S-trans Conformation Research Articles

Structure and Dynamic Rearrangements of the Pt2dba3 and Pd2dba3 Complexes in Solution.

Although the tris(dibenzylideneacetone)diplatinum complex (Pt2dba3) is an important source of Pt(0) used in catalysis and materials science, its structure has not yet been fully elucidated. A thorough study of the three-dimensional structure of Pt2dba3 and its dynamic behavior in solution was carried out using NMR spectroscopy methods at a high field (600 MHz) and molecular modeling. The complex was shown to contain three dba ligands in the s-cis,s-trans, s-trans,s-cis, and s-trans,s-trans conformations, which are uniformly oriented around the Pt2 backbone. In solution, the Pt2dba3 and Pd2dba3 complexes undergo rapid dynamic rearrangements, as evidenced by the exchange between the signals of the olefin protons of various dba ligands in the EXSY NMR spectra. According to the experimental measurements, the activation energies of the rearrangements were estimated to be 19.9 ± 0.2 and 17.9 ± 0.2 kcal/mol for the platinum and palladium complexes, respectively. Three possible mechanisms for this chemical exchange process were considered within the framework of DFT calculations. According to the calculated data, M2dba3 complexes undergo fluxional isomerization involving successive rotations of the dihedral angles formed by the carbonyl group and the C═C bond. Dissociation of dba ligands does not occur within these processes.

The nature of carotenoid S* state and its role in the nonphotochemical quenching of plants

In plants, light-harvesting complexes serve as antennas to collect and transfer the absorbed energy to reaction centers, but also regulate energy transport by dissipating the excitation energy of chlorophylls. This process, known as nonphotochemical quenching, seems to be activated by conformational changes within the light-harvesting complex, but the quenching mechanisms remain elusive. Recent spectroscopic measurements suggest the carotenoid S* dark state as the quencher of chlorophylls’ excitation. By investigating lutein embedded in different conformations of CP29 (a minor antenna in plants) via nonadiabatic excited state dynamics simulations, we reveal that different conformations of the complex differently stabilize the lutein s-trans conformer with respect to the dominant s-cis one. We show that the s-trans conformer presents the spectroscopic signatures of the S* state and rationalize its ability to accept energy from the closest excited chlorophylls, providing thus a relationship between the complex’s conformation and the nonphotochemical quenching.

Structural Elucidation of 2-(6-(Diethylamino)benzofuran-2-yl)-3-hydroxy-4H-chromen-4-one and Labelling of Mycobacterium aurum Cells

Trehalose conjugates of 3-hydroxychromone (3HC) dyes have previously been utilized as fluorescence labels to detect metabolically active mycobacteria with a view to facilitating point-of-care detection of mycobacterial pathogens, especially Mycobacterium tuberculosis. We subjected the 3HC dye 2-(6-(diethylamino)benzofuran-2-yl)-3-hydroxy-4H-chromen-4-one (3HC-2) to a combined X-ray crystallography and density functional theory (DFT) study, and conducted preliminary fluorescence labelling experiments with the model organism Mycobacterium aurum. In the crystal, 3HC-2 exhibits an s-cis conformation of the chromone and the benzofuran moieties about the central C–C bond. According to DFT calculations, the s-cis conformer is about 1.8 kcal mol−1 lower in energy than the s-trans conformer. The solid-state supramolecular structure features hydrogen-bonded dimers and π…π stacking. Fluorescence microscopy revealed fluorescence of M. aurum cells treated with the dye trehalose conjugate 3HC-2-Tre in the GFP channel. It was concluded that s-cis is the preferred conformation of 3HC-2 and that the generally considered non-pathogenic M. aurum can be labelled with the fluorescence probe 3HC-2-Tre for convenient in vitro drug screening of new antimycobacterial agents.

Atomic-level understanding on conformational flexibility of neochlorogenic and chlorogenic acids and their inclusion complexation with β-cyclodextrin

Neochlorogenic acid (NCA) and chlorogenic acid (CGA) are positional isomers, abundant in plums and prunes. Their limited bioavailability due to instability under ambient conditions can be overcome by cyclodexrin (CD) encapsulation. Here, single-crystal X-ray diffraction combined with density functional theory (DFT) calculation has been carried out on NCA in free form (1) and in complex with β-CD (2), providing atomic-level insights into the structural flexibility and the inclusion complexation with β-CD of CGA isomers. X-ray analysis revealed that the two symmetry-independent s-cis-NCA and 0.3 water molecules form elaborated H-bond networks (1). Upon β-CD encapsulation, complex H-bond patterns are disrupted and the converted s-trans-NCA is almost entirely enclosed in the asymmetric capsular β-CD dimer (2). On the contrary, the twofold symmetry-related β-CD–s-cis-CGA dimer forms a rare [4]pseudorotaxane reported previously. DFT full-geometry optimization disclosed that both the 2:1 and 1:1 trimodal β-CD–s-trans-NCA inclusion complexes are energetically stable, as the reported s-cis-CGA complex. Furthermore, the three-dimension potential energy surface (3D PES) profiles and all the DFT-fully optimized NCA and CGA structures existing in different lattice environments showed that both the s-cis and s-trans conformers are thermodynamically stable. This study not only presents crystallographic evidence for the distinct NCA and CGA conformers, unequivocally differentiating and resolving the long-time confusing CGA nomenclature for the first time, but also highlights the prime role of CGA conformational flexibility in their pharmacological functions.

Crystal structure and Hirshfeld surface analysis of 1-[(E)-2-(3-nitro-phen-yl)diazen-1-yl]naphthalen-2-ol.

The title compound, C16H11N3O3, belongs to the family of azo dyes. In the light of a single-crystal X-ray study, it is evident that of the tautomeric forms (azo-hydrazone), the hydrazone form is the predominant form in the solid state, namely, (1E)-1-[2-(3-nitro-phen-yl)hydrazin-1-yl-idene]-1,2-di-hydro-naphthalen-2-one. The naphthol and benzene fragments attached to the -N=N- moiety adopt the s-trans conformation. Furthermore, the mol-ecules are nearly coplanar, subtending a dihedral angle of 2.63 (5)°. An intra-molecular N-H⋯O hydrogen bond occurs. There are only two types of inter-molecular inter-actions in the crystal structure: strong hydrogen-bonding C-H⋯O inter-actions and π-π stacking inter-actions. The importance of C-H⋯O inter-actions in the mol-ecular packing is reflected by the relatively high contributions (28.5%) made by O⋯H/H⋯O contacts to the Hirshfeld surface.

Chain-Length- and Concentration-Dependent Isomerization of Bithiophenyl-Based Diaminotriazine Derivatives in Two-Dimensional Polymorphic Self-Assembly§.

Bithiophenyl-based diaminotriazine derivatives (2TDT-n, n = 10, 12, 16, and 18) with different chain lengths display colhex/p6mm mesophases. Their supramolecular self-assembled mechanism is investigated using scanning tunneling microscopy (STM) at the 1-octanoic acid/graphite interface at various concentrations. The chain length effect on the two-dimensional adlayers is observed in this system, and 2TDT-n molecules show a structural phase transition from the four-leaf arrangement to the two-row linear nanostructure accompanied by the emergence of molecular isomerization with the increase of the side-chain length. The self-assembled structure of 2TDT-10 is composed of a four-leaf pattern with uniform s-cis conformers. In 2TDT-12, three kinds of nanostructures (bamboo-like, two-row linear pattern-I, and flower-like) are observed. These nanostructures are randomly constituted by cis and trans conformers, and the ratios of the s-cis conformer in three kinds of patterns are 55.7, 42.3, and 62.5%, respectively. Furthermore, when n = 16 and 18, the ratio of the s-cis conformer further decreases to 19.0 and 4.3%, respectively. Those molecules mainly form linear nanostructures consisting of s-trans conformers. Therefore, it is reasonable to conclude that the side-chain length has a great effect on the self-assembled patterns and the molecular conformation of bithiophenyl-based diaminotriazine derivatives. Density functional theory calculations are applied to optimize molecular conformers and assess their single-point energies, showing that the s-cis conformation has higher energy than the s-trans conformer. We speculate that the ratio of two conformers in nanostructures might be similar to that of the liquid crystalline phase.

Schistosomicidal evaluation of synthesized bromo and nitro chalcone derivatives

Chalcones are compounds associated to several biological activities. The modification of chemical structures is one of the most widely used tool in the pharmaceutical industry to obtain new drugs. In this study, we synthetized chalcones with nitro and bromo substituents in different positions in the aromatic rings. NMR spectroscopy was used for characterization. Simultaneously, a conformational study of the compounds was carried out employing theoretical calculations. Furthermore, the schistosomicidal in vitro effect of bromo and nitro chalcone substituents on adult Schistosoma mansoni was investigated. The results showed that most chalcones have a conformational preference for s-cis geometry, which is favored by the conjugative effect of electronic delocalization. However, chalcones with ortho substituents dissipate greater stabilization of s-trans conformations, possibly for favoring surfaces with weak interactions such as Van der Waals. In addition, a significant effect of chalcones on female and male S. mansoni was observed. All samples evaluated reduced the motor activity of worms, caused mortality in male and female worms, and resulted in morphological alterations in a concentration- dependent manner (25–200 μg/mL) in a period of 6–24 h of incubation. Additionally, chalcones influenced the separation of couple worms and suppressed egg production at sublethal concentrations. Our results demonstrated that chalcones present potential to be used as schistosomicidal drugs, contributing to the clarification of the relation between the molecule conformation and the associated biological effects.

Synthesis, Crystal Structures, and Molecular Properties of Three Nitro-Substituted Chalcones

Three functionalized chalcones containing combinations of nitro functional groups have been synthesized via Claisen-Schmidt condensation between 2-nitroacetophenone and nitrobenzaldehyde, and the crystal structures obtained ((E)-1,3-bis(2-nitrophenyl)prop-2-en-1-one, 1a, (E)-1-(2-nitrophenyl)-3-(3-nitrophenyl)prop-2-en-1-one, 1b and (E)-1-(2-nitrophenyl)-3-(4-nitrophenyl)prop-2-en-1-one, 1c), C15H10N2O5, are reported. Compounds 1a and 1c crystallized in the triclinic centrosymmetric space group P1¯, whereas compound 1b crystallized in the orthorhombic space group Pbca. The X-ray analysis reveals that structures 1a and 1b exhibits s-trans conformation, whereas structure 1c exists in s-cis conformation, concerning the olefinic double bonds. In addition, the results show that the position of the nitro substituent attached to the aromatic B-ring has a direct effect on the molecular coplanarity of these compounds. The Hirshfeld surface analysis suggests that the non-covalent π-π stacking interactions are the most important contributors for the crystal packing of 1a and 1b. In 1c, the crystal packing is mainly stabilized by weak intermolecular C―H···O interactions due to the planar nature of the molecule.

Structure and dynamics of methacrylamide, a computational and free-jet rotational spectroscopic study

The conformational space of methacrylamide was explored by quantum mechanical modeling and surveyed in the 59.6–104.0 GHz frequency range using a millimeter-wave Stark-modulated free-jet absorption spectrometer. According to the relative orientation of the two unsaturated bonds, two conformers were observed, namely s-trans (A=5234.360(1), B=3364.9717(8) and C=2173.099(1) MHz) and s-cis (A=5207.292(1), B=3470.930(1) and C=2113.496(1) MHz). The s-trans conformation is the global minimum, with relative energy 4(2) kJ mol−1 and calculated isomerization barrier 15 kJ mol−1. Except for the methyl hydrogen atoms, s-cis-methacrylamide is planar and its methyl internal rotation barrier is 10.2(1) kJ mol−1. In s-trans-methacrylamide the allyl and amino frames form a dihedral angle of about 30° and the methyl internal rotation barrier is 7.4 kJ mol−1. This different behaviour is explained in terms of attractive and repulsive intramolecular interactions between groups: CH2/CO and CH3/NH2 for s-cis, CH2/NH2 and CH3/CO for s-trans. The tunneling splitting related to the double-well potential describing the interconversion between the two equivalent s-trans forms is 837.97(2) MHz and was reproduced by a one-dimensional flexible model using a 3.6 kJ mol−1 interconversion barrier.

Theoretical Study on the Conformational Equilibrium of 1’, 2' and 3'-Nitro-4-hydroxy-3-methoxy Chalcone Isomers

This paper presents the conformational analysis of three chalcone compounds, 1'-nitro-4-hydroxy-3-metoxychalcoea (o-CHAL), 2'-nitro-4-hydroxy-3-metoxychalcone (m-CHAL) and 3'-nitro-4-hydroxiy3-metoxychalcone (p-CHAL). By employing theoretical calculations, the most stable conformers of each compound were obtained. The natural bond orbital (NBO) analyses were carried out with all compounds using the Density Functional Theory (DFT) and the M06-2X method combined with the basis set 6-311++G (2d,dp) in isolated phase and indicated greater electron delocalization in s-cis conformers. The theoretical calculations provided the parameters that led to more stable s-cis conformational equilibrium for all the isomers under investigation. However, the s-trans conformer population was influenced by the position of the nitro group in the ring A, mainly o-Chal. DOI: http://dx.doi.org/10.17807/orbital.v13i2.1548

Rotational Spectra of Three Cyanobutadiene Isomers (C5H5N) of Relevance to Astrochemistry and Other Harsh Reaction Environments.

Three cyanobutadiene isomers have been synthesized and their rotational spectra analyzed in the 130-375 GHz frequency range. These species, which are close analogues of known interstellar molecules and are isomers of the heterocyclic aromatic molecule pyridine (C5H5N), offer the opportunity of revealing important insights concerning the chemistry in astronomical environments. The s-trans conformers of E-1-cyano-1,3-butadiene and Z-1-cyano-1,3-butadiene are observed, while both the anti-clinal and syn-periplanar conformers of 4-cyano-1,2-butadiene are evident in the rotational spectra. Over 1000 transitions for s-trans-Z-1-cyano-1,3-butadiene and for syn-periplanar-4-cyano-1,2-butadiene are fit to an octic, distorted-rotor Hamiltonian with low uncertainty (<50 kHz). Although neither s-trans-E-1-cyano-1,3-butadiene nor anti-clinal-4-cyano-1,2-butadiene can be fully treated with a distorted-rotor Hamiltonian in this frequency range, we provide herein minimally perturbed, single-state least-squares fits of over 1000 transitions for each species, yielding sets of spectroscopic constants that are expected to enable accurate prediction of high-intensity transitions at frequencies up to 370 GHz for both isomers. The assigned transitions and spectroscopic constants for these cyanobutadienes have already enabled the identification of two isomers in harsh reaction environments and should be sufficient to enable their identification in astronomical environments by radio astronomy.

(E)-1-(3,4-Dimethoxyphenyl)-2-methyl-3-phenylprop-2-en-1-one: A P-Type Acid-Stable Photochromic α-Methylchalcone

The α-methylated chalcone 3 with an electron-donor substituted A-aryl ring and an unsubstituted B-phenyl ring was synthesized by base-catalyzed aldehyde/acetophenone condensation. Compound 3 can be photo-switched from E→Z by irradiation with long-wavelength light λ &gt; 350 nm, whereas irradiation with shorter wavelengths leads to photo-stationary states (PSS) with lower amounts of the Z-isomer. The limiting wavelength for fully equilibrated E⮀Z (PSS = 1) can be achieved around 240 nm. The stability of both E- and Z-isomers at the wavelength-dependent PSS under UV-irradiation between 250 and 350 nm is remarkably high as observed from UV and NMR spectroscopy. Compound 3 is fatigue resistant even after more than 10 days continuous irradiation and is also oxygenation-stable under singlet oxygen sensitization conditions. In remarkable contrast to many other α-methylated chalcones, no change in the E/Z-ratio was detected when PSS samples were treated with Broensted acids. The negative photochromic E→Z switch of 3 is accompanied by a conformational switch from the E-form in its preferred s-trans conformation to the Z-form in a distorted s-cis conformation (Es-c→Zs-t).

Expected and Unexpected Products in Half Curcuminoid Synthesis: Crystal Structures of But-3-en-2-ones and 3-Methylcyclohex-2-enones

The expected (E)-but-3-en-2-ones compounds I and II (half curcuminoids) were obtained by the Claisen–Schmidt reaction between aldehydes 3,4-dimethoxybenzaldehyde or 4-nitrobenzaldehyde with acetone. Concomitantly, 3-methylcyclohex-2-enones compounds III and IV arose from an unexpected reaction of but-3-en-2-ones in the cascade reaction of a Michael-type addition of a second molecule of acetone followed by Robinson annulation under strong basic conditions. Both enones exhibit the (E)-configuration, compound I displays s-trans conformation, whereas compound II exhibits conformational disorder as solid solution of s-cis and s-trans conformations. The related 3-methylcyclohex-2-enones exhibit envelope conformation. Compound III constitutes an example of the rarest case of racemic solid solution (pseudoracemate), where a lack of chiral discrimination with respect to the two enantiomers leads to an enantiomeric disorder of a racemic mixture with different occupancies at the reference site. Due to the lack of strong hydrogen-bond donors in all compounds, the crystal packing is mainly stabilized by weak intermolecular C-H···O interactions between the molecules. The present work provides a new perspective on the search for by-products normally overlooked in Claisen–Schmidt condensations.

Conformational Preference of 2'-Fluoro-Substituted Acetophenone Derivatives Revealed by Through-Space 1H-19F and 13C-19F Spin-Spin Couplings.

The conformational properties of 2′-fluoro-substituted acetophenone derivatives were elucidated based on Hα–F and Cα–F through-space spin–spin couplings (TS-couplings), which occur between two atoms constrained at a distance smaller than the sum of their van der Waals radii. This study revealed that 2′-fluoro-substituted acetophenone derivatives in solutions form exclusively s-trans conformers by analyzing their NMR spectra focused on the TS-couplings. The magnitudes of the coupling constants 5J (Hα, F) and 4J (Cα, F) correlate linearly with the value of the dielectric constant of the solvents. Furthermore, s-trans conformations of the two derivatives were confirmed by X-ray crystallographic analysis. These conformational preferences were consistent with the DFT calculations. The s-cis conformer, in which fluorine and oxygen atoms lie in a syn-periplanar mode, may be subject to strong repulsion between the two polar atoms and become unstable. The s-trans preference of the 2′-fluoro-substituted acetophenone derivatives may be utilized in drug design.

Characterizing hydrogen and tetrel bonds in clusters of CO2 with carboxylic acids.

The interaction between carbon dioxide and planar carboxylic acids has been investigated through the analysis of the microwave spectrum of the acrylic acid·CO2 complex and quantum chemical modeling of the R-COOH·(CO2)1,16 clusters, where R = H, CH2CH. As regards the 1 : 1 compounds, two species, involving the s-cis and s-trans conformers of acrylic acid were observed. For both of them, a similar bidentate interaction arises between the carbonyl group of CO2 and the carboxylic group of the organic acid, leading to the formation of a planar six-membered ring. The binding energy is estimated to be De ≃ 21 kJ mol-1, 1/3 being the energy contributions of the tetrel to hydrogen bonds, respectively. In the 1 : 16 clusters, the ring arrangement is broken, allowing for the interaction of the acid with several CO2 molecules. The CO2 molecules completely surround formic acid, whereas, in the case of acrylic acid, they tend to avoid the allyl chain.

Reactive atomistic simulations of Diels-Alder-type reactions: conformational and dynamic effects in the polar cycloaddition of 2,3-dibromobutadiene radical ions with maleic anhydride

The kinetics, dynamics and conformational specificities for the ionic Diels-Alder reaction (polar cycloaddition) of maleic anhydride with 2,3-dibromobutadiene radical ions have been studied theoretically using multisurface adiabatic reactive molecular dynamics. A competition of concerted and stepwise reaction pathways was found and both the s-cis and s-trans conformers of the diene are reactive. The analysis of the minimum dynamic path of the reaction indicates that both, rotations and vibrations of the reactant molecules are important for driving the system towards the transition state. The rates were computed as s for the s-cis and s for the s-trans conformer of 2,3-dibromobutadiene at an internal temperature of 300 K. The present results are to be contrasted with the neutral variant of the title system in which only the gauche conformer of the diene was found to undergo a considerably slower, concerted and mostly synchronous reaction driven by the excitation of rotations. The results presented here inform detailed experimental studies of the dynamics of polar cycloadditions under single-collision conditions in the gas phase.

Millimeter wave free-jet spectrum of acrolein and several isotopologues

The millimeter-wave absorption spectrum of acrolein has been investigated in the 59.6–120 GHz region with a Free-Jet Absorption MilliMeter Wave spectrometer. New measured rotational transitions belonging to the s-cis conformer and its three 13C isotopologues and those of 13C and 18O isotopologues of the s-trans conformer, observed in natural abundance, are reported.

Quantum-chemistry-aided identification, synthesis and experimental validation of model systems for conformationally controlled reaction studies: separation of the conformers of 2,3-dibromobuta-1,3-diene in the gas phase.

The Diels-Alder cycloaddition, in which a diene reacts with a dienophile to form a cyclic compound, counts among the most important tools in organic synthesis. Achieving a precise understanding of its mechanistic details on the quantum level requires new experimental and theoretical methods. Here, we present an experimental approach that separates different diene conformers in a molecular beam as a prerequisite for the investigation of their individual cycloaddition reaction kinetics and dynamics under single-collision conditions in the gas phase. A low- and high-level quantum-chemistry-based screening of more than one hundred dienes identified 2,3-dibromobutadiene (DBB) as an optimal candidate for efficient separation of its gauche and s-trans conformers by electrostatic deflection. A preparation method for DBB was developed which enabled the generation of dense molecular beams of this compound. The theoretical predictions of the molecular properties of DBB were validated by the successful separation of the conformers in the molecular beam. A marked difference in photofragment ion yields of the two conformers upon femtosecond-laser pulse ionization was observed, pointing at a pronounced conformer-specific fragmentation dynamics of ionized DBB. Our work sets the stage for a rigorous examination of mechanistic models of cycloaddition reactions under controlled conditions in the gas phase.

Rotational Barrier and Conjugation: Theoretical Study of Resonance Stabilization of Various Substituents for the Donors NH&lt;sub&gt;2&lt;/sub&gt; and OCH&lt;sub&gt;3&lt;/sub&gt; in Substituted 1,3-Butadienes

The barrier to internal rotation around the central C2–C3 single bond of a series of (1E)-monosubstituted 1,3-butadienes and (1E,3E)-1-Y-4-X-disubstituted butadienes, with Y=NH2 or OCH3 and X=NO2, CHO, COOH, CN, CF3, Cl or F, were studied at the density functional w B97X-D/6-31G∗∗ level. The effect of substituents on π-conjugation in disubstituted 1,3-butadienes was studied by correlating the calculated internal rotational barriers with the difference in structural, atomic and molecular properties between the transition state TS and the s-trans conformers. The calculated differences in lengths of C–C, C–NH2 and C–OCH3 single bonds, N-H-N, and C-O-CH3 angles, NH2 out-of-plane angle, natural charges on amino nitrogen and methoxy oxygen, and the maximum electrostatic potential on amino hydrogens, were found to correlate strongly with the rotational barriers. The conjugative interaction was strongly stabilized in the case of strong π-electron acceptors such as NO2 or CHO and is slightly or negligibly affected with Cl and F groups. The resonance stabilization with the remaining acceptors decreases in the order COOH &gt; CN &gt; CF3. Acceptors X maintain their relative order of stabilization for the two donors, and NH2 is more stabilizing. Dominant resonance structures are suggested for highly and negligibly conjugated systems.

Crystal structure and Hirshfeld surface analysis of a conformationally unsymmetrical bis-chalcone: (1E,4E)-1,5-bis-(4-bromo-phen-yl)penta-1,4-dien-3-one.

In the title bis-chalcone, C17H12Br2O, the olefinic double bonds are almost coplanar with their attached 4-bromo-phenyl rings [torsion angles = -10.2 (4) and -6.2 (4)°], while the carbonyl double bond is in an s-trans conformation with with respect to one of the C=C bonds and an s-cis conformation with respect to the other [C=C-C=O = 160.7 (3) and -15.2 (4)°, respectively]. The dihedral angle between the 4-bromo-phenyl rings is 51.56 (2)°. In the crystal, mol-ecules are linked into a zigzag chain propagating along [001] by weak C-H⋯π inter-actions. The conformations of related bis-chalcones are surveyed and a Hirshfeld surface analysis is used to investigate and qu-antify the inter-molecular contacts.