Skewed Conformation Research Articles

Theoretical determination of the standard enthalpies of formation of alkyl radicals using the concept of a complete set of homodesmotic reactions

The complete sets of homodesmotic reactions (HDR) for 107 acyclic alkyl free radicals С4-С9 of normal and branched structure were constructed using the graph-theoretic representation and analysis of a tested compound. The absolute enthalpies of the studied compounds and HDR reference structures were calculated using the M062X/cc-pVTZ level of theory. Based on these data, the thermal effects of HDRs were calculated and then applied to determine the standard enthalpies of formation of the studied radicals using the known enthalpies of formation of reference structures. The dissociation energies of BDE C–H and C–CH3 bonds were also calculated. The effect of radical structure on the BDE value is discussed, and a new effect of stabilization of the radical center in the skewed conformation of free radical is established; this effect has not been previously described in the scientific literature.

Structural analysis and probing the conformational space of dansylamide by means of gas-phase electron diffraction and quantum chemistry

Dansylamide is perhaps the most ubiquitous fluorophore due to its donor-acceptor bifunctionality and its ability to form intra- and intermolecular hydrogen bonding. Among the diversity of its applications is the development of new generation of biosensors for the in vivo monitoring of traces of metals. The structure and conformational stability of dansylamide in the gas phase were investigated for the first time by a combined gas-phase electron diffraction-mass spectrometry (GED/MS), complemented by quantum chemical calculations. GED data indicate that different skewed conformers exist at T = 464 K, which are characterized by the deviation of two S–N bonds from the perpendicular orientation relative to the naphthalene plane. Maybe the most indicative structural parameters for electronic interactions between the donor-acceptor substituents and the aromatic naphthalene and the subsequent stabilization of the favorable skewed eclipsed-syn conformer are the dihedral angles C9–C1–S–N and C10–C5–N–C with the experimentally determined values of 66.8° (32) and 68.1° (72), respectively. The role of –SO2NH2 by forming intramolecular hydrogen bonds was scrutinized by employing the natural bond orbital approach (NBO), quantum theory atoms in molecules (QTAIM), and molecular electrostatic potential (MESP). The non-planarity of the naphthalene skeleton due to the electronic interactions with the substituents and its consequence for the fluorescence activity of dansylamide have been discussed.

2-(Phenylsulfanyl)aniline

In the title compound, C12H11NS, the aniline and phenyl rings have a skewed conformation with a dihedral angle of 81.31 (7)°. There is a short intramolecular N–H...S contact enclosing anS(5) ring motif. In the crystal, molecules are linkedviaN–H...S hydrogen bonds, forming chains along [10-3]. The chains are linkedviaN—H...π and C—H...π interactions, forming layers parallel to plane (010). No π–π interactions are noted between the layers.

Atropisomers of Arylmaleimides: Stereodynamics and Absolute Configuration

4-Aryl-3-bromo-N-benzylmaleimides and 3,4-biaryl-N-benzylmaleimides have been synthesized by a modified Suzuki cross-coupling reaction from 3,4-dibromo-N-benzylmaleimide. The conformational studies by dynamic NMR and DFT calculations showed that the interconversion barrier between the two available skewed conformations is under steric control. When the aryl group was a 2-methylnaphthyl, thermally stable atropisomers were isolated by enantioselective HPLC and their absolute configurations were assigned by TD-DFT simulations of the ECD spectra.

Enlarged helical twisting power in chiral cyclic dimers based on conventional chiral alkyl diols

We prepared a homologous series of chiral cyclic liquid crystal (LC) dimers containing two biphenyl mesogens linked by two alkyl spacers, one of which was based on a R-enantiomeric chiral diol. In solution, the circular dichroism spectra of all the R-enantiomeric dimers showed the first negative and second positive Cotton effects, which indicated that the two biphenyl mesogens were located in a skewed overlapping alignment with counter-clockwise helicity. The helical twisting power (HTP) of these cyclic dimers was confirmed by the cholesteric LCs in mixtures with the nematic host. The induced cholesteric LCs in all mixtures had the same counter-clockwise helical sense as the skewed conformation of the two biphenyl mesogens. Furthermore, HTP values and Cotton effect amplitudes were linearly correlated, indicating direct induction of cholesteric twisting by the skewed biphenyl moieties. The induced HTP values were quite large, irrespective of the use of conventional chiral diols; the largest HTP value exceeded 100 μm−1 and was obtained in the cyclic dimer based on the R,R-1,2-diphenylethane diol.

Triazoyl–phenyl linker system enhancing the aqueous solubility of a molecular probe and its efficiency in affinity labeling of a target protein for jasmonate glucoside

In methods employing molecular probes to explore the targets of bioactive small molecules, long or rigid linker moieties are thought to be critical factors for efficient tagging of target protein. We previously reported the synthesis of a jasmonate glucoside probe with a highly rigid linker consisting of a triazoyl–phenyl (TAzP) moiety, and this probe demonstrated effective target tagging. Here we compare the TAzP probe with other rigid or flexible probes with respect to target tagging efficiency, hydrophobic parameters, aqueous solubility, and dihedral angles around the biaryl linkage by a combination of empirical and calculation methods. The rigid biaryl linkage of the TAzP probe has a skewed conformation that influences its aqueous solubility. Such features that include rigidness and good aqueous solubility resulted in highly efficient target tagging. These findings provide a promising guideline toward designing of better linkers for improving molecular probe performance.

Structural insights into initial and intermediate steps of the ribosome-recycling process

The ribosome-recycling factor (RRF) and elongation factor-G (EF-G) disassemble the 70S post-termination complex (PoTC) into mRNA, tRNA, and two ribosomal subunits. We have determined cryo-electron microscopic structures of the PoTC·RRF complex, with and without EF-G. We find that domain II of RRF initially interacts with universally conserved residues of the 23S rRNA helices 43 and 95, and protein L11 within the 50S ribosomal subunit. Upon EF-G binding, both RRF and tRNA are driven towards the tRNA-exit (E) site, with a large rotational movement of domain II of RRF towards the 30S ribosomal subunit. During this intermediate step of the recycling process, domain II of RRF and domain IV of EF-G adopt hitherto unknown conformations. Furthermore, binding of EF-G to the PoTC·RRF complex reverts the ribosome from ratcheted to unratcheted state. These results suggest that (i) the ribosomal intersubunit reorganizations upon RRF binding and subsequent EF-G binding could be instrumental in destabilizing the PoTC and (ii) the modes of action of EF-G during tRNA translocation and ribosome-recycling steps are markedly different.

Construction of Hydrogen‐Bonded Ternary Organic Crystals Derived from L‐Tartaric Acid and Their Application to Enantioseparation of Secondary Alcohols

Ternary organic crystals consisting of an L-tartaric acid-derived dicarboxylic acid, a commercially available achiral diamine, and a chiral secondary alcohol have been developed and characterized by X-ray crystallography. 1D, 2D, and 3D hydrogen-bonded supramolecular networks were constructed, depending on the structure of the diamine used. Benzylic and aliphatic secondary alcohols were enantioselectively incorporated into the crystal and were successfully enantioseparated with up to 86 and 79% enantiomeric excess (ee), respectively. Selective incorporation of one enantiomer of 2-butanol, which is a small chiral aliphatic alcohol, was achieved by the cooperative effects of hydrogen bonds, CH···π interactions, and van der Waals interactions between the guest and host molecules, with the aid of two water molecules. The high host potential of the binary supramolecular system is mainly attributed to the skewed conformation of two rigid aromatic groups of tartaric acid derivatives, which prevents dense packing of the molecules and enhances the formation of multicomponent inclusion crystals.

Hexadecahydrotetrabenzo[a,c,d,f]fluorene – Ligand, available by Friedel–Crafts fluorene cycloalkylation. Synthesis, crystal and molecular structure of (η 5-C 29H 34)(η 5-C 5H 5)ZrCl 2

Friedel–Crafts cycloalkylation of fluorene with 1,4-dichlorobutane has been studied in different conditions. This reaction allows to obtain the product of exhausting fluorene alkylation, hexadecahydrotetrabenzo[a,c,d,f]fluorene – perspective η 5 ligand. The simplest zirconocene has been synthesized and its structure has been confirmed by X-ray diffraction analysis. The molecule of this compound possesses skewed conformation of metallocene fragment with the phenylene moiety of fluorenyl ligand oriented towards the front side of metallocene wedge.

ChemInform Abstract: Stereochemistry of Benzodiazepinooxazoles: Crystal Structure and NMR Spectroscopic Investigations of New Conformational Variants of Mexazolam Analogues.

The varied stereochemistry of mexazolam analogues is described on the basis of six crystal-structure analyses of the 11b-hydro (2), methyl (3 and 4), phenyl (5) and 2′-chlorophenyl (6; mexazolam) derivatives of 3-methylbenzodiazepinooxazole and the benzodiazepinooxazole (1), all determined by X-ray diffraction techniques. Two new comformations for the benzodiazepinooxazole ring system have been found in these analyses, i.e., a flat conformation YII in the case of 2 and 3, and a skewed conformation YI in 1. The usual ‘boat-wing’ conformation XI has been found in compounds 4–6. The solution-state 1H NMR spectra of 1, 3 and 4 at room temperature have been examined by phenyl ring-current effects and support retention of the three types of solid-state conformation. In polar solvents, all these compounds (except for 1) show a diastereoisomeric equilibrium of trans↔cis interconversion through epimerization at the 11b position. The diastereoisomeric and conformational differences in these compounds are discussed along with the steric interaction of the substituents.

Hydrogen bonding and solution state structure of salicylaldehyde-4-phenylthiosemicarbazone: A combined experimental and theoretical study

Hydrogen bonding in salicylaldehyde-4-phenylthiosemicarbazone ( 1) has been studied by using experimental (NMR, Raman and UV spectroscopies) and quantum chemical (DFT) methods. It has been demonstrated that 1 adopted the hydroxy-thione tautomeric form in solution as found also in the solid state and previously indicated by secondary deuterium isotope effects. Apart from the intra-molecular hydrogen bonds new interactions between 1 and solvent molecules were formed as well. Changes in NMR chemical shifts and calculations have pointed towards a formation of inter-molecular three-centered hydrogen bonds in each of the studied complexes involving OH and NH groups of 1 and associated solvent molecules. Stabilization energies of intra-molecular hydrogen bonds were found to decrease with the increase of the solvent polarity. Two-dimensional NOESY spectra indicated conformational changes in solution with respect to the structure observed in the solid state. These were accounted for by a relatively low barrier of the rotation of the N N single bond thus enabling a molecule to posses a higher conformational flexibility in solution with portions of skewed conformations. The results presented here can help in a better understanding of the role hydrogen bonds can play in bioactivity of related thiosemicarbazone derivatives and their metal complexes.

Low temperature IR spectroscopy and photochemistry of matrix-isolated α-pyridil

α-Pyridil [(C 6H 4NO) 2] has been isolated in low temperature argon and xenon matrices and studied by FTIR spectroscopy, supported by DFT(B3LYP)/6–311++G(d,p) calculations. Calculations predicted the existence of three different conformers exhibiting skewed conformations around the intercarbonyl bond and the two C 5H 4N C( O) fragments nearly planar. The two higher energy forms, TCG and CCSk were estimated theoretically to be, respectively, 21.0 and 35.1 kJ mol −1 higher in energy than the most stable form, TTG . In consonance with the relatively high energies predicted by the calculations for the two less stable conformers of α-pyridil, only the most stable conformer was found spectroscopically to be present in the studied matrices. Infrared spectra obtained for the neat low temperature amorphous and crystalline states reveals that the TTG conformer is also the sole conformer present in these phases. UV irradiation ( λ > 235 nm) of matrix-isolated α-pyridil led to its isomerization into unusual molecular species bearing Hückel-type pyridine (aza-benzvalene) rings.

Stereochemical Study of 2-Substituted N-Vinylpyrroles

Stereochemical study of five 2-substituted N-vinylpyrroles obtained via the Trofimov reaction was carried out based on the experimental measurements of their 13C–1H and 13C–13C spin–spin coupling constants substantiated by the high-level ab initio calculations of the parent 2-methyl-N-vinylpyrrole. The title compounds were shown to adopt a predominantly skewed s-trans conformer with a noticeable population (approximately 10%) of the higher-energy skewed s-cis conformation, however, with the exception of 2-tert-butyl-N-vinylpyrrole adopting almost entirely a skewed s-trans conformation.

Rectangular architectures formed by acyclic diamido-metal-N-heterocyclic carbenes with skewed conformation

Acyclic acetamide functionalized mercury or silver carbene complexes, in which the coordination sphere adopts a skewed core conformation, self-assembled to form rectangular architectures.

Matrix isolation and low temperature solid state FTIR spectroscopic study of α-furil

Alpha-furil [C(4)H(3)O-C(=O)-C(=O)-C(4)H(3)O] has been isolated in argon and xenon matrices and studied by FTIR spectroscopy, supported by DFT(B3LYP)/6-311++G(d,p) calculations. The obtained spectra were fully assigned and revealed the presence in the matrices of three different conformers, all of them exhibiting skewed conformations around the intercarbonyl bond with the two C(4)H(3)O-C(=O) fragments nearly planar. The three conformers differ in the orientation of the furan rings relative to the carbonyl groups: the most stable conformer, I (C(2) symmetry; O=C-C=O intercarbonyl dihedral equal to 153.1 degrees), has both furan rings orientated in such a way that one of their beta-hydrogen atoms approaches the oxygen atom of the most distant carbonyl group, forming two H-C=C-C-C=O six-membered rings; the second most stable conformer, II (C(1) symmetry; O=C-C=O intercarbonyl dihedral equal to 126.9 degrees ), has one furan ring orientated as in I, while the second furan group is rotated by ca. 180 degrees (resulting in an energetically less favourable H-C=C-C=O five-membered ring); in the third conformer, III (C(2) symmetry; O=C-C=O dihedral equal to 106.2 degrees ), both furan rings assume the latter orientation relative to the dicarbonyl group. The theoretical calculations predicted the two higher energy forms being 5.85 and 6.22 kJ mol(-1) higher in energy than the most stable form, respectively, and energy barriers for conformational interconversion higher than 40 kJ mol(-1). These barriers are high enough to prevent observation of conformational isomerization for the matrix isolated compound. The three possible conformers of alpha-furil were also found to be present in CCl(4) solution, as well as in a low temperature neat amorphous phase of the compound prepared from fast condensation of its vapour onto a suitable 10 K cooled substrate. On the other hand, in agreement with the available X-ray data [S. C. Biswas, S. Ray and A. Podder, Chem. Phys. Lett., 1987, 134, 541], the IR spectra obtained for the neat low temperature crystalline state reveals that, in this phase, alpha-furil exists uniquely in its most stable conformational state, I.

Exceptionally Large Difference in Bond Length among Conformational Isomorphs of a Hexaphenylethane Derivative with a Dispiropyracene Skeleton

A large difference of 0.064(3) Å for a chemically equivalent Csp3−Csp3 bond was observed among crystallographically independent molecules with different conformations (conformational isomorphs) of a hexaphenylethane derivative, dispiro[(10-methylacridan)-9,1‘-pyracene-2‘,9‘ ‘-(10-methylacridan)] (1): triclinic, P1̄, a = 17.699(3) Å, b = 18.111(3) Å, c = 18.844(3) Å, α = 111.183(2)°, β = 93.828(1)°, γ = 102.130(2)°, V = 5438.5(14) Å3, T = −180 °C, Z = 8 (four independent molecules: A, A‘, B, and B‘). While B and B‘ adopt the skewed conformation to reduce steric repulsion in 1, in other positions of the crystal, molecules A and A‘ adopt the eclipsed conformation, which induces a much longer bond length [1.771(3) and 1.758(3) Å versus 1.712(2) and 1.707(2) Å].

Dinuclear and mononuclear copper(II) carboxylate complexes with cis-chelating diacids

The synthesis and crystal structures of two new copper complexes with chelating dicarboxylic acids are described. Reaction of copper(II) acetate with diacid H 2 L2 (HO 2CC(Me) 2OArOC(Me) 2CO 2H, Ar=1,3-substituted phenyl) gave a bischelate complex ( L2) 2Cu 2 · 2MeOH with the normal paddlewheel structure and tilted, trans-oriented chelate rings with skewed conformations. The overall structure was reasonably well reproduced by density functional calculations on ( L2) 2Cu 2. Treatment of the product from reaction of Cu 2(OAc) 4 and diacid H 2 L3 (Ar=1,3-substituted 2,4-dibromophenyl) with pyridine gave a six-coordinate mononuclear chelate ( L3)Py 2Cu · H 2O in which one chelate carboxylate is monodentate, the other is unsymmetrically bidentate, and the pyridines are cis-coordinated.

RIS Models and Unperturbed Chain Properties of Polyesters Containing 1,3‐Cyclobutylene and 1,4‐Cyclohexylene Linkages

AbstractPolyesters containing 1,3‐cyclobutylene and 1,4‐cyclohexylene linkages in the main chain are investigated using conformational energy calculations. Rotational isomeric state (RIS) models are developed for poly(1,4‐cyclohexylenedimethylene terephthalate) (PCT), poly(1,4‐cyclohexylenedimethylene 2,5‐dimethylterephthalate) (DMPCT), poly(1,4‐cyclohexylenedimethylene 1,4‐cyclohexylenedicarboxylate) (PCC), and poly(2,2,4,4‐tetramethyl‐1,3‐cyclobutylene terephthalate) (CBDO). In DMPCT, the ester linkage prefers skewed conformations with respect to the phenyl group to relieve the steric strain caused by the methyl groups. The methyl groups on the cyclobutanediol moiety in CBDO restrict the rotational freedom about the oxycyclobutylene linkage. The unperturbed dimensions as described by characteristic ratio and persistence length are calculated for the trans and cis configurations of these polyesters. CBDO shows highly extended chain conformations among these polyesters indicating relative chain rigidity of the backbone. For DMPCT and PCC, in their trans configuration, the chain dimensions decrease with an increase in temperature while for their cis configurations, the chain dimensions increase with temperature, arising from basic differences in the fragment structures that control the competition of the relative populations as affected by temperature. Temperature has negligible influence on the unperturbed dimensions of both isomeric linkages of CBDO, while this is true for the trans configuration of PCT. The study shows that induction of cyclobutylene groups in the main chain results in a greater rigidity for homopolyesters than for chains with cyclohexylene groups. Structure of the repeat units of polyesters in the planar trans configuration and the schematic of the RIS models with definition of geometrical parameters.imageStructure of the repeat units of polyesters in the planar trans configuration and the schematic of the RIS models with definition of geometrical parameters.

The central region of meso-3,4-diphenylhexane-2,5-dione

As with 1,2-diphenylethane (dpe), X-ray crystallographic methods measure the central bond in meso-3,4-diphenylhexane-2,5-done (dphd) as significantly shorter than normal for an sp 3–sp 3 bond. The same methods measure the benzylic (ethane C–Ph) bonds in dphd as unusually long for sp 3–sp 2 liaisons. Torsional motions of the phenyl rings about the C–Ph bonds have been proposed as the artifacts behind the result of a ‘short’ central bond in dpe. While a similar explanation can, presumably, hold for the even ‘shorter’ central bond in dphd, it cannot account for the ‘long’ C–Ph bonds. The phenyl groups, departing much from regular hexagonal shape, adopt highly skewed conformations with respect to the plane constituted by the four central atoms. It is thought that the thermal motions of the phenyl rings, conditioned by the potential wells in which they are ensconced in the unit cell, are largely libratory around their normal axes. In what appears to be a straightforward explanation under the ‘rigid-body’ concept, it appears that these libratory motions of the phenyl rings, that account, at the same time, for the ‘short’ central bond, are the artifacts behind the ‘long’ measurement of the C–Ph bonds. These motions could be superimposed on torsional motions analogous to those proposed in the case of dpe. An inspection of the ORTEP diagram from the 298 K data on dphd clearly suggests these possibilities. Supportive evidence for these qualitative explanations from an analysis of the differences between the mean square displacements of C(1) and C(7)/C(1a) and C(7a) based on the ‘rigid-body model’ is discussed.

Separation, conformation in solution and absolute configuration of ethopropazine enantiomers.

Enantiomers of ethopropazine x HCl (10-(2-diethylaminopropyl)phenothiazine hydrochloride) were prepared by fractional crystallization of diastereomeric dibenzoyltartaric acid salts, and their optical purity (enantiomeric excess, ee) determined by HPLC on Chiralcel OJ column. With a solvent mixture n-hexane/t-butanol/triethylamine (100:3:0.5) as eluent a very good enantioseparation (alpha = 1.68) for racemic ethopropazine was obtained. Enantiomeric purity for (-)-enantiomer was 99.1% and for (+)-enantiomer 97.9%. Combined data from NMR and CD spectra of both enantiomers, along with previously reported X-ray structure analyses of racemic ethopropazine, revealed skewed conformation of tricyclic system in solution, and (S)-configuration on the stereogenic center for (-)-enantiomer, and (R)-configuration for (+)-enantiomer.