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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.

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.

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...

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.

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.

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 (

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.

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.

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)

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.

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.

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 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.

This research was based on the quantum chemical calculations of a set of valid photoswitches of azobenzene compounds, with the aim of describing their thermal isomerization. The influences of familiar fluorine substitution and additional electron-donating groups (EDGs) and electron-withdrawing groups (EWGs) on the para-position were also systematically studied. The results show that the presence of fluorine in different ortho-positions has a distinct effect on the molecular orbital distribution of the E isomer, which realizes the purpose of splitting the n → π* transition between the E and Z isomers. On this basis, further para-substitution can allow tunability on the order of the energy level to the molecular orbitals through their influence on the conjugation pattern of the compound. It is the modification of the substituent on these positions that allows the photoisomerization to proceed under visible wavelength light surroundings. The thermal Z → E isomerization mechanism has also been analyzed, and a detailed comparison of these compounds has been made with respect to the thermal half-life τ1/2, and the rate constants kZ–E. The results reveal that isomerization is thought to be a process of globally structural change, during which the effect of the substituents is determined by the extent of their influence on the conjugated system.

Besides the photochromism isomerization, scientists are likely to focus more and more on the influence on the electrochemical reduction conditions of the azobenzene isomerization process. Diverse azobenzene compounds were chosen to study the behavior of their trans and cis isomers upon electrochemical reduction. Hence, thermal reaction mechanisms for the neutral, cationic and anionic azobenzene derivatives isomerization with a wide variety of electron-donating and electron-withdrawing groups in the para-position of the benzene ring in ground state have been systematically examined applying the density functional theory method. Some prominent changes in structure, energy barrier and reaction rate arose from charge changes of azobenzenes have been detected and interpreted in terms of the strengths of substituents, the polarity of solvents and charge effect. Our findings indicate that the radical anion of the cis isomer can isomerize to the corresponding trans configured counterpart rapidly with a tremendously enhanced rate and obvious decreased energy barriers with respect to the neutral species as the distribution of the electron density changed, signifying that the metastable isomer of a photoswitch is able to isomerize to the more stable one catalytically upon reduction and the charge effect has obvious influence on the reaction mechanism.

The trans-configured square-planar complex of dichloropalladium and chiral monodentate phosphine ligands forms self-complementary dimers through 16 hydrogen bonded amides and π-π stacking in chlorinated solvents. The self-assembly is controlled by cis-trans isomerisation of the metal center, where the trans-configuration governs the dimer formation.

2-Ethylhexyl methoxycinnamate (EHMC) is one of the most used ultraviolet filters in personal care products. It undergoes cis/trans isomerization in sunlight, and there is limited toxicological understanding of the effects of the cis-isomer. It is known that two geometric isomers of one compound can have different physico-chemical properties and effects. However, there are no studies focusing on toxicokinetics of EHMC isomerization products to compare their potential difference in dermal exposure to cis-EHMC and trans-EHMC due to the difference in their dermatotoxicokinetics. In this study, dermal absorption of the parental trans-EHMC and its cis isomer was studied. A commercially available sunscreen lotion containing trans-EHMC and spiked with laboratory-prepared cis-EHMC was locally applied on the forearm skin of two volunteers. After 8 h of skin exposure, the stratum corneum (SC) layer was removed by tape stripping. The removed thickness of the SC was determined spectrophotometrically using a total protein assay. The concentration of both isomers in the removed SC was measured by HPLC-DAD. A new diffusion and permeability coefficient of both EHMC isomers in SC were determined by Fick's second law of diffusion in vivo. The difference in dermatotoxicokinetic parameters between the two isomers was not statistically significant. However, separate toxicological studies of isomeric forms and the determination of their dermatotoxicokinetic parameters are crucial for refinement of human risk assessment.

Quantum chemical calculations of a potent class of photoswitches acylhydrazones have been carried out with the goal to describe their thermal cis → trans isomerization. The effects of substituents, in particular their number, position and nature of the substituents (electron donating/withdrawing groups (EDGs/EWGs)), on activation energies incorporating solvent effects have been systematically researched with the ultimate goal to illuminate the isomerization process. Our results show that most parameters are highly dependent on the substitution pattern on the crucial positions (R1 and R2 position) of the backbone fragment, which in turn has a significant impact on the absorption spectra, the energy levels of molecular orbitals, the transition properties for the trans/cis isomers, the half-lives τ1/2 and the rate constants for the thermal cis → trans isomerization of the compounds. In summary, both relative strength of the donor/accept groups and solvent polarity have significant impact on the electric properties. Finally, the nature of the transition state(s) and its dependence on substituents and the environment are discussed. An ingenious approach to the construction of reaction path was realized, and energy barriers were determined from two-dimensional potential energy surfaces of the ground states.

Cis/trans isomerization of 2°-amide bonds is a key step in a wide range of important processes. Here we present a theoretical assessment of cis/trans isomerization of 2°-amide bonds using B3LYP density functional methods, describing two reaction paths and corresponding geometry changes during isomerization of N-methylacetamide (NMA) and glycylglycine methyl ester (GGMe). The isomerization begins via a common path, as the extended π-bonding of the amide bond maintains approximate planarity of the O-C-N-H dihedral angle, with only gradually increasing pyramidalization of the nitrogen atom, until a bifurcation point is reached. Both subsequent paths comprise two phases, an "ω phase" (characterized by a major change in C-C-N-C dihedral) and a "θ phase" (characterized by major change in O-C-N-H dihedral), with two distinct transition states. The θ phase involves inversion of the pyramidal amide-nitrogen geometry. Both reaction paths converge at another bifurcation point near the opposite geometry. Studies on the larger GGMe show in addition that the multiple additional rotamers do not change the qualitative properties of the isomerization, but do affect the energies of the differing transition states. These detailed results provide significant new insights into cis/trans isomerization paths in 2°-amides, and serve as a basis for theoretical studies on larger peptidic systems.

Pyridylethenyl-substituted N-confused porphyrins (NCPs) were synthesized, and their cis–trans isomerization was studied. Among four possible isomers, trans-3H and cis-2H types of structures, of which aromaticity and absorption/emission properties differ largely, were isolated. The cis-isomer was largely stabilized by the intramolecular hydrogen bonding between the pyrrolic-NH and the pyridinic-N in the vicinity. The thermal cis–trans isomerization proceeded even at 30 °C, which was significantly accelerated by the pyridine added to the system. The kinetic studies revealed that the isomerization reaction was second-order and the activation energy of the thermal isomerization from cis to trans isomer was ΔG0⧧cis→trans = 35.7 kcal/mol at 298 K, which is significantly smaller than that of Ni complex (42.3 kcal/mol). An intermolecular proton transfer induced cis–trans isomerization mechanism was proposed.

Excited-state intramolecular proton transfer (ESIPT) dynamics of the amino-type hydrogen-bonding compound 2-(2′-aminophenyl)benzothiazole (PBT-NH2) as well as its two derivatives 2-(5′-cyano-2′-aminophenyl)benzothiazole (CN-PBT-NH2) and 2-(5′-cyano-2′-tosylaminophenyl)benzothiazole (CN-PBT-NHTs) were studied by the time-dependent density functional theory (TD-DFT) approach with the B3LYP density functional, and their absorption and emission spectra were also explored at the same level of theory. A good agreement is observed between the theoretical simulations and experimental spectra, indicating that the present calculations are reasonably reliable. In addition, it is also found that the energy barriers of the first excited singlet state of the three targeted molecules along the ESIPT reaction are computed to be 0.38, 0.34 and 0.12 eV, respectively, showing the trend of gradual decrease, which implies that the introduction of the electron-withdrawing cyano or tosyl group can facilitate the occurrence of the ESIPT reaction of these amino-type H-bonding systems. Following the ESIPT, both CN-PBT-NH2 and CN-PBT-NHTs dye molecules can undergo the cis-trans isomerization reactions in the ground-state and excited-state potential energy curves along the C2-C3 bond between benzothiazole and phenyl moieties, where the energy barriers of the trans-tautomer → cis-tautomer isomerizations in the ground states are calculated to be 0.83 and 0.34 eV, respectively. According to our calculations, it is plausible that there may exist the long-lived trans-tautomer species in the ground states of CN-PBT-NH2 and CN-PBT-NHTs.

The effects of isosteric substitutions of the peptide CO group by CS and CSe on the conformational preference and prolyl cis–trans isomerization of Ac-Pro-NHMe and Ac-Ala-Pro-NHMe in water were studied using DFT methods. The isosteric replacement of a peptide bond resulted in changes in the preferences of the backbone conformation and puckering of the proline residue within both peptides depending on the substituent and its position (i.e., at the N- or C-termini). The polyproline II conformers with up puckering were highly populated in water for both Ac-ψ[CX-NH]Pro-NHMe and Ac-Ala-ψ[CX-NH]Pro-NHMe (X = O, S, and Se), although these peptides exist as ensembles of various conformers. For both peptides, the CX and C–N bond lengths became longer and shorter, respectively, in the order X = O, S, and Se, which is consistent with the values of the X-ray structures of the peptides. The isosteric substitutions at the N-terminus reduced the prolyl cis population in the order O < S < Se for Ac-Pro-NHMe, whereas there was a decrease and an increase in the cis population for Ac-Ala-Pro-NHMe with CS and CSe, respectively. The rotational barriers to the prolyl cis–trans isomerization of Ac-Pro-NHMe and Ac-Ala-Pro-NHMe increased with the isosteric replacement in the order O < S < Se. The calculated changes in the cis population and rotational barriers are reasonably consistent with the observed results of the relevant peptides. The strength of the nN → π*CX interaction for the preferred trans conformer relative to the transition state and the difference in the overlap of the C–N bond for the two conformers are consistent with prolyl rotational barriers in the order O < S < Se. The results for isosterically substituted Ac-Pro-NHMe and Ac-Ala-Pro-NHMe reported here are expected to be useful for understanding the conformational preferences and cis–trans isomerization of other proline-containing peptides with CS and CSe groups in the peptide backbone.

Light exposure of a monoclonal antibody formulation containing polysorbate 80 (PS80) leads to cis/trans isomerization of monounsaturated and polyunsaturated fatty acids. This cis/trans isomerization was monitored by positive electrospray ionization mass spectrometry of intact PS80 components as well as by negative ion electrospray ionization mass spectrometry analysis of free fatty acids generated via esterase-catalyzed hydrolysis. The light-induced cis/trans isomerization of unsaturated fatty acids in PS80 required the presence of the monoclonal antibody, or, at a minimum (for mechanistic studies), a combination of N-acetyltryptophan amide and glutathione disulfide, suggesting the involvement of thiyl radicals generated by photoinduced electron transfer from Trp to the disulfide. Product analysis confirmed the conversion of PS80-bound oleic acid to elaidic acid; furthermore, together with linoleic acid, we detected conjugated linoleic acids in PS80, which underwent light-induced cis/trans isomerization.

Proline is often found as a turn inducer in peptide or protein domains. Exploitation of its restricted conformational freedom led to the development of the d-Pro-l-Pro (corresponding to (R)-Pro–(S)-Pro) segment as a “templating” unit, frequently used in the design of β-hairpin peptidomimetics, in which conformational stability is, however, inherently linked to the cis–trans isomerization of the prolyl amide bonds. In this context, the stereoelectronic properties of the CF 3 group can aid in conformational control. Herein, the impact of α-trifluoromethylated proline analogues is examined for the design of enhanced β-turn inducers. A theoretical conformational study permitted the dipeptide (R)-Pro–(R)-TfmOxa (TfmOxa: 2-trifluoromethyloxazolidine-2-carboxylic acid) to be selected as a template with an increased trans–cis rotational energy barrier. NMR spectroscopic analysis of the Ac-(R)-Pro–(R)-TfmOxa–(S)-Val-OtBu β-turn model, obtained through an original synthetic pathway, validated the prevalence of a major trans–trans conformer and indicated the presence of an internal hydrogen bond. Altogether, it was shown that the (R)-Pro–(R)-TfmOxa template fulfilled all crucial β-turn-inducer criteria.

Arylazopyrazoles show significant potential as next‐generation photoswitches, in particular because of the high thermal stability of their Z‐isomers. Herein we investigate the potential to perform Z−E isomer chemical switching of arylazopyrazoles using acid. We show that acid‐accelerated isomerisation allows for robust Z−E switching using mild acids and opens up the possibility to use light‐acid cycles to near quantitatively and reversibly switch the arylazopyrazoles at room temperature. We attribute the chemical switching to azonium formation, facilitated by mesomeric stabilisation by the pyrazole ring. Coupled with their exceptionally long Z‐isomer half‐lives, we believe our study may open up a wider array of functional opportunities for the arylazopyrazoles.

International audience; Fluorinated proline derivatives have found diverse applications in areas ranging from medicinal chemistry over structural biochemistry to organocatalysis. Depending on the stereochemistry of monofluorination at the proline 3- or 4-position, different effects on the conformational properties of proline (ring pucker, cis/ trans isomerization) are introduced. With fluorination at both 3- and 4-positions, matching or mismatching effects can occur depending on the relative stereochemistry. Here we report, in full, the syntheses and conformational properties of three out of the four possible 3,4-difluoro-l-proline diastereoisomers. The yet unreported conformational properties are described for (3 S,4 S)- and (3 R,4 R)-difluoro-l-proline, which are shown to bias ring pucker and cis/ trans ratios on the same order of magnitude as their respective monofluorinated progenitors, although with significantly faster amide cis/ trans isomerization rates. The reported analogues thus expand the scope of available fluorinated proline analogues as tools to tailor proline's distinct conformational and dynamical properties, allowing for the interrogation of its role in, for instance, protein stability or folding.

In this study, a novel trans-(1E,2E)-benzil-O,O-dimethylsulfonyl dioxime (BDMDO) monomer was prepared via a one-step dehydrochlorination reaction. BDMDO was characterized by 1H and 13C NMR, UV–Vis, and FT-IR spectroscopies, CHN elemental analysis, mass spectrometry, energy-dispersive X-ray spectroscopy, and TGA. According to the X-ray diffraction data, the BDMDO crystal structure was solved as a trans-isomer dioxime. The lattice structure was stabilized by two types of H-bonds and a sufficient number of interesting non-covalent supramolecular interactions such as the C H⋯H C bonds. Molecular electrostatic potential measurements and Hirschfeld surface analysis were performed to understand these interaction modes. The cis–trans isomerization in BDMDO as well as the structural, vibrational, NMR, highest occupied molecular orbital/lowest unoccupied molecular orbital bandgap, density of states, and electronic properties were computed by the density functional theory and subsequently compared with available experimental 1H and 13C NMR, UV–Vis, and FT-IR spectral data. The thermogravimetric/derivative thermogravimetric behavior of BDMDO was determined experimentally under an open-room atmosphere.

An ion mobility spectrometer (IMS) with an electrospray ion source is used to investigate photo and thermal isomerization of photoactive molecules in the electrospray syringe. A light emitting diode adjacent to the syringe establishes a photostationary state that relaxes thermally toward the more stable isomer once illumination ceases. The arrangement is demonstrated by measuring Z–E thermal isomerization rates for several azoheteroarene compounds. The IMS technique has a distinct advantage over UV–vis spectrophotometry for measuring isomer populations in situations where there are multiple isomers with overlapping absorption profiles. In another development, an LED array adjacent to the silica capillary connecting the syringe to the electrospray ion source, is used to activate photochromic molecules, and investigate sequential photoswitching events.

Cis-trans isomerization is one of the most common and well-investigated photoreaction of olefins in solution. This occurs via 180° rotation of one of the substituents on C C bond requiring large space around the double bond. One would expect that in crystals the neighboring molecules would prohibit such a process. In spite of this in early 1960s Schmidt and co-workers reported occurrence of such a process in crystals via 2 + 2 ‘meta cyclobutane’ formation. In this study by examining the photochemistry of four cis-stilbazolium salts we show that the photoconversion to the corresponding trans isomers does not occur via 2 + 2 addition. Large separation that ensures considerable space between neighboring olefins favors cis-trans isomerization in crystals. An aspect that is puzzling is that the product trans isomer phase separates and recrystallizes within the parent cis crystals and photodimerizes to the cyclobutane dimer. Details of this phenomenon are to be understood.

Photoalignment of thin films of dipotassium 3,7-bis[1-(4-hydroxy-3-carboxylate)phenylazo]-5,5′-dioxodibenzothiophene (AtA-2) that were prepared by spin-coating of dye solutions in H2O and DMF and aqueous solutions of polyvinylpyrrolidone (PVP) was studied. The UV absorption band of the dye cis-isomer, the position and intensity of which depended on the PVP concentration in the stock solutions, was recorded upon irradiation of films of AtA-2 in a PVP matrix [AtA-2(PVP)] with unfi ltered light from a DRT-1000 lamp in a vacuum or an Ar atmosphere. PVP facilitated trans–cis isomerization of AtA-2 and increased the stability of the cis-isomer with respect to thermal relaxation into the initial trans-isomer. The dichroic ratio (DR) of AtA-2(PVP) films irradiated with linearly polarized light (blue LED with λ = 450 nm, I = 15 mW/cm2) increased by 1.5 times as the PVP concentration in the stock solutions increased from 1.0 to 10.0 mass%. The morphology and roughness of the films depended on the nature of the solvents used to prepare them.

Chiroptical molecular switches play an important role in responsive materials and dynamic molecular systems. Here we present the synthesis of four chiral overcrowded alkenes and the experimental and computational study of their photochemical and thermal behavior. By irradiation with UV light, metastable diastereoisomers with opposite helicity were generated through high yielding E–Z isomerizations. Kinetic studies on metastable 1–4 using CD spectroscopy and HPLC analysis revealed two pathways at higher temperatures for the thermal isomerization, namely a thermal E–Z isomerization (TEZI) and a thermal helix inversion (THI). These processes were also studied computationally whereby a new strategy was developed for calculating the TEZI barrier for second-generation overcrowded alkenes. To demonstrate that these overcrowded alkenes can be employed as bistable switches, photochromic cycling was performed, which showed that the alkenes display good selectivity and fatigue resistance over multiple irradiation cycles. In particular, switch 3 displayed the best performance in forward and backward photoswitching, while 1 excelled in thermal stability of the photogenerated metastable form. Overall, the alkenes studied showed a remarkable and unprecedented combination of switching properties including dynamic helicity, reversibility, selectivity, fatigue resistance, and thermal stability.

The laboratory unit demonstrates a project-based approach to teaching physical chemistry laboratory where upper-division undergraduates carry out a transient-absorption experiment investigating the kinetics of cis–trans isomerization of N,N-dimethyl-4,4′-azodianiline. Students participate in modification of a standard flash-photolysis spectrometer by adding a temperature-controlled sample holder. The sample holder design is open-source and can be reproduced with the 3D-printing technology. Students build the experimental setup, perform the transient spectroscopy experiment, and analyze the obtained kinetics data to estimate the activation energy, enthalpy, entropy, and Gibbs free energy of cis–trans isomerization of N,N-dimethyl-4,4′-azodianiline.

Urea derivatives are ubiquitously found in many chemical disciplines. N,N′-substituted ureas may show different conformational preferences depending on their substitution pattern. The high energetic barrier for isomerization of the cis and trans state poses additional challenges on computational simulation techniques aiming at a reproduction of the biological properties of urea derivatives. Herein, we investigate energetics of urea conformations and their interconversion using a broad spectrum of methodologies ranging from data mining, via quantum chemistry to molecular dynamics simulation and free energy calculations. We find that the inversion of urea conformations is inherently slow and beyond the time scale of typical simulation protocols. Therefore, extra care needs to be taken by computational chemists to work with appropriate model systems. We find that both knowledge-driven approaches as well as physics-based methods may guide molecular modelers towards accurate starting structures for expensive calculations to ensure that conformations of urea derivatives are modeled as adequately as possible. Electronic supplementary material The online version of this article (doi:10.1007/s10822-016-9913-4) contains supplementary material, which is available to authorized users.

In this paper, we performed density-functional theory (DFT) at the B3LYP/6-311++G(d,p) & LANL2DZ quantum level to probe the thermal cis → trans isomerization of Re(CO)3–AB, a diimine ligand with an azo group substituent. We have searched for the transition states (TS) on the S0 and T1 potential energy surfaces and detected two inversion transition states TS-inv-1 and TS-inv-2 following a rotation-assisted inversion mechanism. In the T1 state, only the rotation pathway exists with the energy barrier 1.88 eV. We also investigated the photoisomerization pathway, the potential energy profiles of the vertical excitation for the excited states T1, S1, T2 and S2 were calculated, and we analyzed two possible isomerization routes through the inversion and rotation pathways. In addition, we probed the properties of the isomerization of the azo portion caused by excitation of the MLCT bands.

With three examples, we have established that cis-cinnamic acids can dimerize via a diradical intermediate in the crystalline state provided that the intermolecular distance is less than 4.2 A. In the excited state of cis-isomers, C–C bond formation with an adjacent molecule competes with geometric isomerization.

The paper describes the synthesis and characterization of “T-type” polyimides and their precursors – poly(amic acid)s. Investigated polymers contained azobenzene derivatives with no substituent or with fluorine atom in para position to the N N linkage. The influence of the main chain architecture (open or close imide rings), location and content of azo chromophores in polymers chains on physicochemical properties were studied. To the best of our knowledge, for the first time, the cis-trans isomerization reaction was studied for azo poly(amic acid)s, that was 1–18% after 3-minutes of 405 nm-light irradiation. Poly(amic acid)s characterized higher stability of isomerization than their polyimide counterparts. The studied azo polyimides showed high glass transition temperatures (174–206 °C) and high thermal stability with the beginning of the decomposition at 246–345 °C. The imidization kinetic of the studied poly (amic acid)s were investigated by differential scanning calorimetry (DSC) using Kissinger and Ozawa models. It was found that the studied azo polymers characterized high activation energies (275.4–357.1 kJ mol−1) and frequency factors (6.5 × 1029–1.3 × 1037 s−1).

The subject of the research is a series of azo-dyes based on the quinoline structure, which are practically omitted as materials which use photoinduced optical anisotropy for applications. The work presents the kinetics of thermal cis-trans isomerization reaction of 5-azo-8-hydroxy-2-methylquinoline and 5,5'-((1E,1′E)-[1,1′-biphenyl]-4,4′-diylbis(diazene-2,1-diyl))bis(2-methylquinolin-8-ol) compounds. The impact of the structure of the substituent at the azo linkage on the cis-trans isomerization kinetics was investigated experimentally and theoretically using the UV–Vis spectroscopy and the density-functional theory (DFT). The kinetics of the dark-return of the cis-to trans-isomer of azoquinolines was investigated after UV-irradiation. It was found that attaching the nitro substituent to the azoquinolines structure retards the photoisomerization process in comparison to the other substituents (i.e. F, Cl, Br, N atoms or CH3, OH, COOH, OCH3 groups). The calculated rate constants were in qualitative agreement with the experimental values. To the best of our knowledge, the cis-trans isomerization kinetics for azoquinolines has not been studied yet.

A systematic study on the dynamics of trans-cis, thermal cis-trans backward and light induced cis-trans isomerization of some azobismaleimide derivatives was performed. Systems under study were N-[4-(carbonylaminoazobenzene)-phenyl]-maleimide (AAzM) and a styrene-maleimide copolymer containing azo units in the side chain (AAzMC). The isomerization reactions were followed by electronic absorption spectra. The kinetics of trans-cis photoisomerization was investigated in six solvents with different polarities. Results revealed that the content of the photostationary state depended on the solvent nature. In turn, the chemical environment had a minor influence on the photoisomerization rate constants. The kinetic and thermodynamic activation parameters were evaluated according to Arrhenius and Eyring equations. The theoretical calculations based on density functional theory (DFT) were employed to identify the mechanism of the thermal isomerization in AAzM. In our results, the thermal cis-trans isomerization of azobismaleimide AAzM followed an inversion assisted by rotation pathway in the S0 state.