Thermal Isomerization Research Articles

Single GAF Domain Phytochrome Exhibits a pH-Dependent Shunt on the Millisecond Timescale.

The light-sensing activity of phytochromes is based on the reversible light-induced switching between two isomerization states of the bilin chromophore. These photo-transformations may not necessarily be only unidirectional, but could potentially branch back to the initial ground state in a thermally driven process termed shunt. Such shunts have been rarely reported, and thus our understanding of this process and its governing factors are limited. Here, we aim to close this gap by providing coherent experimental evidence of a shunt process using UV/Vis laser flash photolysis. We studied the Pfr to Pr dynamics of the single GAF domain (g1) construct of the knotless phytochrome All2699 from cyanobacterium Nostoc punctiforme. We identified a shunt that can be switched on and off by ambient buffer conditions. In combination with H/D exchange and kinetic modeling, we propose a keto-enol tautomerism to allow for the thermal isomerization of the chromophore and act as the driver of the shunt transition.

Diazocines as Guests of Cucurbituril Macrocycles: Light-Responsive Binding and Supramolecular Catalysis of Thermal Isomerization.

The photoswitching of supramolecular host-guest complexes is the basis of numerous molecularly controlled macroscopic functions, such as sol-gel transition, photopharmacology, the active transport of ions or molecules, light-powered molecular machines, and much more. The most commonly used systems employ photoactive azobenzene guests and synthetic host molecules, which bind as the stable E isomers and dissociate as the Z forms after exposure to UV light. We present a new, extraordinarily efficient cucurbit[7]uril (CB7)/diazocine host/guest complex with inverted stability that self-assembles under UV irradiation and dissociates in the dark. The association constants of the Z and E isomers in water differ by more than 104-fold. We also show that the thermally activated E → Z isomerization is significantly accelerated by CB7, which is a rare case of enzyme-like catalysis by transition state stabilization without product inhibition. In contrast to CB7, cucurbit[8]uril (CB8) binds both isomers with high affinity, showing good selectivity (∼1000-fold) toward the Z isomer. Notably, this isomer preferentially binds CB8 relative to CB7 by a factor greater than 1 × 106. We also use the system to introduce a supramolecular photoacid that builds on the increased basicity of a guest bound to CB7 and on the extremely high affinity of the E isomer, which is utilized to displace the acid from CB7, thereby switching the pH of the solution.

Utilizing Non-Covalent Interactions to Lock and Facilitate Bond Rotation Enables Wide-range Modulation of the Thermal Isomerization Dynamics of Photoswitches

Utilizing Non-Covalent Interactions to Lock and Facilitate Bond Rotation Enables Wide-range Modulation of the Thermal Isomerization Dynamics of Photoswitches

Accuracy of Reaction Coordinate Based Rate Theories for Modelling Chemical Reactions: Insights From the Thermal Isomerization in Retinal.

Modern potential energy surfaces have shifted attention to molecular simulations of chemical reactions. While various methods can estimate rate constants for conformational transitions in molecular dynamics simulations, their applicability to studying chemical reactions remains uncertain due to the high and sharp energy barriers and complex reaction coordinates involved. This study focuses on the thermal cis-trans isomerization in retinal, employing molecular simulations and comparing rate constant estimates based on one-dimensional rate theories with those based on sampling transitions and grid-based models for low-dimensional collective variable spaces. Even though each individual method to estimate the rate passes its quality tests, the rate constant estimates exhibit considerable disparities. Rate constant estimates based on one-dimensional reaction coordinates prove challenging to converge, even if the reaction coordinate is optimized. However, consistent estimates of the rate constant are achieved by sampling transitions and by multi-dimensional grid-based models.

Enhancing optical absorbance and accelerating rotational speed in molecular motors through oriented external electric fields

Accelerating the rotational speed of light-driven molecular motors is among the foremost concerns in molecular machine research, as this speed directly influences the performance of a motor. Controlling the motor’s rotation is crucial for practical applications, and using an oriented external electric field (OEEF) represents a feasible method to achieve this objective. We have investigated the impact of an OEEF on the optical and kinetic properties of a novel π-donor/acceptor di-substituted molecular motor, R2,3-(NH2, CHO). We employed density functional theory (DFT) and time-dependent DFT methods to analyze the electronic excitation and thermal isomerization behavior. Our results demonstrate that the absorption wavelength, absorption efficiency of the motor, and rate constant of the thermal isomerization reaction can be adjusted by applying OEEFs, which are predictable based on the dipole moment and polarizability of the molecules under consideration. In particular, we observed a shift in the absorption wavelength toward longer ranges, an enhancement in light absorption intensity, and an acceleration in the rotation rate when applying a weak positive directional external electric field to the R2,3-(NH2, CHO) motor. In summary, this theoretical study highlights the potential of OEEFs for improving the performance of molecular motors.

Kinetics and Mechanism of the Thermal Isomerization of Cyclopropane to Propene: A Comprehensive Theoretical Study.

The kinetics of the homogeneous gas-phase thermal isomerization of cyclopropane to propene has been studied theoretically to clarify existing discrepancies regarding the interpretation of its mechanism. High-level ab initio and density functional theory calculations were used to determine the branching ratios of the biradical and carbene reaction channels over wide temperature and pressure ranges. For this, relevant molecular and thermochemical properties of the proposed intermediates and related transition states were computed and compared with literature values. The Arrhenius equation, derived between 400 and 1400 K in the high-pressure limit at the CCSD(T)/6-311++G(3df,3pd)//CCSD/6-311++G(d,p) level of theory, is given by log10(koverall,∞/s-1) = (15.60 ± 0.06) - (65.70 ± 0.17) kcal mol-1 (2.303 RT)-1. This expression is in very good agreement with the available experimental data. According to these results, the biradical pathway is the predominant mechanism, while the carbene pathway contributes 1-2% at higher temperatures. The G4//B3LYP/6-311++G(3df,3pd) and G4//M06-L/6-311++G(3df,3pd) levels showed comparable Arrhenius parameters. Low-pressure limit rate coefficients and falloff curves were also estimated to evaluate the effect of pressure on the reaction. Additionally, the possibility of a concerted path is considered, but calculations showed unstable wave functions, suggesting that this mechanism would not be plausible.

Computational Study on the Photo‐Induced Antibiotic Activity of an Azoquinolone with Promising Applications in Photopharmacology

Azocompounds are among the most important group of molecular photoswitches due to their multiple applications in various scientific areas. We studied the thermal and photochemical reactions of an azocompound with photo‐induced antibiotic properties using ab‐initio calculations based on Kohn‐Shan, Spin‐Flip and time‐dependent Density Functional Theory. Our primary goal is to understand the absorption spectra and isomerization pathways governing the molecule’s light‐controlled antibiotic activity. The nuclear ensemble approach was used for the most stable trans and cis isomers, and the absorption spectra were calculated and fitted to predict the cis/trans isomer ratios in the carboxylate form, using experimental measurements as a reference. We stablished that rotation is involved in the most favorable cis⇄cis and trans⇄trans thermal isomerization pathways, while the inversion mechanism is the most likely for cis⇄trans isomerizations. We found that the photochemical trans→cis isomerization follows a consistent mechanism across all trans isomers, involving excitation to S2(ππ*), an in‐plane ultrafast internal conversion to S1(nπ*), followed by rotation of the azo bond up to a twisted S1(nπ*)/S0 conical intersection. We used a custom approach to evaluate the most favorable decay pathway from the S1(nπ*)/S0 conical intersections to trans and cis photoproducts using static calculations.

Skeletal Isomerization of Ergosterol-5,8-Peroxide Leading to the Discovery of Unprecedented Ergostanes and Collective Syntheses of 5,6-Epoxysterols and (+)-Sarocladione.

Skeletal isomerization of ergosterol peroxide, a primary oxidation product of ergosterol, was investigated under thermal and iron(II)-mediated conditions. Thermal isomerization resulted in not only the isolation of the predicted 7-hydroxy-5,6-epoxides but also the discovery of the unprecedented 7/9/5-ring-fused ergostane for the first time. The iron(II)-mediated isomerization proceeded at ambient temperature, resulting in the formation of the expected 5,6-epoxysterols and a ring-opened bicyclic diketone. The diketone was further converted into novel ergostane under thermal conditions and into (+)-sarocladione under acidic conditions. All transformations from ergosterol to sarocladione, including the isolation of the unstable diketone intermediate, were achieved at ambient temperature, confirming the biosynthetic pathway of sarocladione. Several mushroom ingredients with a 5,6-epoxy group were synthesized stereoselectively from the isomerization products, leading to the confirmation or revision of the structures of natural products. The β-amyloid aggregation inhibitory activity of synthetic sterols was evaluated for the first time to gain insights into the potential for dementia prevention. This study is valuable both for supplying rare sterols found in mushrooms for biological studies and for shedding light on the oxidative metabolic pathways of ergosterol.

A cautionary tale of basic azo photoswitching in dichloromethane finally explained

Many studies of azobenzene photoswitches are carried out in polar aprotic solvents as a first principles characterization of thermal isomerization. Among the most convenient polar aprotic solvents are chlorinated hydrocarbons, such as DCM. However, studies of azobenzene thermal isomerization in such solvents have led to spurious, inconclusive, and irreproducible results, even when scrupulously cleaned and dried, a phenomenon not well understood. We present the results of a comprehensive investigation into the root cause of this problem. We explain how irradiation of an azopyridine photoswitch with UV in DCM acts not just as a trigger for photoisomerization, but protonation of the pyridine moiety through photodecomposition of the solvent. Protonation markedly accelerates the thermal isomerization rate, and DFT calculations demonstrate that the singlet-triplet rotation mechanism assumed for many azo photoswitches is surprisingly abolished. This study implies exploitative advantages of photolytically-generated protons and finally explains the warning against using chlorinated solvent with UV irradiation in isomerization experiments.

Photoresponsive Organic Cages─Computationally Inspired Discovery of Azobenzene-Derived Organic Cages.

The incorporation of photoresponsive groups into porous materials is attractive as it offers potential advantages in controlling the pore size and selectivity to guest molecules. A combination of computational modeling and experiment resulted in the synthesis of two azobenzene-derived organic cages based on building blocks identified in a computational screen. Both cages incorporate three azobenzene moieties, and are therefore capable of 3-fold isomerization, using either ditopic or tetratopic aldehydes containing diazene functionality. The ditopic aldehyde forms a Tri2Di3 cage via a 6-fold imine condensation and the tritopic aldehyde forms a Tet3Di6 cage via a 12-fold imine condensation. The relative energies and corresponding intrinsic cavities of each isomeric state were computed, and the photoswitching behavior of both cages was studied by UV-Vis and 1H NMR spectroscopy, including a detailed kinetic analysis of the thermal isomerization for each of the EEZ, EZZ and ZZZ metastable isomers of the Tet3Di6 cage. Both cages underwent photoisomerization, where a photostationary state of up to 77% of the cis-isomer and overall thermal half-life of 110 h was identified for the Tet3Di6 species. Overall, this work demonstrates the potential of computational modeling to inform the design of photoresponsive materials and highlights the contrasting effects on the photoswitching properties of the azobenzene moieties on incorporation into the different cage species.

Reactivity of Diruthenium Bisborylene Complexes: Formation of B-C and B-H Bonds via Borylene Ligand Coupling.

Thermal or photoinduced isomerization of diruthenium bridging bisborylene complexes [{Cp*(H)2Ru}2(μ-BAr)2] (1a, Ar = Ph; 1b, Ar = 3,4,5-F3C6H2) led to nido-ruthenacarboranes 2a and 2b with newly formed B-C and B-H bonds. The reaction mechanism was analyzed by deuterium-labeling experiments and density functional theory calculations. Additionally, 2-fold B-H coupling between borylene and two hydrido ligands of 1a can be achieved, assisted by Lewis base IPr2Me2 to generate a dinuclear bridging borylene complex [(Cp*Ru)2(μ-H)2(μ-BPh)] (3). Our results provide new reactivity patterns for borylene-based functionalizations.

The unexpected and important role of alcohol stabilizer in thermal cis-trans isomerization of push-pull dyes in chloroform solution

The study demonstrates the influence of ethanol as a stabilizer in chloroform on the thermal cis-trans isomerization kinetics of photochromic compounds based on azobenzene and azopyridine derivatives. The significance of the addition of ethanol as a stabilizer in chloroform-based solutions on the isomerization reaction of the hydroxy- and the 6-hydroxylalkoxy-substituted azo compounds was investigated. The results have revealed that the presence of a polar stabilizer in a solvent can significantly reduce the reaction rate constant of the dark cis-trans isomerization due to the formation of hydrogen bonds at both ends of the azo-chromophore, thereby inhibiting the isomerization. Furthermore, a stabilizer can facilitate the reversion of azo-hydrazone tautomers of azophenols to their azobenzene form, resulting in a decrease in the reaction rate constant. The research presented in this paper can be essential for scientists who study the kinetics of the trans-cis and the cis-trans isomerization reactions of azo-chromophores. The results show that the use of solvents with polar stabilizers should be rather avoided, as their usage without information about stabilizers can lead to different experimental data. The authors should ensure that detailed information about stabilizers used in unstable solvents is included in the experimental section of their works (a detail currently often omitted in the literature).

Strategies to control humidity sensitivity of azobenzene isomerisation kinetics in polymer thin films

Azobenzenes are versatile photoswitches that garner interest in applications ranging from photobiology to energy storage. Despite their great potential, transforming azobenzene-based discoveries and proof-of-concept demonstrations from the lab to the market is highly challenging. Herein we give an overview of a journey that started from a discovery of hydroxyazobenzene’s humidity sensitive isomerisation kinetics, developed into commercialization efforts of azobenzene-containing thin film sensors for optical monitoring of the relative humidity of air, and arrives to the present work aiming for better design of such sensors by understanding the different factors affecting the humidity sensitivity. Our concept is based on thermal isomerisation kinetics of tautomerizable azobenzenes in polymer matrices which, using pre-defined calibration curves, can be converted to relative humidity at known temperature. We present a small library of tautomerizable azobenzenes exhibiting humidity sensitive isomerisation kinetics in hygroscopic polymer films. We also investigate how water absorption properties of the polymer used, and the isomerisation kinetics are linked and how the azobenzene content in the thin film affects both properties. Based on our findings we propose simple strategies for further development of azobenzene-based optical humidity sensors.

One-pot synthesis of 5-norbornene-2,3-dicarboxylic anhydride with high exo/endo ratio in a microreactor under high temperature and appropriate pressure

5-Norbornene-exo-2,3-dicarboxylic anhydride (exo-NDA), widely used in the synthesis of medicine and pesticide, was primarily obtained through the subsequent thermal isomerization of 5-norbornene-endo-2,3-dicarboxylic anhydride (endo-NDA) synthesized from cyclopentadiene (CPD) and maleic anhydride (MAH). Herein, density functional theory (DFT) was employed to elucidate the transition states and reaction pathways of different configurations. The endo-path exhibited a lower energy barrier, and the exo-isomer demonstrates greater structural stability. It was found that both high temperature and solvent polarity influenced the generation of NDA with different configurations. Due to considering solubility of MAH, an acetone/ethylbenzene mixed solvent was chosen for the reaction instead. According to the DFT calculations, we developed continuous-flow microreactor for high-efficiency one-pot synthesis of the isomers with exo/endo ratio of up to 1.19:1 as well as almost 100 % conversion and 98 % selectivity just in 2 min at 260 °C and 4 MPa, which CPD was generated in situ to participate in a series of Diels-Alder reactions instead of dicyclopentadiene as raw material existed at room temperature. Moreover, excessive or insufficient pressure in the reaction system should elevate byproduct formation, resulting in a decrease in reaction selectivity, as could prolonged residence time.

Combined Liposome-Gold Nanoparticles from Honey: The Catalytic Effect of Cassyopea® Gold on the Thermal Isomerization of a Resonance-Activated Azobenzene.

Gold nanoparticles (AuNPs) have been synthesized directly inside liposomes using honey as a reducing agent. The obtained aggregates, named Cassyopea® Gold due to the method used for their preparation, show remarkable properties as reactors and carriers of the investigated AuNPs. A mean size of about 150 nm and negative surface charge of -46 mV were measured for Cassyopea® Gold through dynamic light scattering and zeta potential measurements, respectively. The formation of the investigated gold nanoparticles into Cassyopea® liposomes was spectroscopically confirmed by the presence of their typical absorption band at 516 nm. The catalytic activity of the combined liposome-AuNP nanocomposites was tested via the thermal cis-trans isomerization of resonance-activated 4-methoxyazobenzene (MeO-AB). The kinetic rate constants (kobs) determined at 25 °C in the AuNP aqueous solution and in the Cassyopea® Gold samples were one thousand times higher than the values obtained when performing MeO-AB cis-trans conversion in the presence of pure Cassyopea®. The results reported herein are unprecedented and point to the high versatility of Cassyopea® as a reactor and carrier of metal nanoparticles in chemical, biological, and technological applications.

Self-assembly via hydrogen bonding of bis(18-crown-6)-1,3-distyrylbenzene and [2 + 2] photocycloaddition: Stereoselective synthesis of [2.2]metacyclophanes and butterfly-type thermal isomerization

The photochemistry of bis(18-crown-6)-containing 1,3-distyrylbenzene and its 2 : 2 bis-pseudo-sandwich complex with ethane-1,2-diammonium was studied. The UV irradiation of the supramolecular complex resulted in the formation of three geometric isomers of tetracrown-containing dicyclobutano[2.2]metacyclopane, differing in the orientation of the cyclobutane moieties, with the unsymmetrical isomer (>50 %) predominating. The diammonium cations used as the template could be removed after photolysis by simple extraction, and the product was obtained in high yield (82 %). The 1H NMR signals of a mixture of geometric isomers of [2.2]metacyclophane derivative were assigned resorting to quantum chemistry methods (DFT). The kinetic and thermodynamic parameters of thermal isomerization between the endo,endo- and exo,exo-isomers were measured. Tetracrown-containing dicyclobutano[2.2]metacyclophanes are homotetratopic ligands that contain four binding sites for metal and ammonium cations, which is of interest for the design of photo- and thermo-switchable supramolecular devices with a variable complex formation behavior and supramolecular machines owing to the butterfly-type thermal isomerization.

Modulating the isomerization of bpp-modified azoheteroarene by transition metal ions coordination

A new photoswitchable azoheteroarene L was design and synthesized by replacing one of the phenyl rings of azobenzene moiety with a 2,6-di[pyrazol-1-yl]pyridine(bpp) unit. The assembly of L with transition metal ions results in the formation of three metal complexes, namely, M(L)2(OTf)2 (M=ZnII, FeII and CoII). These complexes are fully characterized by ESI-TOF-MS, UV–vis spectrum, 1H NMR spectrum and single-crystal X-ray diffraction. Upon irradiation with 380 nm light, L exhibits excellent E to Z photoisomerization in solution, achieving up to 82 % Z-configuration with a thermotropic isomerization half-life time of 301 days. After coordination with ZnII, FeII and CoII, the photoisomerization properties of L were significantly varied. Coordinating with the ZnII ion, the conversion of Z-L slightly decreased from 82 % to 77 %. However, this coordination significantly extends thermal isomerization half-life time to 564 days, resulting in a 1.9-fold enhancement compared to free Z-L. In contrast, the coordination with open-shell transition metal ions FeII and CoII noticeably inhibits the formation of Z-L and only yields E-L isomers. Moreover, the spin-crossover behavior of Fe(E-L)2(OTf)2 was also investigated. The analysis of variable temperature NMR indicates that Fe(E-L)2(OTf)2 shows a spin transition temperature of 265 K in solution. This work provides valuable insights into tunning conformational transitions of azoheteroarene molecules.

An AIE-active Schiff base derivative with reversible thermochromism based on two-step isomerization in the solid state

Thermoresponsive aggregation-induced emission (AIE) luminogens, especially in the solid state, have attracted extensive attention due to their potential applications as smart materials. Herein, we report an AIE-active tetraphenylethene (TPE)-based Schiff base derivative (TPENOMe-I) that exhibits rapid and reversible thermochromism along with luminescence in the solid state. The excited-state intramolecular proton transfer-induced AIE and efficient thermochromism (rather than photochromism) are facilitated by the relatively compact crystal packing and polymorphism of TPENOMe-I, which effectively suppress cis-to-trans isomerization. Theoretical calculations demonstrated that the two-step isomerization process between the enol isomer and the cis- and twisted cis-keto isomers is responsible for the thermochromic behavior of solid-state TPENOMe-I. The chromic transitions may result from the reversible interconversion between various twisted cis-keto forms during the thermal isomerization process. Three composites containing TPENOMe-I that were simply prepared with low cost excited reversible thermochromism and were successfully demonstrated in thermochromic patterns. The findings suggest that these TPENOMe-I composites have promising applications for use in warning labels, thermochromic textiles, and thermal printing.

Structure, Dynamics, and Reactivity of Encapsulated Molecules in Restricted Spaces: Arylazoisoxazoles within an Octa Acid Capsule.

In this study, a well-defined organic capsule assembled from two octa acid (OA) molecules acting as host and select arylazoisoxazoles (AAIO) acting as guests were employed to demonstrate that confined molecules have restricted freedom that translates into reaction selectivity in both ground and excited states. The behavior of these AAIO guests in confined capsules was found to be different from that found in both crystals, where there is very little freedom, and in isotropic solvents, where there is complete freedom. Through one-dimensional (1D) and two-dimensional (2D) 1H NMR spectroscopic experiments, we have established a relationship between structure, dynamics and reactivity of molecules confined in an OA capsule. Introduction of CF3 and CH3 substitution at the 4-position of the aryl group of AAIO reveals that in addition to space confinement, weak interactions between the guest and the OA capsule control the dynamics and reactivity of guest molecules. 1H NMR studies revealed that there is a temperature-dependence to guest molecules tumbling (180° rotation along the capsular short axis) within an OA capsule. While 1H NMR points to the occurrence of tumbling motion, MD simulations and simulation of the temperature-dependent NMR signals provide an insight into the mechanism of tumbling within OA capsules. Thermal and photochemical isomerization of AAIO were found to occur within an OA capsule just as in organic solvents. The observed selectivity noted during thermal and photo induced isomerization of OA encapsulated AAIOs can be qualitatively understood in terms of the well-known concepts due to Bell-Evans-Polanyi (BEP principle), Hammond and Zimmerman.

A Photoenzymatic Pathway for Gram-Scale Synthesis of 25-Hydroxyvitamin D3.

Vitamin D and its analogues play a crucial role in promoting the well-being of both humans and animals. However, the current synthesis of this vital class of nutrients heavily relies on chemical transformations, which suffer from low step- and atom-efficiency due to lengthy synthetic pathways. To enhance sustainability in the chemical industry, it is necessary to develop alternative synthetic processes. Herein, we present a photoenzymatic approach for synthesizing 25-hydroxyvitamin D3 from 7-dehydrocholesterol. In this sequential synthesis, 7-dehydrocholesterol is initially hydroxylated at the C25 C-H bond, resulting in an 85 % conversion to 25-hydroxyl-7-dehydrocholesterol. Subsequently, by employing photo-irradiation using a monochromatic LED ultraviolet light source in a batch reactor and thermal isomerization, 25-hydroxyvitamin D3 is obtained in satisfactory yield. This photoenzymatic process significantly reduces the need for purification steps and allows for gram-scale synthesis of the target product. Our work offers a selective, efficient, and environmentally friendly method for synthesizing 25-OH-vitamin D3, addressing the limitations of current synthetic approaches.