Showing papers on "Conformational isomerism published in 2020"
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TL;DR: This dataset will assist benchmarking and transfer learning in two classes of tasks: inferring 3D properties from 2D molecular graphs, and developing generative models to sample 3D conformations.
Abstract: Machine learning (ML) outperforms traditional approaches in many molecular design tasks. ML models usually predict molecular properties from a 2D chemical graph or a single 3D structure, but neither of these representations accounts for the ensemble of 3D conformers accessible to a molecule. Property prediction could be improved by using conformer ensembles as input, but there is no large-scale dataset that contains graphs annotated with high-quality conformers and experimental data. Here we use first-principles simulations to generate accurate conformers for over 430,000 molecules, including 300,000 with experimental data for the inhibition of various pathogens. The Geometric Ensemble Of Molecules (GEOM) dataset contains over 33 million molecular conformers labeled with their relative energies and statistical probabilities at room temperature. GEOM will assist in the development of models that predict properties from conformer ensembles, and generative models that sample 3D conformations.
90 citations
TL;DR: Single-molecule nanopore measurements have revealed ligand-induced conformational changes in the catalytic cycle of dihydrofolate reductase, and showed that the enzyme adopts distinctive conformers, which have different affinities for substrates and products.
Abstract: Conformational heterogeneity is emerging as a defining characteristic of enzyme function. However, understanding the role of protein conformations requires their thermodynamic and kinetic characterization at the single-molecule level, which remains extremely challenging. Here we report the ligand-induced conformational changes of dihydrofolate reductase (DHFR) by measuring the modulation of the nanopore currents. The long observation time of the electrical recordings enabled the detection of rare conformational transitions hidden in ensemble measurements. We show that DHFR exists in at least four ground-state configurations or conformers with different affinities for its ligands. Unliganded DHFR adopted low-affinity conformers, whereas the binding of substrates promoted the switch to the high-affinity conformer. Conversion between the conformers was accelerated by molecules that stabilized the transition state of DHFR, which suggests that the reaction lowers the energy barrier for conformer exchange and thus facilitates product release. This mechanism might be a general feature in enzymatic reactions affected by product inhibition or when the release of products is the rate-limiting step.
71 citations
TL;DR: In this article, the authors have designed and synthesized donor-acceptor (D-A) isomers by functionalizing the para, meta and ortho positions of the benzothiazole (BT) ring with the phenothiazine (PTZ) moiety.
Abstract: The development of solid-state stimuli responsive materials has escalated following their intriguing colour switching properties and versatile material and optoelectronic applications. In this article, we have designed and synthesized donor–acceptor (D–A) isomers, namely p-PTZ, m-PTZ and o-PTZ, by functionalizing the para, meta and ortho positions of the benzothiazole (BT) ring with the phenothiazine (PTZ) moiety. The Suzuki cross-coupling reaction of the mono boronate ester of phenothiazine PTZ with the corresponding bromo derivatives of phenyl BT generated the isomers p-PTZ, m-PTZ and o-PTZ. The attachment of donor PTZ at different positions of the acceptor phenyl BT could exert influence on the donor–acceptor character and the molecular packing modes in the isomers, resulting in discrete photophysical and electronic properties. The isomers manifest contrasting emission properties in different solvents as a consequence of the twisted intramolecular charge transfer (TICT) state. The non-planar twisted structures of the isomers bring about aggregation induced emission (AIE) characteristics and reversible mechanofluorochromism (MFC) behaviour. The isomers display self-reversible colour switching by virtue of the different accessible conformers of the PTZ moiety. The p-PTZ isomer occurs as polymorphs owing to the conformational flexibility of the PTZ moiety. The structural and morphological differences in the polymorphs of p-PTZ were studied in detail using single crystal X-ray analysis, scanning electron microscopy (SEM) and powder X-ray diffraction (PXRD) studies. Density functional theory (DFT) and time-dependent density functional theory (TDDFT) calculations were used to explore the electronic properties of the isomers in the ground and excited state. The isomers were capable of sensing trifluoroacetic acid in solution. A detailed comparison of the photophysical, electronic and structural properties of p-PTZ, m-PTZ and o-PTZ has been done with a view to studying the outcome of the positional change. The adopted design opens up different possibilities for study of novel stimuli responsive materials.
49 citations
TL;DR: The chirality controlled conformational landscape of the trimer of propylene oxide (PO), a prototypical chiral molecule, was investigated using rotational spectroscopy and a range of theoretical tools for conformational searches and for evaluating vibrational contributions to effective structures.
Abstract: The chirality controlled conformational landscape of the trimer of propylene oxide (PO), a prototypical chiral molecule, was investigated using rotational spectroscopy and a range of theoretical tools for conformational searches and for evaluating vibrational contributions to effective structures. Two sets of homochiral (PO) 3 transitions were assigned and the associated conformers identified with theoretical support. One set of heterochiral (PO) 3 transitions was assigned, but no structures generated by one of the latest, advanced conformational search codes could account for them. With the aid of a Python program, the carbon atom backbone and then the heterochiral (PO) 3 structure were generated using the 13 C isotopic data measured in natural abundance. Excellent agreement between theoretical and experimental rotational constants and relative dipole moment components of all three conformers was achieved, especially by applying vibrational corrections to the rotational constants.
40 citations
TL;DR: QM7-X is introduced, a comprehensive dataset of 42 physicochemical properties for ≈4.2 million equilibrium and non-equilibrium structures of small organic molecules with up to seven non-hydrogen atoms that will play a critical role in the development of next-generation machine-learning based models for exploring greater swaths of CCS and performing in silico design of molecules with targeted properties.
Abstract: We introduce QM7-X, a comprehensive dataset of 42 physicochemical properties for $\approx$ 4.2 M equilibrium and non-equilibrium structures of small organic molecules with up to seven non-hydrogen (C, N, O, S, Cl) atoms. To span this fundamentally important region of chemical compound space (CCS), QM7-X includes an exhaustive sampling of (meta-)stable equilibrium structures - comprised of constitutional/structural isomers and stereoisomers, e.g., enantiomers and diastereomers (including cis-/trans- and conformational isomers) - as well as 100 non-equilibrium structural variations thereof to reach a total of $\approx$ 4.2 M molecular structures. Computed at the tightly converged quantum-mechanical PBE0+MBD level of theory, QM7-X contains global (molecular) and local (atom-in-a-molecule) properties ranging from ground state quantities (such as atomization energies and dipole moments) to response quantities (such as polarizability tensors and dispersion coefficients). By providing a systematic, extensive, and tightly-converged dataset of quantum-mechanically computed physicochemical properties, we expect that QM7-X will play a critical role in the development of next-generation machine-learning based models for exploring greater swaths of CCS and performing in silico design of molecules with targeted properties.
40 citations
TL;DR: Investigation of atomic level interactions of 1:1 Choline Chloride: Acetylsalicylic Acid therapeutic deep eutectic solvent has been investigated by combining the molecular dynamics, density functional theory, and spectroscopic techniques to confirm the formation of the THDES.
Abstract: In this study, atomic level interactions of a 1:1 choline chloride (ChCl)/acetylsalicylic acid (ASA) therapeutic deep eutectic solvent (THDES) has been investigated by combining the molecular dynamics (MD), density functional theory (DFT), and spectroscopic (Raman and IR) techniques. Atom-atom radial distribution functions (RDFs) based on MD simulation reveal that hydrogen bonds are formed between Cl-···HOCh+ and Cl-···HOCOOH of the THDES, where Cl- works as a bridge between ASA and Ch+. Cation-anion electrostatic attractions are disrupted by highly interconnected hydrogen bonds. Cluster conformers of the THDES are isolated from MD simulation and optimized using ωB97XD/6-311++G(d,p) level of theory, in which the strongest H bonds are found among OHCh+···Cl- (2.37 A) and Cl-···HOCOOH(2.40 A). Charge transfer calculations, using CHEPLG and NBO analysis, disclose that the charge of Cl- is reduced in the cluster structures and transferred to Ch+ and ASA. Further analyses are conducted using experimental and computed spectroscopic data. These confirm the formation of the THDES as peaks for -COOH, -COOR, and -OH functional groups of ASA and ChCl are either get broadened or disappeared in the spectra of the cluster conformers. Moreover, principal component analysis (PCA) assists to understand the feature of the simulated data and confirms the formation of the THDES. Solvent selectivity triangle (SST) of solvatochromic parameters also demonstrate that this THDES has some important properties similar to ionic liquids and common deep eutectic solvent.
38 citations
TL;DR: In this paper, three hydroxamic acids (HAs) namely AHA, BHA, and oxalohydroxamic acid (OHA) were synthesized, characterized and used as inhibitors for mild steel corrosion in 1-m HCl using chemical, electrochemical, surface and computational methods.
37 citations
TL;DR: Results point to a weakening of the hydrogen bond between cation and anion, which is supported and validated by results of the solvent (water) effect obtained using the polarized continuum model (PCM) of the DFT calculations.
Abstract: The influence of the length of the alkyl chain and water molecules on the hydrogen-bond interaction of the chloride anion and imidazolium-based cation of the ionic liquid (IL) Cnmim Cl (where n = 2, 4, 6, 8, and 10) was investigated by combining attenuated total internal reflection infrared (ATR-IR) spectroscopy and density functional theory (DFT) calculations. Here, for the first time, the conformational isomerism of the alkyl chain of Cnmim Cl (n = 2, 4, 6, 8, and 10) is identified by marker IR bands. The IR peak at 1470 cm−1 related to the alkyl chain vibration exhibits a significant perturbation in its intensity and further shows a red shift upon increasing alkyl chain length. This indeed might be a marker IR band for conformational isomerism and also an indication of the interaction of the alkyl chain with the chloride anion. Further, in the C–H vibration region of the IR spectra, a significant variation of the IR intensities was observed for the νs(CH2) and νas(CH2–CH3) modes at 2931 and 2976 cm−1, respectively. These bands can be considered as further markers for conformational isomerism of the alkyl chain. Moreover, the peak at 2976 cm−1 assigned to an alkyl chain vibration reveals the maximum red shift of 20 cm−1 for n = 10, which suggests charge redistribution among ion-pairs as a result of the alkyl chain variations. Noticeably, the C2–H vibration does not show any significant change of its wavenumber position, suggesting that the alkyl chain length does not interfere with the hydrogen bond interaction between C2–H and the Cl anion. This was also evident from the DFT-calculated bond strength between C2–H and Cl, which remains unchanged upon varying the alkyl chain length. In aqueous solutions, blue shifts of the v(C2–H) band by +65, +60, +67, +62 and +62 cm−1 for Cnmim Cl (n = 2, 4, 6, 8, and 10) are observed, respectively. These results point to a weakening of the hydrogen bond between cation and anion, which is also supported and validated by results of the solvent (water) effect obtained using the polarized continuum model (PCM) of the DFT calculations.
35 citations
TL;DR: In this article, a set of 13 stable mono-and dinitroxide PAs for magic-angle spinning dynamic nuclear polarization (MAS DNP) NMR is presented.
Abstract: The development of magic-angle spinning dynamic nuclear polarization (MAS DNP) has allowed atomic-level characterization of materials for which conventional solid-state NMR is impractical due to the lack of sensitivity. The rapid progress of MAS DNP has been largely enabled through the understanding of rational design concepts for more efficient polarizing agents (PAs). Here, we identify a new design principle which has so far been overlooked. We find that the local geometry around the unpaired electron can change the DNP enhancement by an order of magnitude for two otherwise identical conformers. We present a set of 13 new stable mono- and dinitroxide PAs for MAS DNP NMR where this principle is demonstrated. The radicals are divided into two groups of isomers, named open (O-) and closed (C-), based on the ring conformations in the vicinity of the N-O bond. In all cases, the open conformers exhibit dramatically improved DNP performance as compared to the closed counterparts. In particular, a new urea-based biradical named HydrOPol and a mononitroxide O-MbPyTol yield enhancements of 330 ± 60 and 119 ± 25, respectively, at 9.4 T and 100 K, which are the highest enhancements reported so far in the aqueous solvents used here. We find that while the conformational changes do not significantly affect electron spin-spin distances, they do affect the distribution of the exchange couplings in these biradicals. Electron spin echo envelope modulation (ESEEM) experiments suggest that the improved performance of the open conformers is correlated with higher solvent accessibility.
34 citations
TL;DR: In this paper, a single-molecule approach was developed to identify the conformational isomers of cyclohexane at room temperature through the single-Molecule electrical characterization.
33 citations
TL;DR: Analysis of ovalbumin N-glycans from different sources showed that the G-TIMS EED MS/MS approach can accurately determine the batch-to-batch variations in glycosylation profiles at the isomer level, with confident assignment of each isomeric structure.
Abstract: Ion mobility-mass spectrometry (IM-MS) has become a powerful tool for glycan structural characterization due to its ability to separate isomers and provide collision cross section (CCS) values that facilitate structural assignment. However, IM-based isomer analysis may be complicated by the presence of multiple gas-phase conformations of a single structure that not only increases difficulty in isomer separation but can also introduce the possibility for misinterpretation of conformers as isomers. Here, the ion mobility behavior of several sets of isomeric glycans, analyzed as their permethylated derivatives, in both nonreduced and reduced forms, was investigated by gated-trapped ion mobility spectrometry (G-TIMS). Notably, reducing-end reduction, commonly performed to remove anomerism-induced chromatographic peak splitting, did not eliminate the conformational heterogeneity of permethylated glycans in the gas phase. At a mobility resolving power of ∼100, 14 out of 22 structures showed more than one conformation. These results highlight the need to use IMS devices with high mobility resolving power for better separation of isomers and to acquire additional structural information that can differentiate isomers from conformers. Online electronic excitation dissociation (EED) MS/MS analysis of isomeric glycan mixtures following G-TIMS separation showed that EED can generate isomer-specific fragments while producing nearly identical tandem mass spectra for conformers, thus allowing confident identification of isomers with minimal evidence of any ambiguity resulting from the presence of conformers. G-TIMS EED MS/MS analysis of N-linked glycans released from ovalbumin revealed that several mobility features previously thought to arise from isomeric structures were conformers of a single structure. Finally, analysis of ovalbumin N-glycans from different sources showed that the G-TIMS EED MS/MS approach can accurately determine the batch-to-batch variations in glycosylation profiles at the isomer level, with confident assignment of each isomeric structure.
TL;DR: A method for enantiomeric excess (ee) determination of THFA is presented using a recently proposed chiral self-tag approach, suggesting that the method is effective in providing accurate ee values.
Abstract: Chirality recognition in dimers of tetrahydro-2-furoic acid (THFA) was studied in a conformer-specific manner using rotational spectroscopy and theoretical approaches. THFA shows a strong preference for the trans- over the cis-COOH configuration. Two drastically different scenarios are possible for the detectable (THFA)2 : a kinetically preferred dimer bound by feeble interactions between two trans THFAs or a thermodynamically favored dimer with a double hydrogen-bonded ring structure between two cis subunits. To identify the conformers responsible for the extremely dense rotational spectra observed, it was essential not only to locate several hundred homo/heterochiral (THFA)2 minima in ab initio calculations but also to evaluate the energetic connectivities among the minima. The study further reveals an interesting chirality dependent structure-energy ordering relationship. A method for enantiomeric excess (ee) determination of THFA is presented using a recently proposed chiral self-tag approach.
TL;DR: In this paper, the structural, electronic, and spectroscopic properties as well as the chemical reactivity behavior of the harmine derivatives were comprehensively investigated by computational tools to predict the structural and electronic properties.
Abstract: The harmine derivatives were comprehensively investigated by computational tools to predict the structural, electronic, and spectroscopic properties as well as the chemical reactivity behavior. Physicochemical parameters showed that the harmine derivatives (H2 and H4) containing the –OH group at 2-position were more stabilized with the solvent dielectric constant than those of the other compounds (H1 and H3) including the –OCH3 substitution at 2-position. The PED analysis was used to assign the vibrational modes of all stable conformers of the harmine derivatives. TD-DFT simulations revealed that the lowest energy excitations were related to the H → L transition, which was mainly characterized by n → π* for H1 and H2 compounds and π → π* for H3 and H4 compounds. According to NBO analysis results, the highest contribution to the lowering of the molecular stabilization energy for all compounds was mainly due to the intramolecular charge transfer from the lone pair of the N atom as a donor orbital to π* as an acceptor orbital. Global reactivity descriptors obtained from B3LYP/6-311++G(d,p) level implied that the trans-conformers of the studied compounds could be relatively more effective in their interaction with DNA, while the cis-conformers of them could be more eager to interact with the BSA molecule. Harmine derivatives are investigated by computational tools to predict the structural, electronic, and spectroscopic properties. Global reactivity descriptors implied that the trans-conformers of the compounds could be relatively more effective to interact with DNA, while the cis-conformers could be more eager to interact with the BSA molecule.
TL;DR: The implementation of ESI-MS as a source of dopant molecules expands the diversity of molecules accessible for thermochemical measurements, enabling the study of larger, non-volatile species.
Abstract: Isolation of biomolecules in vacuum facilitates characterization of the intramolecular interactions that determine three-dimensional structure, but experimental quantification of conformer thermochemistry remains challenging. Infrared spectroscopy of molecules trapped in helium nanodroplets is a promising methodology for the measurement of thermochemical parameters. When molecules are captured in a helium nanodroplet, the rate of cooling to an equilibrium temperature of ca. 0.4 K is generally faster than the rate of isomerization, resulting in "shock-freezing" that kinetically traps molecules in local conformational minima. This unique property enables the study of temperature-dependent conformational equilibria via infrared spectroscopy at 0.4 K, thereby avoiding the deleterious effects of spectral broadening at higher temperatures. Herein, we demonstrate the first application of this approach to ionic species by coupling electrospray ionization mass spectrometry (ESI-MS) with helium nanodroplet infrared action spectroscopy to probe the structure and thermochemistry of deprotonated DNA dinucleotides. Dinucleotide anions were generated by ESI, confined in an ion trap at temperatures between 90 and 350 K, and entrained in traversing helium nanodroplets. The infrared action spectra of the entrained ions show a strong dependence on pre-pickup ion temperature, consistent with the preservation of conformer population upon cooling to 0.4 K. Non-negative matrix factorization was utilized to identify component conformer infrared spectra and determine temperature-dependent conformer populations. Relative enthalpies and entropies of conformers were subsequently obtained from a van't Hoff analysis. IR spectra and conformer thermochemistry are compared to results from ion mobility spectrometry (IMS) and electronic structure methods. The implementation of ESI-MS as a source of dopant molecules expands the diversity of molecules accessible for thermochemical measurements, enabling the study of larger, non-volatile species.
TL;DR: This study unraveled the critical impact of solvent conformational isomerism on salt dissociation in 0.1-3.0 M LiPF6 dimethyl carbonate, ethyl methyl carbonate (EMC), and diethylcarbonate (DEC) solutions using Raman and dielectric relaxation spectroscopies to provide an avenue for the design of highly conductive electrolytes by exploiting the conformationalIsomerism of solvent molecules.
Abstract: The marked difference in the ionic conductivities of linear carbonate (LC) electrolyte solutions despite their similar viscosities and permittivities is a long-standing puzzle. This study unraveled the critical impact of solvent conformational isomerism on salt dissociation in 0.1-3.0 M LiPF6 dimethyl carbonate (DMC), ethyl methyl carbonate (EMC), and diethyl carbonate (DEC) solutions using Raman and dielectric relaxation spectroscopies. The extent of salt dissociation in the LC solutions, which decreased in the order DMC > EMC > DEC, is closely related to the fraction of polar cis-trans LC conformers, as this conformer participates in Li ion solvation more readily than the nonpolar cis-cis counterpart. Our first-principles calculations corroborated that the cis-trans conformer facilitates free ion formation more than the cis-cis conformer, and the extent of this effect decreased in the order DMC > EMC > DEC. This study provides an avenue for the design of highly conductive electrolytes by exploiting the conformational isomerism of solvent molecules.
TL;DR: The microwave spectrum of heptan-2-one (CH3COC4H8CH3) was recorded in the frequency range from 2 to 40 GHz using two molecular jet Fourier transform microwave spectrometers and the two energetically most favorable conformers could be identified and fitted with standard deviations close to measurement accuracy.
Abstract: The microwave spectrum of heptan-2-one (CH3COC4H8CH3) was recorded in the frequency range from 2 to 40 GHz using two molecular jet Fourier transform microwave spectrometers. The two energetically most favorable conformers could be identified and fitted with standard deviations close to measurement accuracy. The splittings arising from the internal rotations of two methyl groups, the acetyl methyl group CH3CO- and the pentyl methyl group -C4H8CH3, could be resolved. The barriers to internal rotation of the acetyl methyl group are 185.666(14) and 233.418(32) cm-1 for conformer I and II, respectively, and can be linked to their specific geometries. For the pentyl methyl group, the respective barrier heights are 982.22(86) and 979.2(21) cm-1.
TL;DR: Results of this study suggest that the aqueous-phase photochemistry of pyruvic acid proceeds through hydrogen bonded conformers lacking an intramolecular hydrogen bond.
Abstract: The conformer-specific reactivity of gas-phase pyruvic acid following the S1(nπ*) ← S0 excitation at λmax = 350 nm (290-380 nm) and the effect of water are investigated for the two lowest energy conformers. Conformer-specific gas-phase pyruvic acid photolysis rate constants and their respective populations are measured by monitoring their distinct vibrational OH-stretching frequencies. The geometry, relative energies, fundamental vibrational frequencies, and electronic transitions of the pyruvic acid conformers and their monohydrated complexes are calculated with density functional theory and ab initio methods. Results from experiment and theory show that the more stable conformer with an intramolecular hydrogen bond dominates the gas-phase photolysis of pyruvic acid. Water greatly affects the gas-phase pyruvic acid conformer population and photochemistry through hydrogen bonding interactions. The addition of water decreases the gas-phase relative population of the more stable conformer and decreases the molecule's gas-phase photolysis rate constants. The theoretical results show that even a single water molecule interrupts the intramolecular hydrogen bond, which is essential for the efficient photodissociation of gas-phase pyruvic acid. Results of this study suggest that the aqueous-phase photochemistry of pyruvic acid proceeds through hydrogen-bonded conformers lacking an intramolecular hydrogen bond.
TL;DR: High-level quantum chemical calculations were used to elucidate the gas and solution phase conformational equilibria for a series of symmetrically substituted (thio)ureas, (thIO)squaramides and croconamides, and predict that the thermodynamic conformer of many of these anion receptors is not the dual-hydrogen-bond-facilitating anti-anti conformer as is commonly assumed.
Abstract: High-level quantum chemical calculations were used to elucidate the gas- and solution-phase conformational equilibria for a series of symmetrically substituted (thio)ureas, (thio)squaramides, and croconamides. Gas-phase calculations predict that the thermodynamic conformer of many of these anion receptors is not the dual-hydrogen-bond-facilitating anti-anti conformer as is commonly assumed. For ,'-diaryl thiosquaramides and croconamides, the syn-syn conformer is typically the predominant conformer. Solution-phase calculations show that the anti-anti conformer is increasingly stabilized as the polarity of the solvent increases. However, the syn-syn conformer remains the lowest energy conformation for croconamides. These predictions are used to explain the acidity versus chloride binding affinity correlations recently reported for some of these compounds. The chloride binding constants for thioureas and croconamides are significantly lower than expected on the basis of their p values, and this may be due in part to the need for these receptors to reorganize into the anti-anti conformer. Experimental NMR nuclear Overhauser effect (NOE) measurements of an asymmetrically substituted squaramide and its thio analogue are consistent with the syn-syn conformation being predominant at 298 K. The conformational equilibria should therefore be an important consideration for the design and development of future anion receptors and organocatalysts.
TL;DR: It is demonstrated that both N-H⋯S and C5-C6γ H-bonding modes exist simultaneously in low-energy conformers of capped derivatives of Attc, a thietane α-amino acid.
Abstract: In addition to the classical N–H⋯OC non-covalent interaction, less conventional types of hydrogen bonding, such as N–H⋯S, may play a key role in determining the molecular structure. In this work, using theoretical calculations in combination with spectroscopic analysis in both gas phase and solution phase, we demonstrate that both these H-bonding modes exist simultaneously in low-energy conformers of capped derivatives of Attc, a thietane α-amino acid. 6-Membered ring inter-residue N–H⋯S interactions (C6γ), assisted by hyperconjugation between the thietane ring and the backbone, combine with 5-membered ring intra-residue backbone N–H⋯OC interactions (C5) to provide a C5–C6γ feature that stabilizes a planar geometry in the monomer unit. Two contiguous C5–C6γ features in the planar dimer implicate an unprecedented three-centre H-bond of the type CO⋯H(N)⋯SR2, while the trimer adopts two C5–C6γ features separated by a Ramachandran α-type backbone configuration. These low-energy conformers are fully characterized in the gas phase and support is presented for their existence in solution state.
TL;DR: This work demonstrates a self-consistent effective technique of analyzing the conformational equilibria of active pharmaceutical ingredient (API) molecules dissolved in supercritical carbon dioxide in a wide range of thermodynamic parameters of state and validates it by applying it to the study of carbamazepine dissolved in scCO2 being in permanent contact with an excess of crystalline carbamazEPine.
TL;DR: A Sergeant and Soldiers effect is produced in two diastereomeric copolymer series due to the presence in chloroform of a preferred conformation in ( S )- 2, and a conformational equilibrium in 1, where a P helix is induced independently of the absolute configuration of the Soldier.
Abstract: Different communication mechanisms can be switched within a copolymer by acting on the conformational composition of the components and their chirality. Thus, a sergeant and soldiers effect is produced in two diastereomeric copolymer series, poly[(S)-1r -co-(S)-2(1-r) ] and poly[(R)-1r -co-(S)-2(1-r) ], owing to the presence in chloroform of a preferred conformation in (S)-2, and a conformational equilibrium in 1, where a P helix is induced independently of the absolute configuration of the soldier. In THF, the presence of a conformational equilibrium at the pendants of the two components produces a reciprocal chiral enhancement effect by copolymerization of the two monomers, while in DMF, a third chiral to chiral communication switch is produced due to the presence of a single conformer at the pendant group of the two components. In such a case, a chiral conflict or chiral accord effect is produced depending if the two components induce the same or the opposite helical sense.
TL;DR: In this paper, an experimental approach in conducting NMR measurements at supercritical parameters of state is discussed, where a novel design of the high-pressure NMR cell was developed which allowed eliminating the field inhomogeneity and, thus, increasing the sensitivity of the experiment at the supercritical state.
TL;DR: In this article, three new 2-hydroxyethyl substituted N-heterocyclic carbene (NHC) precursors were synthesized from 1-(alkyl/aryl)benzimidazole and alkyl halides.
TL;DR: It is demonstrated that temperature-controlled IM-MS coupled with the introduction of appropriate bulky groups, such as aromatic rings to host molecules, could reveal the dynamic aspects of encapsulation in host-guest systems.
Abstract: The conformation and electronic structure of dibenzo-24-crown-8 (DB24C8) complexes with K+ ion were examined by ion mobility-mass spectrometry (IM-MS), ultraviolet (UV) photodissociation (UVPD) spectroscopy in the gas phase, and fluorescence spectroscopy in solution. Three structural isomers of DB24C8 (SymDB24C8, Asym1DB24C8, and Asym2DB24C8) in which the relative positions of the two benzene rings were different from each other were investigated. The IM-MS results at 86 K revealed a clear separation of two sets of conformers for the K+(SymDB24C8) and K+(Asym1DB24C8) complexes whereas the K+(Asym2DB24C8) complex revealed only one set. The two sets of conformers were attributed to the open and closed forms in which the benzene-benzene distances in the complexes were long (>6 A) and short (<6 A), respectively. IM-MS at 300 K could not separate the two conformer sets of the K+(SymDB24C8) complex because the interconversion between the open and closed conformations occurred at 300 K and not at 86 K. The crown cavity of DB24C8 was wrapped around the K+ ion in the complex, although the IM-MS results availed direct evidence of rapid cavity deformation and the reconstruction of stable conformers at 300 K. The UVPD spectra of the K+(SymDB24C8) and K+(Asym1DB24C8) complexes at ∼10 K displayed broad features that were accompanied by a few sharp vibronic bands, which were attributable to the coexistence of multiple conformers. The fluorescence spectra obtained in a methanol solution suggested that the intramolecular excimer was formed only in K+(SymDB24C8) among the three complexes because only SymDB24C8 could possibly assume a parallel configuration between the two benzene rings upon K+ encapsulation. The encapsulation methods for K+ ion (the "wraparound" arrangement) are similar in the three structural isomers of DB24C8, although the difference in the relative positions of the two benzene rings affected the overall cross-section. This study demonstrated that temperature-controlled IM-MS coupled with the introduction of appropriate bulky groups, such as aromatic rings to host molecules, could reveal the dynamic aspects of encapsulation in host-guest systems.
TL;DR: The conformational stability and internal rotation barriers, HOMO-LUMO gap and related properties, molecular static polarizability and hyperpolarizability parameters, and the NBO delocalization energies associated with the internal charge transfer of 2.3-trimethylpentane in the ground state were carried out taking into account the long range dispersion correction through CAM-B3LYP and WB97XD levels at aug-cc-pvtz basis set.
Abstract: The conformational stability and internal rotation barriers, HOMO-LUMO gap and related properties, molecular static polarizability and hyperpolarizability parameters, and the NBO delocalization energies associated with the internal charge transfer (ICT) of 2.2.3-trimethylpentane in the ground state were carried out taking into account the long range dispersion correction through CAM-B3LYP and WB97XD levels at aug-cc-pvtz basis set. The six lowest conformations were differentiated by a deep and multiple spectroscopic investigation. The ultraviolet-visible (UV-Vis) absorption bands are assigned using molecular orbital data obtained by TD-WB97XD/aug-cc-pvtz calculations, and carbon 13C NMR signal peaks have been assigned using GIAO-WB97XD/aug-cc-pvtz method. In addition, the normal mode calculations of the most and less stable conformers using a scaled force field in terms of non-redundant local symmetry coordinates have been confronted to the experimental vibrational spectra temperature dependency.
TL;DR: High-resolution rotational spectroscopy is deeply integrated with state-of-the-art quantum-chemical methodology to accurately determine intermolecular parameters and interaction energies, with the latter interpreted by means of powerful energy decomposition analyses (EDAs).
Abstract: Several gas-phase spectroscopic investigations have focused on a better understanding of the nature of weak, non-covalent interactions in model systems. However, their characterization and interpretation are still far from being satisfactory. A promising route to fill this gap is offered by strategies in which high-resolution rotational spectroscopy is deeply integrated with state-of-the-art quantum-chemical methodology to accurately determine intermolecular parameters and interaction energies, with the latter interpreted by means of powerful energy decomposition analyses (EDAs). As a proof of concept of this approach, we have selected the adducts formed by n-propylamine (PA) and iso-propylamine (IPA) with water. Among the stable structures computationally predicted, four (out of five) isomers of the PA-water complex and two isomers (trans and gauche) of the IPA-water adduct have been characterized with supersonic jet Fourier transform microwave spectroscopy. Starting from the experimental rotational constants for different isotopic species, computation of the corresponding vibrational corrections allowed a semi-experimental determination of the intermolecular parameters. Different EDAs point out that in all cases a strong O-HN hydrogen bond is the primary interaction. Accurate computations indicate that the length and ramification of the alkyl chain do not significantly affect the water-amine interactions, which - on the contrary - modify the stability order of PA conformers with respect to the isolated systems.
TL;DR: It is demonstrated that the Li+-PEG complexation induces a conformational change of the PEG chain from gauche/anti-conformers to a syn conformer, implying a folding behavior of polymer chains through multiple OpegLi+Opeg interactions.
Abstract: We report the structure of poly(ethylene glycol) (PEG) in a imidazolium-based ionic liquid (IL) electrolyte containing lithium bis(trifluoromethanesulfonyl)amide (LiTFSA) salt, as determined using Raman spectroscopy, high-energy X-ray total scattering (HEXTS), and molecular dynamics (MD) simulations. The Raman spectral study indicated that the TFSA anions bound to Li ions are desolvated when PEG is added to the LiTFSA/IL solution to form stable Li+-PEG complexes. Via quantitative analysis of the obtained Raman spectra, the desolvation number of the TFSA [nd, per one oxygen atom of the ethylene glycol unit (Opeg)] was determined to be ∼0.4, irrespective of the shape (star or linear) and molecular weight of the polymer. On the basis of radial distribution functions obtained from the HEXTS experiments and MD simulations, we demonstrated that the Li+-PEG complexation induces a conformational change of the PEG chain from gauche/anti-conformers to a syn conformer. This Li+-coordination-induced conformation resulted in a decrease in the radius of gyration (Rg) of the PEG chain, implying a folding behavior of polymer chains through multiple OpegLi+Opeg interactions.
TL;DR: This study uses the momentum correlation of fragment ions produced after inner-shell photoionization to distinguish conformational isomers of 1,2-dibromoethane (C2H4Br2) and paves the way for using Coulomb explosion imaging to track subtle molecular structural changes.
Abstract: Conformational isomerism plays a crucial role in defining the physical and chemical properties and biological activity of molecules ranging from simple organic compounds to complex biopolymers. However, it is often a significant challenge to differentiate and separate these isomers experimentally as they can easily interconvert due to their low rotational energy barrier. Here, we use the momentum correlation of fragment ions produced after inner-shell photoionization to distinguish conformational isomers of 1,2-dibromoethane (C2H4Br2). We demonstrate that the three-body breakup channel, C2H4+ + Br+ + Br+, contains signatures of both sequential and concerted breakup, which are decoupled to distinguish the geometries of two conformational isomers and to quantify their relative abundance. The sensitivity of our method to quantify these yields is established by measuring the relative abundance change with sample temperature, which agrees well with calculations. Our study paves the way for using Coulomb explosion imaging to track subtle molecular structural changes.
TL;DR: In this paper, the gas phase reaction of pyruvic acid (PA) with the OH radical was studied theoretically using accurate quantum chemistry and transition state theory, and two chemically distinct H-atom abstraction reactions and two distinct OH addition reactions were identified.
Abstract: The gas-phase reaction of pyruvic acid (PA) with the OH radical is studied theoretically using accurate quantum chemistry and transition state theory. Two chemically distinct H-atom abstraction reactions and two distinct OH addition reactions have been identified. The rate coefficients for these four processes were calculated. Quantum tunneling was included in each rate using the small curvature tunneling method. The influence of the conformational structure of PA was found to be particularly intriguing. While the trans-cis structure was found to dominantly react by H-atom abstraction from the methyl site, the trans-trans conformer was found to react mostly through H-atom abstraction from the acid site. A general formalism was developed to model the kinetics of the reactions that involve multiple conformers, interconverting prereactive complexes, and multiple transition states. Comparison of the results obtained with available experimental rate observations reveals agreement with the trans-trans conformer of PA but disagreement with the results obtained for a full statistical mixture of reagents. The role of these reactions in the atmospheric processing of PA is discussed.