Search Results (17)

Among azobenzene derivatives, azothiophenes represent a relatively recent family of compounds that exhibit similar characteristics as dyes and photoreactive systems. Their technological applications are extensive thanks to the additional design flexibility conferred by the heteroaromatic ring. In this study, we present a comprehensive investigation of the structural and electronic properties of novel dyes derived from 3-thiophenamine, utilizing a multilevel approach. We thoroughly examined the potential energy surfaces of the E and Z isomers for three molecules, each bearing different substituents on the phenyl ring at the para position relative to the diazo group. This exploration was conducted through quantum chemistry calculations at various levels of theory, employing a continuum solvent model. Subsequently, we incorporated an explicit solvent (a dimethyl sulfoxide–water mixture) to simulate the most stable isomers using classical molecular dynamics, delivering a clear picture of the local solvation structure and intermolecular interactions. Finally, a hybrid quantum mechanics/molecular mechanics (QM/MM) approach was employed to accurately describe the evolution of the solutes’ properties within their environment, accounting for finite temperature effects. Full article

A family of acylhydrazones have been prepared and characterized with the aim of investigating their potential as information storage systems. Their well-established synthetic methodologies allowed for the preparation of seven chemically stable acylhydrazones in excellent yields that have been photophysically and photochemically characterized. In addition, DFT and TD-DFT calculations have been performed to gain more insights into the structural, energetic and photophysical properties of the E/Z isomers. Our results reveal that E/Z configurational isomerization upon irradiation is highly dependent on the stabilization of the E or Z isomers due to the formation of intramolecular H bonds and the electronic/steric effects intrinsically related to their structures. In addition, Raman spectroscopy is also used to confirm the molecular structural changes after the formation of hydrogen bonds in the isomers. Full article

The multitarget therapeutic strategy, as opposed to the more traditional ‘one disease-one target-one drug’, may hold promise in treating multifactorial neurodegenerative syndromes, such as Alzheimer’s disease (AD) and related dementias. Recently, combining a photopharmacology approach with the multitarget-directed ligand (MTDL) design strategy, we disclosed a novel donepezil-like compound, namely 2-(4-((diethylamino)methyl)benzylidene)-5-methoxy-2,3-dihydro-1H-inden-1-one (1a), which in the E isomeric form (and about tenfold less in the UV-B photo-induced isomer Z) showed the best activity as dual inhibitor of the AD-related targets acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B). Herein, we investigated further photoisomerizable 2-benzylideneindan-1-one analogs 1b–h with the unconjugated tertiary amino moiety bearing alkyls of different bulkiness and lipophilicity. For each compound, the thermal stable E geometric isomer, along with the E/Z mixture as produced by UV-B light irradiation in the photostationary state (PSS, 75% Z), was investigated for the inhibition of human ChEs and MAOs. The pure E-isomer of the N-benzyl(ethyl)amino analog 1h achieved low nanomolar AChE and high nanomolar MAO-B inhibition potencies (IC₅₀s 39 and 355 nM, respectively), whereas photoisomerization to the Z isomer (75% Z in the PSS mixture) resulted in a decrease (about 30%) of AChE inhibitory potency, and not in the MAO-B one. Molecular docking studies were performed to rationalize the different E/Z selectivity of 1h toward the two target enzymes. Full article

Azobenzene/tetraethyl ammonium photochromic ligands (ATPLs) are photoactive compounds with a large variety of photopharmacological applications such as nociception control or vision restoration. Absorption band maximum and lifetime of the less stable isomer are important characteristics that determine the applicability of ATPLs. Substituents allow to adjust these characteristics in a range limited by the azobenzene/tetraethyl ammonium scaffold. The aim of the current study is to find the scope and limitations for the design of ATPLs with specific spectral and kinetic properties by introducing para substituents with different electronic effects. To perform this task we synthesized ATPLs with various electron acceptor and electron donor functional groups and studied their spectral and kinetic properties using flash photolysis and conventional spectroscopy techniques as well as quantum chemical modeling. As a result, we obtained diagrams that describe correlations between spectral and kinetic properties of ATPLs (absorption maxima of E and Z isomers of ATPLs, the thermal lifetime of their Z form) and both the electronic effect of substituents described by Hammett constants and structural parameters obtained from quantum chemical calculations. The provided results can be used for the design of ATPLs with properties that are optimal for photopharmacological applications. Full article

Photosensitive liquid crystals represent an important class of functional materials that experience rapid development. Hereby, we present novel bent-core liquid crystals bearing a lateral substitution on the central core and in the vicinity of the photosensitive unit—an azo group. The azo group enables fast (E)-to-(Z)-isomerization upon irradiation with UV-light and visible light, while the substitution facilitates the high stability of the photochemically formed (Z)-isomer. The effectiveness of the irradiation and the composition of photostationary states was determined by UV/Vis and ¹H NMR spectroscopy. A nematic phase formed by the materials was characterized by differential scanning calorimetry and optical polarizing microscopy. We show that the materials easily change their relative configuration of the N=N double bond not only in solution, but also in the mesophase, which leads to fast isothermal phase transition from the nematic phase to isotropic liquid. Full article

Cis-3-hexenal and its more stable isomer, trans-2-hexenal, are highly valued chemicals used in the food and perfume industries. They are produced by the plant lipoxygenase pathway, where two enzymes, lipoxygenase (LOX) and hydroperoxide lyase (HPL), are involved. However, the application of this pathway is limited, especially due to the instability of HPL. This enzyme belongs to the cytochrome P450 enzyme family and needs heme as a prosthetic group. Its synthesis must be effectively performed by a host organism in order to produce an active protein. In this work, Pseudomonas aeruginosa LOX was expressed in Escherichia coli BL21(DE3), and whole cells were used for the synthesis of 13(S)-hydroperoxy-(Z,E,Z)-9,11,15-octadecatrienoic acid (13-HPOT) as a substrate for HPL. Expression of Psidium guajava HPL was carried out by recombinant E. coli JM109(DE3) in autoinduction media, and the influence of the addition of heme precursors δ-ALA and Fe^II+ was studied. Specific activity of whole cells expressing HPL was measured by the direct use of a synthesized 13-HPOT solution (2.94 mM of total hydroperoxides, 75.35% of 13-HPOT (2.22 mM)) and increased 2.6-fold (from 61.78 U·mg⁻¹ to 159.95 U·mg⁻¹) with the addition of 1 mM Fe^II+ to the autoinduction media. Productivity and activity were further enhanced by an increase in the expression temperature, and a total of 3.30·10⁵ U·dm⁻³ of culture media was produced in the optimized process. Full article

The effects of some sulfur-containing compounds on the isomerization and degradation of lycopene, phytofluene, and phytoene under different thermal treatment conditions were studied in detail. Isothiocyanates such as allyl isothiocyanate (AITC) and polysulfides like dimethyl trisulfide (DMTS) had the effect on the configuration of PTF (phytofluene), PT (phytoene), and lycopene. The proportion of their naturally occurring Z-isomers (Z1,2-PTF and 15-Z-PT) decreased and transformed into other isomers including all-trans configuration, while Z-lycopene increased significantly after thermal treatment, especially for 5-Z-lycopene. The results showed that increase in heating temperature, time, and the concentration of DMTS and AITC could promote the isomerization reaction effectively to some extent. In addition, 15-Z-PT and the newly formed Z4-PTF were the predominant isomers in tomato at the equilibrium. Unlike the lycopene, which degraded significantly during heat treatment, the isomers of PTF and PT were stable enough to resist decomposition. Moreover, the isomerization of three carotenoids was enhanced, and the bioaccessibility of lycopene increased significantly with the addition of shii-take mushroom containing sulfur compounds, while there was no positive effect observed in that of PTF and PT. Full article

The α-methylated chalcone 3 with an electron-donor substituted A-aryl ring and an unsubstituted B-phenyl ring was synthesized by base-catalyzed aldehyde/acetophenone condensation. Compound 3 can be photo-switched from E→Z by irradiation with long-wavelength light λ > 350 nm, whereas irradiation with shorter wavelengths leads to photo-stationary states (PSS) with lower amounts of the Z-isomer. The limiting wavelength for fully equilibrated E⮀Z (PSS = 1) can be achieved around 240 nm. The stability of both E- and Z-isomers at the wavelength-dependent PSS under UV-irradiation between 250 and 350 nm is remarkably high as observed from UV and NMR spectroscopy. Compound 3 is fatigue resistant even after more than 10 days continuous irradiation and is also oxygenation-stable under singlet oxygen sensitization conditions. In remarkable contrast to many other α-methylated chalcones, no change in the E/Z-ratio was detected when PSS samples were treated with Broensted acids. The negative photochromic E→Z switch of 3 is accompanied by a conformational switch from the E-form in its preferred s-trans conformation to the Z-form in a distorted s-cis conformation (E_s-c→Z_s-t). Full article

A new Schiff base compound, 3-(5-bromo-2-hydroxybenzylideneamino)phenol (abbreviated as BHAP) was synthesized and characterized by ¹H- and ¹³C- nuclear magnetic resonance and infrared spectroscopies. DFT/B3LYP/6-311++G(d,p) calculations were undertaken in order to explore the conformational space of both the E- and Z- geometrical isomers of the enol-imine and keto-amine tautomers of the compound. Optimized geometries and relative energies were obtained, and it was shown that the most stable species is the E-enol-imine form, which may exist in four low-energy intramolecularly hydrogen-bonded forms (I, II, V, and VI) that are almost isoenergetic. These conformers were concluded to exist in the gas phase equilibrium with nearly equal populations. On the other hand, the infrared spectra of the compound isolated in a cryogenic argon matrix (10 K) are compatible with the presence in the matrix of only two of these conformers (conformers II and V), while conformers I and VI convert to these ones by quantum mechanical tunneling through the barrier associated with the rotation of the OH phenolic group around the C–O bond. The matrix isolation infrared spectrum was then assigned and interpreted with help of the DFT(B3LYP)/6-311++G(d,p) calculated infrared spectra for conformers II and V. In addition, natural bond orbital (NBO) analysis was performed on the most stable conformer of the experimentally relevant isomeric form (E-enol-imino conformer V) to shed light on details of its electronic structure. This investigation stresses the fundamental structural relevance of the O–H···N intramolecular H-bond in o-hydroxyaryl Schiff base compounds. Full article

Esters of iminophosphonic acids (iminophosphonates, or IPs), including a fragment, >P(=O)-C=N, can be easily functionalized, for instance to aminophosphonic acids with a wide range of biological activity. Depending on the character of the substitution, the Z- or E-configuration is favorable for IPs, which in turn can influence the stereochemistry of the products of chemical transformations of IPs. While the Z,E-isomerism in IPs has been thoroughly studied by NMR spectroscopy, the factors stabilizing a definite isomer are still not clear. In the current work, density functional theory (DFT, using M06-2X functional) and ab initio spin-component–scaled second-order Møller–Plesset perturbation theory (SCS-MP2) calculations were carried out for a broad series of IPs. The calculations reproduce well a subtle balance between the preferred Z-configuration inherent for C-trifluoromethyl substituted IPs and the E-form, which is more stable for C-alkyl- or aryl-substituted IPs. The predicted trend of changing activation energy values agrees well with the recently determined experimental ΔG^≠₂₉₈ magnitudes. Depending on the substitution in the aromatic moiety, the Z/E-isomerization of N-aryl-substituted IPs proceeds via two types of close-in energy transition states. Not a single main factor but a combination of various contributions should be considered in order to explain the Z/E-isomerization equilibrium for different IPs. Full article

In this study, we aimed at the application of the concept of photopharmacology to the approved vascular endothelial growth factor receptor (VEGFR)-2 kinase inhibitor axitinib. In a previous study, we found out that the photoisomerization of axitinib’s stilbene-like double bond is unidirectional in aqueous solution due to a competing irreversible [2+2]-cycloaddition. Therefore, we next set out to azologize axitinib by means of incorporating azobenzenes as well as diazocine moieties as photoresponsive elements. Conceptually, diazocines (bridged azobenzenes) show favorable photoswitching properties compared to standard azobenzenes because the thermodynamically stable Z-isomer usually is bioinactive, and back isomerization from the bioactive E-isomer occurs thermally. Here, we report on the development of different sulfur–diazocines and carbon–diazocines attached to the axitinib pharmacophore that allow switching the VEGFR-2 activity reversibly. For the best sulfur–diazocine, we could verify in a VEGFR-2 kinase assay that the Z-isomer is biologically inactive (IC₅₀ >> 10,000 nM), while significant VEGFR-2 inhibition can be observed after irradiation with blue light (405 nm), resulting in an IC₅₀ value of 214 nM. In summary, we could successfully develop reversibly photoswitchable kinase inhibitors that exhibit more than 40-fold differences in biological activities upon irradiation. Moreover, we demonstrate the potential advantage of diazocine photoswitches over standard azobenzenes. Full article

Rhodium complexes ligated by imidazolium-substituted phosphine were used as catalysts in the hydrosilylation of alkynes (1-heptyne, 1-octyne, and phenylacetylene) with 1,1,1,3,5,5,5-heptamethyltrisiloxane (HMTS) or triethylsilane (TES). In all cases, the above complexes showed higher activity and selectivity compared to their precursors ([Rh(PPh₃)₃Cl] and [{Rh(µ-Cl)(cod)}₂]). In the reactions with aliphatic alkynes (both when HMTS and TES were used as hydrosilylating agents), β(Z) isomer was mainly formed, but, in the reaction of phenylacetylene with TES, the β(E) product was formed. The catalysts are very durable, stable in air and first and foremost insoluble in the reactants which facilitated their isolation and permitted their multiple use in subsequent catalytic runs. They make a very good alternative to the commonly used homogeneous catalysts. Full article

Transcription factors are proteins lying at the endpoint of signaling pathways that control the complex process of DNA transcription. Typically, they are structurally disordered in the inactive state, but in response to an external stimulus, like a suitable ligand, they change their conformation, thereby activating DNA transcription in a spatiotemporal fashion. The observed disorder or fuzziness is functionally beneficial because it can add adaptability, versatility, and reversibility to the interaction. In this context, mimetics of the basic region of the GCN4 transcription factor (Tf) and their interaction with dsDNA sequences would be suitable models to explore the concept of conformational fuzziness experimentally. Herein, we present the first example of a system that mimics the DNA sequence-specific recognition by the GCN4 Tf through the formation of a non- covalent tetra-component complex: peptide–azoβ-CyD(dimer)–peptide–DNA. The non-covalent complex is constructed on the one hand by a 30 amino acid peptide corresponding to the basic region of GCN4 and functionalized with an adamantane moiety, and on the other hand an allosteric receptor, the azoCyDdimer, that has an azobenzene linker connecting two β-cyclodextrin units. The azoCyDdimer responds to light stimulus, existing as two photo-states: the first thermodynamically stable with an E:Z isomer ratio of 95:5 and the second obtained after irradiation with ultraviolet light, resulting in a photostationary state with a 60:40 E:Z ratio. Through electrophoretic shift assays and circular dichroism spectroscopy, we demonstrate that the E isomer is responsible for dimerization and recognition. The formation of the non-covalent tetra component complex occurs in the presence of the GCN4 cognate dsDNA sequence (′5-..ATGA cg TCAT..-3′) but not with (′5-..ATGA c TCAT..-3′) that differs in only one spacing nucleotide. Thus, we demonstrated that the tetra-component complex is formed in a specific manner that depends on the geometry of the ligand, the peptide length, and the ds DNA sequence. We hypothesized that the mechanism of interaction is sequential, and it can be described by the polymorphism model of static fuzziness. We argue that chemically modified peptides of the GCN4 Tf are suitable minimalist experimental models to investigate conformational fuzziness in protein–DNA interactions. Full article

Creation of organic luminescent materials with high solid-state efficiency is of vital importance for their applications in optoelectronic fields. Here, a series of AIE luminogens (AIE gens), (Z)-2,3-bis(4-(9,9-bis(6-(9H-carbazol-9-yl)hexyl)-9H-fluoren-2-yl)phenyl)-3-phenylacrylonitrile (SFC), and 2,3-bis(4-(9,9-bis(6-(9H-carbazol-9-yl)hexyl)-9H-fluoren-2-yl)phenyl)fumaronitrile (DFC), utilizing 2,3,3-triphenylacrylonitrile and 2,3-diphenylfumaronitrile as respective centers, are designed and synthesized by Suzuki coupling reactions with high yields. The cis- and trans-isomers of DFC are also successfully obtained. All of them are thermally stable and show good solubility in common organic solvents. They all emit weakly in solution, but become strong emitters when fabricated into solid films. It is found introduction of one additional cyano group in DFC induced a big red-shift in solid-state emission, owing to its high electron-withdrawing ability. The cis- and trans-DFC show similar photophysical and Cyclic voltammogram (CV) behaviors. Non-doped solution-processed organic light-emitting diodes (OLEDs) using the three compounds as light-emitting layers are fabricated. SFC gives the best device performance with a maximum luminance of 5201 cd m⁻², a maximum current efficiency of 3.67 cd A⁻¹ and a maximum external quantum efficiencies (EQE) of 1.37%. Red-shifted EL spectra are observed for cis- and trans-DFC-based device, and the OLED using trans-DFC as active layer exhibits better performance, which might derive from their different conformation in film state. Full article

Photocatalytic isomerization of thermodynamically stable E-alkene to less stable Z-alkene has been the subject of numerous studies, being successfully achieved mainly under UV irradiation. Recent development of visible light photoredox catalysis has witnessed it emerging as a powerful tool for the access of new structural complexity and many challenging targets. Herein, we report a visible light-promoted E to Z isomerization of cinnamates. When E-isomer of cinnamates was irradiated with blue light in the presence of an organo-photocatalyst, fac-Ir(ppy)₃, Z-isomer was exclusively obtained in high yields and with good selectivity. The mild, convenient reaction condition has made this protocol an effective synthetic methodology, which was subsequently implemented in an efficient synthesis of coumarins. Full article