Showing papers on "Conformational isomerism published in 2008"
TL;DR: Organic molecules with flexible torsions and low-energy conformers have a greater likelihood of exhibiting polymorphism because (1) different conformations lead to new hydrogen-bonding and close-packing modes and (2) the tradeoff reduces the total energy difference between alternative crystal structures.
Abstract: Polymorphs are different crystalline modifications of the same chemical substance. When different conformers of the same molecule occur in different crystal forms, the phenomenon is termed conformational polymorphism. Occasionally, more than one conformer is present in the same crystal structure. The influence of molecular conformation changes on the formation and stability of polymorphs is the focus of this Account. X-ray crystal structures of conformational polymorphs were analyzed to understand the interplay of intramolecular (conformer) and intermolecular (lattice) energy in the crystallization and stability of polymorphs. Polymorphic structures stabilized by strong O−H···O/N−H···O hydrogen bonds, weak C−H···O interactions, and close packing were considered. 4,4-Diphenyl-2,5-cyclohexadienone (1) and bis(p-tolyl) ketone p-tosylhydrazone (3) are prototypes of C−H···O and N−H···O hydrogen-bonded structures. Distance−angle scatter plots of O−H···O and C−H···O hydrogen bonds extracted from the Cambridge St...
456 citations
TL;DR: The results suggest that drugs stabilizing alpha-helical Abeta conformers (or destabilizing the beta-sheet state) would block formation of neurotoxic oligomers, and the atomic-resolution conformer structures determined in the simulations may serve as useful targets for this purpose.
234 citations
TL;DR: Detailed analyses of the solid-state Möbius structures of compounds 2b, 2c, and 2f showed that singly twisted structures are achieved without serious strain and that cyclic pi-conjugation is well-preserved, as needed for exhibiting strong diatropic ring currents.
Abstract: meso-Aryl-substituted [28]hexaphyrins(1.1.1.1.1.1) have been examined by 1H, 13C, and 19F NMR spectroscopies, UV−vis absorption spectroscopy, magnetic circular dichroism spectroscopy, and single-crystal X-ray diffraction analysis. All of these data consistently indicate that [28]hexaphyrins(1.1.1.1.1.1) in solution at 25 °C exist largely as an equilibrium among several rapidly interconverting twisted Mobius conformations with distinct aromaticities, with a small contribution from a planar rectangular conformation with antiaromatic character at slightly higher energy. In the solid state, [28]hexaphyrins(1.1.1.1.1.1) take either planar or Mobius-twisted conformations, depending upon the meso-aryl substituents and crystallization conditions, indicating a small energy difference between the two conformers. Importantly, when the temperature is decreased to −100 °C in THF, these rapid interconversions among Mobius conformations are frozen, allowing the detection of a single [28]hexaphyrin(1.1.1.1.1.1) species h...
200 citations
TL;DR: A comparison of the populations of the conformers occurring in naked and complexed DNA has revealed a significant broadening of the DNA conformational space in the complexes, but the conformer populations still remain within the limits defined by the A- and B- forms.
Abstract: The geometry of the phosphodiester backbone was analyzed for 7739 dinucleotides from 447 selected crystal structures of naked and complexed DNA Ten torsion angles of a near-dinucleotide unit have been studied by combining Fourier averaging and clustering Besides the known variants of the A-, Band Z-DNA forms, we have also identified combined A+B backbone-deformed conformers, eg with a/c switches, and a few conformers with a syn orientation of bases occurring eg in G-quadruplex structures A plethora of A- and B-like conformers show a close relationship between the A- and B-form double helices A comparison of the populations of the conformers occurring in naked and complexed DNA has revealed a significant broadening of the DNA conformational space in the complexes, but the conformers still remain within the limits defined by the A- and B- forms Possible sequence preferences, important for sequence-dependent recognition, have been assessed for the main A and B conformers by means of statistical goodness-of-fit tests The structural properties of the backbone in quadruplexes, junctions and histone-core particles are discussed in further detail
174 citations
TL;DR: These NMR experiments indicate that the conformational change in RNase A is ligand-stabilized and does not appear to be lig and-induced, and evidence for the coupling of motion and enzyme function comes from the similar solvent deuterium kinetic isotope effect on k ex derived from the NMR measurements and k cat from enzyme kinetic studies.
Abstract: In many enzymes, conformational changes that occur along the reaction coordinate can pose a bottleneck to the rate of conversion of substrates to products. Characterization of these rate-limiting protein motions is essential for obtaining a full understanding of enzyme-catalyzed reactions. Solution NMR experiments such as the Carr-Purcell-Meiboom-Gill (CPMG) spin-echo or off-resonance R 1rho pulse sequences enable quantitation of protein motions in the time range of microseconds to milliseconds. These experiments allow characterization of the conformational exchange rate constant, k ex, the equilibrium populations of the relevant conformations, and the chemical shift differences (Deltaomega) between the conformations. The CPMG experiments were applied to the backbone N-H positions of ribonuclease A (RNase A). To probe the role of dynamic processes in the catalytic cycle of RNase A, stable mimics of the apo enzyme (E), enzyme-substrate (ES) complex, and enzyme-product (EP) complex were formed. The results indicate that the ligand has relatively little influence on the kinetics of motion, which occurs at 1700 s (-1) and is the same as both k cat, and the product dissociation rate constant. Instead, the effect of ligand is to stabilize one of the pre-existing conformations. Thus, these NMR experiments indicate that the conformational change in RNase A is ligand-stabilized and does not appear to be ligand-induced. Further evidence for the coupling of motion and enzyme function comes from the similar solvent deuterium kinetic isotope effect on k ex derived from the NMR measurements and k cat from enzyme kinetic studies. This isotope effect of approximately 2 depends linearly on solvent deuterium content suggesting the involvement of a single proton in RNase A motion and function. Moreover, mutation of His48 to alanine eliminates motion in RNase A and decreases the catalytic turnover rate indicating the involvement of His48, which is far from the active site, in coupling motion and function. For the enzyme triosephosphate isomerase (TIM), the opening and closing motion of a highly conserved active site loop (loop 6) has been implicated in many studies to play an important role in the catalytic cycle of the enzyme. Off-resonance R 1rho experiments were performed on TIM, and results were obtained for amino acid residues in the N-terminal (Val167), and C-terminal (Lys174, Thr177) portions of loop 6. The results indicate that all three loop residues move between the open and closed conformation at about 10,000 s (-1), which is the same as the catalytic rate constant. The O (eta) atom of Tyr208 provides a hydrogen bond to stabilize the closed form of loop 6 by interacting with the amide nitrogen of Ala176; these atoms are outside of hydrogen bonding distance in the open form of the enzyme. Mutation of Tyr208 to phenylalanine results in significant loss of catalytic activity but does not appear to alter the kex value of the N-terminal part of loop 6. Instead, removal of this hydrogen bond appears to result in an increase in the equilibrium population of the open conformer of loop 6, thereby resulting in a loss of activity through a shift in the conformational equilibrium of loop 6. Solution NMR relaxation dispersion experiments are powerful experimental tools that can elucidate protein motions with atomic resolution and can provide insight into the role of these motions in biological function.
155 citations
TL;DR: Ion mobility-mass spectrometry and molecular modeling techniques used to characterize ovalbumin N-linked glycans provide evidence for 19 different glycan structures corresponding to high-mannose and hybrid type carbohydrates with a total of 42 distinct features related to isomers and/or conformers.
135 citations
TL;DR: In this article, the vibrational properties of the 1-butyl-3methylimidazolium tetrafluoroborate [bmim][BF4] ionic liquid were studied by infrared (IR), Raman spectroscopy, and ab initio calculations.
Abstract: As a probe of local structure, the vibrational properties of the 1-butyl-3-methylimidazolium tetrafluoroborate [bmim][BF4] ionic liquid were studied by infrared (IR), Raman spectroscopy, and ab initio calculations. The coexistence of at least four [bmim]+ conformers (GG, GA, TA, and AA) at room temperature was established through unique spectral responses. The Raman modes characteristic of the two most stable [bmim] + conformers, GA and AA, according to the ab initio calculations, increase in intensity with decreasing temperature. To assess the total spectral behavior of the ionic liquid both the contributions of different [bmim] + conformers and the [bmim]+- [BF4]- interactions to the vibrational spectra are discussed.
124 citations
TL;DR: The conformational landscapes of two commonly used ionic liquid ions, the anion bis(trifluoromethanesulfonyl)amide (Ntf2) and the cations N-propyl- and N-butyl-N-methylpyrrolidinium, were investigated using data obtained from Raman spectroscopy, molecular dynamics, and ab initio techniques.
Abstract: The conformational landscapes of two commonly used ionic liquid ions, the anion bis(trifluoromethanesulfonyl)amide (Ntf2) and the cations N-propyl- and N-butyl-N-methylpyrrolidinium, were investigated using data obtained from Raman spectroscopy, molecular dynamics, and ab initio techniques. In the case of Ntf2, the plotting of three-dimensional potential energy surfaces (PES) and the corresponding molecular dynamics (MD) simulations confirmed the existence of two stable isomers (each existing as a pair of enantiomers) and evidenced the nature of the anion as a flexible, albeit hindered, molecule capable of interconversion between conformers in the liquid state, a result confirmed by the Raman data. In the case of the N,N-dialkylpyrrolidinium cations, the PES show a much more limited conformational behavior of the pyrrolidinium ring (pseudorotation). Nevertheless, such pseudorotation produces two stable isomers with the propyl and butyl side chains in completely different positions (axial-envelope and equa...
120 citations
TL;DR: These experiments demonstrate that conformer-selected samples of large molecules can be prepared, offering new possibilities for the study of gas-phase biomolecules.
Abstract: During the last decades, the properties of biomolecules in the gas phase have been studied in ever greater detail [1‐3]. Although the study of biomolecules outside of their natural environment was met with skepticism in the beginning, spectroscopic studies on isolated species in a molecular beam have proven to be very powerful to understand their intrinsic properties. Moreover, their native environment can be mimicked by adding solvent molecules one by one. These studies on well-defined biomolecular systems are particularly relevant to benchmark theoretical calculations. Even in the cold environment of a molecular beam, biomolecules exist in various conformational structures. The existence of multiple conformers (structural isomers) has been observed in the study of jetcooled glycine for the first time [4] and in numerous experiments since then. In many cases, the individual conformers are identified via their different electronic spectra [5, 6]. This has been exploited in multiple-resonance techniques to measure, for instance, conformer-specific infrared spectra from which the conformational structures can be deduced [7, 8].
102 citations
TL;DR: Vibrational spectroscopic proof of intermolecular hydrogen bonds between the carboxylic groups of adjacent ibuprofen molecules, leading to the formation of dimers, was obtained and evidencing the sole presence of one of the lowest energy conformers in the solid state.
90 citations
TL;DR: The origin of the internal rotation barrier between the eclipsed and staggered conformers of ethane and n-butane is systematically investigated and suggests that the new energy partition scheme provides insights from a different perspective of internal rotation barriers.
Abstract: On the basis of an alternative energy partition scheme where density-based quantification of the steric effect was proposed [Liu, S. B. J. Chem. Phys. 2007, 126, 244103], the origin of the internal rotation barrier between the eclipsed and staggered conformers of ethane and n-butane is systematically investigated in this work. Within the new scheme, the total electronic energy is decomposed into three independent components, steric, electrostatic, and fermionic quantum. The steric energy defined in this way is repulsive, exclusive, and extensive and intrinsically linked to Bader's atoms in molecules approach. Two kinds of differences, adiabatic (with optimal structure) and vertical (with fixed geometry), are considered for the molecules in this work. We find that in the adiabatic case the eclipsed conformer possesses a larger steric repulsion than the staggered conformer for both molecules, but in the vertical cases the staggered conformer retains a larger steric repulsion. For ethane, a linear relationship between the total energy difference and the fermionic quantum energy difference is discovered. This linear relationship, however, does not hold for n-butane, whose behaviors in energy component differences are found to be more complicated. The impact of basis set and density functional choices on energy components from the new energy partition scheme has been investigated, as has its comparison with another definition of the steric effect in the literature in terms of the natural bond orbital analysis through the Pauli Exclusion Principle. In addition, profiles of conceptual density functional theory reactivity indices as a function of dihedral angle changes have been examined. Put together, these results suggest that the new energy partition scheme provides insights from a different perspective of internal rotation barriers.
TL;DR: This work predicted the TM conformational changes that are induced by the isomerization of 11-cis retinal to all-trans retinal leading to the fully activated state, metarhodopsin II, and predicted the crystal structure of opsin, which is proposed to be close to the active-state structure.
TL;DR: The anion effects suggest that the GT rotamer is the most stable in ionic liquids, and the positive charge on imidazolium ring does not largely change the conformational energies.
Abstract: Conformational energies for the butyl group of 1-butyl-3-methylimidazolium (bmim) were calculated by high-level ab initio methods. Estimated relative energies for the TT, GT and G′T rotamers of an isolated bmim cation at the CCSD(T)/cc-pVTZ level are 0.0 −0.02 and −0.50 kcal/mol, respectively. The close contact of a Cl anion to the C2−H of imidazolium considerably increases the relative stability of the GT rotamer. Estimated relative energies for the three rotamers of the [bmim]Cl complex, in which the Cl anion exists close to the C2−H, are 0.0, −1.61 and −0.25 kcal/mol, respectively. The GT rotamer is favored by the strong attractive electrostatic interaction between the bmim cation and Cl anion. The C2−H group in the GT rotamer has a larger positive charge compared with those in the TT and G′T rotamers. The contact of a Br anion to the C2−H also stabilizes the GT rotamer. The effects of the Cl anion close to the C4−H and C5−H are small. The anion effects suggest that the GT rotamer is the most stable in...
TL;DR: It is shown that calculation of (13)C NMR chemical shifts using the geometries obtained using molecular mechanics greatly reduces the computational expense without a significant loss of accuracy, even in this demanding system.
Abstract: The stereochemistry of conformationally mobile five-membered rings is often hard to assign from NMR data, and [2,2']bifuranyl systems are even more challenging. GIAO (13)C NMR chemical shifts have been calculated for a series of [2,2']bifuranyl and pyranopyran species, taking into account their conformational flexibility using weighted averages of the data for all low energy conformers. We show that calculation of (13)C NMR chemical shifts using the geometries obtained using molecular mechanics greatly reduces the computational expense without a significant loss of accuracy, even in this demanding system. The results were sufficiently accurate to distinguish not only the pyran and furanyl isomers but also between all the diastereoisomeric forms. As a result of this validation, we predict the stereochemistry for the recently proposed revised structure of the natural product elatenyne, which contains a [2,2']bifuranyl core.
TL;DR: The trend of the Gibbs energy as a function of oligomer length suggests that helix-handedness inversion does not require a complete unfolding of a helical strand and may instead occur through the propagation of a local unfolding separating two segments of opposite handedness.
Abstract: A series of helically folded oligoamides of 8-amino-2-quinoline carboxylic acid possessing 6, 7, 8, 9, 10 or 16 units are prepared following convergent synthetic schemes. The right-handed (P) and the left-handed (M) helical conformers of these oligomers undergo an exchange slow enough to allow their chromatographic separation on a chiral stationary phase. Thus, the M conformer is isolated for each of these oligomers and its slow racemization in hexane/CHCl(3) solutions is monitored at various temperatures using chiral HPLC. The kinetics of racemization at different temperatures in hexane/CHCl(3) (75:25 vol/vol) are fitted to a first order kinetic model to yield the kinetic constant and the Gibbs energy of activation for oligomers having 6, 7, 8, 9, 10 or 16 quinoline units. This energy gives the first quantitative measure of the exceptional stability of the helical conformers of an aromatic amide foldamer with respect to its partly unfolded conformations that occur between an M helix and a P helix. The trend of the Gibbs energy as a function of oligomer length suggests that helix-handedness inversion does not require a complete unfolding of a helical strand and may instead occur through the propagation of a local unfolding separating two segments of opposite handedness.
TL;DR: In this paper, the authors analyzed the conformational landscape of the bis(fluorosulfonyl)amide, [FSI]−, anion using data obtained from Raman spectroscopy, molecular dynamics (MD), and ab initio studies.
Abstract: The conformational landscape of the bis(fluorosulfonyl)amide, [FSI]−, anion was analyzed using data obtained from Raman spectroscopy, molecular dynamics (MD), and ab initio studies. The plotting of three-dimensional potential energy surfaces and the corresponding MD simulation conformer-population histograms show the existence of two stable isomers, C2 (trans) and C1 (cis) conformers, and confirm the nature of the anion as a flexible molecule capable of interconversion between conformers in the liquid state. In ionic liquids, the two [FSI]− conformers coexist in equilibrium, a result confirmed by the Raman data. The implications of the conformational behavior of the ion [FSI]− are discussed in terms of the solvation properties of the corresponding ionic liquids.
TL;DR: In this article, the radial distribution function (RDF) indicates that the ionic liquid involves an ordered structure with significant intermolecular interactions at around 6, 10 and 16 A.
TL;DR: The molecular structure, vibrational frequencies, infrared intensities and Raman scattering activities and theoretical vibrational spectra were calculated a pair of molecules linked by the intermolecular OH...O hydrogen bond and the most stable conformer of 6-CNA is diagnosed as the C1 form.
TL;DR: Electrochemical studies reveal that the first oxidation and reduction potentials of the PDI ring in the cyclophanes increase significantly compared with those of the corresponding monomeric counterparts, in line with the change in the energy of the HOMO and LUMO according to the theoretical calculations.
Abstract: Cyclophanes of perylene tetracarboxylic diimides (PDIs) with different substituents at the bay positions, namely four phenoxy groups at the 1,7-positions (1), four piperidinyl groups at the 1,7-positions (2), and eight phenoxy groups at the 1,6,7,12-positions (3) of the two PDI rings, have been synthesized by the condensation of perylene dianhydride with amine in a dilute solution. These novel cyclophanes were characterized by (1)H NMR spectroscopy, MALDI-TOF mass spectrometry, electronic absorption spectroscopy, and elemental analysis. The conformational isomers of cyclophanes substituted with four piperidinyl groups at the 1,7-positions (2 a and 2 b) were successfully separated by preparative TLC. The main absorption band of the cyclophanes shifts significantly to the higher energy side in comparison with their monomeric counterparts, which indicates significant pi-pi interaction between the PDI units in the cyclophanes. Nevertheless, both the electronic absorption and fluorescence spectra of the cyclophanes were found to change along with the number and nature of the side groups at the bay positions of the PDI ring. Time-dependent DFT calculations on the conformational isomers 2 a and 2 b reproduce well their experimental electronic absorption spectra. Electrochemical studies reveal that the first oxidation and reduction potentials of the PDI ring in the cyclophanes increase significantly compared with those of the corresponding monomeric counterparts, in line with the change in the energy of the HOMO and LUMO according to the theoretical calculations.
TL;DR: Infrared spectra of 1,4-BDO isolated in low-temperature argon and xenon matrixes show a good agreement with a population-weighted mean theoretical spectrum, and the spectral features of the conformers expected to be trapped in the matrixes were observed experimentally.
Abstract: Theoretical calculations at the MP2 level, NBO and AIM analysis, and matrix-isolation infrared spectroscopy have been used to investigate the structure of the isolated molecule of 1,4-butanediol (1,4-BDO). Sixty-five structures were found to be minima on the potential energy surface, and the three most stable forms are characterized by a folded backbone conformation leading to the formation of an intramolecular H-bond. To better characterize the intramolecular interactions and particularly the hydrogen bonds, natural bond orbital analysis (NBO) was performed for the four most stable conformers, and was further complemented with an atoms-in-molecules (AIM) topological analysis. Infrared spectra of 1,4-BDO isolated in low-temperature argon and xenon matrixes show a good agreement with a population-weighted mean theoretical spectrum, and the spectral features of the conformers expected to be trapped in the matrixes were observed experimentally. Annealing the xenon matrix from 20 to 60 K resulted in significant spectral changes, which were interpreted based on the barriers to intramolecular rotation. An estimation of the intramolecular hydrogen bond energy was carried out following three different methodologies.
TL;DR: The results showed that metal(II) ions are all six-coordinated with three TFSA(-) ions, and it was concluded that the conformational equilibrium in the coordination sphere is strongly temperature-sensitive.
Abstract: Solvation structures of manganese(II), cobalt(II), nickel(II) and zinc(II) ions in 1-ethyl-3-methylimidazolium bis(trifluoro-methanesulfonyl) amide (EMI(+)TFSA(-)) have been studied by UV-Vis, FT-IR and FT-Raman spectra. The ionic liquid involves TFSA(-) conformers with C(1) (cis) and C(2) (trans) symmetries, and both conformers coexist in equilibrium in the liquid state. The results showed that these metal(II) ions are all six-coordinated with three TFSA(-) ions, i.e., TFSA(-) ligates as a bidentate O-donor in the ionic liquid. Although the metal ion strongly prefers the C(1) conformer in crystals, the metal ion coordinates both the C(1) and C(2) conformers in the liquid state, and the conformational equilibrium in the bulk only slightly shifts to the C(1) conformer in the coordination sphere. We concluded that the conformational equilibrium in the coordination sphere is strongly temperature-sensitive.
TL;DR: The energy surfaces revealed the reasons for the negligible presence of energetically stable conformers and explained the experimentally observed temperature dependence of the populations and identified four new conformers.
Abstract: Conformational space of cinchonidine has been explored by means of ab initio potential and free energy surfaces, and the temperature-induced changes of conformational populations were studied by a combined NOESY-DFT analysis. The DFT-derived potential energy surface investigation identified four new conformers. Among them, Closed(7) is substantially relevant to fully understand the conformational behavior. The energy surfaces gave access to the favored transformation pathways at different temperatures (280-320 K). They also revealed the reasons for the negligible presence of energetically stable conformers and explained the experimentally observed temperature dependence of the populations.
TL;DR: It is concluded that this excited-state conformational change experienced by the tautomer is associated with an intramolecular charge transfer from the deprotonated dialkylaminophenol or phenol to the protonated benzimidazole (acceptor), affording a nonfluorescent charge-transfer tautomers.
Abstract: The solvent and temperature dependence of the phototautomerization of 1-methyl-2-(2‘-hydroxyphenyl)benzimidazole (4) and the novel compounds 2-(4‘-amino-2‘-hydroxyphenyl)benzimidazole (1), 2-(4‘-N,N-diethylamino-2‘-hydroxyphenyl)benzimidazole (2), and 1-methyl-2-(4‘-N,N-diethylamino-2‘-hydroxyphenyl)benzimidazole (3), together with the ground-state rotamerism and tautomerism of these new compounds, have been studied by UV−vis absorption spectroscopy and steady-state and time-resolved fluorescence spectroscopy. A solvent-modulated rotameric and tautomeric equilibrium is observed in the ground state for 1, 2, and 3. In cyclohexane, these compounds mainly exist as a planar syn normal form, with the hydroxyl group hydrogen-bonded to the benzimidazole N3. In ethanol, the syn form is in equilibrium with its planar anti rotamer (for 1 and 2), with the phenyl ring rotated 180° about the C2−C1‘ bond and with a nonplanar rotamer for compound 3. In aqueous solution, a tautomeric equilibrium is established between th...
TL;DR: Analysis of the conformational space for (His-Ala-Ile + H)(+) precursor cations identified two major conformer groups that differed in their H-bonding patterns and were calculated to collectively account for 39% and 60%, respectively, of the gas-phase ions.
Abstract: Protonated peptides containing histidine or arginine residues and a free carboxyl group (His-Ala-Ile, His-Ala-Leu, Ala-His-Leu, Ala-Ala-His-Ala-Leu, His-Ala-Ala-Ala-Leu, and Arg-Ala-Ile) form stable anions upon collisional double electron transfer from Cs atoms at 50 keV kinetic energies This unusual behavior is explained by hidden rearrangements occurring in peptide radical intermediates formed by transfer of the first electron The rearrangements occur on a ∼120 ns time scale determined by the radical flight time Analysis of the conformational space for (His-Ala-Ile + H)+ precursor cations identified two major conformer groups, 1a+−1m+ and 5a+−5h+, that differed in their H-bonding patterns and were calculated to collectively account for 39% and 60%, respectively, of the gas-phase ions One-electron reduction in 1a+ and 5a+ triggers exothermic hydrogen atom migration from the terminal COOH group onto the His imidazole ring, forming imidazoline radical intermediates The intermediate from 5a is characte
TL;DR: Values suggest that one-step H atom transfer rather than sequential proton loss-electron transfer or electron transfer-proton transfer would be the most favored mechanisms for explaining the antioxidant activity of delphinidin in nonpolar solvents as well as in aqueous solution.
Abstract: Density functional theory calculations were performed to evaluate the antioxidant activity of delphinidin, taking into account its acid/base equilibrium. The conformational behavior of both the isolated and the aqueous solvation species (simulated with the polarizable continuum model) were analyzed at the B3LYP/6-31++G(d,p) level, considering the cationic, neutral, and anionic forms, the latter two forms consisting of diverse tautomers. The analysis of their electron density distributions, using the quantum theory of atoms in molecules, reveals several facts that are not in line with their usual Lewis structures. The prototropic preferences observed in the gas phase and in solution are similar. Thus, in both phases, most stable tautomer of neutral delphinidin is obtained by deprotonating the hydroxyl at C4′, and the most stable tautomer of the anion is obtained by deprotonating the hydroxyls at C4′ and C5. All the planar conformers obtained display an intramolecular hydrogen bond (IHB) between O3 and H6′....
TL;DR: The close similarity between energetic and geometric characteristics of dU and thymidine DNA-like conformers in anti and relevant syn conformations and their transition states of the anti-->syn interconversion implies that mismatch DNA glycosylase discriminates between the two nucleosides, mainly because of the difference in the shapes of their bases.
Abstract: A comprehensive conformational analysis of isolated 2'-deoxyuridine (dU), a minor DNA nucleoside, has been performed by means of ab initio calculations at the MP2/6-311++G (d,p)//DFT B3LYP/6-31G (d,p) level of theory. At 298.15 and 420 K, all 94 allowed conformers of dU are within 8.96 and 7.91 kcal/mol Gibbs energy ranges, respectively. Syn orientation for the base and South (S) conformers for the sugar dominate at 298.15 K: syn/anti=62.3%:37.7% and S/N=77.2%:22.8%. At 420 K in the majority of conformers, the base is anti oriented and the population of North (N) sugars increases: syn/anti=39.3%:60.7% and S/N=63.0%:37.0%. Values of all conformational parameters and correlations between them, as well as their correlations with valence bonds, and also correlations between valence bonds and angles were estimated. In general, 14 types of intramolecular H-bonds were detected (1-3 H-bonds per conformer, the total number 175), namely, C1'H...O2 (16 H-bonds), C2'H1...O5' (9), C2'H2...O2 (21), C3'H...O2 (21), C5'H1...O2 (14), C5'H2...O2 (11), C6H...O4' (37), C6H...O5' (22), C3'H...HC6 (4), O5'H...HC6 (2), O3'H...O5' (5), O5'H...O4' (1), O5'H...O3' (4), and O5'H...O2 (8). Geometric, vibrational, structural-topological, and energetic features of the OH...O intramolecular H-bonds in dU conformers were determined. The close similarity between energetic and geometric characteristics of dU and thymidine DNA-like conformers in anti and relevant syn conformations and their transition states of the anti-->syn interconversion implies that mismatch DNA glycosylase discriminates between the two nucleosides, mainly because of the difference in the shapes of their bases. Convolution of calculated IR spectra of all the dU conformers within the limits 3400-3700 cm(-1) appears to be consistent with its low-temperature matrix IR spectrum (Ivanov et al. Spectrochim. Acta, Part A 2003, 59, 1959), wavenumber discrepancy not exceeding 1%. It was concluded that, for a reliable reproduction of the experimental spectrum, the whole set of conformers should be taken into consideration. The suggested method makes reconstruction of the isolated nucleoside IR spectrum at a physiological interval of temperature reasonably possible.
TL;DR: The conformational preferences and infrared and ultraviolet spectral signatures of two model beta-peptides have been explored under jet-cooled, isolated molecule conditions and the reasons for the preference for C6 over C8 structures and the presence of only two conformations in the jet- cooled spectrum are discussed.
Abstract: The conformational preferences and infrared and ultraviolet spectral signatures of two model beta-peptides, Ac-beta3-hPhe-NHMe (1) and Ac-beta3-hTyr-NHMe (2), have been explored under jet-cooled, isolated molecule conditions. The mass-resolved, resonant two-photon ionization spectra of the two molecules were recorded in the region of the S0-S1 origin of the phenyl or phenol ring substituents, respectively. UV-UV hole-burning spectroscopy was used to determine that two conformations of 1 are present, with the transitions due to conformer A, with S0-S1 origin at 34431 cm(-1), being almost 20 times larger than those due to conformer B, with S0-S1 origin at 34404 cm(-1). Only one conformation of 2 was observed. Resonant ion-dip infrared spectroscopy provided single-conformation infrared spectra in the 3300-3700 cm(-1) region. The spectra of conformer A of both molecules have H-bonded and free amide NH stretch infrared transitions at 3400 and 3488 cm(-1), respectively, while conformer B of 1 possesses bands at 3417 and 3454 cm(-1). For comparison with experiment, full optimizations of all low-lying minima of 1 were carried out at the DFT B3LYP/6-31+G* and RIMP2/aug-cc-pVDZ levels of theory, and single point MP2/6-31+G* calculations at the DFT geometries. On the basis of the comparison with previous studies in solution and the calculated results, conformer A of 1 and 2 were assigned to a C6 conformer, while conformer B of 1 was assigned to a unique C8 structure with a weak intramolecular H-bond. The reasons for the preference for C6 over C8 structures and the presence of only two conformations in the jet-cooled spectrum are discussed in light of the predictions from calculations.
TL;DR: The calculated EA(Ada) values differ considerably from those of EA(Ver) because of the large geometrical relaxation from the neutral to the anionic BDE congeners, highlighted by the lengthening of a C-Br bond.
TL;DR: This review gives an up-dated view of conformational anomeric effect which represents a small fraction of the enthalpic anomersic effect that makes gem-dioxy substituted compounds much more stable that their 1,n-dIOxy substituted isomers (n > 1).
Abstract: Many natural products of biological interest contain [6,5]- and [6,6]-spiroketal moieties that can adopt various configurations, benefiting or not from anomeric conformation stabilizing effects. The spiroketal fragments are often important for the biological activity of the compounds containing them. Most stable spiroketal stereoisomers, including those benefiting from conformational anomeric effects (gauche conformers can be more stable than anti conformers because of a contra-steric stabilizing effect), are obtained easily under acidic conditions that permit acetal heterolysis (formation of tertiary oxycarbenium ion intermediates). The synthesis of less stable stereoisomers requires stereoselective acetal forming reactions that do not permit their equilibration with their most stable stereoisomers or, in the case of suitably substituted derivatives, concomitant reactions generating tricyclic products that quench the less stable spiroketal conformers. Ingenuous approaches have been recently developed for the synthesis of naturally occurring [6,6]- and [5,6]-nonanomeric spiroketals and analogues. The identification of several parameters that can influence the stereochemical outcome of spirocyclization processes has led to seminal improvements in the selective preparation of the non-anomeric isomers that are discussed herein. This review also gives an up-dated view of conformational anomeric effect which represents a small fraction of the enthalpic anomeric effect that makes gem-dioxy substituted compounds much more stable that their 1,n-dioxy substituted isomers (n > 1). Although models assuming sp3-hybridized oxygen atoms have been very popular (rabbit ears for the two non-bonding electron pairs of oxygen atom), sp2-hybridized oxygen atoms are used to describe the conformational anomeric effect.
TL;DR: The interactions between a pyrimidine ring and a substituted benzene ring show that the pyridine is comparable to that of a NO2- or a CN-substituted Benzene ring except for the unpredictable substituent effects.
Abstract: The stacking interactions between an aromatic ring and a pyridine or a pyrimidine ring are studied by using a series of triptycene-derived scaffolds. The indicative ratios of the syn and anti conformers were determined by variable-temperature NMR spectroscopy. The syn conformer aligns the attached aromatic ring and the heterocycle in a parallel-displaced orientation while the anti conformer sets the two rings apart from each other. Comparing to the corresponding control compounds where a benzene ring is in the position of the heterocycle, higher attractive interactions are observed as indicated by the higher syn/anti ratios. In general, the attractive interactions are much less sensitive to the substituent effects than the corresponding nonheterocycles. The greatest attractive interactions were observed between a pyrimidine ring and a N,N-dimethylaminobenzene, consistent with a predominant donor-acceptor interaction. The interactions between a pyridine ring and a substituted benzene ring show that the pyridine is comparable to that of a NO2- or a CN-substituted benzene ring except for the unpredictable substituent effects.