Flor Rodríguez-Prieto

Solvent control of molecular structure and excited-state proton-transfer processes of 1-methyl-2-(2′-hydroxyphenyl)- benzimidazole

The influence of the solvent on the structure and photoinduced proton-transfer processes of 1-methyl-2- (2′-hydroxyphenyl)benzimidazole (MeHBI) was studied by means of UV–VIS absorption and fluorescence spectroscopy. The steric hindrance of the methyl group determines the non-planar structure of the MeHBI anion and cation in their ground state, but they undergo a rotation towards planarity in their excited state. In hydroxylic solvents, the excited cation loses the hydroxylic proton to the solvent, affording the keto tautomer. The neutral form of MeHBI exhibits conformational equilibrium dependent on the solvent. The cis-enol conformer, with an intramolecular hydrogen bond and a planar structure, is the dominant species in non-hydroxylic solvents and undergoes an excited-state intramolecular proton-transfer (ESIPT) reaction, producing the keto tautomer. The non-planar enol conformer is the only species detected in the ground state in water; in the excited state it loses the hydroxyl proton, leaving the excited anion. Comparable proportions of both enol conformers exist in alcoholic solvents, their relative proportions having been determined. In these solvents the cis-enol form undergoes ESIPT, whereas the non-planar enol rapidly undergoes rotation towards planarity in the excited state, emitting fluorescence from this state. The solvent hydrogen-bond donor acidity determines the ratio of non-planar enol to cis-enol conformers.

Solvent-Modulated Ground-State Rotamerism and Tautomerism and Excited-State Proton-Transfer Processes in o-Hydroxynaphthylbenzimidazoles

The ground-state rotamerism and tautomerism and the excited-state proton-transfer processes of 2-(1-hydroxy-2-naphthyl)benzimidazole (1) and 2-(3-hydroxy-2-naphthyl)benzimidazole (2) have been investigated in various solvents by means of UV-vis absorption spectroscopy, steady-state and time-resolved fluorescence spectroscopy, and quantum-mechanical ab initio calculations. For both compounds, a solvent-modulated rotameric equilibrium, and also tautomeric for 1, was observed in the ground state. In apolar solvents, both 1 and 2 exist as planar syn normal forms, with the hydroxyl group hydrogen bonded to the benzimidazole N3. In acetonitrile and ethanol, a rotameric equilibrium is established between the syn form and its planar anti rotamer, with the phenyl ring rotated 180 degrees about the C2-C2 bond. In ethylene glycol, glycerol, and aqueous solution with 40% ethanol, a tautomeric equilibrium was detected for 1 between the syn and anti normal forms and the tautomer form, with the hydroxyl proton transferred to the benzimidazole N3. In all of the solvents studied, the syn normal form of 1 and 2 undergoes an ultrafast excited-state intramolecular proton transfer (ESIPT) to yield the excited tautomer. The anti normal forms of 1 and 2, unable to experience ESIPT, give normal form fluorescence. In addition, the anti normal conformer of 2 partly deprotonates at the hydroxyl group in aqueous solution with 40% ethanol, giving the excited anion. The monocations of 1 and 2, protonated at the benzimidazole N3, are strong photoacids that deprotonate completely in aqueous solution with 40% ethanol and to a great extent in ethanol, giving the excited tautomer.

Photoinduced proton and charge transfer in 2-(2'-hydroxyphenyl)imidazo[4,5-b]pyridine.

This paper deals with the interplay between solvent properties and isomerism of 2-(2-hydroxyphenyl)imidazo[4,5-b]pyridine (1), and the proton and charge-transfer processes that the different isomers undergo in the first-excited singlet state. We demonstrate the strong influence of these processes on the fluorescence properties of 1. We studied the behavior of 1 in several neutral and acidified solvents, by UV-vis absorption spectroscopy and by steady-state and time-resolved fluorescence spectroscopy. The fluorescence of 1 showed a strong sensitivity to the environment. This behavior is the result of conformational and isomeric equilibria and the completely different excited-state behavior of the isomers. For both neutral and cationic 1, isomers with intramolecular hydrogen bond between the hydroxyl group and the benzimidazole N undergo an ultrafast excited-state intramolecular proton transfer (ESIPT), yielding tautomeric species with very large Stokes shift. For both neutral and cationic 1, isomers with the OH group hydrogen-bonded to the solvent behave as strong photoacids, dissociating in the excited state in solvents with basic character. The pyridine nitrogen exhibits photobase character, protonating in the excited state even in some neutral solvents. An efficient radiationless deactivation channel of several species was detected, which we attributed to a twisted intramolecular charge-transfer (TICT) process, facilitated by deprotonation of the hydroxyl group and protonation of the pyridine nitrogen.

Conformational effects on the photoinduced proton-transfer processes in 1-methyl-2-(3′-hydroxy-2′-pyridyl)benzimidazole

The ground- and excited-state behaviour of 1-methyl-2-(3′-hydroxy-2′-pyridyl)benzimidazole (MeHPyBI) in various solvents has been studied by UV–Vis absorption spectroscopy and by time-resolved and steady-state fluorescence spectroscopy. Three species were detected in the ground state in aqueous solutions of pH near to neutrality: a non-planar enol form, a planar cis-enol form and a planar keto tautomer. Electronic excitation of both the cis-enol form and the keto tautomer yields the excited keto form, the former through an ultrafast excited-state intramolecular proton-transfer (ESIPT). The non-planar enol form cannot undergo ESIPT and partly deprotonates at the hydroxy group to afford the anion. In non-aqueous solvents only the cis-enol form was detected in the ground state, yielding the keto tautomer in the excited state. The first protonation of MeHPyBI takes place at the benzimidazole N(3). Whereas the photoexcited cation shows fluorescence in acidified acetonitrile, it deprotonates at the hydroxy group in acidified ethanol, yielding the keto tautomer. In acidic aqueous solution, the excited cation undergoes a two-step tautomerization by two different routes to afford a keto cation, protonated at the pyridyl N. All the protonated and deprotonated forms of MeHPyBI are non-planar in the ground state both in water and ethanol, but they adopt a planar structure in the excited state. Comparison of the behaviour of MeHPyBI with related molecules reveals that the existence of planar forms and the neutral keto species in the ground state is favoured by the presence of the pyridyl nitrogen. The conformational equilibria in the ground state are crucial for the excited-state behaviour of these types of molecules.

Dissociation of a Strong Acid in Neat Solvents: Diffusion Is Observed after Reversible Proton Ejection Inside the Solvent Shell

Strong-acid dissociation was studied in alcohols. Optical excitation of the cationic photoacid N-methyl-6-hydroxyquinolinium triggers proton transfer to the solvent, which was probed by spectral reconstruction of picosecond fluorescence traces. The process fulfills the classical Eigen-Weller mechanism in two stages: (a) solvent-controlled reversible dissociation inside the solvent shell and (b) barrierless splitting of the encounter complex. This can be appreciated only when fluorescence band integrals are used to monitor the time evolution of the reactant and product concentrations. Band integrals are insensitive to solvent dynamics and report relative concentrations directly. This was demonstrated by first measuring the fluorescence decay of the conjugate base across the full emission band, independently of the proton-transfer reaction. Multiexponential decay curves at single wavelengths result from a dynamic red shift of fluorescence in the course of solvent relaxation, whereas clean single exponential decays are obtained if the band integral is monitored instead. The extent of the shift is consistent with previously reported femtosecond transient absorption measurements, continuum theory of solvatochromism, and molecular properties derived from quantum chemical calculations. In turn, band integrals show clean biexponential decay of the photoacid and triexponential evolution of the conjugate base in the course of the proton transfer to solvent reaction. The dissociation step follows the slowest stage of solvation, which was measured here independently by picosecond fluorescence spectroscopy in five aliphatic alcohols. Also, the rate constant of the encounter-complex splitting stage is compatible with proton diffusion. Thus, for this photoacid, both stages reach the highest possible rates: solvation and diffusion control. Under these conditions, the concentration of the encounter complex is substantial during the earliest nanosecond.

Excited-state proton and charge transfer in protonated amino and methylated derivatives of 2-(2'-hydroxyphenyl)benzimidazole.

We studied the excited-state behavior of a family of mono- and diprotonated derivatives of 2-phenylbenzimidazole in different solvents, using steady-state and time-resolved fluorescence spectroscopy. The species investigated were 2-(4-amino-2-hydroxyphenyl)benzimidazole (1), the diethylamino analogue 2-(4-N,N-diethylamino-2-hydroxyphenyl)benzimidazole (2) and its N-methylated derivative 1-methyl-2-(4-N,N-diethylamino-2-hydroxyphenyl)benzimidazole (3). The O-methoxy derivatives of 2 and 3 (2-OMe and 3-OMe), and the simpler models 2-phenylbenzimidazole (4) and its 4-amino (5) and 4-dimethylamino (6) derivatives were also studied. We found that the dications of 1, 2, and 3 (protonated at the benzimidazole N3 and at the amino group) were strong photoacids, which were deprotonated at the hydroxyl group upon excitation in aqueous solution (totally for 2 and 3) to give a tautomer of the ground-state monocation. In contrast, no photodissociation was observed for the monocations of these species. Instead, some of the monocations studied behaved as molecular rotors, for which electronic excitation led to a twisted intramolecular charge transfer (TICT) state. The monocations of 2, 3, 2-OMe, 3-OMe, and 6, protonated at the benzimidazole N3, experienced a polarity- and viscosity-dependent radiationless deactivation associated with a large-amplitude rotational motion. We propose that this process is connected to an intramolecular charge transfer from the dimethylaminophenyl or diethylaminophenyl moiety (donor) to the protonated benzimidazole group (acceptor) of the excited monocation, which yields a twisted charge-transfer species. No fluorescence from this species was detected except for 3 and 3-OMe in low-viscosity solvents.

Principal Component Global Analysis of Series of Fluorescence Spectra

The analysis of series of molecular fluorescence or absorption spectra forms an integral part of innumerable investigations on the physicochemical properties of chemical or biological systems.

Towards Ratiometric Sensing of Amyloid Fibrils In Vitro

The aggregation of amyloid-β peptide and its accumulation in the human brain has an important role in the etiology of Alzheimers disease. Thioflavinu2005T has been widely used as a fluorescent marker for these amyloid aggregates. Nevertheless, its complex photophysical behavior, with strong wavelength dependencies of all its fluorescence properties, requires searching for new fluorescent probes. The use of 2-(2-hydroxyphenyl)imidazo[4,5-b]pyridine (HPIP), which shows two emission bands and a rich excited-state behavior due to the existence of excited-state intramolecular processes of proton transfer and charge transfer, is proposed. These properties result in a high sensitivity of HPIP fluorescence to its microenvironment and cause a large differential fluorescence enhancement of the two bands upon binding to aggregates of the amyloid-β peptide. Based on this behavior, a very sensitive ratiometric method is established for the detection and quantification of amyloid fibrils, which can be combined with the monitoring of fluorescence anisotropy. The binding selectivity of HPIP is discussed on the basis of the apparent binding equilibrium constants of this probe to amyloid-β (1-42) fibrils and to the nonfibrillar protein bovine serum albumin. Finally, an exhaustive comparison between HPIP and thioflavinu2005T is presented to discuss the sensitivity and specificity of these probes to amyloid aggregates and the significant advantages of the HPIP dye for quantitative determinations.

Moderately Strong Photoacid Dissociates in Alcohols with High Transient Concentration of the Proton-Transfer Contact Pair.

Proton transfer from strong photoacids to hydroxylic solvents is much under debate. Experimentally, the main issue stems from relaxation and diffusion processes that are concomitant with ultrafast proton transfer and blur population dynamics. To overcome this, we propose a fast photodissociation reaction that, however, proceeds slower than solvent relaxation. Fluorescence spectroscopy of the cationic photoacid 2-(1-hydroxy-2-naphtyl)benzimidazolium reveals a two-stage mechanism: (a) reversible elementary proton transfer inside the solvent shell and (b) irreversible contact-pair splitting. The time evolution of the fluorescence signal is complex, yet this is explained quantitatively by simultaneous, spectrally overlapping emission of the acid, the conjugate base, and the contact proton-transfer pair. The latter attains high transient concentration in linear alcohols. Microscopic rate constants of dissociation are determined.