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Showing papers on "Conformational isomerism published in 2004"


Journal ArticleDOI
TL;DR: The results suggested that Se...O interactions have a dominant covalent character rather than an electrostatic one.
Abstract: To investigate the nature of nonbonded Se...O interactions, three series of 2-substituted benzeneselenenyl derivatives [2-(CHO)C6H4SeX (1), 2-(CH2OH)C6H4SeX, (2), 2-(CH2OiPr)C6H4SeX (3); X = Cl, Br, CN, SPh, SeAr, Me] were synthesized. The 17O NMR absorption observed for 17O-enriched aldehydes 1 appeared upfield relative to benzaldehyde (PhCHO), while the opposite downfield shifts relative to benzyl alcohol (PhCH2OH) were observed for 17O-enriched alcohols 2 and ethers 3. The magnitude of both the upfield and the downfield shifts became larger as the electron-withdrawing ability of a substituent X increased. Quantum chemical calculations at the B3LYP level revealed that for all model compounds the most stable conformer has an intramolecular nonbonded Se.O interaction. Thus, the relative 17O NMR chemical shifts (DeltadeltaO) for 1-3 would reflect the strengths of the Se...O interactions. The natural bond orbital (NBO) analysis demonstrated that the stabilization energy due to an nO --> sigma Se-X orbital interaction (ESe...O) correlates with the Se...O atomic distance on a single curve irrespective of the type of the O atom. On the other hand, the atoms in molecules (AIM) analysis showed that the nonbonded Se...O interactions can be characterized by the presence of a bond critical point, the total energy density (HSe...O) of which decreases with strengthening of the interaction. The results suggested that Se...O interactions have a dominant covalent character rather than an electrostatic one.

171 citations


Journal ArticleDOI
TL;DR: The jet-cooled rotational spectrum of neutral alanine has been studied using laser-ablation molecular-beam Fourier transform microwave spectroscopy (LA-MB-FTMW), and the independent structures of both conformers have been determined experimentally for the first time.
Abstract: The jet-cooled rotational spectrum of neutral alanine has been studied using laser-ablation molecular-beam Fourier transform microwave spectroscopy (LA-MB-FTMW). The spectra of the two most stable forms were observed in the frequency range 6-18 GHz for the parent, (15)N alanine, three single (13)C species, and four single D species. The (14)N nuclear quadrupole coupling hyperfine structures have been resolved, and their comparison with those calculated theoretically confirms unambiguously the conformer assignments. The independent structures of both conformers have been determined experimentally for the first time using r(s) and r(0) procedures. In both cases, the amino acid backbone is nonplanar. For the most stable conformer I, the COOH group adopts a cis configuration and an asymmetric bifurcated hydrogen bond is formed between the amino group and carbonyl oxygen (r(N-H(a)...O=C) = 2.70(2) A and r(N-H(b)...O=C) = 2.88(2) A). For conformer IIa, the COOH group adopts a trans configuration and is stabilized by a O-H...N hydrogen bond (r(O-H...N) = 1.96(2) A). The relative conformer abundances in the supersonic expansion have also been investigated.

169 citations


Journal ArticleDOI
TL;DR: The enol imine ⇄ enaminone tautomerization constants, KT, and thermodynamic parameters, ΔHT and ΔST, of 1-hydroxy-2-naphthaldehyde Schiff bases are determined by UV/vis spectroscopy as discussed by the authors.
Abstract: The enol imine ⇄ enaminone tautomerization constants, KT, and thermodynamic parameters, ΔHT and ΔST, of 1-hydroxy-2-naphthaldehyde Schiff bases are determined by UV/vis spectroscopy. Polar solvents shift the equilibrium toward the quinone form (for the unsubstituted derivative 1c, KT = 0.20 (cyclohexane) and KT = 1.49 (ethanol)). Both donor (MeO, NMe2) and acceptor (CN, NO2) substituents lead to a decreased KT independent of solvent polarity. In apolar solvents, for all derivatives 1a−1e, the enol imine ⇄ enaminone equilibria are endergonic but exothermic. Linear solvation energy relationships allow extrapolation of ΔGT to the gas phase. Density functional theory calculations (B3LYP/6-311+G**) yield good agreement with these extrapolated ΔGT values. Solvent effects on 1c are also successfully reproduced by the calculations. Geometric (O···N distance) and energetic criteria (conformer energy differences, homodesmotic reactions) establish the importance of intramolecular hydrogen bonding for the tautomerism...

149 citations


Journal ArticleDOI
20 Feb 2004-Science
TL;DR: The combined data from all X→Y isomerizations identify important isomerization pathways on the potential energy surface linking the minima.
Abstract: Stimulated emission pumping (SEP)–hole filling spectroscopy and SEP-induced population transfer spectroscopy have been used to place narrow bounds on the energy thresholds for isomerization between individual reactant-product isomer pairs involving the seven conformational minima of tryptamine. The thresholds for isomerizing conformer A to all six other conformations divided into three groups at 750 wavenumbers (cm–1)(A→B, F), 1000 cm–1 [A→C(2)], and 1280 to 1320 cm–1 [A→D, E, and C(1)]. The appearance of the first band and the absence of the band below it were used to place upper and lower bounds to the barrier heights for each process. The thresholds for A→B and B→A isomerizations were also combined to determine the relative energies of these two lowest energy minima. The combined data from all X→Y isomerizations identify important isomerization pathways on the potential energy surface linking the minima.

144 citations


Journal ArticleDOI
TL;DR: X-ray diffraction analyses of (E)-stilbene and azobenzene were carried out at various temperatures and succeeded in observing thermodynamic nonequilibrium states that were generated by fast freezing of the conformational interconversion at low temperatures.
Abstract: Some molecules with a molecular skeleton similar to that of stilbenes and azobenzenes show orientational disorder in the crystals. If the disorder is dynamic, a conformational interconversion takes place through a pedal motion. In this study X-ray diffraction analyses of (E)-stilbene (1) and azobenzene (2) were carried out at various temperatures. We succeeded in observing thermodynamic nonequilibrium states that were generated by fast freezing of the conformational interconversion at low temperatures. The populations of the two conformers in crystals of 1 at 90 K varied with the cooling rate. Flash cooling of a crystal of 2 from room temperature to 90 K made it possible to observe the minor unstable conformer that does not exist in the equilibrium state at the same temperature.

116 citations


Journal ArticleDOI
TL;DR: It is suggested that explicit water–AD interactions may distort C5 and β (or αR and β) to an intermediate conformation in the strong polar solvents, and the energy surfaces may serve as the basis for developing of strategies enabling the inclusion of solvent polarization in the force field.
Abstract: The effects of solvation on the conformations and energies of alanine dipeptide (AD) have been studied by ab initio calculations up to MP2/cc-pVTZ//MP2/6-31G**, utilizing the polarizable continuum model (PCM) to mimic solvation effects. The energy surfaces in the gas phase, ether, and water bear similar topological features carved by the steric hindrance, but the details differ significantly due to the solvent effects. The gas-phase energy map is qualitatively consistent with the Ramachandran plot showing seven energy minima. With respect to the gas-phase map, the significant changes of the aqueous map include (1) the expanded low-energy regions, (2) the emergence of an energy barrier between C5-β and αR-β2 regions, (3) a clearly pronounced αR minimum, a new β-conformer, and the disappearance of the gas-phase global minimum, and (4) the shift of the dominant region in LEII from the gas-phase C7ax region to the αL region. These changes bring the map in water to be much closer to the Ramachandran plot than the gas-phase map. The solvent effects on the geometries include the elongation of the exposed NH and CO bonds, the shortening of the buried HNCO peptide bonds, and the enhanced planarity of the peptide bonds. The energy surface in ether has features similar to those both in the gas phase and in water. The free energy order computed in the gas phase and in ether is in good agreement with experimental studies that concluded that C5 and C7eq are the dominant species in both the gas phase and nonpolar solvents. The free energy order in water is consistent with the experimental observation that the dominant C7eq in the nonpolar solvent was largely replaced by PII-like (i.e., β) and αR in the strong polar solvents. Based on calculations on AD + 4H2O and other AD–water clusters, we suggest that explicit water–AD interactions may distort C5 and β (or αR and β) to an intermediate conformation. Our analysis also shows that the PCM calculations at the MP2/cc-pVTZ//MP2/6-31G** level give good descriptions to the bulk solvent polarization effect. The results presented in this article should be of sufficient quality to characterize the peptide bonds in the gas phase and solvents. The energy surfaces may serve as the basis for developing of strategies enabling the inclusion of solvent polarization in the force field. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1699–1716, 2004

110 citations


Journal ArticleDOI
TL;DR: In this paper, the peptides Trp-Gly, Gly-Trp and TrpGly-gly were investigated by UV-UV and IR-UV hole burning spectroscopy.
Abstract: The peptides Trp-Gly, Gly-Trp and Trp-Gly-Gly were investigated by UV–UV and IR–UV hole burning spectroscopy. Solid samples of the three peptides were vaporised into an argon jet by laser desorption. The IR–UV spectra of different conformers of the peptides were assigned by comparison with the IR–UV spectra of tryptophan [Snoek et al., Phys. Chem. Chem. Phys., 2001, 3, 1819], the free peptide bond in N-acetyl tryptophan methyl amide [Dian et al., J. Chem. Phys., 2002, 117, 10688] and ab initio calculations performed at the DFT B3LYP 6-31G(d,p) level. Apart from an NH⋯NH2 interaction, the peptide backbone of one conformer of each dipeptide is unfolded. The second conformer of Gly-Trp shows a COOH⋯OC hydrogen bond and the second conformer of Trp-Gly-Gly a hydrogen bond between the peptide backbone and the NH group of the indole ring.

106 citations


Journal ArticleDOI
TL;DR: The energies of the gauche and anti conformers of 2-fluoroethylamine, 2- fluoroethanol and their protonated analogues are calculated using density functional theory to identify the same conformational preference.
Abstract: The energies of the gauche and anti conformers of 2-fluoroethylamine, 2-fluoroethanol and their protonated analogues are calculated using density functional theory. Unlike the non protonated systems, the protonated systems show a strong gauche effect where the C–F and the C–+NH3 or C–F and C–+OH2 bonds are gauche rather than anti to each other. Single crystal X-ray diffraction studies of 2-fluoroethylammonium compounds identify the same conformational preference.

101 citations


Journal ArticleDOI
TL;DR: In this article, the natural optical activity of two chiral amino acids, alanine and proline, has been calculated using Hartree−Fock and density-functional theory with the Becke three-parameter Lee−Yang−Parr (B3LYP) functional employing analytical response theory.
Abstract: The natural optical activity of two chiral amino acids, alanine and proline, has been calculated using Hartree−Fock and density-functional theory with the Becke three-parameter Lee−Yang−Parr (B3LYP) functional employing analytical response theory. The dependence of the optical activity on the molecular conformation in the gas phase was investigated. In the case of proline, calculations were also carried out for the protonated and deprotonated molecules. The increase of the optical rotation of proline with increasing pH, found experimentally, is reproduced by our calculations. The optical rotation of both amino acids is found to be very sensitive to the molecular geometry, to the extent that it changes sign for the different conformers. For alanine, the sign of the optical rotation varies with the rotation of the amino or carbonyl groups.

99 citations


Journal ArticleDOI
TL;DR: In this article, the gas-phase model tripeptides N-acetyl-Phe-Pro-NH2 and Nacetylpro-phe-NH 2 have been studied experimentally and theoretically in order to investigate the local conformational preferences of the peptide backbone and their competition with secondary structures under solvent-free conditions.
Abstract: The gas-phase model tripeptides N-acetyl-Phe-Pro-NH2 and N-acetyl-Pro-Phe-NH2 have been studied experimentally and theoretically in order to investigate the local conformational preferences of the peptide backbone and their competition with secondary structures under solvent-free conditions. The combination of UV and IR spectroscopies shows that, under supersonic beam conditions, only a reduced number of conformations are formed, indicating efficient conformational relaxation processes in these species. IR spectroscopy in the NH stretch spectral range combined with density functional theory calculations proves to be a very efficient tool to assign the structure of these species in terms of intramolecular H-bonding. Classical secondary structures of biology, like repeated γ-turns are observed as major conformations. Only one minor conformation of N-Ac-Phe-Pro-NH2 was assigned to a β-turn structure. According to the nature of the main conformers, the backbone conformational trends on the phenylalanine (Phe) residue is shown to be very dependent upon the neighbouring residues: Phe adopts a β conformation when alone (in N-acetyl-Phe-NH2) or when followed by a proline residue (in N-acetyl-Phe-Pro-NH2) but favours a γL conformation when preceded by proline (in N-acetyl-Pro-Phe-NH2). These subtle preferences, resulting from a competition between weakly polar or dispersive interactions, constitute a very stringent test of the theoretical tools for protein modelling and simulation.

99 citations


Journal ArticleDOI
TL;DR: Single-molecule fluorescence spectroscopy is used to study the dynamic properties of the perfect (4H) four-way helical junction derived from the hairpin ribozyme and suggests that interconversion proceeds via an open intermediate with reduced cation binding in which coaxial stacking between helices is disrupted.

Journal ArticleDOI
01 Sep 2004-Methods
TL;DR: NMR structural investigations of equilibrium conformers under pressure provide information about the structures of kinetic intermediates during folding/unfolding reactions, and can also be used to investigate association/dissociation equilibria of oligomeric or aggregated proteins.

Journal ArticleDOI
TL;DR: In this paper, the conformational equilibria of neutral serine are studied by experimental matrix-isolation Fourier transform infrared spectroscopy in combination with density functional theory (DFT) calculations.
Abstract: The conformational equilibria of neutral serine are studied by experimental matrix-isolation Fourier transform infrared spectroscopy in combination with density functional theory (DFT) calculations. The geometries and energies of the low-energy conformers of serine were optimized using the DFT(B3LYP)/6-31++G** method. In addition, we calculated the infrared frequencies and intensities of the most stable conformers in order to assist in the assignment of the vibrational bands in the experimental spectrum. The calculated relative energies suggest that four conformers are sufficiently stable to appear in the gas phase and all could be distinguished in the experimental matrix infrared spectra. We also calculated theoretical rotamerization constants and compared these with experimental determined constants. For the equilibria SER2/SER1 and SER3/SER1, a deviation between the experimental rotamerization constant and the theoretical constant was found. A relatively strong intramolecular H-bond in conformers SER2 ...

Book ChapterDOI
TL;DR: In this article, the conformational analysis and stereodynamics of saturated six-membered rings are provided, and the preferred conformers with one exo- or endo-double bond in the solid state are tabulated in the chapter.
Abstract: Publisher Summary Saturated six-membered heterocyclic rings can be found in natural products, drugs, and polymers. The methodologies for studying the conformers at equilibrium and their rates of interconversion are mainly based on nuclear magnetic resonance (NMR) spectroscopy. This chapter provides the conformational analysis and stereodynamics of saturated heterocyclic six-membered rings. The cyclohexane-like rings are characterized by the presence of various nonplanar conformations: chair, boat, and twist conformations. The conformational equilibria in six methylcyclohexanes are examined in the chapter using the temperature dependence of the 13 C chemical shifts at temperatures above the coalescence point. The conformational enthalpy (∆H°), entropy (∆S°) and free energy (∆G°) of methyl-, ethyl-, and iso-propyl-cyclohexane for monosubstituted and polysubstituted cyclohexanes in solution are examined in the chapter both experimentally and computationally. The stereochemistry, physical and chemical properties, and some transformations of 1,3-oxathianes—especially alkyl substituent effects on the preferred conformers—are also reviewed in the chapter. The synthesis and conformational analysis of the condensed-skeleton saturated heterocycles are also described in the chapter. The preferred conformers of six-membered rings with one exo- or endo-double bond in the solid state are tabulated in the chapter.

Journal ArticleDOI
TL;DR: In this paper, the α−β anomer energy difference and the stability of 10 rotamers of counterclockwise d-glucopyranose were studied in vacuo and in aqueous solution at the B3LYP/6-31+G(d,p) level.
Abstract: The α−β anomer energy difference and the stability of 10 rotamers of counterclockwise d-glucopyranose were studied in vacuo and in aqueous solution at the B3LYP/6-31+G(d,p) level. To obtain the solute charge distribution and the solvent structure around it, we used the averaged solvent electrostatic potential from molecular dynamics method, ASEP/MD, which alternates molecular dynamics and quantum mechanics calculations in an iterative procedure. The main characteristics of the anomeric equilibrium, both in vacuo and in solution, are well reproduced. The relative stability of the different anomers is related to the availability of the free pairs of electrons in the anomeric oxygen to interact with the water molecules. The influence of solvation in the conformer equilibrium is also analyzed.

Journal ArticleDOI
TL;DR: The prospects for the hole-filling technique for providing insight into energy flow in large molecules are discussed, leaving a more detailed theoretical modeling to the adjoining paper.
Abstract: The conformational isomerization dynamics of N-acetyl tryptophan methyl amide (NATMA) and N-acetyl tryptophan amide (NATA) have been studied using the methods of IR-UV hole-filling spectroscopy (HFS) and IR-induced population transfer spectroscopy (IR-PTS), which were developed for this purpose. Single conformations of these molecules were selectively excited in well-defined NH stretch fundamentals. This excess energy was used to drive conformational isomerization. By carrying out the infrared excitation early in a supersonic expansion, the excited molecules were recooled into their zero-point levels, partially refilling the hole created in the ground state population of one of the conformers, and creating gains in population in other conformers. These changes in population were detected using laser-induced fluorescence downstream in the expansion. In HFS, the IR wavelength is fixed and the UV laser tuned in order to determine where the population went following selective infrared excitation. In IR-PTS, the UV is fixed to monitor the population of a given conformation, and the IR is tuned to record the IR-induced changes in the population of the monitored conformer. Besides demonstrating the capability of the experiment to change the downstream conformational population distribution, the IR-PTS scans were used to extract two quantitative results: (i) The fractional populations of the conformers in the absence of the infrared, and (ii) the isomerization quantum yields for each of the six unique amide NH stretch fundamentals (three conformers each with two amide groups). The method for obtaining quantum yields is described in detail. In both NATMA and NATA, the quantum yields show modest conformational specificity, but only a hint of vibrational mode specificity. The prospects for the hole-filling technique for providing insight into energy flow in large molecules are discussed, leaving a more detailed theoretical modeling to the adjoining paper [Evans et al. J. Chem. Phys. 120, 148 (2004)].

Journal ArticleDOI
TL;DR: In this paper, the first mild routes to the first Ru(η3-pincer) derivatives of bis((dicyclohexylphosphino)methyl)benzene are reported.

Journal ArticleDOI
TL;DR: In this article, a detailed analysis of the vibrational spectra of the cis form of four acetic acid isotopologues (CH 3COOH, CH 3COOD, CD3COOCH and CD3COOD) was performed to evaluate the possible conformational dependence of photodissociation.
Abstract: Acetic acid monomer has two stable geometries, the cis and trans conformers. The high-energy cis conformer has been recently detected experimentally for the first time (Macoas et al.J. Am. Chem. Soc. 2003, 125, 16188). The cis conformer can be produced in low-temperature rare-gas matrixes upon vibrational excitation of the ground-state trans conformer. Fast tunneling from cis -t otrans-acetic acid takes place even at the lowest working temperatures (8 K), limiting the time available to study the high-energy form. Deuteration of the hydroxyl group reduces the tunneling rate by approximately 4 orders of magnitude, increasing accordingly the lifetime of the unstable conformer and its available concentration. In this work, we present a detailed analysis of the vibrational spectra of the cis form of four acetic acid isotopologues (CH 3COOH, CH3COOD, CD3COOH and CD3COOD). Photolysis (193 nm) of the trans and cis forms of the perdeuterated compound was performed to evaluate the possible conformational dependence of photodissociation of acetic acid. However, no evidence of conformer specific photodissociation was found. The UV photolysis of the matrix-isolated acetic acid reveals very different products from the gas phase. Methanol complexed with carbon monoxide is the major product of photolysis of acetic acid isolated in Ar matrixes whereas it has never been observed as a photolysis product in the gas phase.

Journal ArticleDOI
TL;DR: In this article, a combination of electronic, structural, and energetic analyses showed that a somewhat larger intrinsic donor ability of the C−H bonds compared to that of C−C bonds can be overshadowed by cooperative hyperconjugative interactions with participation of remote substituents.
Abstract: A combination of electronic, structural, and energetic analyses shows that a somewhat larger intrinsic donor ability of the C−H bonds compared to that of C−C bonds can be overshadowed by cooperative hyperconjugative interactions with participation of remote substituents (double hyperconjugation or through-bond interaction). The importance of double hyperconjugation was investigated computationally using two independent criteria: (a) relative total energies and geometries of two conformers (“hyperconjomers”) of δ-substituted cyclohexyl cations (b) and natural bond orbital (NBO) analysis of electronic structure and orbital interactions in these molecules. Both criteria clearly show that the apparent donor ability of C−C bonds can vary over a wide range, and the relative order of donor ability of C−H and C−C bonds can be easily inverted depending on molecular connectivity and environment. In general, relative donor abilities of σ bonds can be changed by their through-bond communication with remote substitue...

Journal ArticleDOI
TL;DR: In this X-ray study, a novel intramolecular S-O close contact is discovered and it is suggested that the restricted conformation effected the affinity to S4 subsite of fXa.
Abstract: Our exploratory study was based on the concept that a non-amidine factor Xa (fXa) inhibitor is suitable for an orally available anticoagulant. We synthesized and evaluated a series of N-(6-chloronaphthalen-2-yl)sulfonylpiperazine derivatives incorporating various fused-bicyclic rings containing an aliphatic amine expected to be S4 binding element. Among this series, 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine type 61 displayed orally potent anti-fXa activity and evident prolongation of prothrombin time (PT) with the moderate bioavailability in rats. The X-ray crystal analysis afforded an obvious binding mode that 5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine and 6-chloronaphthalene respectively bound to S4 and S1 subsites. In this X-ray study, we discovered a novel intramolecular S-O close contact. Ab initio energy calculations of model compounds deduced that conformers with the most close S-O proximity were most stable. The Mulliken population analysis proposed that this energy profile was caused by both of electrostatic S-O affinity and N-O repulsion. The results of these calculations and X-ray analysis suggested a possibility that the restricted conformation effected the affinity to S4 subsite of fXa.

Journal ArticleDOI
TL;DR: In this paper, a combined experimental and theoretical study of the 9-methylguanine (9MG) nucleobase and its monohydrate in the gas phase was performed. But the results were limited to the presence of only one tautomer of 9MG, among the three forms expected from an energetic basis.
Abstract: The present work reports a combined experimental and theoretical study of the 9-methylguanine (9MG) nucleobase and its monohydrate in the gas phase. Laser spectroscopy provides optical evidence for the presence of only one tautomer of 9MG, among the three forms expected from an energetic basis. Comparison with the calculated vibrational frequencies enables us to assign with confidence this form to the anti rotamer of the 9MG enol tautomer. The same approach allows us to conclude that the monomer conformation is retained in the monohydrate, with the water molecule bridging the OH proton donor and the N7 acceptor sites of 9MG. A complete comparison between all IR absorption data known for the enol tautomers of guanine and related compounds in the gas phase and the present calculations enables us to propose a consistent assignment for all of these enol tautomers in terms of rotamers. Finally, the fact that one does not observe either the most stable (and biologically relevant) keto form or the other enol rot...

Journal ArticleDOI
TL;DR: Partially resolved ultraviolet rotational band contours associated with the S1 ← S0 origin bands of the six most populated conformers of jet-cooled phenylalanine have been recorded via resonant two-photon ionization as mentioned in this paper.
Abstract: Partially resolved ultraviolet rotational band contours associated with the S1 ← S0 origin bands of the six most populated conformers of jet-cooled phenylalanine have been recorded via resonant two-photon ionization. The strong dependence of their transition moment orientation on the conformation of the alanyl side chain has facilitated their structural assignment through simulations based upon ab initio computation. The S1 lifetimes of all six conformers, measured through pump−probe delayed ionization, reveal an efficient nonradiative decay pathway in the most stable conformer, which is stabilized through a chain of intramolecular hydrogen bonds linking the side chain to the benzene ring.

Journal ArticleDOI
TL;DR: In this paper, solid-state 13C NMR measurements were made for the B2 and B4 phases of the P-14-O-PIMB, which exhibits a direct transformation from B2 phase to B4 phase.
Abstract: Solid-state 13C NMR measurements were made for the B2 and B4 phases of the achiral banana-shaped molecule, P-14-O-PIMB, which exhibits a direct transformation from the B2 phase to the B4 phase. In both phases, an NMR resonance signal assigned to carbonyl carbons of the ester linkages appears as doublet peaks, showing that the two carbonyl carbons are circumstanced in different electronic environments on the NMR time scale. The chemical shifts of the two peaks are 165.6 and 163.9 ppm in the B2 phase, and these values are not changed in the transformation to the low-temperature B4 phase. To explain this distinct splitting of the carbonyl carbon signal, we take three assumptions into account: (1) the molecules are accommodated in the unique phase, but the conformational exchange between two states takes place slowly; (2) the two side wings of each molecule experience fast interconformational jumps, but their “average conformer” is different, thus giving two different peaks in the spectra; and (3) the indivi...

Journal ArticleDOI
TL;DR: In this article, the authors designed a fluorescence sensor that exhibits high selectivity towards copper by integrating 4-dimethylamino-4′-cyano-biphenyl into the ligand backbone of a thioether-rich metal receptor.

Journal ArticleDOI
TL;DR: The water‐assisted tautomerization of glycine has been investigated at the B3LYP/6‐31+G** level using supermolecules containing up to six water molecules as well as considering a 1:1 glycine–water complex embedded in a continuum.
Abstract: The water-assisted tautomerization of glycine has been investigated at the B3LYP/6-31+G** level using supermolecules containing up to six water molecules as well as considering a 1:1 glycine-water complex embedded in a continuum. The conformations of the tautomers in this mechanism do not display an intramolecular H bond, instead the functional groups are bridged by a water molecule. The replacement of the intramolecular H bond by the bridging water reduces the polarity of the N-H bond in the zwitterion and increases that of the O-H bond in the neutral, stabilizing the zwitterion. Both the charge transfer effects and electrostatic interactions stabilize the nonintramolecularly H-bonded zwitterion conformer over the intramolecularly hydrogen bonded one. The nonintramolecularly H-bonded neutral is favored only by charge transfer effects. Although there is no strong evidence whether the intramolecularly hydrogen bonded or non hydrogen bonded structures are favored in the bulk solution represented as a dielectric continuum, it is likely that the latter species are more stable. The free energy of activation of the water-assisted mechanism is higher than the intramolecular proton transfer channel. However, when the presumably higher conformational energy of the zwitterion reacting in the intramolecular mechanism is taken into account, both mechanisms are observed to compete. The various conformers of the neutral glycine may form via multiple proton transfer reactions through several water molecules instead of a conformational rearrangement.

Journal ArticleDOI
TL;DR: The relative energies and structural ordering obtained using the BP86 functional are in agreement with the previously reported relative energies calculated using second-order Moller–Plesset (MP2) ab initio calculations.
Abstract: Conformational preferences of 1,4,7-trithiacyclononane were studied using a highly efficient sampling technique based on local nonstochastic deformations and the MM2(91) force field. The results show that conformers that the molecule adopts in the crystal state were found to be low-energy conformers (LECs) within 5 kcal mol−1 of the global minimum. A conformation with C1 symmetry was the global minimum and the C3 and C2 conformations were calculated to be 0.03 and 1.78 kcal mol−1 higher in energy, respectively. The structures were further minimized using Density Functional Theory (DFT) calculations with two different functionals. The C2 and the C1 conformations were found to be LECs with the C3 conformation more than 4.0 kcal mol-1 above the global minimum. The relative energies and structural ordering obtained using the BP86 functional are in agreement with the previously reported relative energies calculated using second-order Moller–Plesset (MP2) ab initio calculations. With the energy ordering being dependent on the molecular mechanics force field used, the approach of MM→DFT (searching exhaustively the available conformational space at the MM level followed by generating the energy ordering through DFT calculations) appears to be appropriate for thiacrown ethers.

Journal ArticleDOI
TL;DR: A major challenge in mutation structural biology is to carry out adduct- and site-specific experiments in a conformationally specific manner within biologically relevant environments to provide an accurate account of how a single chemically homogenous adduct gives rise to complex multiple mutations, the earliest step in the induction of cancer.
Abstract: Arylamines and polycyclic aromatic hydrocarbons (PAHs), which are known as “bulky” carcinogens, have been studied extensively and upon activation in vivo, react with cellular DNA to form DNA-adducts. The available structure data accumulated thus far has revealed that conformational heterogeneity is a common theme among duplex DNA modified with these carcinogens. Several conformationally diverse structures have been elucidated and found to be in equilibrium in certain cases. The dynamics of the heterogeneity appear to be modulated by the nature of the adduct structure and the base sequences neighboring the lesion site. These can be termed as “adduct- and sequence-induced conformational heterogeneities,” respectively. Due to the small energy differences, the population levels of these conformers could readily be altered within the active sites of repair or replicate enzymes. Thus, the complex role of “enzyme-induced conformational heterogeneity” must also be taken into consideration for the establi...

Journal ArticleDOI
TL;DR: It is demonstrated that the resulting minimal module exists as a folded conformer through the formation of a nine-membered ring stabilized by intramolecular hydrogen bonding, and molecular mechanics calculations and NMR studies support the existence of these folded conformers.
Abstract: Secondary squaramides have considerable potential as hydrogen bond donors and acceptors. In CHCl3 both, anti- and syn-squaramide rotamers are observed by NMR. The energetic barrier for anti/syn mutual interconversion determined by complete band shape analysis is ∼63 kJ mol-1. As in proline derivatives, a low rotational barrier is crucial for the design of foldable modules. In this paper, folding based on the low rotational barrier of squaramides is driven by donor atoms (N or O) located in the γ position of an alkyl chain of a secondary squaramide. We demonstrate that the resulting minimal module exists as a folded conformer through the formation of a nine-membered ring stabilized by intramolecular hydrogen bonding. Molecular mechanics calculations and NMR studies support the existence of these folded conformers. The intramolecularly hydrogen bonded conformers are clearly visible even in CHCl3−EtOH mixtures. Folding occurs even in pure ethanol. As an indirect test, we studied the effectiveness of macrocyc...

Journal ArticleDOI
TL;DR: It is hypothesized that tight packing of co-evolved residues in this region, and the subsequent deformation of Phe228, contributes to the high cooperativity and large energetic barriers for folding and unfolding of alphaLP, a critical role in extending the lifetime of the protease in its harsh environment.

Journal ArticleDOI
TL;DR: It appears that N(OMe) oligosaccharide analogues exhibit a slightly different conformational behavior to their parent natural disaccharides.
Abstract: N(OMe)-linked disaccharide analogues, isosteric to the corresponding natural disaccharides, have been synthesized by chemoselective assembly of unprotected natural monosaccharides with methyl 6-deoxy-6-methoxyamino-alpha-D-glucopyranoside in an aqueous environment. The coupling reactions were found to be chemo- and stereoselective affording beta-(1-->6) disaccharide mimics when using Glc and GlcNAc; in the case of Gal, the beta-anomer was prevalent (beta:alpha=7:1). An iterative method for the synthesis of linear N(OMe) oligosaccharide analogues was demonstrated, based on the use of an unprotected monosaccharide building block in which an oxime functionality at C-6 is converted during the synthesis into the corresponding methoxyamino group. The conformational analysis of these compounds was carried out by using NMR spectroscopy, ab initio, molecular mechanics, and molecular dynamics methods. Optimized geometries and energies of fourteen conformers for each compound have been calculated at the B3LYP/6-31G* level. Predicted conformational equilibria were compared with the results based on NMR experiments and good agreement was found. It appears that N(OMe)-linked disaccharide analogues exhibit a slightly different conformational behavior to their parent natural disaccharides.