Showing papers on "Conformational isomerism published in 2012"

Click Synthesis, Aggregation-Induced Emission, E/Z Isomerization, Self-Organization, and Multiple Chromisms of Pure Stereoisomers of a Tetraphenylethene-Cored Luminogen

Abstract: It has been difficult to decipher the mechanistic issue whether E/Z isomerization is involved in the aggregation-induced emission (AIE) process of a tetraphenylethene (TPE) derivative, due to the difficulty in the synthesis of its pure E and Z conformers. In this work, pure stereoisomers of a TPE derivative named 1,2-bis{4-[1-(6-phenoxyhexyl)-4-(1,2,3-triazol)yl]phenyl}-1,2-diphenylethene (BPHTATPE) are successfully synthesized. Both isomers show remarkable AIE effect (αAIE ≥ 322) and high fluorescence quantum yield in the solid state (ΦF 100%). The conformers readily undergo E/Z isomerization upon exposure to a powerful UV light and treatment at a high temperature (>200 °C). Such conformational change, however, is not observed under normal fluorescence spectrum measurement conditions, excluding the involvement of the E/Z isomerization in the AIE process of the TPE-based luminogen. The molecules of (E)-BPHTATPE self-organize into ordered one-dimensional nanostructures such as microfibers and nanorods that...

Fluorescent Charge-Assisted Halogen-Bonding Macrocyclic Halo-Imidazolium Receptors for Anion Recognition and Sensing in Aqueous Media

Abstract: The synthesis and anion binding properties of a new family of fluorescent halogen bonding (XB) macrocyclic halo-imidazolium receptors are described. The receptors contain chloro-, bromo-, and iodo-imidazolium motifs incorporated into a cyclic structure using naphthalene spacer groups. The large size of the iodine atom substituents resulted in the isolation of anti and syn conformers of the iodo-imidazoliophane, whereas the chloro- and bromo-imidazoliophane analogues exhibit solution dynamic conformational behavior. The syn iodo-imidazoliophane isomer forms novel dimeric isostructural XB complexes of 2:2 stoichiometry with bromide and iodide anions in the solid state. Solution phase DOSY NMR experiments indicate iodide recognition takes place via cooperative convergent XB–iodide 1:1 stoichiometric binding in aqueous solvent mixtures. 1H NMR and fluorescence spectroscopic titration experiments with a variety of anions in the competitive CD3OD/D2O (9:1) aqueous solvent mixture demonstrated the bromo- and syn...

Isomer-Specific IR-IR Double Resonance Spectroscopy of D2-Tagged Protonated Dipeptides Prepared in a Cryogenic Ion Trap.

Abstract: Isomer-specific vibrational predissociation spectra are reported for the gas-phase GlySarH(+) and SarSarH(+) [Gly = glycine; Sar = sarcosine] ions prepared by electrospray ionization and tagged with weakly bound D2 adducts using a cryogenic ion trap. The contributions of individual isomers to the overlapping vibrational band patterns are completely isolated using a pump-probe photochemical hole-burning scheme involving two tunable infrared lasers and two stages of mass selection (hence IR(2)MS(2)). These patterns are then assigned by comparison with harmonic (MP2/6-311+G(d,p)) spectra for various possible conformers. Both systems occur in two conformations based on cis and trans configurations with respect to the amide bond. In addition to the usual single intramolecular hydrogen bond motif between the protonated amine and the nearby amide oxygen atom, cis-SarSarH(+) adopts a previous unreported conformation in which both amino NH's act as H-bond donors. The correlated red shifts in the NH donor and C═O acceptor components of the NH···O═C linkage to the acid group are unambiguously assigned in the double H-bonded conformer.

An RNA hairpin to G-quadruplex conformational transition.

Abstract: RNA molecules can fold into noncanonical structures such as the four-stranded structures known as G-quadruplexes. G-quadruplexes in the transcriptome have recently emerged as relevant regulatory elements of gene expression. Conformational transitions in RNA molecules offer an important way to regulate their biological functions. Here we report on the competition between a canonical hairpin structure and a G-quadruplex structure within an RNA molecule. We show that the conformational preference strongly depends on the relative amounts of mono- and divalent metal ions present in solution. In our system, the G-quadruplex, whose formation is not predicted by available predictive RNA folding programs, is the major conformer at physiologically relevant K(+) and Mg(2+) concentrations. Furthermore, we show that a synthetic small molecule can displace the structural dynamic equilibrium in favor of the hairpin conformer. This work highlights a new and important level of complexity in RNA folding that could be relevant to the biological functions and targeting of RNAs comprising G-quadruplex motifs.

Preferred conformers of proteinogenic glutamic acid.

Abstract: The molecular shape of proteinogenic glutamic acid has been determined for the first time. Vaporization of the solid amino acid by laser ablation in combination with Fourier transform microwave spectroscopy made possible the detection of five different structures in a supersonic jet. These structures have been identified through their rotational and 14N quadrupole coupling constants. All conformers show hydrogen bonds linking the amino and alpha carboxylic group through N–H···O═C (type I) or N···H–O (type II) interactions. In three of them there are additional hydrogen bonds established between the amino group and the carboxylic group in the gamma position. Entropic effects related to the side chain have been found to be significant in determining the most populated conformations.

Designing Fluorinated Cinchona Alkaloids for Enantioselective Catalysis: Controlling Internal Rotation by a Fluorine‐Ammonium Ion gauche Effect (φNCCF)

Abstract: The C9 position of cinchona alkaloids functions as a molecular hinge, with internal rotations around the C8 C9 (tau(1)) and C9 C4' (tau(2)) bonds giving rise to four low energy conformers (1; anti-closed, anti-open, syn-closed, and syn-open). By substituting the C9 carbinol centre by a configurationally defined fluorine substituent, a fluorine-ammonium ion gauche effect (sigma(C-H) -> sigma(C-F)*; F-delta-...N+) encodes for two out of the four possible conformers (2). This constitutes a partial solution to the long-standing problem of governing internal rotations in cinchonium-based catalysts relying solely on a fluorine conformational effect.

Spontaneous tunneling and near-infrared-induced interconversion between the amino-hydroxy conformers of cytosine.

Abstract: Spontaneous and near-infrared/infrared (NIR/IR)-induced interconversions between two amino-hydroxy conformers of monomeric cytosine have been investigated for the compound isolated in a low-temperature argon matrix. Combined use of a laser source (which provides narrowband NIR radiation) and a broadband NIR/IR source of excitation light allowed a detailed investigation of mutual conversions of the two conformers in question. The experiments carried out within the current work demonstrated that upon broadband NIR/IR irradiation (with the IR source of FTIR spectrometer) the population ratio of the two amino-hydroxy conformers changes towards a ratio corresponding to a photostationary state. Evolution of the conformer population ratio towards the photostationary ratio occurred independent of the initial ratio of conformers, which could be prepared by a population shift (in favor of one of the forms) induced by narrowband NIR excitation. Moreover, spontaneous tunneling conversion of the higher-energy conformer into a lower-energy form was observed for cytosine isolated in a low-temperature argon matrix kept in the dark. This process is slow and occurs on a time scale of days. The tunneling process, studied for matrix-isolated cytosine, clearly follows a dispersive type of kinetics rather than the classical monoexponential kinetics.

A Hierarchy of Methods for the Energetically Accurate Modeling of Isomerism in Monosaccharides.

Abstract: The performance of different wave-function-based and density functional theory (DFT) methods was evaluated with respect to the prediction of relative energies for gas-phase monosaccharide isomers. A test set of 58 structures was employed, representing all forms of isomerism encountered in d-aldohexoses. The set was built from eight hexopyranose epimers by deriving subsets of isomers that include hydroxymethyl rotamers, anomers, ring conformers, furanose, and open-chain forms. Each subset of isomers spans a different energy range and involves various stereoelectronic effects. Reference energy values were obtained with coupled-cluster calculations extrapolated to the complete basis set limit, CCSD(T)/CBS. The tested CBS-extrapolated ab initio methods include various types of Moller-Plesset (MP) perturbation theory and the localized paired natural orbital coupled electron pair approach (LPNO-CEPA). Extensive benchmarking of DFT methods was carried out with 31 functionals. The results allow us to establish a hierarchy of methods that forms a reference guide for further computational studies. Among wave-function-based methods, LPNO-CEPA proved indistinguishable from CCSD(T), offering a promising alternative for a reference method that can be applied to larger systems. MP2 and SCS-MP2 follow closely, surpassing SOS-MP2 and MP3. The mPW2PLYP-D double hybrid and the Minnesota M06-2X hybrid meta-GGA are the best performing density functionals and are directly competitive with wave-function-based ab initio methods. Among the remaining functionals, B3PW91, TPSSh, mPW1PW91, and PBE0 yield the best results on average, while PBE is the best general-purpose GGA functional, surpassing meta-GGAs and several hybrids such as B3LYP. The choice of method strongly depends on the type of isomerism that needs to be considered, since many DFT methods perform well for purely conformational isomerism, but most of them fail to describe ring versus open-chain isomerism, where LYP-based GGA functionals perform particularly poorly.

Mixed 14/16 helices in the gas phase: conformation-specific spectroscopy of Z-(Gly)n, n = 1, 3, 5.

Abstract: Single-conformation ultraviolet and infrared spectroscopy has been carried out on the neutral peptide series, Z-(Gly)(n)-OH, n = 1,3,5 (ZGn) and Z-(Gly)(5)-NHMe (ZG5-NHMe) in the isolated environment of a supersonic expansion. The N-terminal Z-cap (carboxybenzyl) provides an ultraviolet chromophore for resonant two-photon ionization (R2PI) spectroscopy. Conformation-specific infrared spectra were recorded in double resonance using resonant ion-dip infrared spectroscopy (RIDIRS). By comparing the experimental spectra with the predictions of DFT M05-2X/6-31+G(d) calculations, the structures could be characterized in terms of the sequence of intramolecular H-bonded rings of varying size. Despite the enhanced flexibility of the glycine residues, a total of only six conformers were observed among the four molecules. Two conformers for ZG1 were found with the major conformation taking on an extended, planar β-strand conformation. Two conformers were observed for ZG3, with the majority of the population in a C11/C7/C7/π(g-) structure that forms a full loop of the glycine chain. Both ZG5 molecules had their population primarily in a single conformation, with structures characteristic of the first stages of a "mixed" β-helix. C14/C16 H-bonded rings in opposing directions (N → C and C → N) tie the helix together, with nearest-neighbor C7 rings turning the backbone so that it forms the helix. φ/ψ angles alternate in sign along the backbone, as is characteristic of the mixed, C14/C16 β-helix. The calculated conformational energies of these structures are unusually stable relative to all others, with energies significantly lower than the PGI/PGII conformations characteristic of polyglycine structures in solution and in the crystalline form, where intermolecular H-bonds play a role.

Double electron–electron resonance shows cytochrome P450cam undergoes a conformational change in solution upon binding substrate

Abstract: Although cytochrome P450cam from Pseudomonas putida, the archetype for all heme monooxygenases, has long been known to have a closed active site, recent reports show that the enzyme can also be crystallized in at least two clusters of open conformations. This suggests that the enzyme may undergo significant conformational changes during substrate binding and catalytic turnover. However, these conformations were observed in the crystalline state, and information is needed about the conformations that are populated in solution. In this study, double electron–electron resonance experiments were performed to observe substrate-induced changes in distance as measured by the dipolar coupling between spin labels introduced onto the surface of the enzyme on opposite sides of the substrate access channel. The double electron–electron resonance data show a decrease of 0.8 nm in the distance between spin labels placed at S48C and S190C upon binding the substrate camphor. A rotamer distribution model based on the crystal structures adequately describes the observed distance distributions. These results demonstrate conclusively that, in the physiologically relevant solution state, the substrate-free enzyme exists in the open P450cam-O conformation and that camphor binding results in conversion to the closed P450cam-C form. This approach should be useful for investigating many other P450s, including mammalian forms, in which the role of conformational change is of central importance but not well understood.

Complete conformational space of the potential HIV-1 reverse transcriptase inhibitors d4U and d4C. A quantum chemical study.

Abstract: A comprehensive quantum-chemical conformational analysis of two nucleoside analogues, 2′,3′-didehydro-2′,3′-dideoxyuridine (d4U) and 2′,3′-didehydro-2′,3′-dideoxycytidine (d4C), is reported. The electronic structure calculations were performed at the MP2/6-311++G(d,p)//B3LYP/6-31++G(d,p) level of theory. It was found that d4U and d4C adopt 20 conformers and 19 conformers, respectively, which correspond to local minima on the respective potential energy landscapes. QTAIM and NBO analyses show that the d4U and d4C conformers are stabilised by a complicated network of specific intramolecular interactions, which includes conventional (OH⋯O) and non-conventional (CH⋯O, CH⋯HC) H-bonds as well as closed-shell van der Waals (C⋯O) contacts. A satisfactory linear correlation was found between Grunenberg's compliance constants for closed-shell intramolecular interactions and their energy. It is shown that there are no conformational obstacles for incorporation of d4U and d4C into the double helical A and B forms of DNA. The less pronounced biological activity of d4U as compared to 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T) is most likely due to the presence of the bulky methyl group at the 5-position of d4T, which can be recognised by target enzymes.

π-Hydrogen Bonding Wins over Conventional Hydrogen Bonding Interaction: A Jet-Cooled Study of Indole···Furan Heterodimer

Abstract: In this study, we have explored the conformational landscape of the indole···furan dimer in a supersonic jet by using resonant two-photon ionization (R2PI) and IR-UV double-resonance spectroscopic techniques combined with dispersion-corrected density functional theory (DFT) calculations. Only one conformer of the dimer has been observed in the experiment. DFT/B97-D level calculation shows that N–H···π hydrogen-bonded conformer (T′) is energetically more stable than the N–H···O hydrogen-bonded conformer (HB). Natural bond orbital (NBO) calculation also shows that the hydrogen-bonding interaction in the HB conformer is very weak. Finally, the structure of the observed dimer has been determined to be tilted T-shaped N–H···π hydrogen-bonded (T′) from very excellent agreement between experimental and theoretical N–H stretch frequency. The most significant finding of this study is the first-time observation of a N–H···π bound conformer of a dimer, which wins over a conventional hydrogen-bonded conformer of the ...

Three hydrogen bond donor catalysts: oxyanion hole mimics and transition state analogues.

Abstract: Enzymes and their mimics use hydrogen bonds to catalyze chemical transformations Small-molecule transition state analogues of oxyanion holes have been characterized by computations, gas-phase IR and photoelectron spectroscopy, and determination of their binding constants in acetonitrile A new class of hydrogen bond catalysts is proposed (donors that can contribute three hydrogen bonds to a single functional group) and demonstrated in a Friedel–Crafts reaction The employed catalyst was observed to react 100 times faster than its rotamer that can employ only two hydrogen bonds The former compound also binds anions more tightly and was found to have a thermodynamic advantage

Conformational Distributions of N-Acetyl-L-cysteine in Aqueous Solutions: A Combined Implicit and Explicit Solvation Treatment of VA and VCD Spectra

Abstract: The conformational distributions of N-acetyl-L-cysteine (NALC) in aqueous solutions at several representative pH values are investigated using vibrational absorption (VA), UV/Vis, and vibrational circular dichroism (VCD) spectroscopy, together with DFT and molecular dynamics (MD) simulations. The experimental VA and UV/Vis spectra of NALC in water are obtained under strongly acid, neutral, and strongly basic conditions, as well as the VCD spectrum at pH 7 in D(2)O. Extensive searches are carried out to locate the most stable conformers of the protonated, neutral, deprotonated, and doubly deprotonated NALC species at the B3LYP/6-311++G(d,p) level. The inclusion of the polarizable continuum model (PCM) modifies the geometries and the relative stabilities of the conformers noticeably. The simulated PCM VA spectra show significantly better agreement with the experimental data than the gas-phase ones, thus allowing assignment of the conformational distributions and dominant species under each experimental condition. To further properly account for the discrepancies noted between the experimental and simulated VCD spectra, PCM and the explicit solvent model are utilized. MD simulations are used to aid the modelling of the NALC-(water)(N) clusters. The geometry optimization, harmonic frequency calculations, and VA and VCD intensities are computed for the NALC-(water)(3,4) clusters at the B3LYP/6-311++G(d,p) level without and with the PCM. The inclusion of both explicit and implicit solvation models at the same time provides a decisively better agreement between theory and experiment and therefore conclusive information about the conformational distributions of NALC in water and hydrogen-bonding interactions between NALC and water molecules.

Viability of Möbius Topologies in [26]‐ and [28]Hexaphyrins

Abstract: Recently, hexaphyrins have emerged as a promising class of π-conjugated molecules that display a range of interesting electronic, optical, and conformational properties, including the formation of stable Mobius aromatic systems. Besides the Mobius topology, hexaphyrins can adopt a variety of conformations with Huckel and twisted Huckel topologies, which can be interconverted under certain conditions. To determine the optimum conditions for viable Mobius topologies, the conformational preferences of [26]- and [28]hexaphyrins and the dynamic interconversion between the Mobius and Huckel topologies were investigated by density functional calculations. In the absence of meso substituents, [26]hexaphyrin prefers a planar dumbbell conformation, strongly aromatic and relatively strain free. The Mobius topology is highly improbable: the most stable tautomer is 33 kcal mol(-1) higher in energy than the global minimum. On the other hand, the Mobius conformer of [28]hexaphyrin is only 6.5 kcal mol(-1) higher in energy than the most stable dumbbell conformation. This marked difference is due to aromatic stabilization in the Mobius 4n electron macrocycle as opposed to antiaromatic destabilization in the 4n+2 electron system, as revealed by several energetic, magnetic, structural, and reactivity indices of aromaticity. For [28]hexaphyrins, the computed activation barrier for interconversion between the Mobius aromatic and Huckel antiaromatic conformers ranges from 7.2 to 10.2 kcal mol(-1), in very good agreement with the available experimental data. The conformation of the hexaphyrin macrocycle is strongly dependent on oxidation state and solvent, and this feature creates a promising platform for the development of molecular switches.

Tedarenes A and B: Structural and Stereochemical Analysis of Two New Strained Cyclic Diarylheptanoids from the Marine Sponge Tedania ignis

Abstract: Ring strain causes planar chirality in tedarenes A and B, two cyclic diarylheptanoids isolated from the marine sponge Tedania ignis. In both molecules, the chiral plane is an olefinic system, which is very rare among natural products. In tedarene A (1), interconversion is too fast to allow isolation of the enantiomeric atropisomers but still slow enough to cause coalescence of some 1H and 13C NMR signals at room temperature. In tedarene B (2), which also shows stable central and axial chirality, the two planar diastereomers are in slow equilibrium. Tedarene B is the smallest natural product with central, axial, and planar chirality in the same simple molecule. The identification of planar chirality as the difference between its conformational isomers allowed the use of theoretical prediction of the CD spectrum to determine the absolute configuration of the stereogenic carbon C-9 as well as of the biphenyl chiral axis.

Conformations of serine in aqueous solutions as revealed by vibrational circular dichroism.

Abstract: Vibrational circular dichroism (VCD) spectroscopy is utilized to reveal the detailed conformational distributions of the dominant serine species in aqueous solutions under three representative pH conditions of 1.0, 5.7, and 13.0, together with vibrational absorption (VA) spectroscopy, density functional theory (DFT), and molecular dynamics simulation. The experimental VA and VCD spectra of serine in H(2)O and D(2)O in the fingerprint region under three pH values are obtained. DFT calculations at the B3LYP/6-311++G(d,p) level are carried out for the protonated, zwitterionic, and deprotonated serine species. The lowest-energy conformers of all three species are identified and their corresponding VA and VCD spectra simulated. A comparison between the gas-phase simulations and the experimental VA and VCD spectra suggests that one or two of the most stable conformers of each species contribute predominantly to the observed data, although some discrepancies are noted. To account for the solvent effects, both the polarizable continuum model and the explicit solvation model are considered. Hydrogen-bonded protonated, zwitterionic, and deprotonated serine-(water)(6) clusters are constructed based on radial distribution function analyses and molecular dynamics snapshots. Geometry optimization and VA and VCD simulations are performed for these clusters at the B3LYP/6-311++G(d,p) level. Inclusion of the explicit water molecules is found to improve the agreement between theory and experiment noticeably in all three cases, thus enabling conclusive conformational distribution analyses of serine in aqueous solutions directly.

Real-time monitoring of protein conformational dynamics in solution using kinetic capillary electrophoresis.

Abstract: Conformational analysis: Capillary electrophoresis (CE) allows for the rapid separation of slowly interconverting protein conformers. Kinetic analysis (k(open), k(closed), and K(d)) of electropherograms in the presence and absence of effector ligands allows the measurement of kinetic and thermodynamic constants associated with conformational changes and ligand binding.

Crystal Structure, Thermal Behavior, and Photochemical Reactivity of a Series of Co-Crystals of trans-1,2-Bis(4-pyridyl) Ethylene with Dicarboxylic Acids

Abstract: A series of co-crystals of trans-1,2-bis(4-pyridyl) ethylene (bpe) with aliphatic saturated or unsaturated dicarboxylic acids, of the type [(bpe)(L)] (L = dicarboxylic acid), were prepared and characterized by single crystal X-ray crystallography. In all cases chains of the type acid···bpe···acid were formed via strong O–H···N hydrogen bonds. The chains were further linked between them by weak C–H···O hydrogen bonds, π–π and herringbone interactions to form three-dimensional structures. Thermal analysis showed considerable elevation of the melting/decomposition point of the co-crystals with respect either to both components or to bpe, ascribed to the formation of multiple complementary C–H···O bonds as well as to π–π interactions between the two conformer molecules. When L = fumaric acid, the two components stack separately with their C═C bonds strictly parallel between them at 3.83 A from one another. However, photodimerization reaction takes place only between the olefin bonds of bpe. Photodimerization ...

Role of Met80 and Tyr67 in the low-pH conformational equilibria of cytochrome c.

Abstract: The low-pH conformational equilibria of ferric yeast iso-1 cytochrome c (ycc) and its M80A, M80A/Y67H, and M80A/Y67A variants were studied from pH 7 to 2 at low ionic strength through electronic absorption, magnetic circular dichroism, and resonance Raman spectroscopies. For wild-type ycc, the protein structure, axial heme ligands, and spin state of the iron atom convert from the native folded His/Met low-spin (LS) form to a molten globule His/H2O high-spin (HS) form and a totally unfolded bis-aquo HS state, in a single cooperative transition with an apparent pKa of ∼3.0. An analogous cooperative transition occurs for the M80A and M80A/Y67H variants. This is preceded by protonation of heme propionate-7, with a pKa of ∼4.2, and by an equilibrium between a His/OH–-ligated LS and a His/H2O-ligated HS conformer, with a pKa of ∼5.9. In the M80A/Y67A variant, the cooperative low-pH transition is split into two distinct processes because of an increased stability of the molten globule state that is formed at hig...