Population Of Cis Isomers Research Articles

Conductance switching of azobenzene-based self-assembled monolayers on cobalt probed by UHV conductive-AFM.

We report the formation of self-assembled monolayers of a molecular photoswitch (azobenzene-bithiophene derivative, AzBT) on cobalt via a thiol covalent bond. We study the electrical properties of the molecular junctions formed with the tip of a conductive atomic force microscope under ultra-high vacuum. The statistical analysis of the current-voltage curves shows two distinct states of the molecule conductance, suggesting the coexistence of both the trans and cis azobenzene isomers on the surface. The cis isomer population (trans isomer) increases (decreases) upon UV light irradiation. The situation is reversed under blue light irradiation. The experiments are confronted to first-principle calculations performed on the molecular junctions with the Non-Equilibrium Green's Function formalism combined with Density Functional Theory (NEGF/DFT). The theoretical results consider two different molecular orientations for each isomer. Whereas the orientation does not affect the conductance of the trans isomer, it significantly modulates the conductance of the cis isomer and the resulting conductance ON/OFF ratio of the molecular junction. This helps identifying the molecular orientation at the origin of the observed current differences between the trans and cis forms. The ON state is associated to the trans isomer irrespective of its orientation in the junction, while the OFF state is identified as a cis isomer with its azobenzene moiety folded upward with respect to the bithiophene core. The experimental and calculated ON/OFF conductance ratios have a similar order of magnitude. This conductance ratio seems reasonable to make these Co-AzBT molecular junctions a good test-bed to further explore the relationship between the spin-polarized charge transport, the molecule conformation and the molecule-Co spinterface.

Morphology-Mediated Photoresponsive and Fluorescence Behaviors of Azobenzene-Containing Block Copolymers.

We investigated the relationship between the self-assembled morphology of poly( tert-butyl acrylate)- block-poly(6-[4-(4'-methoxyphenylazo)phenoxy]hexyl methacrylate) (P tBA- b-PAzoMA) block copolymers and their photoresponsive and fluorescence behaviors. The morphology of P tBA- b-PAzoMA copolymers was manipulated by dissolving them in mixed dimethylformamide (DMF)/hexanol solvents. When P tBA- b-PAzoMA was dissolved in DMF-rich (neutral) solvents, a favorable interaction between the DMF molecules and both blocks resulted in a random-coiled conformation. The unconfined morphology facilitated the formation of both nonassociated and head-to-head organized azobenzene mesogens, which promoted fluorescence emission. When hexanol, a P tBA-selective solvent, was added to DMF, the solvency of P tBA- b-PAzoMA worsened, leading to its assembly into micelles, with PAzoMA in the micelle core. The confinement of azobenzene moieties in the micelle core hindered their trans-to- cis photoisomerization, thereby considerably decreasing the kinetics of photoisomerization and the population of cis isomers. Additionally, a nanoconfined geometry resulted in compactly packed chromophores, causing fluorescence loss. When P tBA- b-PAzoMA was exposed to UV light, the increased number of cis isomers hampered the closely packed mesogens, resulting in a substantial enhancement of fluorescence emission. When the mole fraction of the PAzoMA block was increased, P tBA- b-PAzoMA formed clusters, causing the slow kinetics of photoisomerization and fluorescence quenching.

Photo- and electro-isomerization of azobenzenes based on polymer-dispersed liquid crystals doped with azobenzenes and their applications

We report the photo-isomerization and electro-isomerization effects in azobenzenes-doped polymer-dispersed liquid crystals during the switching of the liquid crystal (LC) device between transparent (cis-isomers dominant) and scattering states (trans-isomers dominant). The isothermal phase transition, which is a result of the illumination of UV light and the application of DC voltage, was the main mechanism to switch the LC device between transparency, scattering, and gray scales. This study discusses in detail the variations in the population of cis-isomers as functions of the period and the amplitude of the applied DC voltage.

Kinetics and Equilibria of Cis/Trans Isomerization of Secondary Amide Peptide Bonds in Linear and Cyclic Peptides

The secondary amide peptide bonds that comprise up to one-third of the bonds of peptide or protein backbones can exist as cis and trans isomers, with the trans isomer being highly favored. However, there is little quantitative data on the kinetics and equilibria of cis-trans isomerization of secondary amide peptide bonds due to the difficulty of detecting the very small population of cis isomers. Knowledge of factors that influence the kinetics and equilibria of cis-trans isomerization of secondary amide peptide bonds will contribute to a more complete understanding of the structural and dynamic behavior of the backbones of peptides and unfolded proteins and of complex protein folding kinetics. We have characterized the kinetics and equilibria of cis-trans isomerization of the Xaa-Yaa secondary amide peptide bonds of the linear dithiol and cyclic disulfide forms of the peptides Ac-Cys-Xaa-Yaa-Cys-His-NH(2), where Xaa-Yaa is Ala-Phe, Phe-Ala, Ala-Tyr, and Tyr-Ala, by (1)H NMR. Resolved resonances were observed for the Ala-methyl protons of the trans and the much less abundant cis isomers due to differential shielding of the Ala-methyl protons of the trans and cis isomers by ring current effects from the Phe and Tyr side chains. The population of the cis isomers was determined from the relative intensities of the Ala-methyl resonances for the trans and cis isomers, and rate constants for cis-to-trans and trans-to-cis isomerization were determined by the magnetization transfer NMR method. The population of the cis isomers ranges from 0.07 to 0.12%, and the rate constants indicate that, when there is a trans-to-cis interchange, it is rapidly followed by a cis-to-trans interchange back to the more stable trans conformation. Although cyclization by disulfide bond formation imposes conformational constraints on the peptide backbones, cyclization is found to have relatively small affects on the dynamics of cis-trans isomerization.

Effect of sequence on peptide geometry in 5-tert-butylprolyl type VI beta-turn mimics.

The influence of sequence on turn geometry was examined by incorporating (2S,5R)-5-tert-butylproline (5-(t)BuPro) into a series of dipeptides and tetrapeptides. (2S,5R)-5-tert-Butylproline and proline were respectively introduced at the C-terminal residue of N-acetyl dipeptide N'-methylamides 1 and 2. The conformational analysis of these analogues was performed using NMR and CD spectroscopy as well as X-ray diffraction to examine the factors that control the prolyl amide (in this text, the term "prolyl amide" refers to the tertiary amide composed of the pyrrolidine nitrogen of the prolyl residue and the carbonyl of the N-terminal residue) equilibrium and stabilize type VI beta-turn conformation. The high cis-isomer population with aromatic residues N-terminal to proline was shown to result from a stacking interaction between the partial positive charged prolyl amide nitrogen and the aromatic pi-system as seen in the crystal structure of 1c. The effect of sequence on the prolyl amide equilibrium of 5-(t)BuPro-tetrapeptides (Ac-Xaa-Yaa-5-(t)BuPro-Zaa-XMe, 13 and 14) was studied by varying the amino acids at the Xaa, Yaa, and Zaa positions. High (>80%) cis-isomer populations were obtained with alkyl groups at the Xaa position, an aromatic residue at the Yaa position, and either an alanine or a lysine residue at the Zaa position of the 5-(t)BuPro-tetrapeptide methyl esters in water. Tetrapeptides Ac-Ala-Phe-5-(t)BuPro-Zaa-OMe (Zaa = Ala, Lys), 14d and 14f, with high cis-isomer content adopted type VIa beta-turn conformations as shown by their NMR and CD spectra. Although a pattern of amide proton temperature coefficient values indicative of a hairpin geometry was observed in peptides 14d and 14f, the value magnitudes did not indicate strong hydrogen bonding in water.

The influence of steric interactions on the conformation and biology of oxytocin. Synthesis and analysis of penicillamine(6)-oxytocin and penicillamine(6)-5-tert-butylproline(7)-oxytocin analogs.

Six [Pen(6)]oxytocin analogs were synthesized by substituting penicillamine for cysteine in oxytocin, [Mpa(1)]oxytocin, [dPen(1)]oxytocin, [5-t-BuPro(7)]oxytocin, [Mpa(1), 5-t-BuPro(7)]oxytocin and [dPen(1), 5-t-BuPro(7)]oxytocin. When tested in the uterotonic test in vitro [Pen(6)]oxytocin, [Pen(6), 5-t-BuPro(7)]oxytocin, [Mpa(1), Pen(6)]oxytocin and [Mpa(1), Pen(6), 5-t-BuPro(7)]oxytocin, all were found to possess both agonistic and antagonistic properties. Their agonistic potency ranged from negligible (0.08 IU/mg) to low (5.85 IU/mg) and their antagonistic potency (pA2) was estimated to range from 6.6 to 7.9. [dPen(1), Pen(6)]Oxytocin and [dPen(1), Pen(6), 5-t-BuPro(7)]oxytocin were found to be pure antagonists with similarly high pA2 values of approximately 8.2. Replacement of proline by 5-tert-butylproline increased binding affinity by a factor of two in [Pen(6)]oxytocin and had no influence on the binding affinity of [Mpa(1), Pen(6)]oxytocin and [dPen(1), Pen(6)]oxytocin. Assignment of the proton signals for prolyl amide cis- and trans-isomers by NMR experiments in water indicated that the Pen(6)-5-tert-BuPro(7) peptide bond cis-isomer population was augmented relative to the prolyl peptides and measured, respectively, at 20, 35 and 35% in the 5-tert-butylproline(7) analogs of [Pen(6)]oxytocin, [Mpa(1), Pen(6)]oxytocin and [dPen(1), Pen(6)]oxytocin. This augmentation in cis-isomer population was correlated with a 21-fold reduction in the agonistic potency and 2-fold augmentation in antagonistic potency for [Pen(6), 5-t-BuPro(7)]oxytocin relative to [Pen(6)]oxytocin. Augmentation of cis-isomer population was also correlated to reduced agonist potency without effect on antagonism on conversion of [Mpa(1), Pen(6)]oxytocin to [Mpa(1), Pen(6), 5-t-BuPro(7)]oxytocin. In the potent oxytocin antagonist, [dPen(1), Pen(6)]oxytocin, substitution of 5-tert-butylproline for proline augmented the cis-isomer population without affecting antagonistic potency. The synthesis and evaluation of [Pen(6)]oxytocin and [Pen(6), 5-t-BuPro(7)]oxytocin analogs 1-6 indicated that steric interactions influenced agonist and antagonist activity by modifying peptide conformation. Augmentations in the prolyl cis-isomer population caused by 5-tert-butylproline occurred concurrently with enhanced or maintained antagonistic potency and binding affinity and reduced agonistic potency.

A study of the relationship between biological activity and prolyl amide isomer geometry in oxytocin using 5-tert-butylproline to augment the Cys(6)-Pro(7) amide cis-isomer population.

Three [5-t-BuPro(7)]oxytocin analogues were synthesized by substituting (2S,5R)-5-tert-butylproline for proline in oxytocin, [Mpa(1)]oxytocin, and [dPen(1)]oxytocin. Relative to oxytocin, [5-t-BuPro(7)]oxytocin and [Mpa(1),5-t-BuPro(7)]oxytocin exhibited strongly reduced binding affinity to the receptor; however, both peptides maintained the pharmacophore characteristics responsible for signal transfer evoking the same maximal response as oxytocin in the single-dose procedure and exhibiting partial agonistic activity in the cumulative dose-response procedure. Although [dPen(1)]oxytocin exhibited inhibitory as well as partial agonistic activity, [dPen(1),5-t-BuPro(7)]oxytocin exhibited only inhibitory potency with a similar in vitro pA(2) value of 7.50 in the absence of magnesium. In the presence of magnesium, [dPen(1), 5-t-BuPro(7)]oxytocin exhibited stronger inhibitory potency than [dPen(1)]oxytocin and no partial agonism. Assignment of the proton signals for the 5-tert-butylprolyl amide cis- and trans-isomers by two-dimensional NMR experiments in water indicated that the Cys(6)-Pro(7) peptide bond cis-isomer population was augmented relative to the prolyl peptides and measured respectively at 35%, 33%, and 20% in the 5-tert-butylproline(7) analogues of oxytocin, [Mpa(1)]oxytocin and [dPen(1)]oxytocin. Although caution must be taken when relating the increase in cis-isomer population with an influence on biological activity in [5-t-BuPro(7)]oxytocin analogues, the synthesis and evaluation of analogues 1-3 have provided additional evidence that can be used to support the hypothesis that the prolyl amide cis-isomer may favor antagonism and the trans-isomer is necessary for agonist activity.

Imide Cis−Trans Isomerization ofN-Acetyl-N‘-methylprolineamide and Solvent Effects

We report here the results on conformational free energies of N-acetyl-N‘-methylprolineamide (Ac-Pro-NHMe) at the HF, MP2, and B3LYP levels of theory with the 6-31+G(d) basis set to see how well the ab initio and density functional computations with the self-consistent reaction field (SCRF) method would reproduce the observed solvent effects on the cis−trans isomerization of imide bond. The augmentation of the prolyl amide cis-isomer population with increased solvent polarity was reproduced by the MP2 or B3LYP free energies using the SCRF solvation free energies. Furthermore, the energy barriers for amide isomerization that were calculated for Ac-Pro-NHMe in different solvents reflected the experimentally observed trend for dimethylacetamide in which the energy for rotation augmented with increased solvent polarity. However, it should be noted that neither the isodensity polarizable continuum model (IPCM) nor the self-consistent isodensity polarizable continuum model (SCI-PCM) predicted properly both solvent effects. Our results indicate the need for improved solvation theory.

Barriers to Rotation of Secondary Amide Peptide Bonds

We present results on the identification and molecular characterization of conformers with secondary cis amide peptide bonds for a number of oligopeptides containing tyrosine and phenylalanine in aqueous solution. Employing 1H NMR techniques, peptide bonds adjacent to the aromatic amino acid were found to generate a cis isomer population ranging from 0.1% to 1% in dependence on the chain length and the ionization state of the peptide. The rate constant of the trans → cis interconversion for zwitterionic Ala-Tyr was 2.4 × 10-3 s-1 at 298 K and thus in a range typical of imidic prolyl peptide bonds. However, the rate constant kcis → trans = 0.6 s-1 of the reverse isomerization revealed a much faster process in Ala-Tyr. Extending the peptide chain in both directions of the Ala-Tyr moiety led to a decrease of both the cis content and the barrier to rotation in the cis → trans direction. The linear Arrhenius plots gave Ea values of 76.7 ± 1.5 and 64.6 ± 1.5 kJ mol-1 for the dipeptide Ala-Tyr and the corresponding bond in the pentapeptide Ala-Ala-Tyr-Ala-Ala, respectively. Isomerization rates were affected by both the position and the nature of amino acids flanking the isomerizing bond as could be proved by comparison of peptides containing Gly, Tyr, and Phe residues. These studies provide data that permit the extraction of kinetic events originating from the isomerization of “normal” peptide bonds in protein backbone structuring.

The Influence of Solvents and Polymer Matrices on the Photoinduced Isomerization of an Azobenzene Chromophore

Abstract The thermal cis to trans (Z to E) isomerization process following the photoisomerization of N,N- dimethylaminoazobenzene (methyl yellow) in a number of different solvent matrices; solutions, polymers and a liquid crystal are compared. In the solvents, dichloromethane, methanol, and polyacrylonitrile, a photoinduced stable cis isomer population could only be observed at −90[ddot]C. In other solvents such as toluene and polycarbonate, at room temperature, the half-life of the cis form was about thirty minutes. The trans to cis conversion of the methyl yellow was exploited in a low molar mass liquid crystal matrix. Photoinduced shifts of up to 17[ddot]C were observed in the nematic to isotropic phase transition temperature.

Coordination behavior of thiocyanate in the complexes [CH 3P(C 6H 5) 2] 2M(CNS) 2 (M = Ni, Pd, Pt)

The complexes [CH 3P(C 6H 5) 2] 2M(CNS) 2 (M = Ni, Pd, Pt) have been prepared and characterized. The structures of these complexes are markedly metal ion and physical state dependent. All of the complexes are square planar. In the solid state the nickel complex is trans-L 2M(NCS) 2 (by crystal structure analysis), the palladium complex is trans-L 2Pd(SCN) 2 and the platinum complex it cis-L 2(NCS) 2 (both determined by infrared spectroscopy, including integrated intensity measurements). Fourier transform phosphorus nmr spectra on chloroform solutions at ambient temperature indicate that for the platinum complex, all six possible isomers are present in solution in the relative ratios: trans-L 2Pt(NCS) 2: trans-L 2Pt(SCN)(NCS): trans-L 2Pt(SCN) 2: cis-L 2Pt(NCS) 2: cis-L 2Pt(SCN) 2: cis-L 2Pt(SCN)(NCS): 0.38:0.57:0.38: 0.34:0.28:1, respectively. For the palladium complex, under similar conditions, all of the isomers but cis-L 2Pd(SCN)(NCS) are present, with trans-L 2Pd(NCS) 2 and cis-L 2Pd(NCS) 2 predominant in a ratio of O.15:1, respectively. The relative population of cis isomers decreases in the sequence Pd > Pt > Ni, and the relative population of mixed linkage isomers decreases in the sequence Pt > Pd > Ni. The differences in the structures are discussed in light of current theories.

Nuclear magnetic resonance study on the model compounds for poly(N-alkylglycine)s.

AbstractCis‐trans isomerism was investigated with N‐acetyl and N‐propionyl, N‐alkylglycine dimethylamides as model compounds for poly(N‐alkylglycine dimethlamides as model compounds for (N‐alkylglycine)s using n.m.r. spectroscopy. The population of the cis isomer measured in benzene and methylene chloride solutions did not show any marked dependence on the bulkiness of N‐alkyl substituents. This contrasts with polyN‐alkylglycine)s, whose cis isomer population increased with the introduction of bulky N‐alkyl groups. Kinetics of the Cis‐trans isomerization was also investigated with N‐acetyldimethylamides of sacrosine, N‐n‐propylglycine, and N‐isopropylglycine in tetrachloroethane solution. The δG‡ values for Cis‐trans isomerization in these amides were 18 ∼ 19 kcal/mole, which were virtually the same as that of polysacrosine.