Showing papers on "Conformational isomerism published in 2014"
TL;DR: In this paper, the conformations adopted by flexible molecules in their crystal structures are assessed in terms of their relationship to the calculated global conformational landscape, which leads to a dramatic improvement in the ability to predict the conformation adopted by molecules in the crystal structures.
Abstract: The ability to anticipate the shape adopted by flexible molecules in the solid state is crucial for engineering and predicting crystal packing and, hence, properties. In this study, the conformations adopted by flexible molecules in their crystal structures are assessed in terms of their relationship to the calculated global conformational landscape. The study quantifies the limits on molecular strain that can be induced by intermolecular interactions in single-component crystal structures of molecules with no intramolecular hydrogen bonding, demonstrating that some molecules are distorted by up to 20 kJ mol−1 by crystal packing forces. Furthermore, we find that crystallisation often selects high energy conformers, but only when the high energy conformer is more extended than the lower energy options, allowing for greater intermolecular stabilisation. Based on these observations, we propose that the crystallisability of conformers is assessed in terms of their energies and surface areas. We formulate this as a parameterised pseudo-energy related to molecular surface area, which leads to a dramatic improvement in our ability to predict the conformations adopted by molecules in their crystal structures.
146 citations
TL;DR: The strength of the intrahelical bifurcated H bond is consistent with its prevalence in hydrophobic environments and is shown to significantly impact side-chain rotamer distribution.
Abstract: Macromolecules are characterized by their particular arrangement of H bonds. Many of these interactions involve a single donor and acceptor pair, such as the regular H-bonding pattern between carbonyl oxygens and amide H+s four residues apart in α-helices. The H-bonding potential of some acceptors, however, leads to the phenomenon of overcoordination between two donors and one acceptor. Herein, using isotope-edited Fourier transform infrared measurements and density functional theory (DFT) calculations, we measured the strength of such bifurcated H bonds in a transmembrane α-helix. Frequency shifts of the 13C=18O amide I mode were used as a reporter of the strength of the bifurcated H bond from a thiol and hydroxyl H+ at residue i + 4. DFT calculations yielded very similar frequency shifts and an energy of −2.6 and −3.4 kcal/mol for the thiol and hydroxyl bifurcated H bonds, respectively. The strength of the intrahelical bifurcated H bond is consistent with its prevalence in hydrophobic environments and is shown to significantly impact side-chain rotamer distribution.
100 citations
TL;DR: NMR experiments are presented and a simple strategy for studies of such conformationally excited states based on measurement of histidine 13Cγ, 13Cδ2 chemical shifts and 1Hε-13Cε one-bond scalar couplings are developed.
Abstract: The histidine imidazole side chain plays a critical role in protein function and stability Its importance for catalysis is underscored by the fact that histidines are localized to active sites in ∼50% of all enzymes NMR spectroscopy has become an important tool for studies of histidine side chains through the measurement of site-specific pKas and tautomer populations To date, such studies have been confined to observable protein ground states; however, a complete understanding of the role of histidine electrostatics in protein function and stability requires that similar investigations be extended to rare, transiently formed conformers that populate the energy landscape, yet are often “invisible” in standard NMR spectra Here we present NMR experiments and a simple strategy for studies of such conformationally excited states based on measurement of histidine 13Cγ, 13Cδ2 chemical shifts and 1He-13Ce one-bond scalar couplings The methodology is first validated and then used to obtain pKa values and tautomer distributions for histidine residues of an invisible on-pathway folding intermediate of the colicin E7 immunity protein Our results imply that the side chains of H40 and H47 are exposed in the intermediate state and undergo significant conformational rearrangements during folding to the native structure Further, the pKa values explain the pH-dependent stability differences between native and intermediate states over the pH range 55–65 and they suggest that imidazole deprotonation is not a barrier to the folding of this protein
99 citations
TL;DR: Electronic structure theory and vibrational spectroscopy are employed to study molecular interactions in the room-temperature ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide and the results are compared with experimental observations from Raman scattering and IR absorption spectroscopies.
Abstract: Electronic structure theory (density functional and Moller-Plesset perturbation theory) and vibrational spectroscopy (FT-IR and Raman) are employed to study molecular interactions in the room-temperature ionic liquid 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide. Different conformers of a cation-anion pair based on their molecular interactions are simulated in the gas phase and in a dielectric continuum solvent environment. Although the ordering of conformers in energy varies with theoretical methods, their predictions for three lowest energy conformers in the gas phase are similar. Strong C-H---N interactions between the acidic hydrogen atom of the cation imidazole ring and the nitrogen atom of the anion are predicted for either the lowest or second lowest energy conformer. In a continuum solvent, different theoretical methods yield the same ion-pair conformation for the lowest energy state. In both phases, the density functional method predicts that the anion is in a trans conformation in the lowest energy ion pair state. The theoretical results are compared with experimental observations from Raman scattering and IR absorption spectroscopies and manifestations of the molecular interactions in the vibrational spectra are discussed. The directions of the frequency shifts of the characteristic vibrations relative to the free anion and cation are explained by calculating the difference electron density coupled with electron density topography.
87 citations
TL;DR: A series of computational models have been used to demonstrate that the mutual conformation of the metal fragments--and even more importantly the orientation of the bridging ligand relative to those metal centers--influences the electronic coupling sufficiently to afford valence-trapped conformations, which are of sufficiently low energy to be thermally populated.
Abstract: The conformational energy landscape and the associated electronic structure and spectroscopic properties (UV/Vis/near-infrared (NIR) and IR) of three formally d5/d6 mixed-valence diruthenium complex cations, [{Ru(dppe)Cp*}2(μ-C≡CC6H4C≡C)]+, [1]+, [trans-{RuCl(dppe)2}2(μ-C≡CC6H4C≡C)]+, [2]+, and the Creutz–Taube ion, [{Ru(NH3)5}2(μ-pz)]5+, [3]5+ (Cp=cyclopentadienyl; dppe=1,2-bis(diphenylphosphino)ethane; pz=pyrazine), have been studied using a nonstandard hybrid density functional BLYP35 with 35 % exact exchange and continuum solvent models. For the closely related monocations [1]+ and [2]+, the calculations indicated that the lowest-energy conformers exhibited delocalized electronic structures (or class III mixed-valence character). However, these minima alone explained neither the presence of shoulder(s) in the NIR absorption envelope nor the presence of features in the observed vibrational spectra characteristic of both delocalized and valence-trapped electronic structures. A series of computational models have been used to demonstrate that the mutual conformation of the metal fragments—and even more importantly the orientation of the bridging ligand relative to those metal centers—influences the electronic coupling sufficiently to afford valence-trapped conformations, which are of sufficiently low energy to be thermally populated. Areas in the conformational phase space with variable degrees of symmetry breaking of structures and spin-density distributions are shown to be responsible for the characteristic spectroscopic features of these two complexes. The Creutz–Taube ion [3]5+ also exhibits low-lying valence-trapped conformational areas, but the electronic transitions that characterize these conformations with valence-localized electronic structures have low intensities and do not influence the observed spectroscopic characteristics to any notable extent.
76 citations
TL;DR: In this article, the conformational behavior of isolated D-glucose has been revealed using Fourier transform microwave spectroscopy coupled with laser ablation of crystalline α- and β- glucopyranose samples.
Abstract: The conformational behaviour of isolated D-glucose has been revealed in this work using Fourier transform microwave spectroscopy coupled with laser ablation of crystalline α- and β-glucopyranose samples. Four conformers of α-D-glucopyranose and three of β-D-glucopyranose have been unequivocally identified on the basis of the spectroscopic rotational parameters in conjunction with ab initio predictions. Stereoelectronic hyperconjugative factors, like those associated with anomeric or gauche effects, as well as the cooperative OH⋯O chains extended along the entire molecule, are the main factors driving the conformational behaviour. The most abundant conformers exhibit a counter-clockwise arrangement (cc) of the network of intramolecular hydrogen bonds.
73 citations
TL;DR: In this article, a combined computational/Raman spectroscopic analyses of ethylene carbonate (EC) and propylene carbonates (PC) solvation interactions with lithium salts are reported.
68 citations
TL;DR: It is shown that the conformational ensemble of PaaA2 is highly compact and that the protein exists in solution as two preformed helices, connected by a flexible linker, that probably act as molecular recognition elements for toxin inhibition.
59 citations
TL;DR: Conformational dynamics from the solvent state distribution to the gas-phase "de-solvated" state distribution demonstrated that ATHP is "structured", and relative abundances are associated with the relative stability between the proposed conformers.
Abstract: The mammalian high mobility group protein HMGA2 contains three DNA binding motifs associated with many physiological functions including oncogenesis, obesity, stem cell youth, human height, and human intelligence. In the present paper, trapped ion mobility spectrometry-mass spectrometry (TIMS-MS) has been utilized to study the conformational dynamics of the third DNA binding motif using the “AT hook” decapeptide unit (Lys1-Arg2-Prol3-Arg4-Gly5-Arg6-Prol7-Arg8-Lys9-Trp10, ATHP) as a function of the solvent state. Solvent state distributions were preserved during electrospray ion formation, and multiple IMS bands were identified for the [M + 2H]2+ and for the [M + 3H]3+ charge states. Conformational isomer interconversion rates were measured as a function of the trapping time for the [M + 2H]2+ and [M + 3H]3+ charge states. Candidate structures were proposed for all IMS bands observed. Protonation site, proline residue conformation, and side chain orientations were identified as the main motifs governing th...
58 citations
TL;DR: It is found that increasing the electron-withdrawing character of the substituents gives oligomers with substantially improved folding properties, and stronger electron withdrawing groups give oligomers for which misfolded states are undetectable by NMR.
Abstract: The ortho-phenylenes are a simple class of foldamers, with the formation of helices driven by offset aromatic stacking interactions parallel to the helical axis. For the majority of reported o-phenylene oligomers, the perfectly folded conformer comprises perhaps 50–75% of the total population. Given the hundreds or thousands of possible conformers for even short oligomers, this distribution represents a substantial bias toward the folded state. However, “next-generation” o-phenylenes with better folding properties are needed if these structures are to be exploited as functional units within more complex architectures. Here, we report several new series of o-phenylene oligomers, varying both the nature and orientation of the substituents on every repeat unit. The conformational behavior was probed using a combination of NMR spectroscopy, DFT calculations, and X-ray crystallography. We find that increasing the electron-withdrawing character of the substituents gives oligomers with substantially improved fol...
54 citations
TL;DR: A statistical analysis of the linear trajectories of NMR chemical shifts (CONCISE, COordiNated ChemIcal Shifts bEhavior) for the interpretation of protein conformational equilibria is proposed and tested with the catalytic subunit of cAMP-dependent protein kinase A, a ubiquitous enzyme that undergoes conformational transitions upon both nucleotide and pseudo-substrate binding.
Abstract: Proteins exist as an ensemble of conformers that are distributed on free energy landscapes resembling folding funnels. While the most stable conformers populate low energy basins, protein function is often carried out through low-populated conformational states that occupy high energy basins. Ligand binding shifts the populations of these states, changing the distribution of these conformers. Understanding how the equilibrium among the states is altered upon ligand binding, interaction with other binding partners, and/or mutations and post-translational modifications is of critical importance for explaining allosteric signaling in proteins. Here, we propose a statistical analysis of the linear trajectories of NMR chemical shifts (CONCISE, COordiNated ChemIcal Shifts bEhavior) for the interpretation of protein conformational equilibria. CONCISE enables one to quantitatively measure the population shifts associated with ligand titrations and estimate the degree of collectiveness of the protein residues' response to ligand binding, giving a concise view of the structural transitions. The combination of CONCISE with thermocalorimetric and kinetic data allows one to depict a protein's approximate conformational energy landscape. We tested this method with the catalytic subunit of cAMP-dependent protein kinase A, a ubiquitous enzyme that undergoes conformational transitions upon both nucleotide and pseudo-substrate binding. When complemented with chemical shift covariance analysis (CHESCA), this new method offers both collective response and residue-specific correlations for ligand binding to proteins.
TL;DR: Interactions determining the dissolution of a monomer of β-cellulose, i.e., cellobiose in a room temperature ionic liquid, [Emim][OAc], have been studied using ab initio molecular dynamics simulations.
Abstract: Interactions determining the dissolution of a monomer of β-cellulose, i.e., cellobiose in a room temperature ionic liquid, [Emim][OAc], have been studied using ab initio molecular dynamics simulations. Although anions are the predominant species in the first coordination shell of cellobiose, cations too are present to a minor extent around it. The presence of low concentration of water in the solution does not significantly alter the nature of the coordination environment of cellobiose. All intra-molecular hydrogen bonds of anti–syn cellobiose are replaced by inter-molecular hydrogen bonds formed with the anions, whereas the anti–anti conformer retains an intramolecular hydrogen bond.
TL;DR: Surprisingly, these small hydration clusters show highly specific binding preferences, and strongly prefer the insertion H-bonding topology, but they also favor specific pointing direction(s) for their non-H-bonded hydroxy group(s).
Abstract: Hydration of chiral molecules is a subject of significant current interest in light of recent experimental observations of chirality transfer from chiral solutes to water in solution and the important roles which water plays in biological events. Using a broadband chirped pulse and a cavity based microwave spectrometer, we detected spectroscopic signatures of the mono- and dihydrates of methyl lactate, a chiral hydroxy ester. Surprisingly, these small hydration clusters show highly specific binding preferences. Not only do they strongly prefer the insertion H-bonding topology, but they also favor specific pointing direction(s) for their non-H-bonded hydroxy group(s). We observed that the particular dihydrate conformer identified is not the most stable one predicted. This work highlights the superior capability of high-resolution spectroscopy to identify specific water binding topologies, and provides quantitative data to test state-of-the-art theory.
TL;DR: In this paper, the solution and the solid state structure of an α-lithiated aryloxirane (1-Li) were determined using a single crystal X-ray diffraction analysis of 1-Li performed at 100 K applying the X-TEMP-2 device.
Abstract: α-Lithiated epoxides, long considered “fleeting” intermediates in the reactions of epoxides with strong bases, have nowadays proven to be key synthons for asymmetric synthesis. In this study, the solution and the solid state structure of an α-lithiated aryloxirane, namely α-lithiated ortho-trifluoromethyl styrene oxide (1-Li), were determined. Single crystal X-ray diffraction analysis of 1-Li performed at 100 K applying the X-TEMP-2 device revealed a self-assembled heterochiral dimeric structure with a rare central six-membered (O–Li–C)2 planar core, which is unprecedented in Li/oxygen carbenoids. Multinuclear magnetic resonance (1H, 13C, 19F, 7Li) studies suggested that 1-Li exists in THF solution as a mixture of two interconverting diastereomeric dimeric aggregates, each one featuring a single σ-contact between lithium and a carbon atom. Line shape analysis provided activation parameters for both the dynamic interconversion of the two dimers and the enantiomerisation of 1-Li, which proved to be mostly entropy controlled. The structural assignment in solution was supported by density functional theory computations through the investigation of conformers of monomeric and dimeric complexes of 1-Li featuring different degrees of specific solvation. A mechanism based on the equilibration of six-membered homo- and heterochiral dimers was proposed to explain the configurational instability exhibited by 1-Li in THF.
TL;DR: In this case, upon near-IR excitation, the most stable SSC form converted solely into a new conformer (SST), where the acid OH group is rotated by 180°, and this conformational transformation was found to be photoreversible.
Abstract: Structural transformations were induced in conformers of glycolic acid by selective excitation with monochromatic tunable near-infrared laser light. For the compound isolated in Ar matrixes, near-IR excitation led to generation of two higher-energy conformers (GAC; AAT) differing from the most stable SSC form by 180° rotation around the C–C bond. A detailed investigation of this transformation revealed that one conformer (GAC) is produced directly from the near-IR-excited most stable conformer. The other higher-energy conformer (AAT) was effectively generated only upon excitation of the primary photoproduct (GAC) with another near-IR photon. Once these higher-energy conformers of glycolic acid were generated in an Ar matrix, they could be subsequently transformed into one another upon selective near-IR excitations. Interestingly, no repopulation of the initial most stable SSC conformer occurred upon near-IR excitation of the higher-energy forms of the compound isolated in solid Ar. A dramatically differen...
TL;DR: The electronic properties of the complexes are strongly, and independently, influenced by the P-substituents at the P(R)2N(Ph)2 ligand as well as by modifications of the bdt bridge, illustrating the advantages of this modular platform, which allows independent and selective tuning through site specific modifications.
Abstract: A series of six mononuclear iron complexes of the type [Fe(X-bdt)(PR2NPh2)(CO)] (PR2NPh2 = 1,5-diaza-3,7-diphosphaoctane, bdt = benzenedithiolate with X = H, Cl2 or Me and R = Ph, Bn, Cyc or tert-Bu) was prepared. This new class of penta-coordinate iron complexes contains a free coordination site and a pendant base as essential structural features of the [FeFe]-hydrogenase active site. The bidentate nature of the PR2NPh2 ligands was found to be crucial for the preferential formation of coordinatively unsaturated penta-coordinate complexes, which is supported by first principle calculations. IR-spectroscopic data suggest the presence of coordination isomers around the metal center, as well as multiple possible conformers of the PR2NPh2 ligand. This finding is further corroborated by X-ray crystallographic and computational studies. 31P{1H}-NMR- and IR-spectroscopic as well as electrochemical measurements show that the electronic properties of the complexes are strongly, and independently, influenced by the P-substituents at the PR2NPh2 ligand as well as by modifications of the bdt bridge. These results illustrate the advantages of this modular platform, which allows independent and selective tuning through site specific modifications. Potential catalytic intermediates, namely singly reduced and protonated complexes, have been further investigated by spectroscopic methods and exhibit remarkable stability. Finally, their general capacity for electro-catalytic reduction of protons to molecular hydrogen was verified.
TL;DR: This work presents complete structural and functional snapshots of nine equilibrium conformers of human hemoglobin in the half-liganded and fully liganded states by using a novel combination of X-ray diffraction analysis and microspectrophotometric O2 equilibrium measurements on three isomorphous crystals.
Abstract: Allostery in many oligomeric proteins has been postulated to occur via a ligand-binding-driven conformational transition from the tense (T) to relaxed (R) state, largely on the basis of the knowledge of the structure and function of hemoglobin, the most thoroughly studied of all allosteric proteins. However, a growing body of evidence suggests that hemoglobin possesses a variety of intermediates between the two end states. As such intermediate forms coexist with the end states in dynamic equilibrium and cannot be individually characterized by conventional techniques, very little is known about their properties and functions. Here we present complete structural and functional snapshots of nine equilibrium conformers of human hemoglobin in the half-liganded and fully liganded states by using a novel combination of X-ray diffraction analysis and microspectrophotometric O2 equilibrium measurements on three isomorphous crystals, each capturing three distinct equilibrium conformers. Notably, the conformational ...
TL;DR: Protonated benzylamine presents a relatively straightforward instance of a single stable conformer, providing a trial case for the adopted approach of IRMPD spectroscopy.
Abstract: Phenylalkylamines of the general formula C6H5(CH2)nNH2 (n = 1–4) have been delivered to the gas phase as protonated species using electrospray ionization. The ions thus formed have been assayed by IRMPD spectroscopy in two different spectroscopic domains, namely, the 600–1800 and the 3000–3500 cm–1 regions using either an IR free electron laser or a tabletop OPO/OPA laser source. The interpretation of the experimental spectra is aided by density functional theory calculations of candidate species and vibrational frequency analyses. Protonated benzylamine presents a relatively straightforward instance of a single stable conformer, providing a trial case for the adopted approach. Turning to the higher homologues, C6H5(CH2)nNH3+ (n = 2–4), more conformations become accessible. For each C6H5(CH2)nNH3+ ion (n = 2–4), the most stable geometry is characterized by cation−π interactions between the positively charged ammonium group and the aromatic π-electronic system, permitted by the folding of the polymethylene...
TL;DR: An NMR chemical shift study of conformationally challenging seven-membered lactones is reported, and the use of a "match ratio"--the ratio of the larger CMAE (worse fit) to the smaller CMAe (better fit) is introduced; a greater match ratio value indicates better distinguishing ability.
Abstract: We report an NMR chemical shift study of conformationally challenging seven-membered lactones (1–11); computed and experimental data sets are compared. The computations involved full conformational analysis of each lactone, Boltzmann-weighted averaging of the chemical shifts across all conformers, and linear correction of the computed chemical shifts. DFT geometry optimizations [M06-2X/6-31+G(d,p)] and GIAO NMR chemical shift calculations [B3LYP/6-311+G(2d,p)] provided the computed chemical shifts. The corrected mean absolute error (CMAE), the average of the differences between the computed and experimental chemical shifts for each of the 11 lactones, is encouragingly small (0.02–0.08 ppm for 1H or 0.8–2.2 ppm for 13C). Three pairs of cis versus trans diastereomeric lactones were used to assess the ability of the method to distinguish between stereoisomers. The experimental shifts were compared with the computed shifts for each of the two possible isomers. We introduce the use of a “match ratio”—the ratio...
TL;DR: In this article, a salt screen of Lornoxicam (LXM) was undertaken to improve drug solubility and to study different conformations of the molecule by varying the counterion.
Abstract: Lornoxicam (LXM), a nonsteroidal anti-inflammatory drug (NSAID), is an amphiprotic molecule that exists as a zwitterion in the solid state. The formation of two strong intramolecular N+–H···O and N–H···O– hydrogen bonds in a stable six-member ring geometry, S(6), renders this otherwise flexible molecule in a rigid conformation (conformer A). A salt screen of LXM was undertaken to improve drug solubility and to study different conformations of the molecule by varying the counterion. As an amphoteric molecule, LXM salts are both cationic (ammonia, piperazine) and anionic (hydrochloric acid, methanesulfonic acid). The crystal structures of these salts exhibit an intramolecular H bond with different conformations of LXM in the acid and base salts (conformations B and C). The conformational variability of LXM in acidic and basic salts is explained by steric and hydrogen bonding factors. All the new salts were characterized by spectroscopic, thermal, powder X-ray diffraction techniques and showed enhanced solub...
Journal Article•
TL;DR: The results verify the role of the gauche effect between O5 and O6 atoms in gluco- and manno-configured pyranosides causing the ω torsion angle to sample an equilibrium between the gt and gg rotamers.
Abstract: Conformational sampling for a set of 10 α- or β-(1→6)-linked oligosaccharides has been studied using explicit solvent Hamiltonian replica exchange (HREX) simulations and NMR spectroscopy techniques. Validation of the force field and simulation methodology is done by comparing calculated transglycosidic J coupling constants and proton–proton distances with the corresponding NMR data. Initial calculations showed poor agreement, for example, with >3 Hz deviation of the calculated ³J(H5,H6R) values from the experimental data, prompting optimization of the ω torsion angle parameters associated with (1→6)-linkages. The resulting force field is in overall good agreement (i.e., within ∼0.5 Hz deviation) from experimental ³J(H5,H6R) values, although some small limitations are evident. Detailed hydrogen bonding analysis indicates that most of the compounds lack direct intramolecular H-bonds between the two monosaccharides; however, minor sampling of the O6···HO2′ hydrogen bond is present in three compounds. The results verify the role of the gauche effect between O5 and O6 atoms in gluco- and manno-configured pyranosides causing the ω torsion angle to sample an equilibrium between the gt and gg rotamers. Conversely, galacto-configured pyranosides sample a population distribution in equilibrium between gt and tg rotamers, while the gg rotamer populations are minor. Water radial distribution functions suggest decreased accessibility to the O6 atom in the (1→6)-linkage as compared to the O6′ atom in the nonreducing sugar. The role of bridging water molecules between two sugar moieties on the distributions of ω torsion angles in oligosaccharides is also explored.
TL;DR: A mechanistic discussion of the tautomerization process occurring during sublimation, accounting also for the observed minor decomposition of TAA leading to CO2 and 5-methyl-tetrazole, is proposed.
Abstract: Monomers of (tetrazol-5-yl)-acetic acid (TAA) were obtained by sublimation of the crystalline compound and the resulting vapors were isolated in cryogenic nitrogen matrices at 13 K. The conformational and tautomeric composition of TAA in the matrix was characterized by infrared spectroscopy and vibrational calculations carried out at the B3LYP/6-311++G(d,p) level. TAA may adopt two tautomeric modifications, 1H- and 2H-, depending on the position of the annular hydrogen atom. Two-dimensional potential energy surfaces (PESs) of TAA were theoretically calculated at the MP2/6-311++G(d,p) level, for each tautomer. Four and six symmetry-unique minima were located on these PESs, for 1H- and 2H-TAA, respectively. The energetics of the detected minima was subsequently refined by calculations at the QCISD level. Two 1H- and three 2H-conformers fall within the 0–8 kJ mol−1 energy range and should be appreciably populated at the sublimation temperature (∼330 K). Observation of only one conformer for each tautomer (1ccc and 2pcc) is explained in terms of calculated barriers to conformational rearrangements. All conformers with the cis O=COH moiety are separated by low barriers (less than 10 kJ mol−1) and collapse to the most stable 1ccc (1H-) and 2pcc (2H-) forms during deposition of the matrix. On the trans O=COH surfaces, the relative energies are very high (between 12 and 27 kJ mol−1). The trans forms are not thermally populated at the sublimation conditions and were not detected in matrices. One high-energy form in each tautomer, 1cct (1H-) and 2pct (2H-), was found to differ from the most stable form only by rotation of the OH group and separated from other forms by high barriers. This opened a perspective for their stabilization in a matrix. 1cct and 2pct were generated in the matrices selectively by means of narrow-band near-infrared (NIR) irradiations of the samples at 6920 and 6937 cm−1, where the first OH stretching overtone vibrations of 1ccc and 2pcc occur. The reverse transformations could be induced by irradiations at 7010 and 7030 cm−1, transforming 1cct and 2pct back to 1ccc and 2pcc, also selectively. Besides the NIR-induced transformations, the photogenerated 1cct and 2pct forms also decay in N2 matrices back to 1ccc and 2pcc spontaneously, with characteristic decay times of hours (1H) and tens of minutes (2H). The decay mechanism is rationalized in terms of the proton tunneling. In crystals, TAA exists exclusively as 1H-tautomer. By contrast, the tautomeric composition of the matrix-isolated monomers was found to consist of both 1H- and 2H-tautomers, in comparable amounts. A mechanistic discussion of the tautomerization process occurring during sublimation, accounting also for the observed minor decomposition of TAA leading to CO2 and 5-methyl-tetrazole, is proposed.
TL;DR: This paper describes the application of a fluorine gauche effect to predictably control torsional rotation in a class of fluorinated 4-(dimethylamino)pyridine (DMAP) analogues and validate this design approach to control molecular space.
TL;DR: A new free energy calculation method for molecular dynamics simulations using the two pseudorotation parameters directly as the collective variables and reveals the main transition path between the stable conformations of the five-membered furanose ring.
Abstract: The five-membered furanose ring is a central component of the chemical structure of biological nucleic acids. The conformations of the furanose ring can be analytically described using the concept of pseudorotation, and for RNA and DNA they are dominated by the C2'-endo and C3'-endo conformers. While the free energy difference between these two conformers can be inferred from NMR measurements, a free energy landscape of the complete pseudorotation cycle of nucleic acids in solution has remained elusive. Here, we describe a new free energy calculation method for molecular dynamics (MD) simulations using the two pseudorotation parameters directly as the collective variables. To validate our approach, we calculated the free energy surface of ribose pseudorotation in guanosine and 2'-deoxyguanosine. The calculated free energy landscape reveals not only the relative stability of the different pseudorotation conformers, but also the main transition path between the stable conformations. Applying this method to a standard A-form RNA duplex uncovered the expected minimum at the C3'-endo state. However, at a 2'-5' linkage, the minimum shifts to the C2'-endo conformation. The free energy of the C3'-endo conformation is 3 kcal/mol higher due to a weaker hydrogen bond and a reduced base stacking interaction. Unrestrained MD simulations suggest that the conversion from C3'-endo to C2'-endo and vice versa is on the nanosecond and microsecond time scale, respectively. These calculations suggest that 2'-5' linkages may enable folded RNAs to sample a wider spectrum of their pseudorotation conformations.
TL;DR: The rotational spectrum of one conformer of the tetramer of difluoromethane (CH2F2)4 is reported, and the network of weak hydrogen bonds which connect the four subunits is described.
TL;DR: It is shown that both FS as FC share a singly γ-folded backbone conformation as the most stable conformer, resulting in a more compact gamma turn structure.
Abstract: The conformational preferences of peptides are mainly controlled by the stabilizing effect of intramolecular interactions. In peptides with polar side chains, not only the backbone but also the side chain interactions determine the resulting conformations. In this paper, the conformational preferences of the capped dipeptides Ac-Phe-Ser-NH2 (FS) and Ac-Phe-Cys-NH2 (FC) are resolved under laser-desorbed jet cooling conditions using IR-UV ion dip spectroscopy and density functional theory (DFT) quantum chemistry calculations. As serine (Ser) and cysteine (Cys) only differ in an OH (Ser) or SH (Cys) moiety; this subtle alteration allows us to study the effect of the difference in hydrogen bonding for an OH and SH group in detail, and its effect on the secondary structure. IR absorption spectra are recorded in the NH stretching region (3200–3600 cm−1). In combination with quantum chemical calculations the spectra provide a direct view of intramolecular interactions. Here, we show that both FS as FC share a singly γ-folded backbone conformation as the most stable conformer. The hydrogen bond strength of OH⋯O (FS) is stronger than that of SH⋯O (FC), resulting in a more compact gamma turn structure. A second conformer is found for FC, showing a β turn interaction.
TL;DR: In this article, the rotational constants of the most stable conformer of the Ala dipeptide consistent with the values from microwave experiments were evaluated for the CCSD(T), MP2, dispersion-corrected DFT, CBS-QB3, and G4(MP2) levels of theory with various basis sets.
TL;DR: The conformational persistence observed in solution indicates that bis(dicarbollyl)nickel complexes may provide attractive templates for building electrically driven and/or photodriven molecular motors.
Abstract: As a continuation of work on metallacarborane-based molecular motors, the structures of substituted bis(dicarbollyl)nickel complexes in NiIII and NiIV oxidation states were investigated in solution by fluorescence spectroscopy. Symmetrically positioned cage-linked pyrene molecules served as fluorescent probes to enable the observation of mixed meso-trans/dl-gauche (pyrene monomer fluorescence) and dl-cis/dl-gauche (intramolecular pyrene excimer fluorescence with residual monomer fluorescence) cage conformations of the nickelacarboranes in the NiIII and NiIV oxidation states, respectively. The absence of energetically disfavored conformers in solution—dl-cis in the case of nickel(III) complexes and meso-trans in the case of nickel(IV)—was demonstrated based on spectroscopic data and conformer energy calculations in solution. The conformational persistence observed in solution indicates that bis(dicarbollyl)nickel complexes may provide attractive templates for building electrically driven and/or photodriven...
TL;DR: In this paper, the effect of multiple conformers in solution on nucleation, growth rate and polymorphism is reviewed and methods for crystallizing substances present as slow inter-converting conformers, including the evaluation of the propensity for nucleation of specific conformers via calculation of the intrinsic supersaturation.
TL;DR: Chang et al. as discussed by the authors reported a new experimental method for the characterization of conformer-specific effects in chemical reactions, where different conformers are spatially separated using inhomogeneous electric fields and reacted with a Coulomb crystal of cold, spatially localized ions in a trap.
Abstract: Many molecules exhibit multiple conformers that often easily interconvert under thermal conditions. Therefore, single conformations are difficult to isolate which renders the study of their distinct chemical reactivities challenging. We have recently reported a new experimental method for the characterization of conformer-specific effects in chemical reactions [Y.-P. Chang, K. Dlugolecki, J. Kupper, D. Rosch, D. Wild, and S. Willitsch, "Specific chemical reactivities of spatially separated 3-aminophenol conformers with cold Ca(+) ions," Science 342, 98-101 (2013)]. Different conformers are spatially separated using inhomogeneous electric fields and reacted with a Coulomb crystal of cold, spatially localized ions in a trap. As a first application, we studied reactions between the two conformers of 3-aminophenol and Ca(+). We observed a twofold larger rate constant for the cis compared to the trans conformer which was rationalized in terms of the differences in the long-range ion-molecule interactions. The present article provides a detailed description of the new method and a full account of the experimental results as well as the accompanying theoretical calculations.