Showing papers on "Conformational isomerism published in 2019"

Impact of Size and Electronegativity of Halide Anions on Hydrogen Bonds and Properties of 1-Ethyl-3-methylimidazolium-Based Ionic Liquids.

Abstract: The effect of the anion size and electronegativity of halide-based anions (Cl-, Br-, I-, and BF4-) on the interionic interaction in 1-ethyl-3-methylimidazolium-based ionic liquids (ILs) C2mim X (X = Cl, Br, I, and BF4) is studied by a combined approach of experiments (Raman, IR, UV-vis spectroscopy) and quantum chemical calculations. The fingerprint region of the Raman spectra of these C2mim X ion-pairs provides evidence of the presence of the conformational isomerism in the alkyl chain of the C2mim+ cation. The Raman and IR bands of the imidazolium C2-H stretch vibration for C2mim X (X = Cl, Br, I, and BF4) were noticeably blue-shifted with the systematic change in size of anions and the electronegativity. The observed blue shift in the C2-H stretch vibration follows the order C2mim BF4 > C2mim I > C2mim Br > C2mim Cl, which essentially indicates the strong hydrogen bonding in the C2mim Cl ion-pair. DFT calculations predict at least four configurations for the cation-anion interaction. On the basis of relative optimized energies and basis-set-superposition-error (BSSE) corrected binding energies for all ion-pair configurations, the most active site for the anion interaction was found at the C2H position of the cation. Besides information about the C2H position, our DFT results give insights into the anion interaction with the ethyl and methyl chain of the cation, which was also confirmed experimentally [ Chem. Commun. 2015 , 51 , 3193 ]. The anion interaction at the C2H site of the cation favors a planar geometry in C2mim X for X = Cl, Br, and I; however, for BF4, the system prefers a nonplanar geometry where the anion is located over the imidazolium ring. TD-DFT results were used to analyze the observed UV-vis absorption spectra in a more adequate way giving insights into the electronic structure of the ILs. Overall, a reasonable correlation between the observed and the DFT-predicted results is established.

The FELion cryogenic ion trap beam line at the FELIX free-electron laser laboratory: infrared signatures of primary alcohol cations

Abstract: The combination of a 4 K 22-pole ion trap instrument, FELion, with the widely tunable free electron lasers at the FELIX Laboratory is described in detail. It allows for wide-range infrared vibrational spectroscopy of molecular ions. In this study, the apparatus is used for infrared vibrational predissociation (IR-PD) measurements of the simple alcohol cations of methanol and ethanol as well as their protonated forms. Spectra are taken by tagging the cold molecular ions with He atoms. The infrared spectrum of protonated methanol is recorded for the first time, and the wavelength coverage for all other species is substantially extended. The bands of all spectra are analysed by comparison to ab initio calculation results at different levels of theory. Vibrational bands of different isomers and conformers (rotamers) are discussed and identified in the experimental spectra. Besides the measurement of IR-PD spectra, the method of infrared multiple photon dissociation IR-MPD is applied for some cases. Spectral narrowing due to the cold environment is observed and rotational band contours are simulated. This will help in identifying more complex species using the IR-MPD method in future measurements. Overall the IR-PD spectra reveal more bands than are observed for the IR-MPD spectra. In particular, many new bands are observed in the fingerprint region. Depletion saturation of the finite number of trapped ions is observed for the IR-PD spectra of the ethanol cation and the presence of only one isomeric species is concluded. This special feature of ion trapping spectroscopy may be used in future studies for addressing specific isomers or cleaning the ion cloud from specific isomers or conformers. In addition, the results of this study can be used as a basis to obtain high-resolution infrared vibrational and THz rotational spectra of alcohol ions in order to detect them in space.

The rich conformational landscape of perillyl alcohol revealed by broadband rotational spectroscopy and theoretical modelling.

Abstract: The rotational spectrum of perillyl alcohol, a naturally occurring, chiral, dietary monoterpene, was investigated using a chirped pulse Fourier transform microwave spectrometer and a cavity-based Fourier transform microwave spectrometer. To aid the assignment of the dense chirped pulse spectrum obtained, extensive theoretical conformational searches were carried out. In one approach, several one and two-dimensional scans along three dihedral angles associated with the rotational motions of the –OH, –CH2OH, and –C(CH2)CH3 groups were performed. These scans, combined with the equatorial and axial positions of the –C(CH2)CH3 group, resulted in 54 conformers. The same conformers were identified in the second approach where a semi-classical conformational search code was used. The relative stabilities of the conformers and the interconversion barriers among them were explored extensively at the DFT B3LYP-D3(BJ)/def2-TZVP and B3LYP-D3(BJ)/6-311++G(2d,p), as well as local MP2/aug-cc-pVQZ levels of theory, and 12 conformers were ultimately identified as possibly observable candidates in a molecular jet expansion. Rotational spectra of eight out of the 12 candidates were observed experimentally and analyzed. The non-observation of the remaining four conformers may be attributed to their low abundances. The study points out the importance of identifying all conformers of relevant abundance, even those which could not be detected experimentally, in order to properly benchmark the theoretical relative stabilities with the experimental ones. A comprehensive study of the conformational distribution of perillyl alcohol contributes to our understanding of its structural properties which may influence its functions.

Conformational isomerism controls collective flexibility in metal-organic framework DUT-8(Ni)

Abstract: Metal-organic frameworks (MOFs) are coordination networks with organic ligands containing potential voids. Some MOFs show pronounced structural flexibility that may result in closing and re-opening these pores. Here, we show that collective flexibility in a MOF-DUT-8(Ni) - is controlled by conformational isomerism. DUT-8(Ni), a pillared-layer MOF with Ni2 paddle-wheels, dabco pillars and naphthalene dicarboxylate (ndc) linkers, can crystallize in many conformational isomers that depend on the orientation of the non-linear ndc linkers with respect to each other. While the open form is compatible with several of these conformations, only one of them, with alternating linker orientations, is stable as the closed form. We show, by means of first principles calculations, that in the stable closed form, the appreciable lattice strain is compensated by London-dispersion forces between the ndc linkers that arrange with maximum overlap in a stacking order similar to the stacking in graphite. We substantiate these results by well-tempered metadynamics calculations on the DFT-based Born-Oppenheimer potential energy surface, by refined X-ray diffraction data and by nitrogen adsorption data obtained by experiment and grand-canonical Monte-Carlo simulations based on the DFT-optimized and PXRD-derived geometries. While the reported origin of flexibility cannot be generalized to all flexible MOFs, it offers a rational design concept of folding mechanisms in switchable MOFs by exploitation of the stabilization effect of linker stacking in the closed form.

Diphenanthrioctaphyrin(1.1.1.0.1.1.1.0): Conformational Switching Controls the Stereochemical Dynamics of the Topologically Chiral System.

Abstract: The analogue of octaphyrin(1.1.1.0.1.1.1.0) bearing two dimethoxyphenanthrene units was synthesized and characterized in solution and solid state. The macrocycle was demonstrated to exist as two locked conformers that can be easily separated and handled individually. The conversion of conformers was proven to be facilitated by the presence of hydrogen-bond acceptors, such as amines. The bis-boron(III) complex of diphenanthrioctaphyrin has been obtained, proving that the metalloid center acts as the topology selector stabilizing only one conformation of the macrocycle, irrespective of the stereoisomer used for the insertion. Both conformers of diphenanthrioctaphyrin, as well as the boron complex formed from them, have been separated into enantiomers using HPLC with a chiral stationary phase. All of these systems have shown strikingly different stereodynamic behavior.

Conformational Effect on the Large Amplitude Motions of 3,4-Dimethylanisole Explored by Microwave Spectroscopy.

Abstract: The microwave spectrum of 3,4-dimethylanisole, a molecule containing three methyl groups allowing for internal rotation, was recorded using a pulsed molecular jet Fourier transform microwave spectrometer operating in the frequency range from 2.0 to 26.5 GHz. Quantum chemical calculations yielded two conformers with an anti and a syn configuration of the methoxy group, both of which were assigned in the experimental spectrum. Torsional splittings due to the internal rotations of two methyl groups attached to the aromatic ring were resolved and analyzed. The rotational-torsional transitions could be reproduced to measurement accuracy, yielding well-determined rotational and internal rotation parameters. The torsional barriers of the methyl groups at the meta and para position were deduced to be 430.00(37) and 467.90(17) cm-1, respectively, for the syn-conformer. The respective values for the anti-conformer are 499.64(26) and 533.54(22) cm-1. A labeling scheme for the G18 group written as the semidirect product ( C3I ⊗ C3I) (× C s was introduced.

Guest-mediated chirality transfer in the host–guest complexes of an atropisomeric perylene bisimide cyclophane host

Abstract: The dynamic equilibrium of stereoisomers of a cyclophane, which is comprised of two atropisomeric perylene bisimide (PBI) subunits, and its host–guest binding with an achiral and a series of chiral guests have been studied. Temperature-dependent 1H NMR spectroscopic studies have shown that at higher temperature all three stereoisomers ((M,M) and (P,P) enantiomers and (M,P)/(P,M) mesomers) of the cyclophane are in a dynamic equilibrium as only one set of proton signals was observed. However, at a lower temperature (260 K) two sets of signals in a ratio of 2 : 1, instead of the theoretically expected 1 : 1 ratio, were observed for the diastereomers (M,M)/(P,P) and (M,P)/(P,M) of the cyclophane presumably due to the chiral recognition of the enantiomeric (M,M)/(P,P) conformers. The 1H NMR studies further revealed that the achiral guest perylene mostly selects the (M,M)/(P,P) enantiomeric pair of the host for encapsulation. The induction of chirality in the host–guest complexes of the cyclophane with chiral guests has been investigated by circular dichroism (CD) spectroscopy. A distinct CD effect was observed upon addition of chiral guests to the solution of a racemic cyclophane host, indicating a pronounced preference of the chiral guests for one of the two homochiral stereoisomers, (M,M) and (P,P), for encapsulation. Kinetic studies by time-dependent NMR spectroscopy did not lead to conclusive results to assign the recognition process of chiral guests to either the induced fit or the conformational selection model.

Interplay of Ring Puckering and Hydrogen Bonding in Deoxyribonucleosides.

Abstract: The Cremer-Pople ring puckering analysis and the Konkoli-Cremer local mode analysis supported by the topological analysis of the electron density were applied for the first comprehensive analysis of the interplay between deoxyribose ring puckering and intramolecular H-bonding in 2'-deoxycytidine, 2'-deoxyadenosine, 2'-deoxythymidine, and 2'-deoxyguanosine. We mapped for each deoxyribonucleoside the complete conformational energy surface and the corresponding pseudorotation path. We found only incomplete pseudorotation cycles, caused by ring inversion, which we coined as pseudolibration paths. On each pseudolibration path a global and a local minimum separated by a transition state were identified. The investigation of H-bond free deoxyribonucleoside analogs revealed that removal of the H-bond does not restore the full conformational flexibility of the sugar ring. Our work showed that ring puckering predominantly determines the conformational energy; the larger the puckering amplitude, the lower the conformational energy. In contrast no direct correlation between conformational energy and H-bond strength was found. The longest and weakest H-bonds are located in the local minimum region, whereas the shortest and strongest H-bonds are located outside the global and local minimum regions at the turning points of the pseudolibration paths, i.e., H-bonding determines the shape and length of the pseudolibration paths. In addition to the H-bond strength, we evaluated the covalent/electrostatic character of the H-bonds applying the Cremer-Kraka criterion of covalent bonding. H-bonding in the puric bases has a more covalent character whereas in the pyrimidic bases the H-bond character is more electrostatic. We investigated how the mutual orientation of the CH2OH group and the base influences H-bond formation via two geometrical parameters describing the rotation of the substituents perpendicular to the sugar ring and their tilting relative to the ring center. According to our results, rotation is more important for H-bond formation. In addition we assessed the influence of the H-bond acceptor, the lone pair (N, respectively O), via the delocalization energy. We found larger delocalization energies corresponding to stronger H-bonds for the puric bases. The global minimum conformation of 2'-deoxyguanosine has the strongest H-bond of all conformers investigated in this work with a bond strength of 0.436 which is even stronger than the H-bond in the water dimer (0.360). The application of our new analysis to DNA deoxyribonucleotides and to unnatural base pairs, which have recently drawn a lot of attention, is in progress.

PEPCONF, a diverse data set of peptide conformational energies.

Abstract: We present an extensive and diverse database of peptide conformational energies. Our database contains five different classes of model geometries: dipeptides, tripeptides, and disulfide-bridged, bioactive, and cyclic peptides. In total, the database consists of 3775 conformational energy data points and 4530 conformer geometries. All the reference energies have been calculated at the LC-ωPBE-XDM/aug-cc-pVTZ level of theory, which is shown to yield conformational energies with an accuracy in the order of tenths of a kcal/mol when compared to complete-basis-set coupled-cluster reference data. The peptide conformational data set (PEPCONF) is presented as a high-quality reference set for the development and benchmarking of molecular-mechanics and semi-empirical electronic structure methods, which are the most commonly used techniques in the modeling of medium to large proteins.

Unravelling the solvent polarity effect on the excited state intramolecular proton transfer mechanism of the 1- and 2-salicylideneanthrylamine. A TD-DFT case study.

Abstract: Time dependent density functional theory has been used to investigate the photochemical and photophysical processes involved in the excited states relaxation of 1- and 2-salicylideneanthrylamine in different solvent environments. This investigation reveals that the pathways involved in the relaxation of the first excited state depend on the solvent polarity. The emission spectrum in acetonitrile and methanol is dominated by the cis-keto tautomers, while in cyclohexane, the spectrum is dominated by the fluorescence emission of the locally excited trans-enol form. Our results showed that, for each compound, two nearly isoenergetic trans-enol conformers can coexist in equilibrium, which upon photoexcitation, can relax by two competitive processes: rotation about the azomethine NC bond leading to the twisted-enol conformer, and the excited state intramolecular proton transfer leading to the fluorescent cis-keto tautomer, which can undergo a cis–trans isomerization producing the trans-keto photochromic product. The TD-DFT relaxed potential energy profiles for the ESIPT show that the effect of changing the solvent from polar to nonpolar solvents results on an increment of the energy barrier, and therefore, the ESIPT become kinetically less favoured. In constrast, this change favours the relaxation of the excited trans-enol form towards the twisted conformers, in both the enol and keto regions.

Internal dynamics of cyclohexanol and the cyclohexanol–water adduct

Abstract: Two conformers of cyclohexanol and the cyclohexanol–water adduct have been characterized in a jet expansion using rotational spectroscopy. In the gas phase, cyclohexanol adopts an equatorial position for the hydroxyl group, with the two conformers differing in the orientation of the hydroxylic hydrogen, either gauche or trans with respect to the aliphatic hydrogen at C(1). Axial cyclohexanol was not detected in the jet. The transitions of the gauche conformer are split into two component lines due to the tunneling effect of the O–H internal rotation, which connects two equivalent gauche minima. The tunneling splitting in the vibrational ground state has been determined to be ΔE0+0− = 52(2) GHz. From this splitting, the inversion barriers connecting the two equivalent gauche conformers have been determined using a flexible model to be B2 = 377 cm−1. A single isomer is detected for the cyclohexanol–water dimer, in which the water molecule acts as a proton donor to the equatorial gauche ring. The presence of torsional tunneling in the adduct suggests a concerted large-amplitude-motion in which the internal rotation in the ring is accompanied by a torsion of the water molecule, to produce an equivalent enantiomer. The torsional tunneling in the adduct is reduced to ΔE0+0− = 32.7(4) GHz and the potential barrier in the complex increases to B2 = 494 cm−1.

Effects of Entangled IR Radiation and Tunneling on the Conformational Interconversion of 2-Cyanophenol

Abstract: The conformers of 2-cyanophenol (2CP) and their interconversions were studied by infrared (IR) spectroscopy after trapping the monomers of the gaseous compound into low-temperature (15 K) argon (Ar...

Understanding the structural complexity of dissolved organic matter: isomeric diversity.

Abstract: In the present work, the advantages of ESI-TIMS-FT-ICR MS to address the isomeric content of dissolved organic matter are studied. While the MS spectra allowed the observation of a high number of peaks (e.g., PAN-L: 5004 and PAN-S: 4660), over 4× features were observed in the IMS-MS domain (e.g., PAN-L: 22 015 and PAN-S: 20 954). Assuming a total general formula of CxHyN0–3O0–19S0–1, 3066 and 2830 chemical assignments were made in a single infusion experiment for PAN-L and PAN-S, respectively. Most of the identified chemical compounds (∼80%) corresponded to highly conjugated oxygen compounds (O1–O20). ESI-TIMS-FT-ICR MS provided a lower estimate of the number of structural and conformational isomers (e.g., an average of 6–10 isomers per chemical formula were observed). Moreover, ESI-q-FT-ICR MS/MS at the level of nominal mass (i.e., 1 Da isolation) allowed for further estimation of the number of isomers based on unique fragmentation patterns and core fragments; the later suggested that multiple structural isomers could have very closely related CCS. These studies demonstrate the need for ultrahigh resolution TIMS mobility scan functions (e.g., R = 200–500) in addition to tandem MS/MS isolation strategies.

Conformer-dependent self-assembled metallacycles with photo-reversible response.

Abstract: Discrete, well-defined metallacycles and metallacages with stimuli-responsive behaviors have been largely predominated by the organic donor/metal acceptor paradigm with spontaneous formation of coordination bonds. However, light-driven self-assembly systems usually show relatively low utilization yield of photons and low fatigue resistance. Given that almost no example illustrates the different self-assembly behaviors of antiparallel and parallel conformers in the traditional photochromic diarylethene (DAE) system, here we have for the first time constructed a unique series of photoactive conformer-dependent metallacycles, focusing on the characterization and comparison of self-assembly behavior in different ligand conformers with different di-platinum(II) acceptors. Their photoswitchable scaffold sizes and shapes are precisely controlled by photochromically separable parallel or anti-parallel conformers via coordination-driven self-assembly. The ap-conformer and closed form provide larger bending angles upon coordination with di-Pt(II) acceptors into hexagon [6 + 6] or [3 + 3] while the p-conformer only can form smaller polygon cycles. Notably, in contrast with the non-photoactive parallel conformer, the reversible interconversion of anti-parallel ring-open and ring-closed conformer metallacycles can be achieved by alternate irradiation with UV and visible light, respectively, along with a relatively high conversion ratio and good fatigue resistance. This work provides a potential way to construct smart materials for use in sensing, catalysis and drug delivery systems.

̇QOOH-mediated reactions in cyclohexene oxidation

Abstract: Multiplexed photoionization mass spectrometry (MPIMS) is utilized to examine reaction mechanisms of QOOH radicals derived from cyclohexene, a primary intermediate in low-temperature oxidation of cyclohexane, in order to assess the influence of a single C=C bond in a cyclic hydrocarbon on reactions relevant to chain-branching. The experiments were conducted using Cl-initiated oxidation at 10 Torr and from 500 to 700 K; [O2]0 remained fixed at 3 ⋅1016 cm–3. To complement the experiments, ab initio calculations of single point energies on the potential energy surfaces (PES) of cyclohex-1-en-3-peroxy and cyclohex-1-en-4-peroxy were conducted at the CBS-QB3 level of theory. In total, single point energies for 32 pathways were calculated across four surfaces, accounting for axial/equatorial conformers of ROȮ. The combined experimental and computational results confirm that cyclohexene – a primary intermediate of cyclohexane oxidation – undergoes complex QOOH-mediated chemistry. The main results from the experiments and calculations include: (i) Ketohydroperoxide formation is identified by exact mass measurements (m/z 128.047, C6H8O3). Notably, the measured photoionization spectra are nearly identical to those of analogous species formed in n-butane and cyclohexane oxidation. Single point energy calculations reveal that, relative to the equivalent pathway in cyclohexane oxidation, resonance-stabilization in the γ-QOOH radical cyclohex-1-en-3-yl-5-hydroperoxy decreases the barrier for ROȮ → QOOH isomerization by 8.3 kcal/mol, yet increases the barrier for unimolecular QOOH decomposition by a similar amount. The net effect is facilitation of QOOH + O2 reactions and subsequent ketohydroperoxide formation, evident by the observation of C6H8O3 despite [O2] of only ∼1016 cm–3, approximately 102 lower than in prior measurements in n-butane and cyclohexane oxidation. The same effect also occurs for resonance-stabilized β-QOOH. (ii) Co-products from chain-propagating ȮH-formation via QOOH decomposition were measured directly, including 3,4-epoxycyclohex-1-ene and 4,5-epoxycyclohex-1-ene. Evidence for QOOH ring-opening to hexa-3,5-dienal is also observed experimentally and supported by adiabatic ionization energy calculations. Other products from ring-opening reactions were identified, including ethene, formaldehyde, 1,3-butadiene, acrolein, and 3-butenal, and potential reaction mechanisms are postulated.

Sensing the Molecular Structures of Hexan-2-one by Internal Rotation and Microwave Spectroscopy.

Abstract: Using two molecular jet Fourier transform spectrometers, the microwave spectrum of hexan-2-one, also called methyl n-butyl ketone, was recorded in the frequency range from 2 to 40 GHz. Three conformers were assigned and fine splittings caused by the internal rotations of the two terminal methyl groups were analyzed. For the acetyl methyl group CH3 COC3 H6 CH3 , the torsional barrier is 186.9198(50) cm-1 , 233.5913(97) cm-1 , and 182.2481(25) cm-1 for the three observed conformers, respectively. The value of this parameter could be linked to the structure of the individual conformer, which enabled us to create a rule for predicting the barrier height of the acetyl methyl torsion in ketones. The very small splittings arising from the internal rotation of the butyl methyl group CH3 COC3 H6 CH3 could be resolved as well, yielding the respective torsional barriers of 979.99(88) cm-1 , 1016.30(77) cm-1 , and 961.9(32) cm-1 .

Stereochemistry of polypeptoid chain configurations.

Abstract: Like polypeptides, peptoids, or N-substituted glycine oligomers, have intrinsic conformational preferences due to their amide backbones and close spacing of side chain substituents. However, the conformations that peptoids adopt are distinct from polypeptides due to several structural differences: the peptoid backbone is composed of tertiary amide bonds that have trans and cis conformers similar in energy, they lack a backbone hydrogen bond donor, and have an N-substituent. To better understand how these differences manifest in actual peptoid structures, we analyzed 46 high quality, experimentally determined peptoid structures reported in the literature to extract their backbone conformational preferences. One hundred thirty-two monomer dihedral angle pairs were compared to the calculated energy landscape for the peptoid Ramachandran plot, and were found to fall within the expected minima. Interestingly, only two regions of the backbone dihedral angles ϕ and ψ were found to be populated that are mirror images of each other. Furthermore, these two conformers are present in both cis and trans forms. Thus, there are four primary conformers that are sufficient to describe almost all known backbone conformations for peptoid oligomers, despite conformational constraints imposed by a variety of side chains, macrocyclization, or crystal packing forces. Because these conformers are predominant in peptoid structure, and are distinct from those found in protein secondary structures, we propose a simple naming system to aid in the description and classification of peptoid structure.

Comprehensive Assessment of Torsional Strain in Crystal Structures of Small Molecules and Protein-Ligand Complexes using ab Initio Calculations.

Abstract: The energetics of rotation around single bonds (torsions) is a key determinant of the three-dimensional shape that druglike molecules adopt in solution, the solid state, and in different biological environments, which in turn defines their unique physical and pharmacological properties. Therefore, accurate characterization of torsion angle preference and energetics is essential for the success of computational drug discovery and design. Here, we analyze torsional strain in crystal structures of druglike molecules in Cambridge structure database (CSD) and bioactive ligand conformations in protein data bank (PDB), expressing the total strain energy as a sum of strain energy from constituent rotatable bonds. We utilized cloud computing to generate torsion scan profiles of a very large collection of chemically diverse neutral fragments at DFT(B3LYP)/6-31G*//6-31G** or DFT(B3LYP)/6-31+G*//6-31+G** (for sulfur-containing molecule). With the data generated from these ab initio calculations, we performed rigorous analysis of strain due to deviation of observed torsion angles relative to their ideal gas-phase geometries. Contrary to the previous studies based on molecular mechanics, we find that in the crystalline state, molecules generally adopt low-strain conformations, with median per-torsion strain energy in CSD and PDB under one-tenth and one-third of a kcal/mol, respectively. However, for a small fraction (<5%) of motifs, external effects such as steric hindrance and hydrogen bonds result in strain penalty exceeding 2.5 kcal/mol. We find that due to poor quality of PDB structures in general, bioactive structures tend to have higher torsional strain compared to small-molecule crystal conformations. However, in the absence of structural fitting artifacts in PDB structures, protein-induced strain in bioactive conformations is quantitatively similar to those due to the packing forces in small-molecule crystal structures. This analysis allows us to establish strain energy thresholds to help identify biologically relevant conformers in a given ensemble. The work presented here is the most comprehensive study to date that demonstrates the utility and feasibility of gas-phase quantum mechanics (QM) calculations to study conformational preference and energetics of drug-size molecules. Potential applications of this study in computational lead discovery and structure-based design are discussed.

Explaining crystallization preferences of two polyphenolic diastereoisomers by crystal structure prediction

Abstract: Despite their structural similarity, two naturally occuring polyphenols, epicatechin and catechin, display significantly distinct crystallization behaviour. Epicatechin crystallizes only as a pure compound, and appears to be monomorphic, whereas no pure crystalline form of catechin is known, but it can form a variety of solvates with polar solvents. This work aims to explain these experimentally observed differences using the results of crystal structure prediction calculations. The entire conformational space of both molecules has been included in the crystal structure prediction study, which also explored the crystal structure landscapes of the pure crystals, 1 : 1 solvates and 2 : 1 solvates. From the computational results, we were able to show that the experimental observations with regard to crystallization behavior are the result of a trade-off between intra- and intermolecular energy contributions to the total energy of a crystalline system. In the case of epicatechin, conformers with low gas phase energies are at the same time the ones able to form crystal structures with favourable intermolecular interactions. In contrast, only high energy gas phase conformers of catechin were found to be able to pack efficiently. Consequently, the unfavorable intramolecular energy contribution has to be compensated by stabilizing intermolecular interactions. The calculations for 2 : 1 and 1 : 1 methanol solvates of both molecules demonstrate that such compensation can be readily provided by solvent molecules able to form hydrogen bonds with catechin.

Pure E/Z isomers of N-methylpyrrole-benzohydrazide-based BF2 complexes: remarkable aggregation-, crystallization-induced emission switching properties and application in sensing intracellular pH microenvironment

Abstract: Organic fluorescent molecules with E/Z isomers usually have different photophysical properties owing to their disparate configurations, which lead to differences in molecular polarity and the chemical environment of atoms. However, due to the difficulty in the synthesis of their pure E and Z conformers, very limited research efforts have been devoted to studying the different photophysical properties of these isomers. In this work, two pairs of pure E/Z isomers of novel fluoroboron acylhydrozone dyes based on 2,2-difluoro-3-[(N-methylpyrrol-2-yl)methylene]-5-phenyl-1,3,4,2-oxadiazaborole (MPOAB) with two different electronic substituent groups (OMe or NEt2) were developed for the first time. These isomers were each characterized by NMR, X-ray structure analysis, HRMS, and absorption and PL spectroscopy. All isomers showed weak fluorescence properties in organic solvents and strong fluorescence in the solid state as well as excellent aggregation-induced emission (AIE) properties. More interestingly, the photophysical properties of the E/Z isomers, especially their aggregation and crystallization-induced emission, are significantly different. These results indicate that the AIE properties of these compounds are mainly attributed to the restriction of single bond rotations between the two aromatic rings and the five-membered fluoroboric ring, while participation of E/Z isomerization is finite. Besides, their photoisomerization, grinding, viscosity, and acid–base fluorescence response properties were also studied. In addition, an isomer of them, as an example, was successfully applied for analyzing the intracellular pH microenvironment of living cancer cells.

Unimolecular Reaction Rate Measurement of syn-CH3CHOO.

Abstract: The unimolecular reactions of Criegee intermediates (CIs) are thought to be one of the significant sources of atmospheric OH radicals. However, stark discrepancies exist in the unimolecular reaction rate of the methyl-substituted CI CH3CHOO, typically from ozonolysis of alkenes such as trans-2-butene, between the results of ozonolysis of alkene experiments and the up-to-date theoretical calculations. That no further progress has been made since the method that directly produces CIs in the laboratory was developed is mostly attributed to the existence of two conformers, syn- and anti-CH3CHOO, and the methodological limitations of sensitive conformer-specific detection. We report a conformer-specific measurement of the unimolecular reaction rate of syn-CH3CHOO by using a high-repetition-rate laser-induced fluorescence method. At 298 K, the observed value of 182 ± 66 s-1 is in good agreement with recent theoretical calculations.

Intramolecular π–hole interactions with nitro aromatics

Abstract: A thorough evaluation of the CSD and DFT computations were conducted to assess if intramolecular π–hole interactions can stabilize a conformer of nitro aromatics. It was found that this can only be the case when the nitro N-atom and an interacting electron-rich atom are separated by at least four bonds. Data from the solid state correspond well to the gas phase calculations and stabilizing energies were estimated to be as large as about 2–3 kcal mol−1, which is in the order of weak hydrogen bonding interactions.