Showing papers on "Conformational isomerism published in 2021"
TL;DR: For 68% of the investigated complexes at least one low-energy conformer was found that is more stable than the respective crystal structure conformation, which signals the importance of conformational studies.
Abstract: Conformational energies are an important chemical property for which a performance assessment of theoretical methods is mandatory. Existing benchmark sets are often limited to biochemical or main group element containing molecules, while organometallic systems are generally less studied. A key problem herein is to routinely generate conformers for these molecules due to their complexity and manifold of possible coordination patterns. In this study we used our recently published CREST protocol [Pracht et al., Phys. Chem. Chem. Phys., 2020, 22, 7169-7192] to generate conformer ensembles for a variety of 40 challenging transition metal containing molecules, which were then used to form a comprehensive conformational energy benchmark set termed TMCONF40. Several low-cost semiempirical, density functional theory (DFT) and force-field methods were compared to high level DLPNO-CCSD(T1) and double-hybrid DFT reference values. Close attention was paid to the energetic ordering of the conformers in the statistical evaluation. With respect to the double-hybrid references, both tested low-cost composite DFT methods produce high Pearson correlation coefficients of rp,mean,B97-3c//B97-3c = 0.922 and rp,mean,PBEh-3c//B97-3c = 0.890, with mean absolute deviations close to or below 1 kcal mol-1. This good performance also holds for a comparison to DLPNO-CCSD(T1) reference energies for a smaller subset termed TMCONF5. Based on DFT geometries, the GFNn-xTB methods yield reasonable Pearson correlation coefficients of rp,mean,GFN1-xTB//B97-3c = 0.617 (MADmean = 2.15 kcal mol-1) and rp,mean,GFN2-xTB//B97-3c = 0.567 (MADmean = 2.68 kcal mol-1), outperforming the widely used PMx methods on the TMCONF40 test set. Employing the low-cost composite DFT method B97-3c on GFN2-xTB geometries yields an slightly improved correlation of rp,mean,B97-3c//GFN2-xTB = 0.632. Furthermore, for 68% of the investigated complexes at least one low-energy conformer was found that is more stable than the respective crystal structure conformation, which signals the importance of conformational studies. General recommendations for the application of the CREST protocol and DFT methods for transition metal conformational energies are given.
40 citations
TL;DR: In this article, a trihexylsilylethynyl-substituted dimer was constructed with bright emission in solution at 616nm with quantum yield up to 80% representing the brightest CPP-based emitter beyond 600nm.
Abstract: Dimeric cycloparaphenylene (CPP) architectures with well-defined flipping motion are constructed taking advantage of an efficient cyclocondensation reaction. Variable-temperature nuclear magnetic resonance (VT-NMR) analyses and theoretical calculations indicate rapid interconversion of cis and trans conformers at room temperature, while energetically favorable trans conformer exists at low temperature with the metastable cis conformer hidden. The trihexylsilylethynyl-substituted dimer exhibits bright emission in solution at 616 nm with quantum yield up to 80 %, representing the brightest CPP-based emitter beyond 600 nm. A 1:2 host-guest complex of the dimer and C60 is established with negative cooperativity, demonstrating the first example of 1:2 complex from CPP derivatives.
28 citations
TL;DR: In this article, a review of the literature where different force fields are compared by their performances in conformational analysis and searching of organic molecules was carried out, and a distinct lack of comparisons were found, and the need for more work was emphasised.
25 citations
TL;DR: In this paper, a σ-π extended aryldisilane, comprising a thienopyrazine group as an acceptor fragment and phenothiazine groups as the donor moiety, has been prepared through the introduction of two Si-Si bridges (compound 1).
Abstract: A σ-π extended aryldisilane, comprising a thienopyrazine group as an acceptor fragment and phenothiazine groups as the donor moiety, has been prepared through the introduction of two Si-Si bridges (compound 1). X-ray diffraction analysis determined the crystal structure of 1, and experimental and theoretical approaches investigated its optical properties. Solvatochromic studies revealed the dual emission of 1 in all solvents tested. Compound 1 also exhibited fluorescence in the solid state upon excitation with a hand-held UV lamp, as well as mechanochromic luminescent properties. The packing mode in the crystal structure, variation of phenothiazine conformation, morphological changes between crystalline and amorphous phases are the major factors showing reversible fluorescence under external stimuli. A theoretical conformer study found that 1 exists in distinct conformational groups differing in Gibbs free energy by less than 3 kcal mol-1 . The conformer in the crystalline state of 1 can promote the complete separation of the HOMO and LUMO between the phenothiazine donor and the thienopyrazine acceptor, linked by the disilane linker. HOMO-LUMO energy transition in the crystalline state is forbidden due to the lack of frontier orbital overlap. Crystalline state emission showed LUMO → HOMO-1 transition (locally excited (LE) state). In the amorphous state, the partial presence of quasi-axial conformers allows intramolecular charge-transfer type emission via energy transfer from dominant quasi-equatorial conformers. The strategy proposed in this work provides important guidance for developing stimuli-responsive materials with controlled excited states.
22 citations
TL;DR: This paper used a curated collection of apo-holo conformations to evaluate the performance of AlphaFold2 in predicting protein 3D models and found that it was unable to reproduce observed conformational diversity with an equivalent error than in the estimation of a single conformation.
Abstract: After the outstanding breakthrough of AlphaFold in predicting protein 3D models, new questions appeared and remain unanswered. The ensemble nature of proteins, for example, challenges the structural prediction methods because the models should represent a set of conformers instead of single structures. The evolutionary and structural features captured by effective deep learning techniques may unveil the information to generate several diverse conformations from a single sequence. Here we address the performance of AlphaFold2 predictions under this ensemble paradigm. Using a curated collection of apo-holo conformations, we found that AlphaFold2 predicts the holo form of a protein in 70% of the cases, being unable to reproduce the observed conformational diversity with an equivalent error than in the estimation of a single conformation. More importantly, we found that AlphaFold29s performance worsens with the increasing conformational diversity of the studied protein. This impairment is related to the heterogeneity in the degree of conformational diversity found between different members of the homologous family of the protein under study. Finally, we found that main-chain flexibility associated with apo-holo pairs of conformers negatively correlates with the predicted local model quality score plDDT, indicating that plDDT values in a single 3D model could be used to infer local conformational changes linked to ligand binding transitions.
20 citations
TL;DR: A series of perylene bisimide (PBI) dyes bearing various aryl substituents in 1,6,7,12 bay positions has been synthesized by Suzuki cross-coupling reaction.
Abstract: A series of perylene bisimide (PBI) dyes bearing various aryl substituents in 1,6,7,12 bay positions has been synthesized by Suzuki cross-coupling reaction. These molecules exhibit an exceptionally large and conformationally fixed twist angle of the PBI π-core due to the high steric congestion imparted by the aryl substituents in bay positions. Single crystal X-ray analyses of phenyl-, naphthyl- and pyrenyl-functionalized PBIs reveal interlocked π-π-stacking motifs, leading to conformational chirality and the possibility for the isolation of enantiopure atropoisomers by semipreparative HPLC. The interlocked arrangement endows these molecules with substantial racemization barriers of about 120 kJ mol-1 for the tetraphenyl- and tetra-2-naphthyl-substituted derivatives, which is among the highest racemization barriers for axially chiral PBIs. Variable temperature NMR studies reveal the presence of a multitude of up to fourteen conformational isomers in solution that are interconverted via smaller activation barriers of about 65 kJ mol-1 . The redox and optical properties of these core-twisted PBIs have been characterized by cyclic voltammetry, UV/Vis/NIR and fluorescence spectroscopy and their respective atropo-enantiomers were further characterized by circular dichroism (CD) and circular polarized luminescence (CPL) spectroscopy.
19 citations
20 May 2021
TL;DR: In this paper, the conformer-specific photoelectron circular dichroism (PECD) was measured in the vacuum ultraviolet (VUV) photoionization of proline, as well as a conformerdependent cation fragmentation behavior.
Abstract: Proline is a unique amino-acid, with a secondary amine fixed within a pyrrolidine ring providing specific structural properties to proline-rich biopolymers. Gas-phase proline possesses four main H-bond stabilized conformers differing by the ring puckering and carboxylic acid orientation. The latter defines two classes of conformation, whose large ionization energy difference allows a unique conformer-class tagging via electron spectroscopy. Photoelectron circular dichroism (PECD) is an intense chiroptical effect sensitive to molecular structures, hence theorized to be highly conformation-dependent. Here, we present experimental evidence of an intense and striking conformer-specific PECD, measured in the vacuum ultraviolet (VUV) photoionization of proline, as well as a conformer-dependent cation fragmentation behavior. This finding, combined with theoretical modeling, allows a refinement of the conformational landscape and energetic ordering, that proves inaccessible to current molecular electronic structure calculations. Additionally, astrochemical implications regarding a possible link of PECD to the origin of life’s homochirality are considered in terms of plausible temperature constraints. Proline plays an important role in determining the structures of proteins and peptides, but the conformer landscape of proline is still not fully mapped. Here, the authors show the conformer-specific cation fragmentation and photoelectron circular dichroism of proline during its vacuum ultraviolet photoionization.
18 citations
TL;DR: In this article, the chameleonic behavior of cyclosporin A (CsA) was investigated through conformational ensembles employing multicanonical molecular dynamics simulations that could sample the cis and trans isomers of N-methylated amino acids.
Abstract: The chameleonic behavior of cyclosporin A (CsA) was investigated through conformational ensembles employing multicanonical molecular dynamics simulations that could sample the cis and trans isomers of N-methylated amino acids; these assessments were conducted in explicit water, dimethyl sulfoxide, acetonitrile, methanol, chloroform, cyclohexane (CHX), and n-hexane (HEX) using AMBER ff03, AMBER10:EHT, AMBER12:EHT, and AMBER14:EHT force fields. The conformational details were discussed employing the free-energy landscapes (FELs) at T = 300 K; it was observed that the experimentally determined structures of CsA were only a part of the conformational space. Comparing the ROESY measurements in CHX-d12 and HEX-d14, the major conformations in those apolar solvents were essentially the same as that in CDCl3 except for the observation of some sidechain rotamers. The effects of the metal ions on the conformations, including the cis/trans isomerization, were also investigated. Based on the analysis of FELs, it was concluded that the AMBER ff03 force field best described the experimentally derived conformations, indicating that CsA intrinsically formed membrane-permeable conformations and that the metal ions might be the key to the cis/trans isomerization of N-methylated amino acids before binding a partner protein.
16 citations
TL;DR: In this paper, a cross-validated physically motivated statistical model was proposed to predict conformational entropy across a wide range of molecules and achieved a mean absolute error of ∼4.8 J/mol·K or under 0.4 kcal/mol at 300 K. The model implies a high degree of correlation between torsions in most molecules.
Abstract: The calculation of the entropy of flexible molecules can be challenging, since the number of possible conformers can grow exponentially with molecule size and many low-energy conformers may be thermally accessible. Different methods have been proposed to approximate the contribution of conformational entropy to the molecular standard entropy, including performing thermochemistry calculations with all possible stable conformations and developing empirical corrections from experimental data. We have performed conformer sampling on over 120,000 small molecules generating some 12 million conformers, to develop models to predict conformational entropy across a wide range of molecules. Using insight into the nature of conformational disorder, our cross-validated physically motivated statistical model gives a mean absolute error of ∼4.8 J/mol·K or under 0.4 kcal/mol at 300 K. Beyond predicting molecular entropies and free energies, the model implies a high degree of correlation between torsions in most molecules, often assumed to be independent. While individual dihedral rotations may have low energetic barriers, the shape and chemical functionality of most molecules necessarily correlate their torsional degrees of freedom and hence restrict the number of low-energy conformations immensely. Our simple models capture these correlations and advance our understanding of small molecule conformational entropy.
15 citations
TL;DR: In this paper, the authors used potential energy scans for various rotable bonds to obtain the lowest energy conformer, conformational analysis was achieved, and charge delocalization patterns and second-order perturbation energies of the most interacting natural bond orbitals were also computed and predicted from wavefunction analysis.
15 citations
TL;DR: In this article, a conformational analysis and theoretical study of the first and second oxygen addition of cyclohexane was performed using quantum chemical calculations and kinetic calculations, and the theoretical results indicated that the rapid inversion-topomerization processes facilitate fast equilibrium between axial and equatorial conformers.
TL;DR: In this article, the fundamental structural aspects of these derivatives have been examined based on optimized geometry, spectroscopic behavior, intermolecular interaction, chemical reactivity and molecular docking analysis.
TL;DR: In this paper, the authors synthesize π-extended corannulenes bearing quintuple azahelicene units, and their dynamic behaviors were studied both experimentally and theoretically.
Abstract: Peripherally π-extended corannulenes bearing quintuple azahelicene units, 10 and 11 , were prepared and their dynamic behaviors were studied both experimentally and theoretically. The fused corannulenes were synthesized from sym -pentabromocorannulene in three steps, including Buchwald-Hartwig amination, Pd-catalyzed intramolecular C-H arylation, and N -methylation. X-Ray diffraction analysis for 10 displayed a conformer possessing a P(M) bowl chirality and a PPMPM ( PMPMM ) helical chirality, which was found to be the most stable conformer(s). Variable-temperature NMR measurements of 10 and 11 revealed that their structural isomers can be interconvertible in solution, depending on their steric congestion around the helical scaffolds. Automated search for conformers in the equilibrium and transition states by Artificial Force Induced Reaction (AFIR) method revealed their interconversion networks, including bowl-inversion and helical-inversion, the activation barriers of which were estimated to be 2.6-3.6 kcal·mol -1 and 9.8-26.9 kcal·mol -1 , respectively. These values are smaller than those of the pristine corannulene (12.5 kcal·mol -1 ) and the corresponding azahelicenes (22.0 and 35.3 kcal·mol -1 ), respectively. This analysis indicated that the co-existing corannulene and azahelicene moieties influence the conformational dynamics, which leads to mitigation of the activation energy barriers for isomerization.
TL;DR: In this article, the Boltzmann populations calculated for implicitly solvated single conformers are used to weight the IR spectra of explicitly Solvated clusters with a size of typically ten solvent molecules, accounting for the first solvation shell.
Abstract: The recently developed efficient protocols to implicit [Grimme et al., J. Phys. Chem. A 125, 4039-4054 (2021)] and explicit quantum mechanical modeling of non-rigid molecules in solution [Katsyuba et al., J. Phys. Chem. B 124, 6664-6670 (2020)] are applied to methyl lactate (ML). Building upon this work, a new combination scheme is proposed to incorporate solvation effects for the computation of infrared (IR) absorption spectra. Herein, Boltzmann populations calculated for implicitly solvated single conformers are used to weight the IR spectra of explicitly solvated clusters with a size of typically ten solvent molecules, i.e., accounting for the first solvation shell. It is found that in water and methanol, the most abundant conformers of ML are structurally modified relative to the gas phase, where the major form is ML1, in which the syn conformation of the -OH moiety is stabilized by a OH⋯O=C intramolecular hydrogen bond (HB). In solution, this syn conformation transforms to the gauche form because the intramolecular HB is disrupted by explicit water molecules that form intermolecular HBs with the hydroxyl and carbonyl groups. Similar changes induced by the gas-solution transition are observed for the minor conformers, ML2 and/or ML3, characterized by OH⋯OCH3 intramolecular HB in the gas phase. The relative abundance of ML1 is shown to decrease from ∼96% in gas to ∼51% in water and ∼92% in methanol. The solvent strongly influences frequencies, IR intensities, and normal modes, resulting in qualitatively different spectra compared to the gas phase. Some liquid-state conformational markers in the fingerprint region of IR spectra are revealed.
TL;DR: In this paper, the conformational behavior of two hydrazones derived from pyridoxal 5′-phosphate and 2-,3-pyridine carbohydrazide was studied utilizing quantum chemistry and NMR techniques.
TL;DR: The conformational rotamer ensemble sampling tool (CREST) as discussed by the authors uses an iterative scheme to efficiently sample the conformational space and calculates energies using the semi-empirical 'Geometry, Frequency, Noncovalent, eXtended Tight Binding' (GFN2-xTB) method.
Abstract: Small molecule receptor-binding is dominated by weak, non-covalent interactions such as van-der-Waals hydrogen bonding or electrostatics. Calculating these non-covalent ligand-receptor interactions is a challenge to computational means in terms of accuracy and efficacy since the ligand may bind in a number of thermally accessible conformations. The conformational rotamer ensemble sampling tool (CREST) uses an iterative scheme to efficiently sample the conformational space and calculates energies using the semi-empirical 'Geometry, Frequency, Noncovalent, eXtended Tight Binding' (GFN2-xTB) method. This combined approach is applied to blind predictions of the modes and free energies of binding for a set of 10 drug molecule ligands to the cucurbit[n]urils CB[8] receptor from the recent 'Statistical Assessment of the Modeling of Proteins and Ligands' (SAMPL) challenge including morphine, hydromorphine, cocaine, fentanyl, and ketamine. For each system, the conformational space was sufficiently sampled for the free ligand and the ligand-receptor complexes using the quantum chemical Hamiltonian. A multitude of structures makes up the final conformer-rotamer ensemble, for which then free energies of binding are calculated. For those large and complex molecules, the results are in good agreement with experimental values with a mean error of 3 kcal/mol. The GFN2-xTB energies of binding are validated by advanced density functional theory calculations and found to be in good agreement. The efficacy of the automated QM sampling workflow allows the extension towards other complex molecular interaction scenarios.
TL;DR: In this paper, the microwave spectrum of 2-acetylfuran was recorded in the frequency range from 2 to 26.5 GHz using a molecular jet Fourier transform microwave spectrometer, confirming the presence of both conformers.
Abstract: For 2-acetylfuran, quantum chemistry predicted and proton magnetic resonance study reported two conformers, anti and syn, differing in the position of the carbonyl group with respect to the O1-C2 bond of the furan ring. The microwave spectrum of the title molecule was recorded in the frequency range from 2 to 26.5 GHz using a molecular jet Fourier transform microwave spectrometer, confirming the presence of both conformers. Spectroscopic parameters such as the rotational and centrifugal distortion constants could be determined with high precision. The spectra of all 13C- and 18O-isotopologues of the energetically more favorable anti-conformer could be assigned, allowing the experimental determination of bond lengths and bond angles from the heavy atom substitution rs and the semi-experimental equilibrium reSE structures. Splittings arising from the internal rotation of the acetyl methyl group could be resolved for both conformers as well as for all assigned isotopologues, from which the barrier to methyl internal rotation was determined. The torsional barrier is largely invariant at around 319 cm-1 in the parent species of anti-2-acetylfuran and its isotopologues, showing that though isotopic substitution greatly influences the rotational properties of the molecule and causes a different microwave spectrum, its effect on the methyl torsion is negligible. On the other hand, conformational effects play a decisive role, as the torsional barrier of 239.780(13) cm-1 found for syn-2-acetylfuran differs significantly from the value for anti-2-acetylfuran. The results are compared and discussed with other methyl-substituted furan derivatives and acetyl group containing ketones for a better understanding of different effects influencing molecular geometry parameters and methyl internal rotations.
TL;DR: In this paper, experimental methods for investigating chemical reaction dynamics are typically not used for the analysis of isomers in biology and organic chemistry, however, experimental methods are used to investigate the properties of the isomers.
Abstract: Conformational isomers (conformers) of molecules play a decisive role in biology and organic chemistry. However, experimental methods for investigating chemical reaction dynamics are typically not ...
TL;DR: In this article, the fundamental structural aspects of these derivatives have been examined based on optimized geometry, spectroscopic behavior, intermolecular interaction, chemical reactivity, and molecular docking analysis.
Abstract: 1-[([1,1I-Biphenyl]-4-yl](phenyl)methyl]-1H-imidazolium-2,5-dichloro-3,6-dihydroxy-cyclohexa-2,5-diene-1,4-dione (BCAA) and 1-[([1,1I-Biphenyl]-4-yl](phenyl)methyl]-1H-imidazolium-4,5-dichloro-3,6-dioxocyclohexa-1,4-diene-1,2-dicarbonitrile (BDDQ) were synthesized and characterized using spectral analysis. The fundamental structural aspects of these derivatives have been examined based on optimized geometry, spectroscopic behavior, intermolecular interaction, chemical reactivity, and molecular docking analysis. The most stable minimum energy conformer of the title molecules was identified by potential energy surface scan along the rotational bonds. Accordingly, global and local chemical reactivity descriptors were investigated. The wavenumber downshift of different modes is noted. Title molecules exhibit inhibitory activity against different receptors.
TL;DR: In this paper, structural and photophysical properties of two new bulky base dyes 1 and 2, obtained from the reaction of cyclohexylamine with the 5-bromosalicylaldehyde or 2-hydroxy-1-naphthaldehyde, were investigated.
TL;DR: In this paper, a combined experimental and computational investigation aimed at determining the nature of the dimeric species formed by BTA Gly was conducted, and two distinct dimeric structures were characterized by single-crystal X-ray diffraction measurements.
Abstract: Precise characterization of the hydrogen bond network present in discrete self-assemblies of benzene-1,3,5-tricarboxamide monomers derived from amino-esters (ester BTAs) is crucial for the construction of elaborated functional co-assemblies. For all ester BTA dimeric structures previously reported, ester carbonyls in the side chain acted as hydrogen bond acceptors, yielding well-defined dimers stabilized by six hydrogen bonds. The ester BTA monomer derived from glycine (BTA Gly) shows a markedly different self-assembly behaviour. We report herein a combined experimental and computational investigation aimed at determining the nature of the dimeric species formed by BTA Gly. Two distinct dimeric structures were characterized by single-crystal X-ray diffraction measurements. Likewise, a range of spectroscopic and scattering techniques as well as molecular modelling were employed to diagnose the nature of dynamic dimeric structures in toluene. Our results unambiguously establish that both ester and amide carbonyls are involved in the hydrogen bond network of the discrete dimeric species formed by BTA Gly. The participation of roughly 4.5 ester carbonyls and 1.5 amide carbonyls per dimer as determined by FT-IR spectroscopy implies that several conformations coexist in solution. Moreover, NMR analysis and modelling data reveal rapid interconversion between these different conformers leading to a symmetric structure on the NMR timescale. Rapid hydrogen bond shuffling between conformers having three (three), two (four), one (five) and zero (six) amide carbonyl groups (ester carbonyl groups, respectively) as hydrogen bond acceptors is proposed to explain the magnetic equivalence of the amide N–H on the NMR timescale. When compared to other ester BTA derivatives in which only ester carbonyls act as hydrogen bond acceptors, the fluxional behaviour of the hydrogen-bonded dimers of BTA Gly likely originates from a larger range of energetically favorable conformations accessible through rotation of the BTA side chains.
TL;DR: The rotational spectra of 1-butanol, 1-BuOH, 1butanethiol (1-BuSH), 2-methyl-1-propanol (iso-BuH), and 2-mixture of 1butanol and iso-HOOH were measured by Fourier transform microwave spectroscopy in the frequency region from 3.7 up to 25 GHz as mentioned in this paper.
Abstract: The rotational spectra of 1-butanol (1-BuOH), 1-butanethiol (1-BuSH), 2-methyl-1-propanol (iso-BuOH), and 2-methyl-1-propanethiol (iso-BuSH) were measured by Fourier transform microwave spectroscopy in the frequency region from 3.7 up to 25 GHz. The observed spectral lines were assigned by observation of the deuterium substitution effect and by ab initio or density functional theory calculations at the levels of MP2/6-311++G(d,p) or B3LYP and cam-B3LYP, respectively. For 1-BuOH and 1-BuSH, seven of the 14 conformations, anticipated to exist as stable, were detected, whereas four and three among the five possible conformations were identified for iso-BuOH and iso-BuSH, respectively. We further found that, of the seven conformers of 1-BuOH, five were trans and two gauche, with respect to the internal rotation axis: the C2-C3 bond, while three of iso-BuOH existed in gauche and one in trans. The most stable conformer of the two BuOH molecules was trans with respect to the C-O bond, while all the sulfur analogues were gauche to the C-S axis. The rare isotopomers examined included 13C and OD of 1-BuOH and OD of iso-BuOH, 34S, 13C, and SD of the two sulfur molecules, and the rotational constants obtained on these isotopomers were employed in the molecular structure derivation. The potential barrier to CH3 internal rotation and the deuterium quadrupole coupling constant, where available, were also derived from the spectral analysis, and the molecular parameters thus obtained were compared with those derived using quantum-chemical calculations; the values derived using cam-B3LYP/6-311++G(d,p) were in better agreement with the observed than those derived using MP2/6-311++G(d,p) and B3LYP/6-311++G(d,p). The TTg form of 1-BuOH and of 1-BuSH and the Tg form of iso-BuSH exhibited additional spectral splittings, which were interpreted as caused by the OH or SH group tunneling between the symmetric and antisymmetric states. Some of the J = 8 rotational levels of 1-BuSH happened to be near-degenerate with others, and the splittings in them caused by mutual repulsion could be precisely determined by the observation of the transitions involving those split levels. Such splittings were determined for 1-BuSH, 1-BuSD, and iso-BuSH to be 1694.1731 (22), 56.3174 (16), and 6.4678 (14) MHz, respectively. A natural bond orbital analysis was performed to show that the most stable conformation of the primary and secondary alcohols is Gt because of the charge transfer from the lone-pair electron of the oxygen atom to the antibonding orbital of the C-H bond in 1-BuOH, whereas in iso-BuOH, the charge transfer to the antibonding orbital of the C1-C2 bond.
TL;DR: A chiral adduct formed between a chiral carboxylic acid, tetrahydro-2-furoic acid (THFA), and propylene oxide (PO) was investigated using rotational spectroscopy and DFT calculations as discussed by the authors.
Abstract: A chiral adduct formed between a chiral carboxylic acid, tetrahydro-2-furoic acid (THFA), and a chiral ester, propylene oxide (PO), was investigated using rotational spectroscopy and DFT calculations. Isolated THFA exists dominantly as three different conformers: I, II, and III in a jet, with I and II taking on the trans-COOH configuration and III having the cis-COOH configuration. We utilized CREST, a conformational ensemble space exploration tool, to identify the possible conformations of the binary adduct, THFA⋅⋅⋅PO. Subsequent DFT geometry optimizations predicted about two hundred homochiral and heterochiral binary structures with 28 low energy structures within an energy window of 15 kJ mol-1 . A rich broadband rotational spectrum was obtained with a mixture of trace amounts of THFA+PO in neon in a supersonic jet expansion. Six THFA⋅⋅⋅PO conformers were identified experimentally. Kinetically favored binary products which contain trans-COOH I dominate among the observed conformers, while thermodynamically more stable adducts were also detected. Detailed analyses of the structures of the observed conformers show interesting chirality-controlled structural preferences. Such non-covalently bound chiral contact pairs are the foundation of chiral-tag rotational spectroscopy, an exciting new analytical application of rotational spectroscopy for determination of enantiomeric excess. Enantiomeric excess analyses were performed and the results are discussed.
TL;DR: In this paper, a synthesis of N'-(benzylidene)-2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazides and their structural interpretation by NMR experiments is described in an attempt to explain the duplication of some peaks in their 1H and 13C-NMR spectra.
Abstract: In this article, a synthesis of N’-(benzylidene)-2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazides and their structural interpretation by NMR experiments is described in an attempt to explain the duplication of some peaks in their 1H- and 13C-NMR spectra. Twenty new 6-methyl-1H-pyrazolo[3,4-b]quinoline substituted N-acylhydrazones 6(a–t) were synthesized from 2-chloro-6-methylquinoline-3-carbaldehyde (1) in four steps. 2-Chloro-6-methylquinoline-3-carbaldehyde (1) afforded 6-methyl-1H-pyrazolo[3,4-b]quinoline (2), which upon N-alkylation yielded 2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetate (3). The hydrazinolysis of 3 followed by the condensation of resulting 2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazide (4) with aromatic aldehydes gave N-acylhydrazones 6(a–t). Structures of the synthesized compounds were established by readily available techniques such as FT-IR, NMR and mass spectral studies. The stereochemical behavior of 6(a–t) was studied in dimethyl sulfoxide-d6 solvent by means of 1H NMR and 13C NMR techniques at room temperature. NMR spectra revealed the presence of N’-(benzylidene)-2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazides as a mixture of two conformers, i.e., E(C=N)(N-N) synperiplanar and E(C=N)(N-N)antiperiplanar at room temperature in DMSO-d6. The ratio of both conformers was also calculated and E(C=N) (N-N) syn-periplanar conformer was established to be in higher percentage in equilibrium with the E(C=N) (N-N)anti-periplanar form.
TL;DR: All four rotamers of the nonplanar 5,10,15,20‐tetrakis(2‐aminophenyl)‐2,3,7,8,12,13,17,18‐octaethylporphyirin as restricted H‐bonding complexes are characterized and charge‐assisted complexation is suggested as a key to unravel the atropisomeric enigma.
Abstract: Atropisomerism is a fundamental feature of substituted biaryls resulting from rotation around the biaryl axis. Different stereoisomers are formed due to restricted rotation about the single bond, a situation often found in substituted porphyrins. Previously NMR determination of porphyrin atropisomers proved difficult, if not almost impossible to accomplish, due to low resolution or unresolvable resonance signals that predominantly overlapped. Here, we shed some light on this fundamental issue found in porphyrinoid stereochemistry. Using benzenesulfonic acid (BSA) for host-guest interactions and performing 1D, 2D NMR spectroscopic analyses, we were able to characterize all four rotamers of the nonplanar 5,10,15,20-tetrakis(2-aminophenyl)-2,3,7,8,12,13,17,18-octaethylporphyirin as restricted H-bonding complexes. Additionally, X-ray structural analysis was used to investigate aspects of the weak host-guest interactions. A detailed assignment of the chemical signals suggests charge-assisted complexation as a key to unravel the atropisomeric enigma. From a method development perspective, symmetry operations unique to porphyrin atropisomers offer an essential handle to accurately identify the rotamers using NMR techniques only.
TL;DR: In this paper, a non-linear multivariate analysis by employing a kernel method using two homologous highmannose-type oligosaccharides composed of ten and eleven residues as model molecules is presented.
Abstract: Oligosaccharides play versatile roles in various biological systems but are difficult to characterize from a structural viewpoint due to their remarkable degrees of freedom in internal motion. Therefore, molecular dynamics simulations have been widely used to delineate the dynamic conformations of oligosaccharides. However, hardly any methods have thus far been available for the comprehensive characterization of simulation-derived conformational ensembles of oligosaccharides. In this research, we attempted to develop a non-linear multivariate analysis by employing a kernel method using two homologous high-mannose-type oligosaccharides composed of ten and eleven residues as model molecules. These oligosaccharides' conformers derived from simulations were mapped into reproductive kernel Hilbert space with a positive definite function in which all required non-redundant variables for describing the oligosaccharide conformations can be treated in a non-biased manner. By applying Gaussian mixture model clustering, the oligosaccharide conformers were successfully classified by different funnels in the free-energy landscape, enabling a systematic comparison of conformational ensembles of the homologous oligosaccharides. The results shed light on the contributions of intraresidue conformational factors such as the hydroxyl group orientation and/or ring puckering state to their global conformational dynamics. Our methodology will open opportunities to explore oligosaccharides' conformational spaces, and more generally, molecules with high degrees of motional freedom.
TL;DR: The cationic structure of the twisted chair conformer is revealed, which was attributed to the effect of electron removal from the highest occupied molecular orbital (HOMO) consisting of the nonbonding orbital of the oxygen atom, reveals the role of electrons in the HOMO.
Abstract: Isolating and identifying the conformational forms of molecules are imperative processes to investigate the chemical reaction pathways of individual conformers. Herein, we explored the conformational structures of tetrahydropyran in the neutral (S0) and cationic (D0) states by varying the supersonic expansion conditions using one-photon vacuum ultraviolet mass-analyzed threshold ionization (VUV-MATI) spectroscopy. The constructed 2D potential energy surfaces associated with conformational interconversion between the chair and boat forms in the S0 and D0 states revealed that the ionic transitions observed in the MATI spectra correspond to the most stable chair conformer. Accordingly, based on the 0–0 band in the VUV-MATI spectrum supported by the VUV photoionization efficiency curve, the adiabatic ionization energy for the conversion of the chair conformer to a cationic state was determined to be 74 687 ± 4 cm−1 (9.2600 ± 0.0005 eV). Definitive vibrational assignment of the measured MATI spectra using Franck–Condon fitting revealed the cationic structure of the twisted chair conformer. The geometrical change upon ionization promoted the vibrational modes associated with ring inversion and deformation motions in the cationic state. This behavior, which was attributed to the effect of electron removal from the highest occupied molecular orbital (HOMO) consisting of the nonbonding orbital of the oxygen atom, reveals the role of electrons in the HOMO.
TL;DR: In this paper, the authors demonstrate that VCD spectroscopy can reveal insights into the conformational preferences of the iminium ion obtained from MacMillan's imidazolidinone catalyst.
Abstract: We demonstrate that VCD spectroscopy can reveal insights into the conformational preferences of the iminium ion obtained from MacMillan's imidazolidinone catalyst. For both the isolated and in situ generated iminium ion, the comparison of experimental and computed VCD spectra directly confirms that conformer 2b ("Houk-conformer") is the dominant structure in solution. This conclusion is reached without any in-depth interpretation of the spectroscopic data, just by visual comparison of the spectral signatures. For the parent catalyst 1 and its salts 1·HCl and 1·HClO4, we report a comprehensive analysis of the conformational preferences in two solvents. VCD spectroscopy is subsequently shown to be able to reveal small conformational changes induced by solute-solvent and solute-anion interactions.
TL;DR: In this paper, a density functional theory (DFT) based analysis of the structures and infrared and Raman spectra of all tetrahydrocannabinol (THC) and cannabidiol (CBD) conformers was performed at the B3LYP-D3BJ/6-31+G(d,p) level.