Thermal Half-life Research Articles

Azobenzene-Attached (NHC)Gold(I) and (NHC)Copper(I) Complexes as Photoswitchable Catalysts.

Photoswitchable (pre)catalysts, N,N'-bis-azobenzene-based (NHC)gold(I) and N,N'-bis-azobenzene-derived (NHC)copper(I) complexes are reported. Trans to cis isomerization of the attached photoswitchable moieties in the Au(I) complex enables four-fold decrement in the rate of oxazoline formation reaction. Whereas the progress of the copper(I) catalyzed, azide-alkyne cycloaddition reaction gets reduced by at least threefold. Alternate exposure to UV and blue light could easily toggle the rate of reactions remotely. The catalytic activity of thermodynamically stable trans-trans isomers is found to be similar to the common N-aryl substituted NHC-Au/Cu(I) complexes. NHC-Au(I) and -Cu(I) compounds bearing (trans)azobenzene moieties were characterized by X-ray diffraction. Photoswitching, recyclability studies, and the metastable isomer's thermal half-life in both complexes were studied via UV-visible spectroscopy. Whereas the extent of photoswitching and concomitant formation of geometrical isomers were investigated by using 1H-NMR spectroscopic study. Calculated percentage buried volumes of the three geometrical isomers show the trend trans-trans<trans-cis<cis-cis.

Transient Photoactivation of Anionophores by Using Redshifted Fast-Relaxing Azobenzenes.

Photo-regulated transmembrane ionophores enable spatial and temporal control over activity, offering promise as targeted therapeutics. Key to such applications is control using bio-compatible visible light. Herein, we report red-shifted azobenzene-derived synthetic anionophores that use amber or red light to trigger (E)-(Z) photoisomerisation and activation of transmembrane chloride transport. We demonstrate that by tuning the thermal half-life of the more active, but thermodynamically unstable, Z isomer to relax on the timescale of minutes, transient activation of ion transport can be achieved by activating solely with visible light and deactivating by thermal relaxation.

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.

Dinickel-Catalyzed N=N Coupling Reactions for the Synthesis of Hindered Azoarenes.

Azoarenes are the largest class of photoswitching molecules, and they have a broad range of applications in photopharmacology and materials science. Azoarenes possessing ortho-substitution often display improved properties, including isomerization under visible light irradiation, near-quantitative switching, and long thermal half-lives in the cis form. The synthesis of hindered ortho-substituted azoarenes is often low-yielding using established oxidative or reductive coupling methods. Here, we describe the design and synthesis of a new dinickel complex that catalyzes the dimerization of ortho-substituted aryl azides in high yield. Applications of this method in the synthesis of high-performance photoswitches, photoactive peptide cross-linkers, hindered diazocines, and main-chain azoarene polymers are described.

Photoresponsive conductive polymer network based on azobenzene bridging crosslinked polycarbazole for boosting solar thermal storage

Azobenzene is one of the most extensively researched multifunctional chromophores and azobenzene including materials has a wide variety of applications due to their photoisomerization behavior. In this study, electroactive and light-harvesting carbazole and photoresponsive azobenzene units have been combined with a special macromolecular design. In this design the azo groups can be effectively isomerized in solid state, and free-standing films can be obtained by the electrochemical method. Thermal characterizations of both monomer and polymer have been performed and isomerization kinetics and solar-thermal properties have been investigated. The half-life at 60 °C and the gravimetric energy storage density of polymer was calculated as 103 min and 179.9 j g−1, respectively. Cross-linked polycarbazole structure causes dramatically increased solar thermal storage and half-life compared to respective monomer and brought unexpected mechanical and solvatochromic properties.

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.

Accessing a Diverse Set of Functional Red-Light Photoswitches by Selective Copper-Catalyzed Indigo N-Arylation.

The ability to correlate the structure of a molecule with its properties is the key to the rational and accelerated design of new functional compounds and materials. Taking photoswitches as an example, the thermal stability of the metastable state is a crucial property that dictates their application in molecular systems. Indigos have recently emerged as an attractive motif for designing photoswitchable molecules due to their red-light addressability, which can be advantageous in biomedical and material applications. The lack of synthetic techniques to derivatize the abundant parent dye and a thorough understanding of the impact of structural factors on the photochemical and thermal properties hinder broad applications of this emerging photoswitch class. Herein, we report an efficient copper-catalyzed indigo N-arylation that enables the installation of a wide variety of aryl moieties carrying useful functional groups. The exclusive selectivity for monoarylation likely originates from a bimetallic cooperative mechanism through a binuclear copper-indigo intermediate. Functional N-aryl-N'-alkylindigos were prepared and shown to photoisomerize efficiently under red light. Moreover, this design allows for the modulation of thermal half-lives through N-aryl substituents, while the N'-alkyl groups enable the independent attachment of functional moieties without affecting the photochromic properties. A strong correlation between the structure of the N-aryl moiety and the thermal stability of the photogenerated Z-isomers was achieved by multivariate linear regression models obtained through a data-science workflow. This work thus builds an avenue leading to versatile red-light photoswitches and a general method for structure-property correlation that is expected to be broadly applicable to the design of photoresponsive molecules.

The stability of phycocyanin extracted from Arthrospira platensis against osmotic, acid, and temperature stress conditions

The main problem of using natural blue pigment of phycocyanin produced by Arthrospira platensis (spirulina) is its instability in the food matrix because of environmental stress. This study aimed to investigate the stability of phycocyanin under simulated conditions in food formulations against osmotic, acid, and temperature stress conditions. Thermal degradation constant (Dc) and half-life (t½) of phycocyanin extracted from Arthrospira platensis were analyzed using response surface methodology followed by a first-order kinetic reaction. The stability of phycocyanin was assessed under various temperature (50–98ºC), NaCl (0–2% w/w), and pH (4–7) values. Results showed that the stability of phycocyanin extracted from Arthrospira platensis is high at neutral pH and concentration of 1% (w/w) NaCl. The stability decreased with increase in temperature at ≥75°C. The highest stability of phycocyanin (the lowest Dc and the maximum t½ were 0.011 min-1 and 54.03 min, respectively) was achieved at 66.89°C, pH = 6.6, and NaCl of 0.40% w/w. According to processing conditions, content of phycocyanin required for a food matrix is successfully calculated by the response surface method. This research showed that phycocyanin is stable at thermal shock in a neutral pH medium and low content of NaCl (0.40% w/w).

Visible-Light-Activated Heteroaryl Azoswitches: Toward a More Colorful Future.

Azobenzenes (Ph-N═N-Ph) are known as the most widely studied molecular photoswitches, and the recent rise of azoheteroarenes (Het-N═N-Ph or Het-N═N-Het) offers great opportunities to advance this already mature field. A common limitation is that azo-switches generally require harmful UV light for activation, which hinders their application across various fields. Despite great efforts in developing visible-light azobenzenes over the past few decades, the potential of visible-light heteroaryl azoswitches remains largely unexplored. This Perspective summarizes the state-of-the-art advancements in visible-light heteroaryl azoswitches, covering molecular design strategies, the structure-property relationship, and potential applications. We highlight the distinctive advantages of azoheteroarenes over azobenzenes in the research and development of visible-light switches. Furthermore, we discuss the opportunities and challenges in this emerging field and propose potential solutions to address crucial issues such as spectral red-shift and thermal half-life. Through this Perspective paper, we aim to provide inspiration for further exploration in this field, in anticipation of the growing prosperity and bright future of visible-light azoheteroarene photoswitches.

Biochemical characterization of a novel hyperthermophilic chitinase from a deep-sea Thermotogae bacterium

Chitin represents the most abundant source of renewable biomass in marine ecosystems, and its degradation by chitinase holds potential for numerous industrial applications. In this study, a novel hyperthermophilic chitinase, TbChi52, derived from a deep-sea bacterium of the Thermotogae phylum was introduced. TbChi52 exhibits optimal enzymatic activity at 90 ℃ and pH 5.5. Furthermore, it shows exceptional thermal stability characterized by a prolonged thermal denaturation half-life and a significant melting temperature. Functionally, TbChi52 displays dual activities, acting as both an exo-chitinase and a β-N-acetylaminoglucosidase (NAGase). It yields N-acetyl-D-glucosamine (GlcNAc) as the primary product during the hydrolysis of colloidal chitin. Leveraging the robust thermo-stability of TbChi52, a streamlined, one-step purification protocol was developed. A mere 10-minute thermal treatment at 75 ℃ suffices to yield a highly pure TbChi52 preparation with minimal enzyme activity loss in chitin hydrolysis, achieving an 87.4 % hydrolysis rate of colloidal chitin and a 92.7 % purity of GlcNAc. Collectively, the outstanding thermal properties and the simple preparation of TbChi52 highlight its potential for industrial applications. It provides a sustainable and eco-friendly approach to harnessing the world's most abundant marine biomass, along with serving as a potential enzyme-engineered template tailored for specific applications.

Push-Pull Bis-Norbornadienes for Solar Thermal Energy Storage.

The norbornadiene/quadricyclane (NBD/QC) photoswitch pair represents a promising system for application in molecular solar thermal energy storage (MOST). Often, the NBD derivatives have very limited overlap with the solar spectrum, and substitution to redshift the absorption leads to a decrease in the gravimetric energy density. Dimeric systems mitigate this factor because two switches can 'share' a substituent. Here, we present five new NBD dimers with red-shifted absorption spectra. One dimer features the most red-shifted absorption onset (539 nm) and a significantly red-shifted absorption maximum (404 nm) for NBD systems reported so far, without compromising thermal half-life. Promising properties for high-performance MOST applications are demonstrated, such as high absorption onsets reaching 539 nm, and energy densities of 379 kJ/kg, while still maintaining long half-lives of the metastable isomer, up to 23 hours at 25 °C.

Aryl Azocyclopropeniums: Minimalist, Visible-Light Photoswitches.

We report convenient syntheses of aryl azocyclopropeniums and a study of their photochemical properties. Incorporation of the smallest arene leads to pronounced redshift of the π-π* absorbance band, compared to azobenzenes. Photoisomerization under purple or green light irradiation affords Z- or E-isomers in ratios up to 94% Z or 90% E, and the switches proved stable over multiple irradiation cycles. Thermal half-lives of metastable Z-isomers range from minutes to hours in acetonitrile and water. These properties together with the concise, versatile syntheses render aryl azocyclopropeniums exciting additions to the tool kit of readily available molecular photoswitches for wide ranging applications.

Photoisomerization and Light-Controlled Antibacterial Activity of Fluoroquinolone-Azoisoxazole Hybrids.

Photopharmacology holds a huge untapped potential to locally treat diseases involving photoswitchable drugs via the elimination of drugs' off-target effects. The growth of this field has created a pressing demand to develop such light-active drugs. We explored the potential for creating photoswitchable antibiotic hybrids by attaching pharmacophores norfloxacin/ciprofloxacin and azoisoxazole (photoswitch). All compounds exhibited a moderate to a high degree of bidirectional photoisomerization, long thermal cis half-lives, and impressive photoresistance. Gram-negative pathogens were found to be insensitive to these hybrids, while against Gram-positive pathogens, all hybrids in their trans states exhibited antibacterial activity that is comparable to that of the parent drugs. Notably, the toxicity of the irradiated hybrid 6 was found to be 2-fold lower than the nonirradiated trans isomer, indicating that the pre-inactivated cis-enriched drug can be employed for the site-specific treatment of bacterial infection using light, which could potentially eliminate the unwanted exposure of toxic antibiotics to both beneficial and untargeted harmful microbes in our body. Molecular docking revealed different binding affinity of the cis and trans isomers with the topoisomerase IV enzyme, due to their different shapes.

Wheat Protein Hydrolysates Improving the Stability of Purple Sweet Potato Anthocyanins under Neutral pH after Commercial Sterilization at 121 °C.

Anthocyanins are prone to degradation and color fading after sterilization. This work examined the potential of wheat protein hydrolysates (WPHs, 40 g/L) in improving the stability of purple sweet potato anthocyanins (PSPAs) under a pH of 6.8 after sterilization at 121 °C followed by storage. Results showed that WPHs increased the thermal degradation half-life of PSPAs 1.65 times after sterilization. Compared to PSPAs alone, after being stored at 37 °C and 45 °C for 7 days, the retention concentration of PSPAs with WPHs was 5.4 and 32.2 times higher, and the color change of PSPAs with WPHs decreased from 6.19 and 10.46 to 0.29 and 0.77, respectively. AFM data, fluorescence and UV spectrograms indicated the formation of complexes between PSPAs and WPHs by hydrophobic attraction confirmed by zeta-potential data. PSPAs with WPHs had stable particle size and zeta potential, which may also significantly increase the concentrations after digestion and antioxidant power of PSPAs. This work indicated that the assembled PSPAs composite structure by WPHs significantly reduced the degradation of PSPAs at a pH of 6.8 after sterilization at 121 °C followed by long-term storage.

1,2-BF2 Shift and Photoisomerization Induced Multichromatic Response.

Adaptive materials that exhibit a multichromatic response as a function of applied stimulus are highly desirable, as they can result in applications ranging from smart surfaces to anticounterfeit devices. Here we report on such a system based on an intriguing thermal 1,2-BF2 shift that transforms a visible-light-activated azo-BF2 photoswitch into a BF2-hydrazone fluorophore (BODIHY) in both solution and the solid-state. Structure-property analysis, in conjunction with DFT calculations, reveals that the shift is catalyzed by the spatial proximity of an oxygen atom next to the BF2 group and that the activation originates from an electronic and not steric effect. Theoretical calculations also show that while the energy barrier for the trans → BODIHY transformation is accessible at room temperature (thermal half-life of 30 h), the cis → BODIHY transformation has a much higher barrier, which is why the 1,2-BF2 shift is not observed for the cis form. The photoswitching of the azo-BF2, in conjunction with the 1,2-BF2 shift, was then used in the multicolor modulation of a switch-containing cross-linked polydimethylsiloxane film using light and/or heat stimuli, elaborating the usefulness of the sophisticated reaction cascade that can be accessed from this simple system.

Phenolylazoindole scaffold for facilely synthesized and bis-functional photoswitches combining controllable fluorescence and antifungal properties using theoretical methods.

Functionalization is a major challenge for the application of photoswitches. With the aim to develop novel bis-functional azo photoswitches with stationary photophysical properties, a series of phenolylazoindole derivatives were designed, synthesized, and characterized via NMR spectroscopy studies and high-resolution mass spectrometry (HRMS). Herein, UV/Vis and 1H NMR spectra revealed that the photostationary state (PSS) proportions for PSScis and PSStrans were 76-80% and 68-81%, respectively. Furthermore, the thermal half-lives (t1/2) of compounds A2-A4 and B2 ranged from 0.9 to 5.3 h, affected by the diverse substituents at the R1 and R2 positions. The results indicated that azo photoswitches based on the phenolylazoindole scaffold had stationary photophysical properties and wouldn't be excessively affected by modifying the functional groups. Compounds A4 and B2, which were modified with an aryl group, also exhibited fluorescence emission properties (the quantum yields of A4 and B2 were 2.32% and 13.34%) through the modification of the flexible conjugated structure (benzene) at the R2 position. Significantly, compound C1 was obtained via modification with a pharmacophore in order to acquire antifungal activities against three plant fungi, Rhizoctonia solani (R. solani), Botrytis cinerea (B. cinerea), and Fusarium graminearum (F. graminearum). Strikingly, the inhibitory activity of the cis-isomer of compound C1towards R. solani (53.3%) was significantly better than that of the trans-isomer (34.2%) at 50 μg mL-1. In order to further reveal the antifungal mechanism, molecular docking simulations demonstrated that compound C1 effectively integrates into the cavity of succinate dehydrogenase (SDH); the optically controlled cis-isomer showed a lower binding energy with SDH than that of the trans-isomer. This research confirmed that phenolylazoindole photoswitches can be appropriately applied as molecular regulatory devices and functional photoswitch molecules via bis-functionalization.

Photoswitchable Antibiotic Hybrids: Spacer Length-Dependent Photochemical Control of Antibacterial Activity.

Photopharmacology holds huge potential for the permanent (long-term) eradication of antibiotic resistance by the application of photoswitchable antibiotics. To construct such antibiotics, various methods have been employed to modify known antibiotics with photoswitches, such that the irradiated state shows activity comparable to or higher than that of the parent antibiotic and that a large activity difference between irradiated and nonirradiated states is achieved. However, most of those methods are ineffective when dealing with more than one drug with dissimilar structures. Here, we have demonstrated a new approach, in which two pharmacophores, one being a photoswitch, are covalently linked via a spacer of variable lengths, leading to a set of azopyrazole-norfloxacin antibiotic hybrids. All compounds showed a high degree of bidirectional photoisomerization, long thermal cis half-lives, and excellent photoresistance. Notably, the hybrid with an optimal four-carbon spacer length enabled the irradiated state to become 12-fold more potent than its nonirradiated state without losing much antimicrobial activity of norfloxacin. Only Gram-positive bacteria were found to be sensitive to this hybrid, and the full antibacterial potency of its irradiated state was found to be retained for nearly 24 h.

Mycelium-bound lipase as skillful biocatalysts: Production of fatty acid concentrates from waste oils for the food industry

This study aimed to produce Rhizopus oryzae whole-cells having high lipolytic activity. The hydrolytic activity of 558.99 U.g−1 and total lipase activity of 7440.17 U was obtained in 72 h of cultivation using 30 g.L−1 of canola oil. Optimal activity was observed at pH 7.5 and 30 °C. Kinetic parameters were determined through olive oil hydrolysis (Km = 59.96 mM, Vmax = 344.09 μmol.g−1.min−1). Thermal inactivation constant and half-life were 0.15 h−1 and 4.62 h at 50 °C. Hydrolysis of vegetable oils achieved 80% yield in 24 h. These results suggest that the biocatalyst shows the potential to produce free fatty acids of great industrial interest.

Systematic Investigation into the Photoswitching and Thermal Properties of Arylazopyrazole-based MOF Host-Guest Complexes.

A series of arylazopyrazole-loaded metal-organic frameworks were synthesized with the general formula Zn2(BDC)2(DABCO)(AAP)x (BDC = 1,4-benzenedicarboxylate; DABCO = 1,4-diazabicyclo-[2.2.2]octane; AAP = arylazopyrazole guest). The empty framework adopts a large pore tetragonal structure. Upon occlusion of the E-AAP guests, the frameworks contract to form narrow pore tetragonal structures. The extent of framework contraction is dependent on guest shapes and pendant groups and ranges between 1.5 and 5.8%. When irradiated with 365 nm light, the framework expands due to the photoisomerization of E-AAP to Z-AAP. The proportion of Z-isomer at the photostationary state varies between 19 and 57% for the AAP guests studied and appears to be limited by the framework which inhibits further isomerization once fully expanded. Interestingly, confinement within the framework significantly extends the thermal half-life of the Z-AAP isomers to a maximum of approximately 56 years. This finding provides scope for the design of photoresponsive host-guest complexes with high stability of the metastable isomer for long-duration information or energy storage applications.

On the Simulation of Thermal Isomerization of Molecular Photoswitches in Biological Systems.

Molecular photoswitches offer precise, reversible photocontrol over biomolecular functions and are promising light-regulated drug candidates with minimal side effects. Quantifying thermal isomerization rates of photoswitches in their target biomolecules is essential for fine-tuning their light-controlled drug activity. However, the effects of protein binding on isomerization kinetics remain poorly understood, and simulations are crucial for filling this gap. Challenges in the simulation include describing multireference electronic structures near transition states, disentangling competing reaction pathways, and sampling protein-ligand interactions. To overcome these challenges, we used multiscale simulations to characterize the thermal isomerization of photostatins (PSTs), which are light-regulated microtubule inhibitors for potential cancer phototherapy. We employed a new ab initio multireference electronic structure method in a quantum mechanics/molecular mechanics setting and combined it with enhanced sampling techniques to characterize the cis to trans free-energy profiles of three PSTs in a vacuum, aqueous solution, and tubulin dimer. The significant advantage of our novel approach is the efficient treatment of the multireference character in PSTs' electronic wavefunction throughout the conformational sampling of protein-ligand interactions along their isomerization pathways. We also benchmarked our calculations using high-level ab initio multireference electronic structure methods and explored the competing isomerization pathways. Notably, calculations in a vacuum and implicit solvent models cannot predict the order of the PSTs' thermal half-lives in the aqueous solution observed in the experiment. Only by explicitly treating the solvent molecules can the correct order of isomerization kinetics be reproduced. Protein binding perturbs free-energy barriers due to hydrogen bonding between PSTs and nearby polar residues. Our work generates comprehensive, high-quality benchmark data and offers guidance for selecting computational methods to study the thermal isomerization of photoswitches. Ab initio multireference free-energy calculations in explicit molecular environments are crucial for predicting the effects of substituents on the thermal half-lives of photoswitches in biological systems.