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The discovery of small molecules that exhibit turn-on far-red or near-infrared (NIR) fluorescence upon DNA binding and understanding how they bind DNA are important for imaging and bioanalytical applications. Here we report the DNA-bound structure and the DNA binding mechanism of quinone cyanine dithiazole (QCy-DT), a recently reported AT-specific turn-on NIR fluorescent probe for double-stranded DNA. The nuclear magnetic resonance (NMR)-derived structure showed minor groove binding but no specific ligand-DNA interactions, consistent with an endothermic and entropy-driven binding mechanism deduced from isothermal titration calorimetry. Minor groove binding is typically fast because it minimally perturbs the DNA structure. However, QCy-DT exhibited unusually slow DNA binding. The cyanine-based probe is capable of cis-trans isomerization due to overlapping methine bridges, with 16 possible slowly interconverting cis/trans isomers. Using NMR, density functional theory, and free energy calculations, we show that the DNA-free and DNA-bound environments of QCy-DT prefer distinctly different isomers, indicating that the origin of the slow kinetics is a cis-trans isomerization and that the minor groove preferentially selects an otherwise unstable cis/trans isomer of QCy-DT. Flux analysis showed the conformational selection pathway to be the dominating DNA binding mechanism at low DNA concentrations, which switches to the induced fit pathway at high DNA concentrations. This report of cis/trans isomerization of a ligand, upon binding the DNA minor groove, expands the prevailing understanding of unique discriminatory powers of the minor groove and has an important bearing on using polymethine cyanine dyes to probe the kinetics of molecular interactions.

Nitrogen-rich compounds based on heteroaromatic rings with different lengths of nitrogen chains are at the forefront of the energetic materials field. We studied the decomposition processes and rea...

The rapid cis-trans isomerization of α-anionic stilbene was regioselectively controlled by using flow microreactors, and its reaction with various electrophiles was conducted. The reaction time was precisely controlled within milliseconds to seconds at -50 °C to selectively give the cis- or trans-isomer in high yields. This synthetic method in flow was well-applied to synthesize precursors of commercial drug compound, (E)- and (Z)-tamoxifen with high regioselectivity and productivity.

Pin1 enzyme protein recognizes specifically phosphorylated serine/threonine (pSer/pThr) and catalyzes the slow interconversion of the peptidyl-prolyl bond between cis and trans forms. Structural dynamics between the cis and trans forms are essential to reveal the underlying molecular mechanism of the catalysis. In this study, we apply the weighted ensemble (WE) simulation method to obtain comprehensive path ensembles for the Pin1-catalyzed isomerization process. Associated rate constants for both cis-to-trans and trans-to-cis isomerization are calculated to be submicroseconds time scales, which are in good agreement with the calculated free energy landscape where the cis form is slightly less favorable. The committor-like analysis indicates the shift of the transition state toward trans form (at the isomerization angle ω ∼ 110°) compared to the intrinsic position for the isolated substrate (ω ∼ 90°). The calculated structural ensemble clarifies a role of both the dual-histidine motif, His59/His157, and the basic residues, Lys63/Arg68/Arg69, to anchor both sides of the peptidyl-prolyl bond, the aromatic ring in Pro, and the phosphate in pSer, respectively. The rotation of the torsion angle is found to be facilitated by relaying the hydrogen-bond partner of the main-chain oxygen in pSer from Cys113 in the cis form to Arg68 in the trans form, through Ser154 at the transition state, which is really the cause of the shift in the transition state. The role of Ser154 as a driving force of the isomerization is confirmed by additional WE and free energy calculations for S154A mutant where the isomerization takes place slightly slower and the free energy barrier increases through the mutation. The present study shows the usefulness of the WE simulation for substantial path samplings between the reactant and product states, unraveling the molecular mechanism of the enzyme catalysis.

Apurinic/apyrimidinic (AP) endonucleases are vital DNA repair enzymes, and proposed to be a prognostic biomarker for various types of cancer in humans. Numerous DNA sensors have been developed to evaluate the extent of nuclease activity but their DNA termini are not protected against other nucleases, hampering accurate quantification. Here we developed a new fluorescence enhancement (FE)-based method as an enzyme-specific DNA biosensor with nuclease-protection by three functional units (an AP-site, Cy3 and termini that are protected from exonucleolytic cleavage). A robust FE signal arises from the fluorescent cis–trans isomerization of a cyanine dye (e.g., Cy3) upon the enzyme-triggered structural change from double-stranded (ds)DNA to single-stranded (ss)DNA that carries Cy3. The FE-based assay reveals a linear dependency on sub-nanomolar concentrations as low as 10−11 M for the target enzyme and can be also utilized as a sensitive readout of other nuclease activities.

3‐Methylglutaconic (3MGC) aciduria is a common phenotypic feature of a growing number of inborn errors of metabolism. “Primary” 3MGC aciduria is caused by deficiencies in leucine pathway enzymes while “secondary” 3MGC aciduria results from inborn errors of metabolism that impact mitochondrial energy production. The metabolic precursor of 3MGC acid is trans‐3MGC CoA, an intermediate in the leucine catabolism pathway. Gas chromatography‐mass spectrometry (GC‐MS) analysis of commercially available trans‐3MGC acid yielded a mixture of cis and trans isomers while 1H‐NMR spectroscopy of trans‐3MGC acid at 25°C provided no evidence for the cis isomer. When trans‐3MGC acid was incubated under conditions used for sample derivatization prior to GC‐MS (but with no trimethylsilane added), 1H‐NMR spectroscopy provided evidence of trans to cis isomerization. Incubation of trans‐3MGC acid at 37°C resulted in time‐dependent isomerization to cis‐3MGC acid. Cis‐3MGC acid behaved in a similar manner except that, under identical incubation conditions, less isomerization occurred. In agreement with these experimental results, molecular modeling studies provided evidence that the energy minimized structure of cis‐3MGC acid is 4 kJ/mol more stable than that for trans‐3MGC acid. Once generated in vivo, trans‐3MGC acid is proposed to isomerize via a mechanism involving π electron delocalization with formation of a resonance structure that permits bond rotation. The data presented are consistent with the occurrence of both diastereomers in urine samples of subjects with 3MGC aciduria.

The cis-trans isomerization of a metal-centred molecular gear was investigated by density functional theory (DFT). The gear uses Pt(II) as stator, the azaphospha-triptycene as rotor, and the ligand...

The aryl transmetalation processes between cis-[PdRf2(AsPh3)2] (Rf = C6Cl2F3) and [AuPf(AsPh3)] (Pf = C6F5) has been studied experimentally and by DFT calculations. Aryl exchange with or without is...

Understanding the correlation between the molecular structure of triacylglycerols (TAGs) and their crystallization behavior is a prerequisite for engineering the nanostructures of fats to enhance s...

Azo dyes, such as azobenzene, are able to convert absorbed light into motion or deformation on the macroscopic scale on the basis of their remarkable ability to undergo repeatedly and in 100% yield reversible trans-to-cis photoisomerization. Current needs for multiresponsive and fast photoswitches have led to the development of heteroaryl azo dyes, such as azopyridine. This remarkable azo compound combines the photoresponse of the azo chromophore with the chemistry of the pyridine ring, in particular its responsiveness to changes in pH and its ability to form hydrogen- and halogen-bonds. This mini-review summarizes key features of the photoisomerization of polymer-tethered azopyridine in aqueous media and describes a few recent research accomplishments in emerging areas that have benefited of the fast thermal cis-to-trans relaxation characteristics of azopyridinium or H-bonded azopyridine. It also discusses the effects of the photoisomerization of azopyridine on the thermoresponsive properties of azopyridine-tethered heat-sensitive polymers. Overall, azopyridine is a highly versatile actuator to consider when designing photo/multiresponsive polymeric materials.

Cis-trans isomerization of the peptide bond prior to proline is an intrinsically slow process but plays an essential role in protein folding. In vivo cis-trans isomerization reaction is catalyzed by Peptidyl-prolyl isomerase (PPIases), a category of proteins widely distributed among all the three domains of life. The present study is majorly focused on the distribution of different types of PPIases in the archaeal domain. All the three hitherto known families of PPIases (namely FKBP, Cyclophilin and parvulin) were studied to identify the evolutionary conservation across the phylum archaea. The basic function of cyclophilin, FKBP and parvulin has been conserved whereas the sequence alignment suggested variations in each clade. The conserved residues within the predicted motif of each family are unique. The available protein structures of different PPIase across various domains were aligned to ascertain the structural variation in the catalytic site. The structural alignment of native PPIase proteins among various groups suggested that the apo-protein may have variable conformations but when bound to their specific inhibitors, they attain similar active site configuration. This is the first study of its kind which explores the distribution of archaeal PPIases, along with detailed structural and functional analysis of each type of PPIase found in archaea.

Cyclocurcumin (CyCUR) is a non-diarylheptanoid curcuminoid characterized by an α,β-unsaturated dihydropyranone moiety generally existing as trans isomer in the ground state but able to convert into the cis form by photoisomerization. Herein the kinetics of thermal cis–trans isomerization of cyclocurcumin was spectroscopically determined in ethanol, pure water and silver nanoparticles (AgNPs) aqueous solution. Energetic parameters were calculated by Arrhenius and Eyring plots in the temperature range 294–314 K. The presence of AgNPs increases the rate of the reaction, according to the polarizability of the environment. The solvatochromism of cyclocurcumin was also studied by using the Catalan empirical solvent parameters scale in a series of organic solvents. The bathochromic shift of CyCUR suggests that polarizability of the medium plays the major role in the investigated conditions.

The kinetics and mechanism of the stepwise cis-trans isomerization reactions of all-trans-β-carotene dissolved in MCT (medium-chain triglyceride) oil at temperatures in the range of 80-160 °C have been analyzed using multiresponse modeling. Quantitation of the cis-isomers was performed using HPLC-DAD and quantitation at the reaction isosbestic point at 421 nm. Multiresponse kinetic modeling using the Bayesian criterion was initially performed at 120 °C to determine the best model. Subsequently, the reparametrized Arrhenius equation was used to calculate the activation energies of all reactions. The equilibrium constants for the individual isomerization reactions were determined from the rate constants and the final product distributions. The enthalpies and entropies of the isomerization reactions were determined from the temperature dependence of the equilibrium constants. The 13-cis and 13,13'-di-cis isomers were found to be the fastest formed isomers followed by the 9-cis, 9,13-di-cis, and 13,15-di-cis isomers, where the latter was found to be formed from 13-cis and not the 15-cis isomer. The relative free energies of the β-carotene isomers were determined as all-trans < 13-cis < 9-cis < 13,13'-di-cis < 9,13-di-cis ≈ 15-cis < 13,15-di-cis. The entropic contribution of each reaction was found to play an important role in the ordering. It is concluded that the β-carotene system is quite labile at temperatures ranging from 80 to 160 °C and resulting in equilibrium distributions of the cis-trans isomers.

A possibility of lowering the formation of trans-isomers during hydrogenation of plant oil over a low-loaded palladium catalyst supported on activated diatomite was studied. The comparison to the commercial nickel catalyst led to establish that the activated diatomite is a promising support of the catalyst for hydrogenation of plant oil. Palladium particles of 2–10 nm in size (3–6 nm particles predominated) were shown to be uniformly distributed over the support surface. It was shown experimentally that the Pd catalyst was more active and selective at low temperature than the nickel catalyst to provide two-fold decrease in the concentration of trans-isomers in the hydrogenated fat.

Recently, it has been shown that the thermochemical cis→trans isomerization of azobenzenes is accelerated by a factor of more than 1000 by electronic coupling to a gold surface via a conjugated system with 11 bonds and a distance of 14 Å. The corresponding molecular architecture consists of a platform (triazatriangulenium (TATA)) which adsorbs on the gold surface, with an acetylene spacer standing upright, like a post in the middle of the platform and the azobenzene unit mounted on top. The rate acceleration is due to a very peculiar thermal singlet–triplet–singlet mechanism mediated by bulk gold. To investigate this mechanism further and to examine scope and limitation of the “spin-switch catalysis” we now prepared analogous diazocine systems. Diazocines, in contrast to azobenzenes, are stable in the cis-configuration. Upon irradiation with light of 405 nm the cis-configuration isomerizes to the trans-form, which slowly returns back to the stable cis-isomer. To investigate the thermal trans→cis isomerization as a function of the conjugation to the metal surface, we connected the acetylene spacer in meta (weak conjugation) and in para (strong conjugation) position. Both isomers form ordered monolayers on Au(111) surfaces.

A series of cis–trans isomers of cyclicparaphenylenediazenes (CPPDs) have been designed to explore their potential applications in solar thermal fuels and photoswitchable devices. In this work, three isomers of cis–trans-[3]CPPD, seven isomers of cis–trans-[4]CPPD, eleven isomers of cis–trans-[5]CPPD, and sixteen isomers of cis–trans-[6]CPPD have been proposed using density functional theory (DFT) at the B3LYP/6-31+G(d,p) level of theory. The stability of these CPPDs has been quantified by the homodesmotic reaction approach. Strain energies (SE) indicate that 3-cct, 4-ctct-anti, 5-cctct-anti, and 6-cttttc-anti are stable molecules in their respective CPPDs. The SE and heats of formation of cis–trans-CPPDs were also compared with those of all-cis-CPPDs and all-trans-CPPD isomers. The calculations suggest that cis–trans-CPPDs are more stable than all-cis and all-trans-CPPDs. The SE and also suggest that 3-cct, 4-ctct-anti, 5-cctct-anti, and 6-cttttc-anti are important candidates for laboratory test. The calculated highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO) energy gaps of cis–trans-CPPDs indicate that these oligomers are potential materials for the construction of solar cells. Time-dependent (TD) DFT calculations of CPPDs show a characteristic peak in the range of 450 nm to 600 nm, which is consistent with previous studies. The predicted structures, and thermochemical and electronic properties can be a good starting point for the synthesis of CPPD-based photoswitchable and solar fuel cell devices.

Biodiesel is a renewable fuel source comprising of fatty acid methyl esters (FAMEs). However, biodiesel (FAMEs) is susceptible to autoxidation. Therefore, structural modification of FAMEs through decreasing the number of double bonds (e.g., hydrogenation) or trans isomerization of original double bonds in the cis configuration, could improve the oxidative stability of FAMEs. In this work, the trans isomerization of carbon-carbon double bonds in unsaturated FAMEs obtained from edible oils has been successfully achieved using simple and safe p-toluenesulfinic acid as catalyst. And the effects of reaction time, temperature, catalyst loading, amount of water and antioxidants on the trans isomerization were investigated systematically. The results indicated that the amount of water (0–20 wt%) and antioxidants (

International audience; Microcin J25 is a ribosomal synthesized and post-translationally modified peptide (RiPP) characterized by a mechanically interlocked topology called the lasso fold. This structure provides microcin J25 a potent antimicrobial activity resulting from internalization via the siderophore receptor FhuA and further inhibition of the RNA polymerase. In the present work, nuclear magnetic resonance (NMR) and trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) were used to investigate the lasso structure of microcin J25. NMR experiments showed that the lasso peptide microcin J25 can adopt conformational states where Pro16 can be found in the cisand transorientations. The high-resolution mobility analysis, aided by site-directed mutagenesis ([P7A], [P16A], and [P7A/ P16A] variants), demonstrated that microcin J25 can adopt cis/cis-, cis/trans-, trans/cis-, and trans/trans-conformations at the Pro7 and Pro16 peptide bonds. It was also shown that interconversion between the conformers can occur as a function of the starting solvent conditions and ion heating (collision-induced activation, CIA) despite the lasso topology. Complementary to NMR findings, the cis-conformations at Pro7 were assigned using TIMS-MS. This study highlights the analytical power of TIMS-MS and site-directed mutagenesis for the study of biological systems with large micro-heterogeneity as a way to further increase our understanding of the receptorbinding dynamics and biological activity.

Propiolic acid (HCCCOOH, PA) was studied experimentally by infrared spectroscopy in a nitrogen matrix and by ab initio calculations. The vibrational spectra of the cis and trans monomers (O═C—O—H dihedral equal to 0 and 180°, respectively) were measured and assigned. The trans-PA monomer was produced by selective vibrational excitation of the cis-PA monomer molecules trapped in different matrix sites. Broadband in situ UV irradiation (λ > 235 nm) of matrix-isolated PA yielded as product the higher-energy trans conformer, with no other photoproducts being detected. Two cis–cis dimers were also identified in the matrixes and characterized structurally and vibrationally. trans-PA was found to decay back to cis-PA in the dark, by tunneling, and the different lifetimes of the higher-energy PA conformer resulting from pumping different matrix sites and different experimental conditions (using a filter blocking the higher-energy IR radiation of the spectrometer source and without using such a filter) were discussed.

Thermal cis-trans isomerization of azobenzene and azopyridine derivatives was studied. The impact of the structural features of azo derivatives on its isomerization kinetics being important for molecular switching materials was investigated experimentally and theoretically based on the density-functional theory (DFT). Eleven azo-dyes in which the phenyl rings were substituted in the para-position to N N– linkage were prepared. Additionally, their thermal properties were evaluated by thermogravimetric analysis and differential scanning calorimetry. DFT calculations were also used for optimization ground and transition state geometries, the density of states, electronic structures of studied azo-dyes. The kinetics of the dark-return cis to trans-form of azo-compounds was investigated after UV-irradiation. It was found that attaching hydroxyalkoxy-substituents to the azo-dyes structure retarding the photoisomerization process in comparison to the hydroxyl group. Moreover, dark-return cis to trans-isomer was ca. twice times faster for azopyridine derivatives than for their azobenzene analogues. The calculated rate constants were in qualitative agreement with the experimental values.

This work reported for the first time a systematic investigation on a BiOBr photocatalyzed oleic acid isomerization process in different (air, N2 and O2) atmospheres and proposed the cis–trans isomerization mechanism to effectively restrain the formation of trans fatty acids with deleterious effects on human health. The phase structures, optical properties, and morphologies of as-prepared BiOBr were characterized by XRD, UV-vis DRS, SEM and TEM. Besides, the photocatalyzed isomerization products over BiOBr in different atmospheres were analyzed with FT-IR and 1H NMR for comparison. The results demonstrate that there are significant differences in the photocatalytic isomerization process of oleic acid in different atmospheres, and especially the N2 atmosphere is the most favorable atmosphere, while the presence of O2 will inhibit the formation of elaidic acid. Moreover, density functional theory (DFT) was employed to calculate the charge density and energy difference of ground states between cis- and trans-isomers of oleic acid. Combining the theoretical and experimental findings, the radical cation and photo-induced h+ action mechanisms in the photocatalytic isomerization process were discussed and proposed. Our findings should provide new insights and basic data for understanding the photocatalytic isomerization of unsaturated fatty acids.

The performances of the M06-2X and ωB97X-D functionals with various basis sets as well as the double-hybrid DSD-PBEP86-D3BJ/cc-pVTZ level of theory with the implicit PCM and SMD solvation methods were assessed for the conformational preferences of Ac-Pro-NHMe in chloroform and water. The M06-2X/def2-TZVP//M06-2X/6-31+G(d) and DSD-PBEP86-D3BJ/cc-pVTZ//M06-2X/6-31+G(d) methods with PCM in chloroform and SMD in water exhibited the best performances for these conformational preferences consistent with experimental results in chloroform and water. As a further step in checking the applicability of these DFT methods, we have undertaken a study of the conformational preferences of Ac-Pro-OMe, Ac-X-OMe, and Ac-X-NHMe (X = Pro derivatives) in chloroform and/or water. Almost the same results were obtained at both levels of theory. The order of the distributions of puckerings depending on the trans and cis peptide bonds was different depending on the substitution position, the chirality, and the solvent polarity. The cis populations of the prolyl peptide bond for Ac-X-OMe and Ac-X-NHMe (X = Pro and its derivatives) were well predicted with RMSD < 6% in chloroform and water, compared with the experimental values. In addition, the calculated barriers ΔG‡c→t to the cis-to-trans isomerization of the prolyl peptide bond for Ac-Pro-NHMe, Ac-X-OMe (X = Pro, Hyp, Flp, and flp), and Ac-X-NHMe (X = 5-Mep, 5-Tbp, and 5-tbp) in chloroform and/or water were consistent with the experimental values within 1 kcal mol−1. Hence, the M06-2X/def2-TZVP//M06-2X/6-31+G(d) and DSD-PBEP86-D3BJ/cc-pVTZ//M06-2X/6-31+G(d) methods with PCM in chloroform and SMD in water appeared to be appropriate in predicting the conformational preferences and the cis–trans isomerization of the longer peptides containing Pro or Pro derivatives in chloroform and water.

The current work provides a study on the cis–trans isomerization behaviour of N-alkylated peptides decorated with phosphonate ester groups. A Ugi four-component reaction was chosen for the synthesis of N-alkylated peptides, where almost only the cis isomer was detected when the phosphonate ester group was incorporated as an amine component in the side chain. However, the phosphonate ester group inserted in the backbone, as an isocyanide component, leads preferably to the trans isomer of this kind of peptides. The diverse behaviour of cis–trans isomerization has been explained via spectroscopic nuclear magnetic resonance analysis and computational calculations.

Photolabile protecting groups offer synthetic routes with facile deprotection by photolysis, providing higher yields with less workup. Protecting groups producing only gaseous byproducts upon removal are particularly desirable as sustainable reagents. Cheletropic reactions provide just this combination of photocleavable groups with gaseous byproducts. However, only few protecting groups for cheletropic reactions have been described and little is known about their photochemistry and associated stereochemistry. Here we show that the sulfolene protecting group, used for diene protection and functionalization, can be photochemically removed. First, using TD-DFT, we conclude that the photochemical ring-opening occurs conrotatorily in a concerted process, consistent with the Woodward-Hoffmann rules. Experimentally, we demonstrate that this process can be photoinitiated by radiation between 180 and 300 nm and confirm the proposed stereochemistry in solution. Using time-resolved photoelectron spectroscopy, we determine that the first steps in the photochemical ring-opening of sulfolene occur on ultrafast timescales (≤84 fs), consistent with a fully concerted process. Our findings expand applications of the sulfolene protecting group and promise an easy strategy for control of cis-trans isomerization.

A new methodology for the pH-triggered degradation of polymers or for the release of drugs under visible light irradiation based on the cyclization of ortho-hydroxy-cinnamates (oHC) to coumarins is described. The key oHC structural motif can be readily incorporated into the rational design of novel photocleavable polymers via click chemistry. This main-chain moiety undergoes a fast photocleavage when irradiated with 455 nm light provided that a suitable base is added. A series of polyethylene glycol-alt-ortho-hydroxy cinnamate (polyethylene glycol (PEG)n-alt-oHC)-based polymers are synthesized and the time-dependent visible-light initiated cleavage of the photoactive monomer and polymer is investigated in solution by a variety of spectroscopic and chromatographic techniques. The photo-degradation behavior of the water-soluble poly(PEG2000-alt-oHC) is investigated within a broad pH range (pH = 2.1–11.8), demonstrating fast degradation at pH 11.8, while the stability of the polymer is greatly enhanced at pH 2.1. Moreover, the neat polymer shows long-term stability under daylight conditions, thus allowing its storage without special precautions. In addition, two water-soluble PEG-based drug-carrier molecules (mPEG2000-oHC-benzhydrol/phenol) are synthesized and used for drug delivery studies, monitoring the process by UV–vis spectroscopy in an ON/OFF intermittent manner.

Synthesis and structural and photophysical characterization of platinum dihalogenide complexes formulated as [PtHal2L2], where Hal = Cl and I, with different 10-(aryl)phenoxarsine ligands such as 10-(p-chlorophenyl)phenoxarsine, 10-(p-tolyl)phenoxarsine, and 10-(phenyl)phenoxarsine are reported. The structures of complexes were determined by NMR spectroscopy, mass spectrometry, and X-ray analysis. Cis/trans isomerism of the complexes in solution was studied by NMR spectroscopy. In the solid state, under UV irradiation, platinum diiodide trans complexes exhibit an intense orange-red emission, which was attributed to a metal halide-centered triplet state. The UV/vis absorption and emission properties were studied and rationalized by density functional theory (DFT) and time-dependent DFT calculations.

Azobenzene-containing polymers, also known as azopolymers, are a wide group of materials interesting from the point of view of their potential utilization in the fields of photonics, optoelectronics, and biology as cell culture substrates and biomaterials. They are utilized as thin films on the substrates or free-standing foils. This class of polymers contains light-sensitive linkages -N=N- in their chemical structure. Azobenzene derivatives occur in the form of two isomers: an energetically stable trans-isomer and a metastable cis-isomer. Under the irradiation of azochromophores with a specific wavelength, the reversible trans–cis–trans isomerization is observed. The stability of cis-isomer in the solid state is crucial in some azopolymers applications, which can be tailored by changing the azochromophore structure, kinds of azo-molecules incorporation to the polymer backbone (covalent or non-covalent), and polymer molar masses. The knowledge about the influence of mentioned factors supports designing azopolymers with desired properties adjusted to a particular device. This paper is devoted to showing the impact of azopolyimide structure (main chain, side chain or T-type polymers, and “guest–host” systems) on trans–cis and cis–trans isomerization process in the solid state based on literature review and investigations published in our previous works.

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) specifically binds and isomerizes the phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif, which leads to changes in protein conformation and function. Pin1 is widely overexpressed in cancers and plays an important role in tumorigenesis. Mounting evidence has revealed that targeting Pin1 is a potential therapeutic approach for various cancers by inhibiting cell proliferation, reducing metastasis, and maintaining genome stability. In this review, we summarize the underlying mechanisms of Pin1-mediated upregulation of oncogenes and downregulation of tumor suppressors in cancer development. Furthermore, we also discuss the multiple roles of Pin1 in cancer hallmarks and examine Pin1 as a desirable pharmaceutical target for cancer therapy. We also summarize the recent progress of Pin1-targeted small-molecule compounds for anticancer activity.

Producción Científica, The kinetics of the transmetalation reaction between trans-[PdCl(C6Cl2F3)(PPh3)2] and [ZnMeCl(THF)2] shows a complex dependence on [PPh3] for the rate of formation of different reaction products: cis and trans-[Pd(C6Cl2F3)Me(PPh3)2], trans-[PdClMe(PPh3)] (which further reacts with [ZnClMe(THF)2]), and [Zn(C6Cl2F3)Cl(THF)2]. To better understand the system the reactions between cis and trans-[Pd(C6Cl2F3)Me(PPh3)2] and [ZnCl2(THF)2] (the retro-transmetalation reactions) and their kinetic dependence on [PPh3] were studied. These reactions lead to the formation of trans-[PdClMe(PPh3)] and [Zn(C6Cl2F3)Cl(THF)2] as main products. Additionally, the experiments show that the isomerization of cis to trans-[Pd(C6Cl2F3)Me(PPh3)2] is catalyzed by [ZnCl2(THF)2]. In this catalyzed isomerization the concentration of PPh3 is involved in two ways: It modulates the concentration of the organozinc [Zn(C6Cl2F3)Cl(THF)2], and also it shifts a ligand substitution equilibrium in the palladium complex, producing an anomalous dependence of the reaction rate on the concentration of triphenylphosphine., Ministerio de Economía, Industria y Competitividad (project CTQ2016-80913-P), Ministerio de Ciencia e Innovación (project PID2019-111406GB-100), Junta de Castilla y León (projects VA051P17 and VA062G18)

Falling outside of Lipinski's rule of five, macrocyclic drugs have accessed unique binding sites of their target receptors unreachable by traditional small molecules. Cyclosporin(e) A (CycA), an extensively studied macrocyclic natural product, is an immunosuppressant with undesirable side effects such as electrolytic imbalances. In this work, a comprehensive view on the conformational landscape of CycA, its interactions with Ca2+, and host-guest interactions with cyclophilin A (CypA) is reported through exhaustive analyses that combine ion-mobility spectrometry-mass spectrometry (IMS-MS), nuclear magnetic resonance (NMR) spectroscopy, distance-geometry modeling, and NMR-driven molecular dynamics. Our IMS-MS data show that CycA can adopt extremely compact conformations with significantly smaller collisional cross sections than the closed conformation observed in CDCl3. To adopt these conformations, the macrocyclic ring has to twist and bend via cis-trans isomerization of backbone amides, and thus, we termed this family of structures the 'bent' conformation. Furthermore, NMR measurements indicate that the closed conformation exists at 19% in CD3OD/H2O and 55% in CD3CN. However, upon interacting with Ca2+, in addition to the bent and previously reported closed conformations of free CycA, the CycA:Ca2+ complex is open and has all-trans peptide bonds. Previous NMR studies using calcium perchlorate reported only the closed conformation of CycA (which contains one cis peptide bond). Here, calcium chloride, a more biologically relevant salt, was used, and interestingly, it helps converting the cis-MeLeu9-MeLeu10 peptide bond into a trans bond. Last, we were able to capture the native binding of CycA and CypA to give forth evidence that IMS-MS is able to probe the solution-phase structures of the complexes and that the Ca2+:CycA complex may play an essential role in the binding of CycA to CypA.

Photochemical reactions are being increasingly used to construct complex molecular architectures with mild and straightforward reaction conditions. Computational techniques are increasingly important to understand the reactivities and chemoselectivities of photochemical isomerization reactions because they offer molecular bonding information along the excited-state(s) of photodynamics. These photodynamics simulations are resource-intensive and are typically limited to 1–10 picoseconds and 1,000 trajectories due to high computational cost. Most organic photochemical reactions have excited-state lifetimes exceeding 1 picosecond, which places them outside possible computational studies. Westermeyr et al. demonstrated that a machine learning approach could significantly lengthen photodynamics simulation times for a model system, methylenimmonium cation (CH2NH2+).We have developed a Python-based code, Python Rapid Artificial Intelligence Ab Initio Molecular Dynamics (PyRAI2MD), to accomplish the unprecedented 10 ns cis-trans photodynamics of trans-hexafluoro-2-butene (CF3–CH=CH–CF3) in 3.5 days. The same simulation would take approximately 58 years with ground-truth multiconfigurational dynamics. We proposed an innovative scheme combining Wigner sampling, geometrical interpolations, and short-time quantum chemical trajectories to effectively sample the initial data, facilitating the adaptive sampling to generate an informative and data-efficient training set with 6,232 data points. Our neural networks achieved chemical accuracy (mean absolute error of 0.032 eV). Our 4,814 trajectories reproduced the S1 half-life (60.5 fs), the photochemical product ratio (trans: cis = 2.3: 1), and autonomously discovered a pathway towards a carbene. The neural networks have also shown the capability of generalizing the full potential energy surface with chemically incomplete data (trans → cis but not cis → trans pathways) that may offer future automated photochemical reaction discoveries.

Free-radical-mediated processes, such as peroxidation, isomerization and hydrogenation affecting fatty acid integrity and biological functions, have a trans-disciplinary relevance. Cardiolipins (CL, (1,3-diphosphatidyl-sn-glycerol)) and tetra-linoleoyl-CL are complex phospholipids, exclusively present in the Inner Mitochondrial Membrane (IMM) lipids, where they maintain membrane integrity and regulate enzyme functionalities. Peroxidation pathways and fatty acid remodeling are known causes of mitochondrial disfunctions and pathologies, including cancer. Free-radical-mediated isomerization with the change of the cis CL into geometrical trans isomers is an unknown process with possible consequences on the supramolecular membrane lipid organization. Here, the formation of mono-trans CL (MT-CL) and other trans CL isomers (T-CL) is reported using CL from bovine heart mitochondria and thiyl radicals generated by UV-photolysis from 2-mercaptoethanol. Analytical approaches for CL isomer separation and identification via 1H/13C NMR are provided, together with the chemical study of CL derivatization to fatty acid methyl esters (FAME), useful for lipidomics and metabolomics research. Kinetics information of the radical chain isomerization process was obtained using &gamma, irradiation conditions. The CL isomerization affected the structural organization of membranes, as tested by the reduction in unilamellar liposome diameter, and accompanied the well-known process of oxidative consumption induced by Fenton reagents. These results highlight a potential new molecular modification pathway of mitochondrial lipids with wide applications to membrane functions and biological consequences.

Since the one-way cis → trans isomerization was discovered in several types of arylethenes, interest in the photochemical cis-trans isomerization has continued to grow in recent years [1-11]. Conventional two-way isomerization and highly selective photochemical cis-trans isomerization can take place on the singlet excited state as well as in the triplet excited state [11-15]. In this chapter, a concept for various types of cis-trans isomerization in the triplet state is described, mainly from the viewpoints of the modes of isomerization and the difference in potential energy surfaces of cis-trans isomerization.

A series of Co(II), Ni(II) and Cu(II) coordination polymers and dinuclear metallocycles containing 4-aminopyridine (4-ampy) and benzenedicarboxylate ligands, {[M(4-ampy)2(1,4-BDC)]&middot, H2O&middot, CH3CH2OH}n (M = Ni, 1a, Co, 1b, 1,4-H2BDC = benzene-1,4-dicarboxylic acid), {[Ni2(4-ampy)4(1,3-BDC)2]&middot, CH3CH2OH}n (1,3-H2BDC = benzene-1,3-dicarboxylic acid), 2, [M2(4-ampy)4(1,2-BDC)2] (M = Ni, 3a, Co, 3b, 1,2-H2BDC = benzene-1,2-dicarboxylic acid), [Co(4-ampy)2(1,3-BDC)]n, 4, {[Cu(4-ampy)2(1,4-BDC)] CH3CH2OH}n, 5a, and {[Cu(4-ampy)2(1,4-BDC)]&middot, H2O}n, 5b&middot, H2O, are reported, which were hydrothermally prepared and structurally characterized by using single crystal X-ray diffraction. Complexes 1a and 1b are isomorphous 1D zigzag chains, while 2 displays a concave&ndash, convex chain and 3a and 3b are dinuclear metallocycles that differ in the boding modes of the 1,2-BDC2&minus, ligands, forming a 3D and a 2D supramolecular structures with the pcu and sql topologies, respectively. Complex 4 exhibit a 1D helical chain and complexes 5a and 5b&middot, H2O are 1D linear and zigzag chains, in which the Cu2-1,4-BDC2&minus, units adopt the cis and trans configurations, respectively. A novel irreversible structural transformation due to cis&rarr, trans isomerization of the Cu2-1,4-BDC2&minus, units was observed in 5b&sdot, H2O and 5a upon water adsorption of the desolvated product of 5b&middot, H2O.

The rovibrational spectra of metaphosphorous acid, HOPO, and its deuterated isotopologue have been studied by vibrational configuration interaction calculations, relying on the internal coordinate path Hamiltonian and the Watson Hamiltonian. Tunneling effects for the overtones of the torsional mode, which gives rise to the cis-trans isomerization, and its rovibrational transitions have been investigated in detail. Due to strong matrix effects, comparison with experimental data is hindered, and thus, the calculations provide accurate estimates for the fundamental modes of these species.

Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) is an evolutionally conserved and unique enzyme that specifically catalyzes the cis-trans isomerization of phosphorylated serine/threonine-proline (pSer/Thr-Pro) motif and, subsequently, induces the conformational change of its substrates. Mounting evidence has demonstrated that Pin1 is widely overexpressed and/or overactivated in cancer, exerting a critical influence on tumor initiation and progression via regulation of the biological activity, protein degradation, or nucleus-cytoplasmic distribution of its substrates. Moreover, Pin1 participates in the cancer hallmarks through activating some oncogenes and growth enhancers, or inactivating some tumor suppressors and growth inhibitors, suggesting that Pin1 could be an attractive target for cancer therapy. In this review, we summarize the findings on the dysregulation, mechanisms, and biological functions of Pin1 in cancer cells, and also discuss the significance and potential applications of Pin1 dysregulation in human cancer.

Phosphorylation-dependent peptidyl-prolyl cis-trans isomerization plays key roles in cell cycle progression, the pathogenesis of cancer, and age-related neurodegeneration. Most of our knowledge about the role of phosphorylation-dependent peptidyl-prolyl cis-trans isomerization and the enzyme catalyzing this reaction, the peptidyl-prolyl isomerase (Pin1), is largely limited to proteins not present in neurons. Only a handful of examples have shown that phosphorylation-dependent peptidyl-prolyl cis-trans isomerization, Pin1 binding, or Pin1-mediated peptidyl-prolyl cis-trans isomerization regulate proteins present at excitatory synapses. In this work, I confirm previous findings showing that Pin1 binds postsynaptic density protein-95 (PSD-95) and identify an alternative binding site in the phosphorylated N-terminus of the PSD-95. Pin1 associates via its WW domain with phosphorylated threonine (T19) and serine (S25) in the N-terminus domain of PSD-95 and this association alters the local conformation of PSD-95. Most importantly, I show that proline-directed phosphorylation of the N-terminus domain of PSD-95 alters the local conformation of this region. Therefore, proline-directed phosphorylation of the N-terminus of PSD-95, Pin1 association, and peptidyl-prolyl cis-trans isomerization may all play a role in excitatory synaptic function and synapse development.

The post-synaptic density protein 95 (PSD-95) plays a central role in excitatory synapse development and synaptic plasticity. Phosphorylation of the N-terminus of PSD-95 at threonine 19 (T19) and serine 25 (S25) decreases PSD-95 stability at synapses; however, a molecular mechanism linking PSD-95 phosphorylation to altered synaptic stability is lacking. Here, we show that phosphorylation of T19/S25 recruits the phosphorylation-dependent peptidyl-prolyl cis–trans isomerase (Pin1) and reduces the palmitoylation of Cysteine 3 and Cysteine 5 in PSD-95. This reduction in PSD-95 palmitoylation accounts for the observed loss in the number of dendritic PSD-95 clusters, the increased AMPAR mobility, and the decreased number of functional excitatory synapses. We find the effects of Pin1 overexpression were all rescued by manipulations aimed at increasing the levels of PSD-95 palmitoylation. Therefore, Pin1 is a key signaling molecule that regulates the stability of excitatory synapses and may participate in the destabilization of PSD-95 following the induction of synaptic plasticity.

The effect of elevated temperature (44 °C) and ultraviolet (UV) radiation on molecular structure of linoleic acid (LA) was studied by Attenuated Total Reflection Infrared (ATR-IR) spectroscopy. To obtain more detailed information on molecular mechanism of these changes we applied moving-window analysis and two-dimensional correlation spectroscopy (2DCOS). Analysis of the time-dependent ATR-IR spectra of LA before and after UV irradiation revealed the structural changes in molecules of LA. The extent of these changes was significantly higher after an application of UV radiation. During 24 h experiment temperature was constant, therefore the spectral changes result from relatively slow processes (and requiring more energy), e.g. cis/trans isomerization, disruption of the C=C double bonds and partial breaking of hydrogen bonds in the cyclic dimers. As a side effect of these structural changes one can observe variations in the orientation of the chains. It is of note that the methyl and methylene groups reveal slightly different behaviour.

Azobenzene polymers have been the subject of intensive research due to their unique and unexpected properties that allow various applications. Many interesting properties of azopolymers are caused by or related with photoinduced trans–cis isomerization of azo chromophores, where the azo group undergoes a transition from the lower energy trans-form to less stable cis-form through the excited states. One of the most investigated properties of the azobenzene polymers is the capability to generate surface relief gratings (SRG). The effort to understand the SRG formation process remains unclear until now in defiance to many explorations. This chapter presents a study concerning the azopolymer response to the pulse laser irradiation, in the context of the SRG inscription.

The oncogenic transcription factor B-Myb is an essential regulator of late cell cycle genes whose activation by phosphorylation is still poorly understood. We describe a stepwise phosphorylation mechanism of B-Myb, which involves sequential phosphorylations mediated by cyclin-dependent kinase (Cdk) and Polo-like kinase 1 (Plk1) and Pin1-facilitated peptidyl-prolyl cis/trans isomerization. Our data suggest a model in which initial Cdk-dependent phosphorylation of B-Myb enables subsequent Pin1 binding and Pin1-induced conformational changes of B-Myb. This, in turn, initiates further phosphorylation of Cdk-phosphosites, enabling Plk1 docking and subsequent Plk1-mediated phosphorylation of B-Myb to finally allow B-Myb to stimulate transcription of late cell cycle genes. Our observations reveal novel mechanistic hierarchies of B-Myb phosphorylation and activation and uncover regulatory principles that might also apply to other Myb family members. Strikingly, overexpression of B-Myb and of factors mediating its activation strongly correlates with adverse prognoses for tumor patients, emphasizing B-Myb's role in tumorigenesis.

Four new complexes of copper(II) with D-allo, L- isoleucine were prepared by solution and mechanochemical synthesis: three complexes of aqua cis isomers, cis-[Cu(D-allo-Ile)2(H2O)] (2), cis-[Cu(D-allo-Ile)(L-Ile)(H2O)]0.7[Cu(L- Ile)2(H2O)]0.3 (3), cis-[Cu(D-allo- Ile)2(H2O)]0.75[Cu(D-allo-Ile)(L-Ile)(H2O)]0.25 (4), and anhydrous trans-[Cu(D-allo-Ile)(L-Ile)] (5). The previously characterized orthorhombic cis-[Cu(L-Ile)2(H2O)] (1a) cocrystallized with 3 and either 2 or 4, depending on the synthetic conditions. In 2, a disorder of the side chain was found, while 3 and 4 had a rare positional disorder of two diastereomers, namely, D-allo- Ile and L-Ile, resulting in two positions of the Cα chiral center in their crystal structures. The complexes were analyzed by X-ray diffraction methods, solid-state NMR spectroscopy, and density functional theory calculated 13C and 1H Fermi contact shifts. Room-temperature solid- state cis-to-trans isomerization of Cu(D-allo- Ile)(L-Ile) occurred by liquid-assisted grinding (LAG) of 3 with methanol, by aging in methanol vapor, and by soaking 3 in methanol. The latter was a fast process. The isomerization also happened in the 140–160 °C temperature interval. Reverse trans-to-cis isomerization occurred by LAG of 5 with water and very slowly by aging in water vapor. Low activation energy for the Cu(D- allo-Ile)(L-Ile) cis–trans isomerization in the solid state could explain why subtle changes in the experimental conditions affected the final product.

The synthesis and characterization of dicarbonyl Fe(II) PNP pincer complexes of the type cis-[Fe(PNP-iPr)(CO)2(X)]+ (X = Br, Cl) is described. These complexes are slowly formed when solutions of complexes trans-[Fe(PNP-iPr)(CO)2(X)]+ are kept in the dark for 9 h (X = Br) and 3 days (X = Cl). Upon exposure to visible light these complexes isomerize to the respective trans-dicarbonyl complexes within a few hours. The visible-light reaction seems to involve reversible CO dissociation. The isomerization can be repeated serval times. A mechanistic rationale for this isomerization process is established by means of DFT calculations.

The energy barrier for cis-to-trans isomerization is among the key parameters for photoswitchable molecules such as azobenzene. Recently, we introduced a well-defined model system based on thin films of crystalline, nanoporous metal-organic frameworks, MOFs. The system enables the precise investigation of the thermal cis-to-trans relaxation of virtually isolated azobenzene pendant groups by means of infrared spectroscopy in vacuum. Here, this approach is extended by using localized surface plasmon resonance spectroscopy. This simple and relatively inexpensive setup enables the investigation of the thermal cis-to-trans isomerization in different environments, here in argon gas or in liquid butanediol. The energy barrier for the cis-to-trans-relaxation in argon, 1.17±0.20eV, is identical to the barrier in vacuum, while the energy barrier in liquid butanediol is slightly larger, 1.26±0.15eV.