state can recover to the normal dimer through the reverse proton transfer reaction.

Stepwise double excited-state proton transfer is not possible in 7-azaindole dimer.

The nature of the excited-state double proton transfer in 7-azaindole (7AI) dimer-whether it is stepwise or concerted-has been under a fierce debate for two decades. Based on high-level computational simulations of static and dynamic properties, we show that much of the earlier discussions was induced by inappropriate theoretical modelling, which led to biased conclusions towards one or other mechanism. A proper topographical description of the excited-state potential energy surface of 7AI dimer in the gas phase clearly reveals that the stepwise mechanism is not accessible due to kinetic and thermodynamic reasons. Single proton transfer can occur, but when it does, an energy barrier blocks the transfer of the second proton and the dimer relaxes through internal conversion. Double proton transfer takes place exclusively by an asynchronous concerted mechanism. This case-study illustrates how computational simulations may lead to unphysical interpretation of experimental results.

Dynamics of proton transfer reactions of model base pairs in the ground and excited states: Revisited

A review of the proton transfer reactions (PTR) of model base pairs such as the 7-azaindole and 1-azacarbazole dimers is presented, including some of the recent progress in the laser spectroscopy of these dimers. Advances in computational chemistry now allow to calculate reliable potential energy surfaces of the excited-state PTR, which is indispensable to understand the experimental results. The comprehensive results on the spectroscopy and reactivity of these dimers are outlined for fully explaining the excited state PTR of model base pairs on the basis of the current theoretical studies. Moreover, the recent studies on the PTR in the ground state relating to a back proton translocation of tautomeric dimer of 7-azaindole are presented. Finally, the outlook on the study of the PTR of model base pairs is addressed to further explore the reaction dynamics of these benchmark systems.

Nuclear quantum effect and temperature dependency on the hydrogen-bonded structure of 7-azaindole dimer

The structure of 7-azaindole dimer (7AI2) as a model compound for DNA base pair has been studied by classical molecular dynamics (MD) and path integral molecular dynamics (PIMD) simulations on the semi-empirical PM6 potential energy surface at various temperatures, to investigate the nuclear quantum effect and temperature dependency on the hydrogen-bonded moiety of 7AI2. At 75 K, two H-bondings are maintained throughout a given simulation time in both classical and PIMD (quantum) simulations. At 150 K, these two H-bondings are maintained in only quantum simulation, while in classical simulation, the two H-bondings (or one H-bonding) are sometimes broken and reformed. For 225 K, these two H-bondings are broken in both classical and quantum simulations. We have also applied a principal component analysis to MD and PIMD simulations to analyze the intermolecular motions. We found that the ratio of the second lowest (dimer butterfly out-of-plane) vibrational mode from normal mode analysis which is the most dominant motion decreases with increasing temperature, whereas that of first lowest (dimer torsion out-of-plane) vibrational mode which is the second most dominant motion increases with increasing temperature from temperature 75 to 150 K and then decreases at 225 K due to the nuclear quantum effect. Moreover, the motions of two hydrogen-bonded structures are significantly different with increasing temperature. This difference is revealed by the principal component analysis which shows that the ratio of opening in-plane motion decreases and the ratio of stretching in-plane motion decreases.

DNAモデル塩基対の励起状態二重プロトン移動の協奏的機構と段階的機構の長い論争の始まりから終わりまで

Excited-state double-proton transfer (ESDPT) in the coplanar 7-azaindole dimer (7AI2) has been studied as a model base pair. Concerted and stepwise mechanisms were proposed for ESDPT in 7AI2. In the concerted mechanism, two protons transfer concertedly on the excited-state potential energy surfaces where a local minimum does not exist. On the other hand, an intermediate state exists in the stepwise mechanism. Therefore, after one single-proton transfer, the second single-proton transfers via the intermediate state. Numerous spectroscopic and theoretical studies were conducted to determine the mechanism of ESDPT of 7AI2. This review focuses on the ESDPT mechanisms in the gas phase. A prologue and epilogue of the concerted and stepwise mechanism controversy are presented. Spectroscopic experiments in the condensed phase and theoretical calculations related to the potential energy surfaces are important for deriving a final conclusion. In addition, some significant results are comparatively discussed.

Deuteration effect on the NH/ND stretch band of the jet-cooled 7-azaindole and its tautomeric dimers: Relation between the vibrational relaxation and the ground-state double proton-transfer reaction

Infrared spectra of NH and ND stretch bands of the 7-azaindole (7-AI) dimer and its tautomeric dimer are observed to investigate a deuteration effect on the spectra and also a ground-state double proton-transfer (DPT) reaction. We examined the three isotopic species for each dimers; undeuterated one (NH–NH) and one or two hydrogen atom(s) of the NH groups is deuterated ones (NH–ND and ND–ND, respectively). It is found that the ND stretch band profiles of the NH–ND and ND–ND tautomeric dimers are very similar with each other. This result is very distinct from the result of the comparison of the NH stretch band profiles of the NH–NH and NH–ND dimers in our previous paper. For a further discussion, we examined the deuteration effect in the case of the 7-AI dimer. It is found that band profiles of the NH stretch of the NH–NH and the NH–ND dimers and also the ND stretch of the NH–ND and the ND–ND dimers exhibit similar patterns, respectively. These facts indicates that the vibrational relaxation from the NH/ND stretch level of the dimer basically proceed within a monomer unit. The large deuteration effect of the NH stretch band profile observed previously is found to be characteristic of the tautomeric dimer. This behavior is related to a large anharmonicity of the potential energy surface originating from an existence of the double-proton transfer reaction barrier.

Ultraviolet and infrared spectroscopy of matrix-isolated 7-azaindole dimer: Matrix effect on excited state tautomerization

Photophysics of 7-azaindole homodimer has been studied in Ar and N2 matrixes for the first time. The infrared spectra reveal that a doubly hydrogen bonded dimer is predominantly produced upon annealing the seeded matrixes at 28K. However, unlike in hydrocarbon solutions or a supersonic jet expansion, the matrix-isolated doubly hydrogen bonded dimer emits exclusively in ultraviolet from the locally excited state, and the vital photophysical process, the excited state double proton transfer, is slowed down dramatically. We have interpreted the observation in terms of matrix effect on the double proton transfer potential and promoting vibrational modes.

Intermolecular vibrational modes and orientational dynamics of cooperative hydrogen-bonding dimer of 7-azaindole in solution

We observed the low-frequency Raman-active intermolecular vibrational modes of 7-azaindole in CCl(4) by femtosecond Raman-induced Kerr effect spectroscopy. To understand the dynamical aspects and vibrational modes of 7-azaindole in the solution, the ultrafast dynamics of 1-benzofuran in CCl(4) was also examined as a reference and ab initio quantum chemistry calculations were performed for 7-azaindole and 1-benzofuran. The cooperative hydrogen-bonding vibrational bands of 7-azaindole dimer in CCl(4) appeared at 89 cm(-1) and 105 cm(-1) represent the overlap of stagger and wheeling modes and the intermolecular stretching mode, respectively. They are almost independent of the concentration in the solution. We further found from the low-frequency differential Kerr spectra of the solutions with neat CCl(4) that the intermolecular motion in the low frequency region below 20 cm(-1) was less active in the case of 7-azaindole/CCl(4) than in the case of 1-benzofuran/CCl(4). The slow orientational relaxation time in 7-azaindole/CCl(4) is ~3.5 times that in 1-benzofuran/CCl(4) because of the nature of the dimerization of 7-azaindole.

Excited‐State Double Proton Transfer of 7‐Azaindole Dimers in a Low‐Temperature Organic Glass

The excited-state double proton transfer of model DNA base pairs, 7-azaindole (7AI) dimers, is explored in a low-temperature organic glass of n-dodecane using picosecond time-resolved fluorescence spectroscopy. Reaction mechanisms are found to depend on the conformations of 7AI dimers at the moment of excitation; whereas planar conformers tautomerize rapidly (<10 ps), twisted conformers undergo double proton transfer to form tautomeric dimers on the time scale of 250 ps at 8 K. The proton transfer is found to consist of two orthogonal steps: precursor-configurational optimization and intrinsic proton transfer via tunneling. The rate is almost isotope independent at cryogenic temperatures because configurational optimization is the rate-determining step of the overall proton transfer. This optimization is assisted by lattice vibrations below 150 K or by librational motions above 150 K.

Concerted or Stepwise Mechanism? CASPT2 and LC-TDDFT Study of the Excited-State Double Proton Transfer in the 7-Azaindole Dimer.

Excited-state double proton transfer (ESDPT) in the 7-azaindole dimer is investigated using the complete active space second-order perturbation theory (CASPT2) method and the long-range corrected time-dependent density functional theory (LC-TDDFT) method. These methods are employed for geometry optimizations as well as single-point energy calculations of the excited-state potential energy profiles along the reaction paths. It is shown that three main reaction routes involving double proton transfer exist. In the first route, the ESDPT reaction takes place in the locally excited state through a single transition state following the concerted mechanism in which each proton-transfer process occurs simultaneously without forming any stable zwitterionic intermediate. The concerted ESDPT reaction is found to proceed asynchronously in Cs symmetry rather than synchronously in C2h symmetry. In the second and third routes, on the other hand, the ESDPT reaction takes place following the stepwise mechanism in which each proton-transfer process occurs sequentially forming a neutral intermediate in the charge-transfer state. The calculated energy profiles of the three routes exhibit a lower barrier in the first route than in the other routes, suggesting that the ESDPT in the gas phase is likely to follow the asynchronous concerted mechanism at the lowest excitation energy.

From insertion of rhodium acetate paddlewheels into functionalized 7-azaindole hydrogen-bonded dimers to infinite architectures

In order to take advantage of the peculiar mode of interaction consisting in the combination of hydrogen and coordination bonding displayed by the 7-azaindole core towards tetraacetate paddlewheel type complexes, a series of new derivatives, bearing peripheral interacting sites at the position 3, have been prepared and their self-assembly into dimeric H-bonded species was established in the solid state. Furthermore, the heterochelate mode of binding was exploited both in the solid state and in solution using [Rh(2)(OAc)(4)] paddlewheel to generate discrete capped complexes resulting from the coordination of the pyridyl nitrogen atom to the axial position of the Rh(ii) cations and hydrogen bonding between the pyrrolic NH and an oxygen atom of one of the equatorial acetate groups. The extension to infinite hybrid networks was achieved using derivatives bearing self complementary H-bond donor and acceptor groups such as a carboxylic moiety.

A theoretical study on excited state double proton transfer reaction of a 7-azaindole dimer: an ab initio potential energy surface and its empirical valence bond model

Double proton transfer (DPT) reaction of a 7-azaindole dimer in the first ππ* electronically excited state was studied theoretically. We investigated the reaction mechanism through constructing a full dimensional empirical valence bond potential energy function (PEF) based on potential energies evaluated by ab initio molecular orbital methods, and carrying out quantum dynamics calculations with the PEF. Potential energy surfaces of the DPT obtained at the multi-reference perturbation level of theory favors a concerted DPT mechanism, although a stepwise channel is suggested to open for an excited initial vibrational state. Reduced two dimensional quantum dynamics calculations for a reaction surface Hamiltonian of DPT coordinates were performed. Time constants of the reaction were evaluated to be on the order of picoseconds, which is consistent with experiments. On the other hand, the computed kinetic isotope effect deviates from experimental evidence, suggesting the importance of intermolecular stretching motion, which is not explicit in the present calculations for the quantum effect.

Activation Energy of the Two-Proton Phototautomerism in 7-Azaindole Dimer and Its Medium-Dependence

A photophysical analysis of 10(-4) M solutions of 7-azaindole in hydrocarbon solvents including 2-methylbutane, 3-methylpentane, ethylcyclohexane, decalin, and squalane revealed that the viability of the two-proton phototautomerism in its dimer is clearly medium-dependent. However, in all media studied, a small tunneling contribution in the photoinduced double proton transfer continues to exist at low temperatures.

Proton Phototransfers in Doubly Hydrogen Bonded Dimers: The Photophysics of 6,7,8,9-Tetrahydro-5H-pyrido[2,3-b]indole Dimers

A photophysical study of 6,7,8,9-tetrahydro-5H-pyrido[2,3-b]indole dissolved in 2-methylbutane at decreasing temperatures from 293 to 93 K revealed the presence of two different fluorescence emissions due to doubly hydrogen-bonded dimers of the monomer species. One of the emissions is assigned to the normal tautomer form of the dimer of C(2) symmetry, and the other is mostly assigned to the most stable dimer, which is nonsymmetric (C(1)) and exhibits single-proton transfer upon electronic excitation. As shown here, when the doubly hydrogen-bonded 7-azaindole dimer loses its centrosymmetry, by fusing a six-membered ring to the molecular structure, its first excited electronic state does not undergo a double-proton transfer but rather a single proton transfer, which, in a fluid medium, causes the dimer to dissociate; if the medium can trap the resulting excited structure, then the compound exhibits fluorescence in the 410 nm region, which is typical of its protonated or deprotonated forms.

Infrared Spectroscopy of Jet-Cooled Tautomeric Dimer of 7-Azaindole: A Model System for the Ground-State Double Proton Transfer Reaction

To investigate the ground-state double proton transfer (GSDPT) reaction, we carried out a laser spectroscopic study on the tautomeric dimer of 7-azaindole in a supersonic jet. We have recorded an infrared (IR) spectrum of the tautomeric dimer in the S(0) state. The NH band exhibits a broad and less-structured pattern. The band pattern is discussed on the basis of the hierarchical vibrational interaction mechanism. As a result, much higher density of state (DOS) at the NH stretch level is expected than that of the normal dimer. Such a high DOS should be related to the anharmonicity of the potential energy surface near the barrier of the GSDPT reaction. To get more information, an N-D deuteration effect is examined. In the present experiment, five deuterated dimers are identified by visible-visible or IR-visible population labeling spectroscopy. The IR band pattern of the NH-ND dimer is very different from that of the NH-NH dimer. Among several N-D deuteration effects, a change in a condition between the inter- or intramolecular vibrational energy flows due to the single N-D deuteration is considered to be important.