Cis-trans Research Articles

Theoretical Study of Structure and Photophysics of Homologous Series of Bis(arylydene)cycloalkanones.

Photophysical properties of a series of bis(arylydene)cycloalkanone dyes with various donor substituents are studied using quantum chemistry. Their capacity for luminescence and nonradiative relaxation through trans-cis isomerization is related to their structure, in particular, to the donor capacity of the substituents and the degree of conjugation due to the central cycloalkanone moiety. It is shown that cyclohexanone central moiety introduces distortions and disrupts the conjugation, thus leading to a nonmonotonic change in their properties. The increasing donor capacity of the substituents causes increase in the HOMO energy (rise in the oxidation potential) and decrease in the HOMO-LUMO gap, which results in the red shift of the absorption spectra. The ability of the excited dye to relax through fluorescence or through trans-cis isomerization is governed by the height of the barrier between the Franck-Condon and S1-S0 conical intersection regions on the potential energy surface of the lowest π-π* excited state. This barrier also correlates with the donor capacity of the substituents and the degree of conjugation between the central and donor moieties. The calculated fluorescence and trans-cis isomerization rates are in good agreement with the observed fluorescence quantum yields.

Peptidyl-prolyl isomerase Cyclophilin71 promotes SERRATE phase separation and miRNA processing in Arabidopsis

MicroRNAs (miRNAs) play an important role in gene regulation. In Arabidopsis, mature miRNAs are processed from primary miRNA transcripts by the Dicing complex that contains Dicer-like 1 (DCL1), SERRATE (SE), and Hyponastic Leaves 1 (HYL1). The Dicing complex can form nuclear dicing bodies (D-bodies) through SE phase separation. Here, we report that Cyclophilin71 (CYP71), a peptidyl-prolyl isomerase (PPIase), positively regulates miRNA processing. We show that CYP71 directly interacts with SE and enhances its phase separation, thereby promoting the formation of D-body and increasing the activity of the Dicing complex. We further show that the PPIase activity is important for the function of CYP71 in miRNA production. Our findings reveal orchestration of miRNA processing by a cyclophilin protein and suggest the involvement of peptidyl-prolyl cis-trans isomerization, a structural mechanism, in SE phase separation and miRNA processing.

Function and regulation of cis P-tau in the pathogenesis and treatment of conventional and nonconventional tauopathies.

Conventional tauopathies are a group of disease characterized by tau inclusions in the brains, including Alzheimer's disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and certain types of frontotemporal dementia (FTD), among which AD is the most prevalent. Extensive post-translational modifications, especially hyperphosphorylation, and abnormal aggregation of tau protein underlie tauopathy. Cis-trans isomerization of protein plays an important role in protein folding, function, and degradation, which is regulated by peptidyl-proline isomerases (PPIases). Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1), the only PPIase found to isomerize Pro following phosphorylated Ser or Thr residues, alters phosphorylated tau protein conformation at pT231-P motif. The cis P-tau but not trans P-tau serves as an early driver of multiple neurodegenerative disease, encompassing AD, traumatic brain injury (TBI), chronic traumatic encephalopathy (CTE), and vascular contributions to cognitive impairment and dementia (VCID). Cis but not trans P-tau is resistant to protein dephosphorylation and degradation, and also prone to protein aggregation. Cis P-tau loses its ability to stabilize microtubule, causing and spreading tauopathy mainly in axons, a pathological process called cistauosis. The conformation-specific monoclonal antibody that targets only the cis P-tau serves as a very early diagnosis method and a potential treatment of not only conventional tauopathies but also nonconventional tauopathies such as VCID, with clinical trials ongoing. Notably, cis P-tau antibody is the only clinical-stage Alzheimer's therapeutic that has shown the efficacy in animal models of not only AD but also TBI and stroke, which are very early stages of dementia. Here we review the identification and pathological consequences of cis pt231-tau, the role of its regulator Pin1, as well as the clinical implication of cis pt231-tau conformation-specific antibody in conventional and nonconventional tauopathies.

Spin-Flip Unitary Coupled Cluster Method: Toward Accurate Description of Strong Electron Correlation on Quantum Computers.

Quantum computers have emerged as a promising platform to simulate strong electron correlation that is crucial to catalysis and photochemistry. However, owing to the choice of a trial wave function employed in the variational quantum eigensolver (VQE) algorithm, accurate simulation is restricted to certain classes of correlated phenomena. Herein, we combine the spin-flip (SF) formalism with the unitary coupled cluster with singles and doubles (UCCSD) method via the quantum equation-of-motion (qEOM) approach to allow for an efficient simulation of a large family of strongly correlated problems. We show that the developed qEOM-SF-UCCSD/VQE method outperforms its UCCSD/VQE counterpart for simulation of the cis-trans isomerization of ethylene, and the automerization of cyclobutadiene and the predicted qEOM-SF-UCCSD/VQE barrier heights are in a good agreement with the experimentally determined values. The developments presented herein will further stimulate the investigation of this approach for simulations of other types of correlated/entangled phenomena on quantum computers.

Synthesis and cis-trans kinetics of an azobenzene-based molecular switch for light-responsive silica surfaces

Light-responsive materials design is an attractive research field that stimulates demand for the synthesis of novel molecular photoswitches. The novel photoswitches should be capable of being attached to a desired surface in order to provide it with light-responsive properties. The switchback to its ground state is expected to be gradual, with the possibility of acceleration. This study presents a comprehensive description of a chemical route to a molecular photoswitch based on an azobenzene derivative with a trifluoromethoxy group and a long alkyl chain. The photoswitch is capable of modifying submicrometer silica particles and silicon wafers as models of curved and flat surfaces, respectively. The thermal relaxation times of the synthesized azobenzene were studied in three different solvents: ethanol, chloroform, and toluene. The results reveal a significantly delayed relaxation process lasting for several days. This observation is found to be related to the polarity of the solvents used. To characterize the extensive thermal relaxation process, a methodology including the use of white-light pulses to accelerate cis-trans isomerization is suggested. The white light spectrum used in pulses affects thermal relaxation but does not alter the relaxation time extrapolated to zero. The density of the photoswitch molecules attached to particles varies from 0.7 to 1.7 molecules/nm2 as the initial amount of azobenzene in the reaction increases. Surface-attached photoswitches demonstrate reversible cis-trans isomerization behavior when exposed to UV and white light irradiation. A 14° contact angle change is observed when flat surfaces modified with photoswitches are irradiated with UV light.

Characterization of stress degradation products of bedaquiline fumarate and bedaquiline by LC-PDA and LC-MS

Bedaquiline fumarate was a first-in-class diarylquinoline drug used for the treatment of M. tuberculosis and its main biologically active form was bedaquiline. This paper studied and compared the degradation products of bedaquiline fumarate and bedaquiline using LC-PDA, LC-MS, and NMR techniques under thermal, alkaline, acidic, oxidative, and photolytic conditions respectively. A LC method was established and optimized to separate all analytes of bedaquiline fumarate and bedaquiline. All degradation products were identified by LC-HRMS/MS and LC-MSn. Bedaquiline fumarate formed three degradation products (DP1, DP2, and DP3) related to fumarate under photolytic condition and formed demethylation product DP4 under acid condition. Bedaquiline formed four degradation products (IM1, IM2, IM3, and IM4) related to the side chains of tertiary alcohol and tertiary amine groups under photolytic condition and formed DP4 under acid condition. The two compounds were stable under thermal, alkaline, and oxidative conditions. DP1 and DP2 indicate that the fumarate could take cis-trans isomerization under light condition. DP3, IM3 and IM4 were first reported degradation products of bedaquiline fumarate and bedaquiline. Compared the degradation behavior of bedaquiline fumarate with bedaquiline, the fumarate form can make the side chain of bedaquiline more stable. It is better to avoid acid and light contact during their storage and manufacturing process.

Photochromic Azobenzene Inverse Opal Film toward Dynamic Anti-Fake Pattern.

Azobenzene mesogens have garnered considerable research attention in the realm of photo-responsive materials due to their reversible trans-cis isomerization. In this paper, we demonstrate an azobenzene inverse opal film synthesized via photo-polymerization from a SiO2 opal template. The proposed design exhibits intriguing optical properties, including dynamic fluorescent features, distinct fluorescent enhancement, and an anti-fake micropattern with a switchable structure color. This work holds significant importance for advancing the development of novel optical devices.

Geometrical isomerization of arachidonic acid during lipid peroxidation interferes with ferroptosis.

Geometrical mono-trans isomers of arachidonic acid (mtAA) are endogenous products of free radical-induced cis-trans double bond isomerization occurring to natural fatty acids during cell metabolism, including lipid peroxidation (LPO). Very little is known about the functional roles of mtAA and in general on the effects of mono-trans isomers of polyunsaturated fatty acids (mtPUFA) in various types of programmed cell death, including ferroptosis. Using HT1080 and MEF cell cultures, supplemented with 20μM PUFA (i.e., AA, EPA or DHA) and their mtPUFA congeners, ferroptosis occurred in the presence of RSL3 (a direct inhibitor of glutathione peroxidase 4) only with the PUFA in their natural cis configuration, whereas mtPUFA showed an anti-ferroptotic effect. By performing the fatty acid-based membrane lipidome analyses, substantial differences emerged in the membrane fatty acid remodeling of the two different cell fates. In particular, during ferroptosis mtPUFA formation and their incorporation, together with the enrichment of SFA, occurred. This opens new perspectives in the role of the membrane composition for a ferroptotic outcome. While pre-treatment with AA promoted cell death for treatment with H2O2 and RSL3, mtAA did not. Cell death by AA supplementation was suppressed also in the presence of either ferroptosis inhibitors, such as the lipophilic antioxidant ferrostatin-1, or NADPH oxidase (NOX) inhibitors, including diphenyleneiodonium chloride and apocynin. Our results confirm a more complex scenario for ferroptosis than actually believed. While LPO processes are active, the importance of environmental lipid levels, balance among SFA, MUFA and PUFA in lipid pools and formation of mtPUFA influence the membrane phospholipid turnover, with crucial effects in the occurrence of cell death by ferroptosis.

Genome-wide chromatin accessibility landscape and dynamics of transcription factor networks during ovule and fiber development in cotton

BackgroundThe development of cotton fiber is regulated by the orchestrated binding of regulatory proteins to cis-regulatory elements associated with developmental genes. The cis–trans regulatory dynamics occurred throughout the course of cotton fiber development are elusive. Here we generated genome-wide high-resolution DNase I hypersensitive sites (DHSs) maps to understand the regulatory mechanisms of cotton ovule and fiber development.ResultsWe generated DNase I hypersensitive site (DHS) profiles from cotton ovules at 0 and 3 days post anthesis (DPA) and fibers at 8, 12, 15, and 18 DPA. We obtained a total of 1185 million reads and identified a total of 199,351 DHSs through ~ 30% unique mapping reads. It should be noted that more than half of DNase-seq reads mapped multiple genome locations and were not analyzed in order to achieve a high specificity of peak profile and to avoid bias from repetitive genomic regions. Distinct chromatin accessibilities were observed in the ovules (0 and 3 DPA) compared to the fiber elongation stages (8, 12, 15, and 18 DPA). Besides, the chromatin accessibility during ovules was particularly elevated in genomic regions enriched with transposable elements (TEs) and genes in TE-enriched regions were involved in ovule cell division. We analyzed cis-regulatory modules and revealed the influence of hormones on fiber development from the regulatory divergence of transcription factor (TF) motifs. Finally, we constructed a reliable regulatory network of TFs related to ovule and fiber development based on chromatin accessibility and gene co-expression network. From this network, we discovered a novel TF, WRKY46, which may shape fiber development by regulating the lignin content.ConclusionsOur results not only reveal the contribution of TEs in fiber development, but also predict and validate the TFs related to fiber development, which will benefit the research of cotton fiber molecular breeding.

The Impact of Amine-Functionalised Iron Oxide Nanoparticles on the Menaquinone-7 Isomer Profile and Production of the Bioactive Isomer

The K family of vitamins includes a collection of molecules with different pharmacokinetic characteristics. Menaquinone-7 (MK-7) has the finest properties and is the most therapeutically beneficial due to its long plasma half-life and outstanding extrahepatic bioavailability. MK-7 exhibits cis–trans isomerism, and merely the all-trans form is biologically efficacious. Therefore, the remedial value of MK-7 end products is exclusively governed by the quantity of all-trans MK-7. Consumers favour fermentation for the production of MK-7; however, it involves several challenges. The low MK-7 yield and extensive downstream processing requirements increase production costs, resulting in an expensive final product that is not universally available. Bacterial cell immobilisation with iron oxide nanoparticles (IONs) can potentially address the limitations of MK-7 fermentation. Uncoated IONs tend to have low stability and can adversely affect cell viability; thus, amine-functionalised IONs, owing to their increased physicochemical stability and biocompatibility, are a favourable alternative. Nonetheless, employing biocompatible IONs for this purpose is only advantageous if the bioactive MK-7 isomer is obtained in the most significant fraction, exploring which formed the aim of this investigation. Two amine-functionalised IONs, namely 3-aminopropyltriethoxysilane (APTES)-coated IONs (IONs@APTES) and L-Lysine (L-Lys)-coated IONs (L-Lys@IONs), were synthesised and characterised, and their impact on various parameters was evaluated. IONs@APTES were superior, and the optimal concentration (300 μ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\upmu$$\\end{document}g/mL) increased all-trans MK-7 production and improved its yield relative to the untreated cells by 2.3- and 3.1-fold, respectively. The outcomes of this study present an opportunity to develop an innovative and effective fermentation method that enhances the production of bioactive MK-7.

Comprehensive investigations of trans-cis-trans isomerization in the solid state for azo polyimides

This work describes the thermal cis-trans isomerization in the solid-state for poly(ether imide)s and poly(ester imide)s with azobenzene or azo pyridine moieties. The cis-trans relaxation was monitored for covalently functionalized polyimides (main-chain, side-chain, „T-type”) and “guest-host” azo systems. The obtained results from the investigations allow us to formulate some general relationships between material aspects such as polyimide structure, its molar mass, the content of azo dye, the value of d-spacing, the thickness of polymer film, and thermal cis-trans isomerization. The reversibility of the trans-cis-trans reaction was studied in 10 subsequent cycles and 100 cycles for the selected polymers. Studies of the reversibility of the trans-cis-trans reaction were realized by irradiation using two wavelengths of radiation λ = 365 nm (P = 2.9 W) and λ = 460 nm (P = 850 mW). To the best of our knowledge, this is the first article that comprehensively presents solid-state cis-trans isomerization for azo polyimides.

Computational Investigation of Conformational Properties of Short Azapeptides: Insights from DFT Study and NBO Analysis.

Azapeptides have gained much attention due to their ability to enhance the stability and bioavailability of peptide drugs. Their structural preferences, essential to understanding their function and potential application in the peptide drug design, remain largely unknown. In this work, we systematically investigated the conformational preferences of three azaamino acid residues in tripeptide models, Ac-azaXaa-Pro-NHMe [Xaa = Asn (4), Asp (5), Ala (6)], using the popular DFT functionals, B3LYP and B3LYP-D3. A solvation model density (SMD) was used to mimic the solvation effect on the conformational behaviors of azapeptides in water. During the calculation, we considered the impact of the amide bond in the azapeptide models on the conformational preferences of models 4-6. We analyzed the effect of the HB between the side-chain main chain and main-chain main-chain on the conformational behaviors of azapeptides 4-6. We found that the predicted lowest energy conformation for the three models differs depending on the calculation methods. In the gas phase, B3LYP functional indicates that the conformers tttANP-1 and tttADP-1 of azapeptides 4 and 5 correspond to the type I of β-turn, the lowest energy conformation with all-trans amide bonds. Considering the dispersion correction, B3LYP-D3 functional predicts the conformers tctANP-2 and tctADP-3 of azapeptide 4 and 5, which contain the cis amide bond preceding the Pro residue, as the lowest energy conformation in the gas phase. The results imply that azaAsx and Pro residues may involve cis-trans isomerization in the gas phase. In water, the predicted lowest energy conformer of azapeptides 4 and 5 differs from the gas phase results and depends on the calculational method. For azapeptide 6, regardless of calculation methods and phases, tttAAP-1 (β-I turn) is predicted as the lowest energy conformer. The results imply that the effect of the side chain that can form HBs on the conformational preferences of azapeptides 4 and 5 may not be negligible. We compared the theoretical results of azaXaa-Pro models with those of Pro-azaXaa models, showing that incorporating azaamino acid residue in peptides at different positions can significantly impact the folding patterns and stability of azapeptides.

Right Answer for the Right Reason? Benchmarking Protocols and Pitfalls on a Ru-Metathesis Example.

A layered meta-benchmarking analysis was devised with the aim of illustrating how to produce an experimental/computational protocol for the method selection and estimation of Gibbs energies of catalytically prominent reactions. Our test subject involved the active-latent equilibrium through the cis-trans isomerism of two metathesis catalysts: mesitylene-Ru-SCF3-Cl and diisopropylphenyl-Ru-SCF3-Cl. The strategy was two-fold: first to perform a computational benchmark for the energies in the gas phase, followed by benchmarking the enthalpy and the Gibbs energy, including solvation and entropy, from experimental references. This "wedding cake" build-up of subsequent methods applied to our particular small test reaction indicates that: (1) DLPNO-CCSD(T)/CBS works well as a reference method for large systems. (2) Among several functionals ωB97XD and M06 were the most accurate. (3) Choosing between IEF-PCM and SMD solvation models turned out to be case dependent. (4) For the vibrational entropic component, low-frequency vibrations often produce humungous errors, which can be improved by Cramer and Truhlar's or Grimme's methods; however, their cut-off parameters had to be lowered from their standard values. (5) Solvation methods are important for enthalpies, but they are inadequate for entropies. (6) All of these components are equally important for the accuracy of organometallic complexes' reactions. The only way to find the right method for the right reasons is to be sure to match all of the Gibbs energy terms to benchmarked experimental and computational values.

Modulation of Isomerization and Ligand Exchange Rates by π Bonding in Bis(iminoxolene)iridium Pyridine Complexes.

The bis(iminoxolene)iridium complex (Diso)2IrCl (Diso = N-(2,6-diisopropylphenyl)-4,6-di-tert-butyl-2-imino-o-benzoquinone) reacts with pyridine to give trans-(Diso)2Ir(py)Cl as the kinetic product, with cis-(Diso)2Ir(py)Cl formed as the exclusive thermodynamic product upon heating. Electronic spectra and density functional theory calculations point to very similar electronic structures for the cis and trans isomers, with a nonbonding iminoxolene-centered HOMO and a metal-iminoxolene π* LUMO. The triplet states of cis-(Diso)2Ir(py)Cl and cis-[(Diso)2Ir(py)2]+ (but not trans-(Diso)2Ir(py)Cl) are unusually low in energy (1000-1500 cm-1 above the singlets), as shown by variable-temperature NMR spectroscopy. The low-energy triplets are attributed to a change in dihedral angle in the iminoxolenes, which allows a partial π interaction that cannot be achieved in the trans octahedral compounds. Mechanistic studies of the trans-cis isomerization in toluene indicate that the reaction proceeds via isomerization of the five-coordinate species to a form with cis iminoxolene ligands and an apical oxygen. This form is high in energy due to the loss of a secondary iminoxolene-to-iridium π-donor interaction that is possible in the trans form but not in the cis form for the square pyramidal structures. This stereoelectronic effect, combined with the poorer binding of pyridine in trans-(Diso)2Ir(py)Cl due to the interactions of the N-aryl substituents with the pyridine, makes the pyridine dissociate faster from the trans isomer by a factor of 108 at room temperature.

Study of homopolymerization and Z-E isomerization of metacryloxyaurones

Radical thermally initiated homopolymerization of methacrylic monomers based on aurone has been studied. Photochemical properties of these methacrylic monomers by UV-visible spectroscopy were investigated. It is shown that the new compounds are capable to radical homopolymerization and photoinduced cis-trans isomerization. It was found that increasing the electron donation of the substituent accelerates the process of radical homopolymerization of monomers. It was found that increasing the electron acceptance of the substituent accelerates the process of cis-trans isomerization. The rate constants and half-transformation times of cis-trans photoisomerization were determined by the tangent of the slope of the dependence Ln(Dfss-D0)/(Dfss-Dt) on the irradiation time of the solutions.

Efficient synthesis and characterization of meso-substituted bis(benzothiazolium) pentamethine cyanine dyes and investigation of the impact of meso-substitution on water solubility and the structural rigidity to improve photophysical properties and fluorescent brightness

To achieve structurally rigid pentamethine cyanine dyes with worthful photophysical properties for biological applications, five series of symmetrical meso-substituted bis(benzothiazolium) pentamethine cyanine dyes were synthesized via an efficient and simple triethylamine-promoted approach involved condensation of various N-substituted benzothiazolium salts with preformed β-substituted vinamidinium salts in high yield and purity without the nontrivial chromatographic separation. The chemical structures of the synthesized dyes were confirmed by HPLC-MS, 1H NMR, 13C NMR, and FTIR techniques. The photophysical properties of the new dyes were investigated in methanol, recognizing that the dyes demonstrate excellent fluorescent brightness. The solutions of the dyes exhibited maximum absorption and fluorescence emission in the range of 600–650 nm with high molar absorption coefficients (around 1-3 × 105 dm3 mol−1 cm−1) and 610–670 nm with remarkable fluorescence quantum yield, respectively. In addition, the photostabilities and photoluminescent stabilities of the synthetic dyes were studied in methanol, revealing their outstanding stability and resistance to photodecomposition. Examining the photochemical behavior (UV light) of the dyes in organic solvents with different polarities verified the main role of various meso substitutions on the rigidity of molecular structures and cis-trans isomerization to improve the photophysical properties. The presence of the pyridinium substituent rings into the polymethine chain makes the dyes rigid and more water-soluble because of their bulky form and positive charge, respectively.

Controlled assembly of perovskite nanoparticles by photoswitchable functional ligands

Organic ligands play a crucial role in the properties and functionality of nanostructures. Functional ligands are an interesting research direction that can be utilized to influence the properties and functionality of nanoparticles (NPs). In this work, we demonstrate controlled assembly of CsPbBr3 perovskite NPs as a result of light. Azobenzene derivative molecules were used as the photoswitchable ligands for the NPs. The assembly and disassembly of the NPs were achieved by cis–trans isomerization. By utilizing polarization-modulated, infrared reflection–absorption spectroscopy and diffusion-ordered nuclear magnetic resonance, we were able to track the attachment of the ligands to the surface of the NPs. Absorbance, photoluminescence and high-resolution, transmission electron microscopy followed the assembly and disassembly of the NPs. This work demonstrates functional ligands paired to perovskite nanostructures through controlling their assembly and disassembly, which opens the way for sensing and photodetection applications.

Conformational and functional regulation of the chicken tumor virus number 10 (CT10) regulator of kinase II (CrkII) adaptor protein by cyclophilin A

The Src homology 2 (SH2) and SH3 domain-containing chicken tumor virus number 10 (CT10) regulator of kinase (Crk) adaptor proteins include three cellular members that serve as integral constituents of multiple receptor-linked signal transduction pathways. CrkI and CrkII are products of alternative RNA-splicing which is transcribed from a single gene, while Crk-like (CrkL), which is highly homologous to CrkII, is encoded by a different gene. Thanks to their modular structure, the Crk adaptor proteins can simultaneously interact with activated receptors and a wide range of effector molecules, and orchestrate the assembly of complexes containing enzymes and substrates at the receptor site. They are involved in the regulation of a large number of cellular processes which control cell growth, differentiation, transformation, and apoptosis. Cell activation-dependent tyrosine phosphorylation of CrkII and CrkL serves as a major posttranslational modification mechanism that introduces conformational changes in the proteins by promoting an intramolecular interaction between the phosphotyrosine and the self SH2 domain. The resulting conformational change induces downregulation of CrkII- and CrkL-dependent biological processes. A second type of posttranslational modification mechanism regulates the structure and function of the CrkII adaptor protein by immunophilin-mediated protein isomerization. Two of the most abundant immunophilins in T lymphocytes which function as peptidyl-prolyl cis-trans isomerases (PPIases), namely cyclophilin A (CypA) and FK506-binding proteins (FKBPs), can associate with CrkII and catalyze its reciprocal cis-trans isomerization. This mechanism is of special importance for the regulation of T lymphocyte functions and for T cell-mediated immune responses, since immunophilin inhibitors, such as cyclosporin A (CsA) and FK506, function as immunosuppressive drugs that can prevent allotransplanted graft rejection. The present manuscript focuses on selected functions of Crk adaptor proteins, predominantly in T lymphocytes, and reviews in more detail the current knowledge on the immunophilin-dependent regulation of the structure and function of the CrkII adaptor protein.

Photon- and Singlet-Oxygen-Induced Cis-Trans Isomerization of the Water-Soluble Carotenoid Crocin.

Studying the cis-trans isomerization process in crocin (CR), one of the few water-soluble carotenoids extracted from saffron, is important to better understand the physiological role of cis-carotenoids in vivo and their potential as antioxidants in therapeutic applications. For that, cis-trans isomerization of both methanol- and water-dissolved CR was induced by light or thermally generated singlet oxygen (1O2). The kinetics of molecular concentrations were monitored by both high-performance liquid chromatography (HPLC) and non-destructive spectrophotometric methods. These last made it possible to simultaneously follow the cis-trans isomerization, the possible bleaching of compounds and the amount of thermally generated 1O2. Our results were in accordance with a comprehensive model where the cis-trans isomerization occurs as relaxation from the triplet state of all-trans- or 13-cis-CR, whatever is the way to populate the CR triplet state, either by photon or 1O2 energy transfer. The process is much more (1.9 to 10-fold) efficient from cis to trans than vice versa. In H2O, a 1O2-induced bleaching effect on the starting CR was not negligible. However, the CR "flip-flop" isomerization reaction could still occur, suggesting that this process can represent an efficient mechanism for quenching of reactive oxygen species (ROS) in vivo, with a limited need of carotenoid regeneration.

Photoisomerization of 2-Arylazoimidazoles under Visible Light: Identifying a Predictive Tool to Anticipate and Tune Likely Photoswitching Performance and Cis Half-Life.

Azopyrazoles are an emerging class of photoswitches, whereas analogous azoimidazole-based switches are unable to draw much attention because of their short cis half-lives, poor cis-trans photoreversion yields, and toxic ultraviolet (UV) light-assisted isomerization. A series of 24 various aryl-substituted N-methyl-2-arylazoimidazoles were synthesized, and their photoswitching performances and cis-trans isomerization kinetics were thoroughly investigated experimentally and theoretically. Para-π-donor-substituted azoimidazoles with highly twisted T-shaped cis conformations showed nearly complete bidirectional photoswitching, whereas di-o-substituted switches exhibited very long cis half-lives (days-years) with nearly ideal T-shaped conformations. This study demonstrates how the electron density in the aryl ring affects cis half-life and cis-trans photoreversion via twisting of the NNAr dihedral angle that can be used as a predictive metric for envisaging and tuning the likely switching performance and half-life of any given 2-arylazoimidazole. By applying this tool, two better-performing azoimidazole photoswitches were engineered. All switches permitted irradiation by violet (400-405 nm) and orange (>585 nm) light for forward and reverse isomerization, respectively, and displayed comparatively high quantum yields and impressive resistance to photobleaching.