cis-trans isomerism of indolyl-enaminocarbonyl compounds

Analysis of the PMR spectra of a series of indolylenaminocarbonyl compounds: 3-(indolylamino)vinyl ketones, β-indolylaminocrotonates, N-(indolyl)aminomethylenemalonates have been performed. We have established that in the solvents used to record the spectra, the studied enamines exist in the cis-S-cis form. Mordovian State Pedagogical Institute, Saransk 430007, Russia; e-mail:mgpi@si.moris.ru. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1336–1344, October, 1999.     

Impact of azaproline on amide cis-trans isomerism: conformational analyses and NMR studies of model peptides including TRH analogues

The beta-turn is a well-studied motif in both proteins and peptides. Four residues, making almost a complete 180 degree-turn in the direction of the peptide chain, define the beta-turn. Several types of the beta-turn are defined according to Phi and Psi torsional angles of the backbone for residues i + 1 and i + 2. One special type of beta-turn, the type VI-turn, usually contains a proline with a cis-amide bond at residue i + 2. In an aza-amino acid, the alpha-carbon of the amino acid is changed to nitrogen. Peptides containing azaproline (azPro) have been shown to prefer the type VI beta-turn both in crystals and in organic solvents by NMR studies. MC/MD simulations using the GB/SA solvation model for water explored the conformational preferences of azPro-containing peptides in aqueous systems. An increase in the conformational preference for the cis-amide conformer of azPro was clearly seen, but the increased stability was relatively minor with respect to the trans-conformer as compared to previous suggestions. To test the validity of the calculations in view of the experimental data from crystal structures and NMR in organic solvents, [azPro(3)]-TRH and [Phe(2), azPro(3)]-TRH were synthesized, and their conformational preferences were determined by NMR in polar solvents as well as the impact of the azPro substitution on their biological activities.     

Pmr spectra and cis-trans isomerism of 2-methylenepyrrolidine and 2-methylenetetrahydrofuran derivatives

A number of secondary enamines and cyclic enol ethers (2-methylenetetrahydrofuran derivatives) were synthesized by the reaction of O-methylbutyrolactim and 2,2-diethoxytetrahydrofuran, respectively, with compounds that have an active methylene link. The absence of reversible cis-trans isomerization was established in a study of the PMR spectra of these compounds. The configuration of the secondary enamines is determined by the possibility of the formation of a strong intramolecular hydrogen bond between the carbonyl-containing substituent and the NH group. In the case of the cyclic enol ethers it was shown that the energy barrier to cis-trans isomerization is greater than 25 kcal/mole and that, as a consequence of this, the geometrical isomers can be separated preparatively.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 914–918, July, 1982.     

1H-DNMR studies on the cis-trans isomerism of diazoacetylchloride and its derivatives

Diazoacetylchloride and its ester derivates show a kinetically caused NMR-line shape for the C$\text{H}$-proton, due to a cis-trans isomerism.     

Optimal control of ultrafast cis-trans photoisomerization of retinal in rhodopsin via a conical intersection

Optimal control simulation is applied to the cis-trans photoisomerization of retinal in rhodopsin within a two-dimensional, two-electronic-state model with a conical intersection [S. Hahn and G. Stock, J. Phys. Chem. B 104, 1146 (2000)]. For this case study, we investigate coherent control mechanisms, in which laser pulses work cooperatively with a conical intersection that acts as a "wave-packet cannon." Optimally designed pulses largely consist of shaping subpulses that prepare a wave packet, which is localized along a reaction coordinate and has little energy in the coupling mode, through multiple electronic transitions. This shaping process is shown to be essential for achieving a high target yield although the envelopes of the calculated pulses depend on the local topography of the potential-energy surfaces around the conical intersection and the choice of target. The control mechanisms are analyzed by considering the motion of reduced wave packets in a nuclear configuration space as well as by snapshots of probability current-density maps.     

Excited state relaxation dynamics of model green fluorescent protein chromophore analogs: evidence for cis-trans isomerism

Two green fluorescent protein (GFP) chromophore analogs (4Z)-4-(N,N-dimethylaminobenzylidene)-1-methyl-2-phenyl-1,4-dihydro-5H-imidazolin-5-one (DMPI) and (4Z)-4-(N,N-diphenylaminobenzylidene)-1-methyl-2-phenyl-1,4-dihydro-5H-imidazolin-5-one (DPMPI) were investigated using femtosecond fluorescence up-conversion spectroscopy and quantum chemical calculations with the results being substantiated by HPLC and NMR measurements. The femtosecond fluorescence transients are found to be biexponential in nature and the time constants exhibit a significant dependence on solvent viscosity and polarity. A multicoordinate relaxation mechanism is proposed for the excited state relaxation behavior of the model GFP analogs. The first time component (τ(1)) was assigned to the formation of twisted intramolecular charge transfer (TICT) state along the rotational coordinate of N-substituted amine group. Time resolved intensity normalized and area normalized emission spectra (TRES and TRANES) were constructed to authenticate the occurrence of TICT state in subpicosecond time scale. Another picosecond time component (τ(2)) was attributed to internal conversion via large amplitude motion along the exomethylenic double bond which has been enunciated by quantum chemical calculations. Quantum chemical calculation also forbids the involvement of hula-twist because of high activation barrier of twisting. HPLC profiles and proton-NMR measurements of the irradiated analogs confirm the presence of Z and E isomers, whose possibility of formation can be accomplished only by the rotation along the exomethylenic double bond. The present observations can be extended to p-HBDI in order to understand the role of protein scaffold in reducing the nonradiative pathways, leading to highly luminescent nature of GFP.     

Correlations between conformational isomerism and chromatographic diastereoselectivity of bis amino amide s-triazine derivatives

NMR spectroscopy was used to probe the conformational behavior of diastereomeric s-triazine derivatives containing two chiral amino amide substituents, in order to shed light onto the mechanism of chromatographic diastereoselectivity. Utilizing the amino hydrogen signals in the proton NMR spectrum, the population of the conformations caused by rotation about the bond between the amino nitrogen and aromatic carbon atoms could be observed. The population distribution between the three possible conformations was similar but not identical between the two diastereomers, with similar trends being observed for both bis alanine amide and bis valine amide derivatives. Based on a simple model in which it is assumed that adsorption to the hydrophobic RP-LC stationary phase occurs only for the conformations having both amino amide R-groups on the same side of the triazine ring plane, the different conformation populations between the two diastereomers obtained by NMR was consistent with the observed RP-LC elution order (L-L diastereomer followed by L-D). The predicted diastereoselectivity values from NMR data were compared to RP-LC diastereoselectivity values obtained using both C18 and polymeric columns, with both acetonitrile/water and DMSO/water mobile phases. Values obtained with the polymeric column were in better agreement with calculated values than those obtained with the C18 column, suggesting that the simple adsorption model used to calculate the diastereoselectivity is more relevant towards a simple hydrophobic polymeric surface rather than a more complex C18 stationary phase. This study indicates that proton NMR is a useful tool for studying the diastereoselective mechanism of these derivatives, due to the relatively slow C-N bond rotation caused by the significant sp(2) character of the amino nitrogen atoms.     

Combined experimental and computational study of cis-trans isomerism in bis(L-valinato)copper(II)

Heating of polycrystalline cis aquabis(L-valinato)copper(II) at 90 °C resulted in a dehydrated powder. Recrystallization from aqueous solution of the obtained product yielded anhydrous trans bis(L-valinato)copper(II). The X-ray crystal and molecular structures of trans bis(L-valinato)copper(II) and cis aquabis(L-valinato)copper(II) are presented. Molecular modeling calculations were attempted to resolve factors that influenced the isomerization and crystallization of either the aqua cis- or the anhydrous trans-isomer. Conformational analyses of trans- and cis-isomers were completed in vacuo and in crystal by molecular mechanics, and in aqueous solution by molecular dynamics (MD) simulations using the same force field. Although the conformers with trans-configuration are the most stable in vacuo, those with cis-configuration form more favorable intermolecular interactions. Consequently, both cis- and trans-isomers are predicted to be present in aqueous solution. According to the crystal structure simulations and predictions, cis-isomer requires water molecules to form energetically more stable crystal packings than trans-isomer. The MD modeling of the self-assembly of 16 bis(L-valinato)copper(II) complexes in aqueous solution for the first time predicted the crystallization nucleus formation to proceed from monomers to oligomers by Cu-to-O(carboxylato) and/or N-H···O(carboxylato) weak bonds; these oligomers then bind together via water molecules until they acquire the right positions for noncovalent bonding like in the experimental crystal structures. Fifty-nanosecond MD simulations accomplished for a system consisting of equal numbers of complexes and water molecules at 298 and 370 K suggested complete cis-to-trans transformation at the higher temperature. Prevalence of either cis- or trans-conformers in water upon dissolvation may explain the crystallization results.     

Facile amide formation via S-nitrosothioacids

Here we report a novel amide bond formation strategy from simple thioacid and amine starting materials. The reaction is mediated by unstable but very reactive S-nitrosothioacid intermediates. This fast reaction under mild conditions should be useful in synthesis.     

Two pathways for the protolysis of 1-(alkythio)-1-buten-3-ynes and the effect of cis-trans isomerism

Conclusions We have used a spectrophotometric method to examine the kinetics of the hydrolysis of 1-(alkylthio)-1-buten-3-ynes to (alkylthio)butenones and acetoacetaldehyde; the rate of reaction depends markedly on the reactant configuration.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 153–159, January, 1978.     

Electronic structure effects of amide group: Vince lactam

HeI photoelectron spectrum of 2-azabicyclo[2.2.1]hept-5-en-3-one (Vince lactam) has been measured. The assignment of the spectrum was made by comparison with photoelectron spectra of related compounds and by taking into account the lactam's molecular structure. The analysis of the electronic structure of amide group, in terms of inductive and conjugative effects, is presented on the basis of photoelectron spectroscopic data.     

Transesterification and amide cis-trans isomerization in Zn and Cd complexes of the chelating amino acid ligand Boc-Asp(Dpa)-OBzl

The amino acid derivative Boc-Asp-OBzl (Boc=N-butyloxycarbonyl; Asp=aspartic acid; Bzl=benzyl) was functionalized by coupling its carboxylate side chain to dipicolylamine. This yielded the tridentate nitrogen donor ligand Boc-Asp(Dpa)-OBzl (-OBzl). The compound -OBzl contains three different carbonyl groups: a tertiary amide linkage between Asp and Dpa, a C-terminal benzyl ester function, and an N-terminal urethane protecting group. NMR spectra were used to compare the reactivity of these moieties. The Boc protecting group gives rise to two isomers, (E, 9%) and (Z, 91%). Coordination of Cd(NO3)2 and Zn(NO3)2 yielded the complexes and. These compounds have significantly reduced barriers to rotation about the tertiary amide C-N bond compared with the free ligand (-OBzl:18.5 kcal mol-1 in CDBr3;: 12.9 kcal mol-1 in (CD3)2CO;: 13.8 kcal mol-1 in (CD3)2CO). Both complexes readily undergo transesterification in methanol or CD3OD. Experimental pseudo-first order rate constants were determined in CD3OD and (CD3)2CO:CD3OD (3:1;). It was found that the zinc complex (k=(2.28+/-0.02)x10(-4) s-1) is significantly more reactive than the cadmium complex (k=(1.41+/-0.03)x10(-6) s-1). In order to study their tertiary amide cis-trans isomerization, the cadmium complex [(-OCH3)Cd(NO3)2] was synthesized, and the zinc complex [(-OCD3)Zn(NO3)2] was generated in situ in (CD3)2CO:CD3OD (3:1). The barriers to rotation were determined (:14.1 kcal mol-1 in CD3OD;: 13.4 kcal mol-1 in (CD3)2CO:CD3OD (3:1)). Our results show that the stronger Lewis-acid zinc(II) is significantly more active than cadmium(II) in the acceleration of the transesterification. This is in marked contrast to the tertiary amide bond rotation which is comparably fast with both metal ions.     

Straightforward synthesis of sphinganines via a serine-derived Weinreb amide

Sphinganines can be synthesized in just three steps from easily prepared serine-derived Weinreb amide 4. Pre-deprotonation of the acidic (N-H and O-H) protons of 4 allows for its efficient conversion to amino ketones 5. Such ketones can be selectively reduced to either erythro- or threo-sphinganines. Partially protected sphinganines 11 are also readily accessible in five steps from 4. Thus, Weinreb amide 4 represents one of the most versatile templates described to date for sphinganine synthesis.     

Synthesis of arylidenepyruvic amide derivatives via Ugi-four component condensation

Arylidenepyruvic acids (APAs) have been successfully employed in an Ugi-four component condensation reaction which yielded polyfunctional amides. Condensation of various APAs, aldehydes, amines, and isocyanides at room temperature in 96% ethanol as a green solvent proceeded in good yields. The extension of the reaction to diamines, formaldehyde, and isocyanides to form more complex molecules is also reported. These novel products may have potential in various pharmaceutical applications.     

Amic acid complexes with aprotic polar solvents V. Complexes with amide solvents and isomerism of trimellite-dianilic acid

Complexes of trimellite-dianilic acid (TMA) with aprotic amide solvents have been sythetized, separated and investigated by TG and MTA methods. It was shown that the composition of these complexes is [TMA]₁ · [Sol]₁. The PMR spectra were used to show the ability of TMA to undergo isomeric transitions under mild conditions in an aprotic solvent.     

Electronic isomerism (electromerism) of 6,8-di-tert-butyl-3H-phenoxazin-3-one oxime radical

Russian Chemical Bulletin - A radical stable at room temperature was prepared by the oxidation of a toluene solution of 6,8-di-(tert-butyl)-3H-phenoxazin-3-one oxime with lead oxide PbO2. The...     

Intramolecular Diels-Alder reaction of N-allyl 2-furoyl amides: effect of steric strain and amide rotational isomerism

Intramolecular Diels-Alder reactions of various N-allyl 2-furoyl amides with different substituents on the nitrogen atom were investigated. The reaction of amides having bulky substituents proceeded at a faster rate than the analogs whose substituents were of less bulkiness. From the systematic experimental survey of the substituent effects and the energetic evaluation based on the DFT calculations at the B3LYP/6-31G(d) level, the enhanced reactivity was ascribed to the relief of steric strain upon cyclization rather than the amide rotational isomerism governed by the bulky substituents.     

Electronic structure of crystals via VLEED

Dispersion relations E(k) of electrons in crystals preserve their meaning in many-electron systems. Interacting electrons become quasiparticles, which apart from energies, are also characterised by lifetimes. As for real systems these characteristics are difficult to evaluate, some experimental evidence is desirable. Attention will be focused on two methods applicable at energies above the vacuum level. Interaction of external beam of slow electrons with crystals in target current spectroscopy (TCS), and in very low energy electron diffraction (VLEED), will be discussed in context with the unoccupied part of the electronic band structure. Knowledge of electron dispersion relations above the vacuum level is important for interpretations of angular resolved photoelectron spectroscopy. Comparison of experimental TCS and VLEED data with theoretical band structure calculations determines positions of energy gaps and more detailed theoretical interpretations of the intensity profiles provides information about electron lifetimes in metals and semiconductors.