Reversible Switching Based on Truly Intramolecular Long-Range Proton Transfer─Turning the Theoretical Concept into Experimental Reality.

Herein, we demonstrate a working prototype of a conjugated proton crane, a reversible tautomeric switching molecule in which truly intramolecular long-range proton transfer occurs in solution at room temperature. The system consists of a benzothiazole rotor attached to a 7-hydroxy quinoline stator. According to the experimental and theoretical results, the OH proton is delivered under irradiation to the quinolyl nitrogen atom through a series of consecutive proton transfer and twisting steps. The use of a rigid rotor prevents undesired side processes that decrease the switching performance in previously described proton cranes and provides an unprecedented switching efficiency and fatigue resistance. The newly designed system confirms the theoretical concept for the application of proton transfer-initiated intramolecular twisting as the switching mechanism, developed more than 10 years ago, and provides unique insights for the further development of tautomeric molecular switches and motors, molecular logic gates, and new molecular-level energy storage systems.

Azaindolizine proton cranes attached to 7-hydroxyquinoline and 3-hydroxypyridine: a comparative theoretical study.

Theoretical design of several proton cranes, based on 7-hydroxyquinoline and 3-hydroxypyridine as proton-transfer frames, has been attempted using ground and excited-state density functional theory (DFT) calculations in various environments. Imidazo[1,2-a]pyridine, pyrazolo[1,5-a]pyridine and benzimidazole were considered as proton crane units. The proton crane action requires the existence of a single enol-like form in the ground state, which under excitation goes to the end keto-like one through a series of consecutive excited-state intramolecular proton transfers (ESIPT) and twisting steps with the participation of a crane unit, resulting in a long-range intramolecular proton transfer. The results suggest that 3-hydroxypyridine is not suitable for a proton-transfer frame and 8-(imidazo[1,2-a]pyridin-2-yl)quinolin-7-ol and 8-(pyrazolo[1,5-a]pyridin-2-yl)quinolin-7-ol behave as non-conjugated proton cranes, instead of tautomeric re-arrangement in the latter, which was thought to be possible.

Theoretical Understanding of the Long-Range Proton Transfer Mechanism in 7-Hydroxy Quinoline-Based Molecular Switches: Varma's Proton Crane and Its Analogues.

Herein, the detailed mechanism of intramolecular proton transfer in molecular switches, constructed from 7-hydroxy quinoline substituted in the eight-position C-C single axle, connected to three different proton cranes (morpholine, piperidine, and 1,3,5-dioxazine), was investigated by means of theoretical chemistry. The theoretical interpretation of the rotational mechanism and its stable structures were proposed for the well-known Varma's proton crane, based on morpholine molecule. The reliability of the theoretical simulations was confirmed by the available literature data from time-dependent IR measurements.

Effects and Influence of External Electric Fields on the Equilibrium Properties of Tautomeric Molecules.

In this review, we have attempted to briefly summarize the influence of an external electric field on an assembly of tautomeric molecules and to what experimentally observable effects this interaction can lead to. We have focused more extensively on the influence of an oriented external electric field (OEEF) on excited-state intramolecular proton transfer (ESIPT) from the studies available to date. The possibilities provided by OEEF for regulating several processes and studying physicochemical processes in tautomers have turned this direction into an attractive area of research due to its numerous applications.

Structure and Conformational Mobility of OLED-Relevant 1,3,5-Triazine Derivatives.

A series of OLED-relevant compounds, consisting of 1,3,5-triazine core linked to various aromatic arms by amino group, has been synthesized and characterized. The studied compounds exist in solution as a mixture of two conformers, a symmetric propeller and asymmetric conformer, in which one of the aromatic arms is rotated around the C-N bond. At temperatures below -40 °C, the VT NMR spectra in DMF-d7 are in a slow exchange regime, and the signals of two conformers can be elucidated. At temperatures above 100 °C, the VT NMR spectra in DMSO-d6 are in a fast exchange regime, and the averaged spectra can be measured. The ratio of symmetric and asymmetric conformers in DMF-d7 varies from 14:86 to 50:50 depending on the substituents. The rotational barriers of symmetric and asymmetric conformers in DMF-d7 were measured for all compounds and are in the interval from 11.7 to 14.7 kcal/mol. The ground-state energy landscapes of the studied compounds, obtained by DFT calculations, show good agreement with the experimental rotational barriers. The DFT calculations reveal that the observed chemical exchange occurs by the rotation around the C(1,3,5-triazine)-N bond. Although some of the compounds are potentially tautomeric, the measured absorption and emission spectra do not indicate proton transfer neither in the ground nor in the excited state.

Solvent-Triggered Long-Range Proton Transport in 7-Hydroxyquinoline Using a Sulfonamide Transporter Group.

The ability of long-range proton transport by substitution of 7-hydroxyquinoline at the eighth position with sulfonamide and sulfonylhydrazone rotor units to act as a crane-arm has been studied. Different proton transport pathways triggered by different stimuli have been established depending on the structure of the crane-arms. Solvent-driven proton switching from OH to the quinoline nitrogen (Nquin) site, facilitated by a sulfonamide transporter group in polar protic and aprotic solvents, has been confirmed by optical (absorption and fluorescence) and NMR spectroscopies as well as by single-crystal X-ray structure analysis. Photoinduced long-range proton transport to the Nquin site upon 340 nm UV light irradiation has been estimated in sulfonylhydrazone, which is not sensitive to solvent-driven switching. Both compounds have exhibited acid-triggered switching by trifluoroacetic acid due to the formation of a stable six-membered intramolecular hydrogen bonding interaction between the protonated Nquin and crane-arm. The structures of acid-switched form were confirmed by NMR spectroscopy and single-crystal X-ray structure analysis. The behavior of the compounds suggests a big step forward in the advanced proton pump-switching architecture because they cover three distinct driving forces in the switching process: solvent, light, and acid.

Acid Dissociation Constants of the Benzimidazole Unit in the Polybenzimidazole Chain: Configuration Effects.

The acid dissociation constant of three benzimidazoles, namely 2,2'-bibenzo[d]imidazole, 2,5'-bibenzo[d]imidazole, and 5,5'-bibenzo[d]imidazole, have been investigated by means of density functional theory calculations in gas phase and in aqueous solution. The theoretical approach was validated by the comparing of predicted and experimentally determined pKa values in imidazole, benzimidazole, and 2-phenylbenzimidazole. From the studied compounds, 2,2'-bibenzo[d]imidazole was found to be the most acidic, which made it a valuable candidate as a material for polymer electrolyte membrane fuel cells.

Long-Range Proton Transfer in 7-Hydroxy-Quinoline-Based Azomethine Dyes: A Hidden Reason for the Low Efficiency.

In the tautomeric Schiff bases, derived from 7-hydroxyquinoline, two competitive channels are possible upon excitation of the enol tautomer, namely proton transfer (PT) through intramolecular hydrogen bonding to the corresponding keto form and trans-cis isomerization around the azomethine double bond. The former leads to switching, based on twist-assisted excited state intramolecular PT, where the long-range proton transfer can occur as a targeted process. The latter, determined by the flexibility of the crane part, reduces the efficiency of the main targeted process. In previously studied molecular switches based on the 7-hydroxyquinoline skeleton, only the intramolecular PT photo-process undergoing from the excited enol form towards the keto tautomer, which is in most cases barrierless, has been discussed. Therefore, in the current study, the ground state PT properties and isomerization of (E)-8-((phenylimino)methyl)quinolin-7-ol and (E)-8-(((pentafluorophenyl)imino)methyl)quinolin-7-ol are investigated in depth using the MP2 methodology, while the excited state energy profiles are calculated with the ADC(2) method. The obtained results are discussed in light of the existing experimental data.

Acylhydrazone Subunits as a Proton Cargo Delivery System in 7-Hydroxyquinoline.

The reimagined concept of long-range tautomeric proton transfer using crane subunits is shown by designing and synthesising two new acylhydrazones containing a 7-hydroxyquinoline (7-OHQ) platform. The acylhydrazone subunits attached to the 7-OHQ at the 8th position act as crane arms for delivering proton cargo to the quinoline nitrogen. Light-induced tautomerization to their keto forms leads to Z/E isomerization of the C=C axle bond, followed by proton delivery to the quinoline nitrogen by the formation of covalent or hydrogen bonds. The axle's being either an imine or ketimine bond is the structural difference between the studied compounds. The -CH3 group in the latter provides steric strain, resulting in different proton transport pathways. Both compounds show long thermal stability in the switched state, which creates a tuneable action of bidirectional proton cargo transport by using different wavelengths of irradiation. Upon the addition of acid, the quinoline nitrogen is protonated; this results in E/Z configuration switching of the acylhydrazone subunits. This was proven by single-crystal X-ray structure analysis and NMR spectroscopy.

Tautomeric influence on the photoinduced birefringence of 4-substituted phthalimide 2-hydroxy Schiff bases in PMMA matrix.

The photoinduced birefringence of two 4-substituted phthalimide 2-hydroxy Schiff bases, containing salicylic (4) and 2-hydroxy-1-naphthyl (5) moieties has been investigated in PMMA matrix. Their optical behaviour as nanocomposite films was revealed by combined use of DFT quantum chemical calculations (in ground and excited state) and experimental optical spectroscopy (UV-Vis and fluorescence). The results have shown that solid-state reversible switching takes place by enol/keto tautomerization and Z/E isomerization. Birefringence study was performed in the PMMA nanocomposite films using pump lasers at λrec = 355 nm and λrec = 442 nm. Fast response time and high stability of anisotropy up to 58% for (4) and 95% for (5) after turning off the excitation laser, was observed, which makes these materials appropriate candidates for cutting-edge optical information technology materials. The possibility for multiple cycles of recording, reading and optical erasure of the photoinduced birefringence at λrec = 442 nm in 5 has been demonstrated. The obtained results have shown that the maximum value of the measured birefringence is close to the anisotropic characteristics of the most frequently used azo materials.

A single isomer rotary switch demonstrating anti-Kasha behaviour: Does acidity function matter?

A novel rotary switch, overcoming the disadvantages of hydrazone based switches with competitive proton acceptor sub-rotors, has been designed. The new compound contains a pyridyl ring and a COOH group as sub-rotors, which provides engagement of the pyridyl nitrogen atom and leads to the existence of a single isomer in the ground state. The availability of acidic functionality in the rotor creates conditions for excited state intramolecular proton transfer (ESIPT), which exhibits anti-Kasha behavior.

Excited-State Intramolecular Proton Transfer: A Short Introductory Review.

In this short review, we attempt to unfold various aspects of excited-state intramolecular proton transfer (ESIPT) from the studies that are available up to date. Since Weller's discovery of ESIPT in salicylic acid (SA) and its derivative methyl salicylate (MS), numerous studies have emerged on the topic and it has become an attractive field of research because of its manifold applications. Here, we discuss some critical aspects of ESIPT and tautomerization from the mechanistic viewpoint. We address excitation wavelength dependence, anti-Kasha ESIPT, fast and slow ESIPT, reversibility and irreversibility of ESIPT, hydrogen bonding and geometrical factors, excited-state double proton transfer (ESDPT), concerted and stepwise ESDPT.

Subcritical Extracts from Major Species of Oil-Bearing Roses-A Comparative Chemical Profiling.

A comprehensive chemical profiling of 1,1,1,2-tetrafluoroethane (freon R134a) subcritical extracts from the main genotypes of oil-bearing roses, was performed by gas chromatography-mass spectrometry (GC/MS) and gas chromatography with flame ionization detection (GC-FID) in order to reveal the differences in their chemical composition. One hundred and three individual compounds were identified using GC/MS and their quantitative content was determined using GC-FID, representing 89.8, 92.5, 89.7 and 93.7% of the total content of Rosa gallica L., Rosa damascena Mill., Rosa alba L. and Rosa centifolia L. extracts, respectively. The compounds found in the extracts are representatives of the following main chemical classes: mono-, sesqui- and triterpenoids, phenylethanoids and phenylpropanoids and aliphatic hydrocarbons. Fatty acids, esters and waxes were found, as well. The study revealed that 2-phenylethanol is the most abundant component, ranging 9.0-60.9% followed by nonadecane and nonadecene with 5.1-18.0% geraniol (2.9-14.4%), heneicosane (3.1-11.8%), tricosane (0.1-8.6%), nerol (1.3-6.1%) and citronellol (1.7-5.3%). The extracts demonstrate a specific chemical profile, depending on the botanical species-phenylethanoids and phenyl propanoids are the main group for R. damascena, aliphatic hydrocarbons for R. alba and R. centifolia, while both are found in almost equal amounts in R. gallica. The terpenoid compounds show relatively broad variations: monoterpenes-11.9-25.5% with maximum in R. centifolia; sesquiterpenes-0.6-7.0% with maximum in R. gallica and triterpenes-0.4-3.7% with maximum in R. gallica extract.

Favipiravir tautomerism: a theoretical insight.

There is no experimental information about the tautomerism of Favipiravir (T-705). Therefore, its tautomeric state was predicted by using density functional theory in gas phase and in solution (toluene, acetonitrile and water). The results have shown that, in neutral state, the enol form is strongly dominating in both gas phase and solution. The carboxamide group is easily protonated in the presence of acid, which leads to shift of the tautomeric equilibrium toward the keto tautomer. In order to validate the theoretical predictions, 2-hydroxy pyridine and 2-hydroxy pyrazine were also included in the set of studied compounds. The available experimental data about their tautomerism are in very good agreement with the theoretical predictions, which validate the conclusions made for T-705.

Tautomerism and Self-Association in the Solution of New Pinene-Bipyridine and Pinene-Phenanthroline Derivatives.

Two novel pinene-type ligands have been synthesized and their tautomeric and self-associating behavior studied in solution and in the solid state. The first ligand, an acetylated derivative of 5,6-pinene-bipyridine, displays keto-enol tautomerism in solution. This tautomeric equilibrium was studied by NMR and UV-Vis spectroscopy in various solvents, and the results were compared with the ones obtained through DFT calculations. The second ligand was obtained by an unusual oxidation of the phenanthroline unit of a pinene-phenanthroline derivative. This compound exists as a single tautomer in solution and aggregates both in solution (as observed by NMR) and in the solid state through H-bonding as observed by X-ray structure determination and confirmed by DFT studies.

Interplay between conformational and solvent effects in UV-visible absorption spectra: curcumin tautomers as a case study.

We present a combined theoretical and experimental study on the UV-vis spectra of enol-keto (EK) and keto-keto (KK) tautomeric forms of curcumin dissolved in aqueous solution. Solvent effects have been investigated by resorting to the implicit polarizable continuum model (QM/PCM) and non-polarizable and fully polarizable QM/MM approaches, the latter based on the fluctuating charges (FQ) force-field. In particular, all methods are challenged to rationalize the contribution of conformational, electrostatic and polarization effects in the calculation of the vertical excitation spectra of curcumin tautomers. The obtained results highlight that for both tautomers specific solute-solvent hydrogen-bond interactions play a minor role with respect to conformational and electrostatic effects.

Tautomerism in Azo and Azomethyne Dyes: When and If Theory Meets Experiment.

The performance of 26 hybrid density functionals was tested against a tautomeric dataset (TautData), containing experimental information for the keto-enol tautomeric equilibrium in 16 tautomeric azodyes and Schiff bases in cyclohexane, carbon tetrachloride and acetonitrile. The results have shown that MN12-SX, BHandH and M06-2X can be used to describe the tautomeric state of the core structures in the frame of ~0.5 kcal/mol error and correctly predict the tautomeric state in respect of dominating tautomeric form. Among them MN12-SX is the best performer, although it fails to describe the nonplanarity of some of the enol tautomers. The same experimental dataset was used to develop and test a special DFT functional (TautLYP) aimed at describing the tautomeric state in azo- and azomethyne compounds in solution when nonspecific solvents are used.

Using Raman Spectroscopy as a Fast Tool to Classify and Analyze Bulgarian Wines-A Feasibility Study.

Raman spectroscopy, being able to provide rich information about the chemical composition of the sample, is gaining an increasing interest in the applications of food. Raman spectroscopy was used to analyze a set of wine samples (red and white) sourced from rarely studied traditional Bulgarian wines. One of the objectives of this study was to attempt the fast classification of Bulgarian wines according to variety and geographic origin. In addition, calibration models between phenolic compounds and Raman spectroscopy were developed using partial least squares (PLS) regression using cross-validation. Good calibration statistics were obtained for total phenolic compounds (by the Folin-Ciocalteu method) and total phenolic compounds and phenolic acids (spectrophotometrically at 280 nm) where the coefficient of determination (R2) and the standard error in the cross-validation (SECV) were 0.81 (474.2 mg/dm3 gallic acid), 0.87 (526.6 mg/dm3 catechin equivalents), and 0.81 (44.8 mg/dm3 caffeic equivalents), respectively. This study has demonstrated that Raman spectroscopy can be suitable for measuring phenolic compounds in both red and white wines.

Tautomerism as primary signaling mechanism in metal sensing: the case of amide group.

The concept for sensing systems using the tautomerism as elementary signaling process has been further developed by synthesizing a ligand containing 4-(phenyldiazenyl)naphthalene-1-ol as a tautomeric block and an amide group as metal capturing antenna. Although it has been expected that the intramolecular hydrogen bonding (between the tautomeric hydroxy group and the nitrogen atom from the amide group) could stabilize the pure enol form in some solvents, the keto tautomer is also observed. This is a result from the formation of intramolecular associates in some solvents. Strong bathochromic and hyperchromic effects in the visible spectra accompany the 1:1 formation of complexes with some alkaline earth metal ions.

Subnanomolar indazole-5-carboxamide inhibitors of monoamine oxidase B (MAO-B) continued: indications of iron binding, experimental evidence for optimised solubility and brain penetration.

Pharmacological and physicochemical studies of N-unsubstituted indazole-5-carboxamides (subclass I) and their structurally optimised N1-methylated analogues (subclass II), initially developed as drug and radioligand candidates for the treatment and diagnosis of Parkinson's disease (PD), are presented. The compounds are highly brain permeable, selective, reversible, and competitive monoamine oxidase B (MAO-B) inhibitors with improved water-solubility and subnanomolar potency (pIC50 >8.8). Using a well-validated, combined X-ray/modelling technology platform, we performed a semi-quantitative analysis of the binding modes of all compounds and investigated the role of the indazole N1 position for their MAO-B inhibitory activity. Moreover, compounds NTZ-1006, 1032, and 1441 were investigated for their ability to bind Fe2+ and Fe3+ ions using UV-visible spectroscopy.