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Lysergic acid diethylamide (LSD) is a hallucinogenic compound that binds to and activates the serotonin 2A receptor and is classified as a controlled narcotic in Japan. Recently, MiPLA, an N‐methyl‐N‐isopropyl derivative of LSD, has been detected in paper‐sheet products in several countries. This study focuses on the synthesis of MiPLA and includes a comprehensive analysis involving structural and liquid chromatography–mass spectrometry (LC‐MS). Particularly, MiPLA was synthesized in three‐steps starting from ergometrine maleate, which resulted in the formation of (8S)‐isomer, iso‐MiPLA, as a by‐product. The LC‐MS results showed that LSD, MiPLA, and iso‐MiPLA exhibited different retention times. Their chemical structures were determined using nuclear magnetic resonance spectroscopy, which revealed the presence of rotamers involving the N‐methyl‐N‐isopropyl groups of tertiary amides in MiPLA and iso‐MiPLA. [ABSTRACT FROM AUTHOR]

Boron-doped organic compounds display unique properties as a result of the presence of an empty p orbital on boron and the ability to switch between a trigonal planar and a tetrahedral geometry. In recent years, they have found several applications not only as synthetic reagents, e.g., in the Suzuki–Miyaura reaction, but also as pharmaceuticals and as specialized materials due to their optical and electronic properties. Some boron compounds may exist as atropisomers, and these rotamers may have different properties according to their sense of rotation. Synthetic strategies to separate them and, more recently, to obtain them in an asymmetric manner are becoming popular. In this review, we survey the literature on this emerging field of research. [ABSTRACT FROM AUTHOR]

Introduction: Stellaria alsine has traditionally been used as both a famine relief food and an alternative medicine in East Asia. Modern pharmacological studies have revealed that S. alsine has various biological effects such as anticancer, anti-hepatoma, anti-inflammatory, and antioxidative effects. However, the anti-inflammatory properties of chemical constituents derived from this plant have not been studied well. Objectives: To identify potential therapeutic candidate for treating inflammatory diseases such as inflammatory bowel disease (IBD). Methods: The distribution of chemical compounds was investigated by Global Natural Product Social (GNPS)-based molecular networking (MN) analysis using UPLC-Orbitrap tandem mass spectrometry. The anti-inflammatory and antioxidative effects of S. alsine extracts and fractions were evaluated by measuring interleukin (IL)-8 and reactive oxygen species (ROS) productions. Results: The active EA layer of S. alsine showed the highest percentage of major compounds by feature-based molecular networking. The top candidate structures of EA fraction were rapidly annotated as flavone C- or O-glycosides via an advanced analysis tool, Network Annotation Propagation (NAP). With the GNPS molecular networking-guided isolation strategy, a new C-glycosyl flavone rotamer (1) was isolated. The structures of the major (1a) and minor (1b) rotational isomers were determined by extensive NMR analysis and MS/MS fragmentation. Finally, the anti-inflammatory activity of 1 was predicted by molecular docking simulations with IL-8 protein. Conclusion: These results suggested that the compound 1 is a potential therapeutic candidate for inflammatory bowel disease (IBD). [ABSTRACT FROM AUTHOR]

From the n‐butanol soluble fraction of the ethanol extract of the medicinal plant Olax subscorpioidea, a previously unreported rotameric biflavonoid glycoside constituted of 4′‐O‐methylgallocatechin‐(4α → 8)‐4′‐O‐methylgallocatechin as aglycone named olasubscorpioside C (1) along with the known 4′‐O‐methylgallocatechin (2) were isolated. Their structures were determined on the basis of spectrometric and spectroscopic techniques including HRFABMS, 1H and 13C NMR, DEPT 135o, HSQC, HMBC, ROESY, and CD followed by comparison with the reported data. [ABSTRACT FROM AUTHOR]

Protein fluorescence signals essential information about the conformational dynamics of proteins. Different types of intrinsic fluorophores reflect different protein local or global structural changes. Bovine Serum Albumin (BSA) is a transport protein that contains two intrinsic fluorophores: Tryptophan134 (Trp134) and Tryptophan213 (Trp213). This protein displays an interesting temperature dependence of the tryptophan fluorescence. However, the molecular mechanism of the temperature dependence is still unclear. In this work, we propose a generic rotamer model to explain this phenomenon. The model assumes the presence of rotamer‐specific fluorescence lifetimes. The fluorescence temperature dependence is caused by the population shifts between different rotamers due to thermal effects. As a proof of concept, we show that the tryptophan's two fluorescence lifetimes (휏1 = 0.4–0.5 ns and 휏2 = 2‐4 ns) are sufficient to qualitatively explain the fluorescence intensity change at different temperatures, both in buffer solution (water) and in the protein. To computationally verify our rotamer hypothesis, we use an all‐atom molecular dynamics simulation to study the effects of temperature on the two tryptophans' rotamer dynamics. The simulations show that Trp134 is more sensitive to temperature, consistent with experimental observations. Overall, the results support that the temperature dependence of fluorescence in the protein BSA is due to local conformational changes at the residue level. This work sheds light on the relationship between tryptophan's rotamer dynamics and its ability to fluorescence. [ABSTRACT FROM AUTHOR]

A new type of chirality, orientational chirality, consisting of a tetrahedron center and a remotely anchored blocker, has been discovered. The key structural element of this chirality is characterized by multiple orientations directed by a through-space functional group. The multi-step synthesis of orientational chiral targets was conducted by taking advantage of asymmetric nucleophilic addition, Suzuki-Miyaura cross-coupling and Sonogashira coupling. An unprecedented catalytic species showing a five-membered ring consisting of C (sp2)-Br-Pd-C (sp2) bonds was isolated during performing Suzuki-Miyaura cross-coupling. X-ray diffraction analysis confirmed the species structure and absolute configuration of chiral orientation products. Based on X-ray structures, a model was proposed for the new chirality phenomenon to differentiate the present molecular framework from previous others. DFT computational study presented the relative stability of individual orientatiomers. This discovery would be anticipated to result in a new stereochemistry branch and to have a broad impact on chemical, biomedical, and material sciences in the future.

Cancer cells can escape the effects of chemotherapy through mutations and upregulation of a tyrosine kinase protein called the epidermal growth factor receptor (EGFR). In the past two decades, four generations of tyrosine kinase inhibitors targeting EGFR have been developed. Using comparative structure analysis of 116 EGFR-drug complex crystal structures, cluster analysis produces two clans of 73 and 43 structures, respectively. The first clan of 73 structures is larger and is comprised mostly of the C-helix-IN conformation while the second clan of 43 structures correlates with the C-helix-OUT conformation. A deep rotamer analysis identifies 43 residues (18%) of the total of 237 residues spanning the kinase structures under investigation with significant rotamer variations between the C-helix-IN and C-helix-OUT clans. The locations of these rotamer variations take on the appearance of side chain conformational relays extending out from points of EGFR mutation to different regions of the EGFR kinase. Accordingly, we propose that key EGFR mutations act singly or together to induce drug resistant conformational changes in EGFR that are communicated via these side chain conformational relays. Accordingly, these side chain conformational relays appear to play a significant role in the development of tumour resistance. This phenomenon also suggests a new paradigm in protein conformational change that is mediated by supportive relays of rotamers on the protein surface, rather than through conventional backbone movements.

Rotamers are stereoisomers produced by rotation (twisting) about σ bonds and are often rapidly interconverting at room temperature. Xylitol—massively produced sweetener—(2R,3r,4S)-pentane-1,2,3,4,5-pentol) forms rotamers from the linear conformer by rotation of a xylitol fragment around the C2–C3 bond (rotamer 1) or the C3–C4 bond (rotamer 2). The rotamers form two distinguishable structures. Small differences in geometry of rotamers of the main carbon chain were confirmed by theoretical calculations; however, they were beyond the capabilities of the X-ray powder diffraction technique due to the almost identical unit cell parameters. In the case of rotamers of similar compounds, the rotations occurred mostly within hydroxyl groups likewise rotations in L-arabitol and D-arabitol, which are discussed in this work. Our results, supported by theoretical calculations, showed that energetic differences are slightly higher for rotamers with rotations within hydroxyl groups instead of a carbon chain. [ABSTRACT FROM AUTHOR]

Obtaining a quantitative description of the membrane proteins stability is crucial for understanding many biological processes. However the advance in this direction has remained a major challenge for both experimental studies and molecular modeling. One of the possible directions is the use of coarse-grained models but such models must be carefully calibrated and validated. Here we use a recent progress in benchmark studies on the energetics of amino acid residue and peptide membrane insertion and membrane protein stability in refining our previously developed coarse-grained model (Vicatos et al., Proteins 2014;82:1168). Our refined model parameters were fitted and/or tested to reproduce water/membrane partitioning energetics of amino acid side chains and a couple of model peptides. This new model provides a reasonable agreement with experiment for absolute folding free energies of several β-barrel membrane proteins as well as effects of point mutations on a relative stability for one of those proteins, OmpLA. The consideration and ranking of different rotameric states for a mutated residue was found to be essential to achieve satisfactory agreement with the reference data.

In this article, a synthesis of N’-(benzylidene)-2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazides and their structural interpretation by NMR experiments is described in an attempt to explain the duplication of some peaks in their 1H- and 13C-NMR spectra. Twenty new 6-methyl-1H-pyrazolo[3,4-b]quinoline substituted N-acylhydrazones 6(a–t) were synthesized from 2-chloro-6-methylquinoline-3-carbaldehyde (1) in four steps. 2-Chloro-6-methylquinoline-3-carbaldehyde (1) afforded 6-methyl-1H-pyrazolo[3,4-b]quinoline (2), which upon N-alkylation yielded 2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetate (3). The hydrazinolysis of 3 followed by the condensation of resulting 2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazide (4) with aromatic aldehydes gave N-acylhydrazones 6(a–t). Structures of the synthesized compounds were established by readily available techniques such as FT-IR, NMR and mass spectral studies. The stereochemical behavior of 6(a–t) was studied in dimethyl sulfoxide-d6 solvent by means of 1H NMR and 13C NMR techniques at room temperature. NMR spectra revealed the presence of N’-(benzylidene)-2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazides as a mixture of two conformers, i.e., E(C=N)(N-N) synperiplanar and E(C=N)(N-N)antiperiplanar at room temperature in DMSO-d6. The ratio of both conformers was also calculated and E(C=N) (N-N) syn-periplanar conformer was established to be in higher percentage in equilibrium with the E(C=N) (N-N)anti-periplanar form.

Few models of sequence evolution incorporate parameters describing protein structure, despite its high conservation, essential functional role and increasing availability. We present a structurally aware empirical substitution model for amino acid sequence evolution in which proteins are expressed using an expanded alphabet that relays both amino acid identity and structural information. Each character specifies an amino acid as well as information about the rotamer configuration of its side-chain: the discrete geometric pattern of permitted side-chain atomic positions, as defined by the dihedral angles between covalently linked atoms. By assigning rotamer states in 251,194 protein structures and identifying 4,508,390 substitutions between closely related sequences, we generate a 55-state "Dayhoff-like" model that shows that the evolutionary properties of amino acids depend strongly upon side-chain geometry. The model performs as well as or better than traditional 20-state models for divergence time estimation, tree inference, and ancestral state reconstruction. We conclude that not only is rotamer configuration a valuable source of information for phylogenetic studies, but that modeling the concomitant evolution of sequence and structure may have important implications for understanding protein folding and function. [ABSTRACT FROM AUTHOR]

C-glycosyl flavonoids are important secondary plant metabolites with a wide range of biological activities. Rotational isomerism, arising from restricted bond rotation, has been observed on a portion of C-glycosyl flavonoids. NMR technique contributes most to the observation and research of this phenomenon. Signal duplication in NMR spectra may be the key characteristic of C-glycosyl flavonoids existing as rotamers. Bulky steric hindrance from the substituents at position 7 and sugar moieties are responsible for the restricted bond rotation. There are other influence factors including temperature, solvents, H-bonds and π-stacking, but these are of lesser importance. Difference exists between 8-C-glycosyl flavonoids and their 6-C-glycosyl isomers despite sharing the same flavonoid aglycone and sugar moiety. 8-C-glycosyl flavonoids are more likely to suffer from restricted rotation. The energy barriers between rotamers of C-glycosyl flavonoids seem not high enough for atropisomerism to be realized and the isolation of rotamers should be difficult. [ABSTRACT FROM AUTHOR]

Stable crystalline phosphorus ylides were obtained in excellent yields from the 1:1:1 addition reactions between triphenylphosphine and dialkyl acetylenedicarboxylates, in the presence of NH-heterocyclic compound, such as 6-chloro-2-benzoxazolethiol. These stable ylides exist in solution as a mixture of the two geometrical isomers as a result of restricted rotation around the carbon–carbon partial double bond resulting from conjugation of the ylide moiety with the adjacent carbonyl group. In the recent work, NMR study and the stability of the Z- and E-isomers were undertaken for the two rotamers of phosphorus ylides involving 6-chloro-2-benzoxazolethiol by atoms in molecules (AIM) and natural population analysis (NPA) methods. The relative energy for the two Z and E isomers was calculated at both HF/6-31G (d,p) and B3LYP/6-311++G (d,p) in the presence of a solvent medium (ethyl acetate) and gas phases. The results were in good agreement with those that obtained by the 1H, 31P and 13C NMR experimental data.

Herein we report a highly efficient and enantiospecific borylation method to synthesize a wide range of enantiopure (>99 % ee) α‐amino tertiary boronic esters. The configurationally stable α‐N‐Boc substituted tertiary organolithium species and pinacolborane (HBpin) underwent enantiospecific borylation at −78 °C with the formation of a new stereogenic C−B bond. This reaction has a broad scope, enabling the synthesis of various α‐amino tertiary boronic esters in excellent yields and, importantly, with universally excellent enantiospecificity (>99 % es) and complete retention of configuration. Enantiospecific borylation: A highly enantiospecific borylation of configurationally stable α‐N‐Boc substituted tertiary organolithium species and HBpin has been developed to synthesize various α‐amino tertiary boronic esters through the formation of a new C−B bond with excellet enantiopurity and complete retention of configuration. [ABSTRACT FROM AUTHOR]

Abstract Populations, protonation constants and octanol-water partition coefficients were determined and assigned specifically to fast interconverting individual conformers, exemplified in baclofen and pregabalin, the GABA-related drug molecules of biaxial, double rotations. Rotamer statuses along both axes in water and octanol were elucidated from 1H NMR vicinal coupling constants. Conformer abundances were obtained by the appropriate combination of the rotamer populations in the two adjacent moieties in the molecule. The bulky aromatic group in baclofen versus the aliphatic side chain of pregabalin explains why baclofen exists mainly in trans-trans conformeric form, throughout the pH range, unlike pregabalin that has no any highly dominant form. Characteristically enough, for pregabalin, the lipophilicity of the conformers is primarily influenced by the conformation state. Conformers in gauche state are of higher lipophilicity. The conformers of the two compounds were ranked by their membrane-influx and –outflow propensities. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

The ν(OH) stretching-mode bands in solution IR spectra of five o-vinylphenol (o-VPh) homologs in the slightly polar solvents CCl4 and n-hexane were studied. Several rotamers with free OH groups were found in solutions of o-VPh and its methyl-substituted derivatives in n-hexane. The proportion of rotamers in o-VPh homologs with intramolecular hydrogen bonds (IHBs) O-H...π varied from 22 to 97% in the gas and cyclohexane according to B3LYP/cc-pVTZ calculations. The theoretically estimated effective enthalpies -ΔH of their IHBs varied in the range 0.20-2.24 kcal/mol. [ABSTRACT FROM AUTHOR]

Three monanionic gold dithiolene complexes with different exocyclic chalcogen atoms (O, S, Se) on the N-isopropyl-1,3-thiazoline-2-chalcogenone-4,5-dithiolate ligand, have been synthetized with the aim of modulating their properties. Due to the presence of the isopropyl ( i Pr) group in the plane of the thiazoline-2-chalcogenone ring, different syn and anti rotamers can exist, in solution and in the solid state. Characterization of these complexes by spectroscopic and electrochemical methods was carried out in order to investigate the influence of the size, electronegativity and polarizability of the exocyclic chalcogen atom. The molecular structure of the three anionic complexes [Au( i Pr-thiazYdt) 2 ] −1 , with Y = O, S, Se, were established by single crystal X-ray diffraction studies. Theoretical calculations carried out at the DFT levels were realized on the three possible rotamers, syn / syn , syn / anti and anti / anti of the trans- [Au( i Pr-thiazYdt) 2 ] −1 complexes. [ABSTRACT FROM AUTHOR]

Transition metal complexes containing dimethyl sulfoxide (DMSO) are important precursors in catalysis and metallodrugs. Understanding the solid-state supramolecular structure is crucial for predicting the properties and biological activity of the material. Several crystalline phases of DMSO-coordinated iridium anions with different cations, potassium (1 a) and n-butylammonium (1 b), were obtained and their structures determined by X-ray crystallography. Compound (1 a) is present in two solvatomorphic forms: α and β; the β form contains disordered solvent water. In addition, the structures exhibit different rotamers of the trans-[IrCl4(DMSO)2]− anion with the trans-DMSO ligands being oriented in anti and gauche conformations. In consideration of these various conformers, the effects of the crystallized solvent and intermolecular interactions on the conformational preferences of the anion are discussed. In addition, density functional theory calculations were used to investigate the energies of the anions in the different conformations. It was found that hydrogen bonds between water and the DMSO complex stabilize the gauche conformation which is the least stable form of the trans-DMSO complex. Consequently, by controlling the number of hydrogen-bond donors and acceptors and the amount of water, it may be possible to obtain different solvatomorphs of clinically significant metallodrugs. [ABSTRACT FROM AUTHOR]

An exhaustive search approach was used to establish all possible rotamers of α- and β- d -galactopyranose using DFT at the B3LYP/6-311+G** and M06-2X/6-311+G** levels, both in vacuum calculations, and including two variants of continuum solvent models as PCM and SMD to simulate water solutions. Free energies were also calculated. MM3 was used as the starting point for calculations, using a dielectric constant of 1.5 for vacuum modeling, and 80 for water solution modeling. For the vacuum calculations, out of the theoretically possible 729 rotamers, only about a hundred rendered stable minima, highly stabilized by hydrogen bonding and scattered in a ca. 14 kcal/mol span. The rotamer with a clockwise arrangement of hydrogen bonds was the most stable for the α-anomer, whereas that with a counterclockwise arrangement was the most stable for the β-anomer. Free energy calculations, and especially solvent modeling, tend to flatten the potential energy surface. With PCM, the total range of energies was reduced to 9–10 kcal/mol (α-anomer) or 7–8 kcal/mol (β-anomer). These figures fall to 4.5–6 kcal/mol using SMD. At the same time, the total number of possible rotamers increases dramatically to about 300 with PCM, and to 400 with SMD. Both models show a divergent behavior: PCM tends to underestimate the effect of solvent, thus rendering as the most stable many common rotamers with vacuum calculations, and giving underestimations of populations of β-anomers and gt rotamers in the equilibrium. On the other hand, SMD gives a better estimation of the solvent effect, yielding correct populations of gt rotamers, but more β-anomers than expected by the experimental values. The best agreement is observed when the functional M06-2X is combined with SMD. Both DFT models show minimal geometrical differences between the optimized conformers. [ABSTRACT FROM AUTHOR]

N -(α- d -Glucofuranurono-6,3-lactone)- p -nitroaniline and N -(methyl β- d -glucopyranuronate)- p -nitroaniline were obtained as crystalline solids. The single-crystal X-ray diffraction, NMR data and DFT calculations for N -(α- d -glucofuranurono-6,3-lactone)- p -nitroaniline indicate that this N -furanoside adopts a 3 T 2 / 3 E -like conformation in the crystal lattice, solution and gas phase. Thus, the structure of recorded for N -furanoside 1 H NMR spectrum is indicative of the 3 T 2 / 3 E region of the pseudorotational itinerary for furanose derivatives with α- d -gluco, β-L-ido and α- d -xylo configurations. Moreover, it is concluded that the 1 T 2 / E 2 / 3 T 2 / 3 E region of the pseudorotational itinerary for furanose derivatives with d -gluco, L-ido and d -xylo configurations should be characterised by the lack of coupling between H2 and H3 protons, irrespective of the anomeric configuration. Such a lack of vicinal coupling is characteristic for some of the trans- oriented furanose ring protons. The single-crystal X-ray diffraction and NMR data for N -(methyl β- d -glucopyranuronate)- p -nitroaniline indicate that this N -glucuronide adopts the 4 C 1 conformation, both in the crystal lattice and solution. The occurrence of anomeric effects in the presented N -glycosides is discussed. The crystal structure analysis of both N -glycosides gives evidence that the amine group in p -nitroaniline is planar due to the nitrogen sp 2 hybridisation. [ABSTRACT FROM AUTHOR]

The reaction of hexafluoropropene trimers with Ruppert-Prakash (CF 3 SiMe 3 ) reagent gave highly congested perfluoroolefins such as the mono-trifluoromethylation products F -2,4-dimethyl-3-isopropyl-2-pentene ( P1 ) and E - and Z -forms of F -4,4-dimethyl-3-isopropyl-2-pentene ( 2 E and 2 Z ), and the bis-trifluoromethylation product F -2,4,4-trimethyl-3-isopropyl-2-pentene ( 3 ). The E -form of 2 was also comprised of two rotamers. Various aprotic polar solvents were surveyed for this reaction, and it was found that the aprotic solvent DMI has a unique solvent effect to selectively give the mono-trifluoromethylated perfluoroolefin P1 , a precursor for the persistent perfluoroalkyl radical F -3-isopropyl-2,4-dimethyl-3-pentyl, in very high yield. [ABSTRACT FROM AUTHOR]

Amyloid β (Aβ) peptide is present as a major component in amyloid plaque that is one of the hallmarks of Alzheimer's disease. The peptide contains a single tyrosine residue and Aβ has a major implication in the pathology of the disease progression. Current investigation revealed that the tyrosine side chain attained two different critical stereo orientations in two dissimilar conformational states of the peptide. The extended α-helical structure of the peptide observed in an apolar solvent or methanol/water mixture became disordered in aqueous medium and the radius of gyration decreased. In aqueous medium, the torsional angle around Cα–Cβ of tyrosine group became −60°. However, in its α-helical conformation in an apolar system, the measured angle was 180° and this rotameric state may be reasoned behind stronger tyrosine fluorescence compared with the disordered state of the peptide. Molecular dynamics simulation analyses and spectroscopic studies have helped us to understand the major structural changes in the secondary structure of the peptide in the two conformational states. A conformational clustering indicated that the compact state is more stable with tyrosine residue attaining the torsion angle value of −60°, whereas the native state (in HFIP/water mixture) is prevalent at a torsion angle value of −180°. High solvent accessibility has possibly stabilized the particular rotameric state (−60°) of the tyrosine residue and could be the reason behind decrease in fluorescence of the sole tyrosine residue in an aqueous buffer solution (pH 7.4) compared with its fluorescence in the α-helical structure in the micellar environment.

Although monodeuterated methyl groups support proton long-lived states, hindering of the methyl rotation limits the singlet relaxation time. We demonstrate an experimental case in which the rapid rotation of the CH 2 D group extends the singlet lifetime but does not quench the chemical shift difference between the CH 2 D protons, induced by the chiral environment. Proton singlet order is accessed using Spin-Lock Induced Crossing (SLIC) experiments, showing that the singlet relaxation time T S is over 2 min, exceeding the longitudinal relaxation time T 1 by a factor of more than 10. This result shows that proton singlet states may be accessible and long-lived in rapidly rotating CH 2 D groups. [ABSTRACT FROM AUTHOR]

Methyl pyropheophorbides- a possessing a (pseudo)planar substituent at the 3-position were prepared from naturally occurring chlorophyll- a . Some of the semisynthetic π-conjugates with the chlorin skeleton took two atropisomeric conformations for the sterically demanding 3-substituents, CONMe 2 , NHCOMe, C[CH C(CN) 2 ] C(CN) 2 , and Ph(2,3,4,5-Ph 4 ). Their rotational isomerization in a solution was analyzed by 1 H NMR and HPLC. Zinc complex of the 3-aryl-chlorin gave a large energy barrier for the rotation of the C3 C3 1 single bond (estimated Δ G ‡ =108 kJ mol −1 at 20 °C) and the atropisomerically pure conformers were separated at room temperature. [ABSTRACT FROM AUTHOR]

The geometry, conformations and energy of mono-, di-, and tri-carboxylic derivatives of benzene were studied by means of the AM1 molecular-orbital method. Whereas the species having no carboxylic groups in the ortho-position (benzoic, isophthalic, terephthalic, and trimesic acids) are planar in all their (stable) conformations, those possessing carboxylic groups in the ortho-position (phthalic, 1,2,3-benzenetricarboxylic, and 1,2,4-benzenetricarboxylic acids) assume a non-planar geometry, with one carboxyl group almost orthogonal to the plane of the benzene ring. Various rotamers of each of the studied benzenecarboxylic acids have nearly the same energy.

The geometry, conformations and energy of mono-, di-, and tri-carboxylic derivatives of benzene were studied by means of the AM1 molecular-orbital method. Whereas the species having no carboxylic groups in the ortho-position (benzoic, isophthalic, terephthalic, and trimesic acids) are planar in all their (stable) conformations, those possessing carboxylic groups in the ortho-position (phthalic, 1,2,3-benzenetricarboxylic, and 1,2,4-benzenetricarboxylic acids) assume a non-planar geometry, with one carboxyl group almost orthogonal to the plane of the benzene ring. Various rotamers of each of the studied benzenecarboxylic acids have nearly the same energy.

Stable crystalline phosphorus ylides were obtained in excellent yields from the 1:1:1 addition reactions between triphenylphosphine and dialkyl acetylenedicarboxylates, in the presence of NH-heterocyclic compound, such as 6-chloro-2-benzoxazolethiol. These stable ylides exist in solution as a mixture of the two geometrical isomers as a result of restricted rotation around the carbon–carbon partial double bond resulting from conjugation of the ylide moiety with the adjacent carbonyl group. In the recent work, NMR study and the stability of the Z - and E -isomers were undertaken for the two rotamers of phosphorus ylides involving 6-chloro-2-benzoxazolethiol by atoms in molecules (AIM) and natural population analysis (NPA) methods. The relative energy for the two Z and E isomers was calculated at both HF/6-31G (d,p) and B3LYP/6-311++G (d,p) in the presence of a solvent medium (ethyl acetate) and gas phases. The results were in good agreement with those that obtained by the 1 H, 31 P and 13 C NMR experimental data. [ABSTRACT FROM AUTHOR]

Nonmuscle myosin-2 is the primary enzyme complex powering contractility of the F-actin cytoskeleton in the model organism Drosophila. Despite myosin's essential function in fly development and homeostasis, its kinetic features remain elusive. The purpose of this in vitro study is a detailed steady-state and presteady-state kinetic characterization of the Drosophila nonmuscle myosin-2 motor domain. Kinetic features are a slow steady-state ATPase activity, high affinities for F-actin and ADP, and a low duty ratio. Comparative analysis of the overall enzymatic signatures across the nonmuscle myosin-2 complement from model organisms indicates that the Drosophila protein resembles nonmuscle myosin-2s from metazoa rather than protozoa, though modulatory aspects of myo-sin motor function are distinct. Drosophila nonmuscle myosin-2 is uniquely insensitive toward blebbistatin, a commonly used myosin-2 inhibitor. An in silico modeling approach together with kinetic studies indicate that the nonconsensus amino acid Met466 in the Drosophila nonmuscle myosin-2 active-site loop switch-2 acts as blebbistatin desensitizer. Introduction of the M466I mutation sensitized the protein for blebbistatin, resulting in a half-maximal inhibitory concentration of 36.3 ± 4.1 µM. Together, these data show that Drosophila nonmuscle myosin-2 is a bonafide molecular motor and establish an important link between switch-2 and blebbistatin sensitivity. [ABSTRACT FROM AUTHOR]

ABSTRACT Side chain optimization is an integral component of many protein modeling applications. In these applications, the conformational freedom of the side chains is often explored using libraries of discrete, frequently occurring conformations. Because side chain optimization can pose a computationally intensive combinatorial problem, the nature of these conformer libraries is important for ensuring efficiency and accuracy in side chain prediction. We have previously developed an innovative method to create a conformer library with enhanced performance. The Energy-based Library (EBL) was obtained by analyzing the energetic interactions between conformers and a large number of natural protein environments from crystal structures. This process guided the selection of conformers with the highest propensity to fit into spaces that should accommodate a side chain. Because the method requires a large crystallographic data-set, the EBL was created in a backbone-independent fashion. However, it is well established that side chain conformation is strongly dependent on the local backbone geometry, and that backbone-dependent libraries are more efficient in side chain optimization. Here we present the backbone-dependent EBL (bEBL), whose conformers are independently sorted for each populated region of Ramachandran space. The resulting library closely mirrors the local backbone-dependent distribution of side chain conformation. Compared to the EBL, we demonstrate that the bEBL uses fewer conformers to produce similar side chain prediction outcomes, thus further improving performance with respect to the already efficient backbone-independent version of the library. Proteins 2014; 82:3177-3187. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

We applied the two-colour resonant two-photon ionisation and mass-analysed threshold ionisation techniques to record the vibrationally resolved spectra of the selected rotamers and35Cl and37Cl isotopologues of 4-chloro-3-fluorophenol in the electronically excited S1and cationic ground D0states. The band origins of the S1← S0electronic transition and the adiabatic ionisation energies of thecisandtransrotamers of 4-chloro-3-fluorophenol are determined to be 35,233 ± 2 and 35,405 ± 2 cm−1, and 69,334 ± 5 and 69,460 ± 5 cm−1, respectively. The electronic transition energies and general spectral features of the two isotopologues are nearly identical. Most of the observed active vibrations result from the in-plane ring deformation and substituent-sensitive motions. The experimental data show that the frequency difference in the observed active vibrations of the rotamers and isotopologues depends on the nature, vibrational pattern, location, and relative orientation of the substituents. [ABSTRACT FROM PUBLISHER]

Absorption bands of OH stretching vibrations in IR spectra of o-vinylphenol ( o-VP) in the weakly polar solvents CCl and n-hexane were studied. Several rotamers of the free OH group were observed for o-VP in n-hexane. The fraction of o-VP rotamers with an O-H...π intramolecular hydrogen bond (IHB) was less than 20% according to experimental estimates for CCl solutions and calculations in the gas phase and cyclohexane. The theoretical effective enthalpy of the o-VP IHB was estimated for rotamer A (-ΔH = 0.20 kcal/mol). [ABSTRACT FROM AUTHOR]

Highlights: [•] Resonant two-photon ionization spectrum of 3-fluoro-N-methylaniline was obtained. [•] The S1 ←S0 electronic transition energy and the ionization energy were determined. [•] The relative stability of two rotamers in the S0, S1 and D0 states was derived. [•] The substitution and conformation effects on 3FNMA were discussed in detail. [•] The calculated results compare well with the experimental observations. [Copyright &y& Elsevier]

Highlights: [•] The REMPI spectra of rotamers were obtained. [•] The S1 ←S0 excitation energies and ionization energies were determined. [•] The relative stability of two rotamers in each of the S0, S1 and D0 states was evaluated by experimental method. [•] La/Lb mixing transition was predicted by theoretical calculation. [•] The calculated results compared well with experimental observations. [ABSTRACT FROM AUTHOR]

Highlights: [•] We report the vibronic and cation spectra of cis- and trans-m-chloroanisole. [•] Spectral features mainly result from substituent-sensitive and in-plane ring vibrations. [•] The chlorine substituent can influence the transition energy and molecular vibration. [ABSTRACT FROM AUTHOR]

Highlights: [•] The REMPI and MATI spectra of rotamers and isotopomers were obtained. [•] The S1 ←S0 excitation energies and ionization energies were determined. [•] The relative stability of two rotamers in each of the S0, S1 and D0 states was evaluated by experimental method. [•] The conformation effect on the frequencies is greater than the isotope effect. [•] The calculated results compared well with experimental observations. [ABSTRACT FROM AUTHOR]

Glucopyranose is the most stable form of glucose in solution. Identification of molecular structure of glucopyranose is very important because of its biological and synthetic significance; it is not an easy task because of the large number of possible configurations. Relative energies of exocyclic hydroxymethyl rotamers and α-β anomers of D-glucopyranose have been determined at the reference MP2/6-31G(d,p) level geometry by ab initio calculations at the infinite basis set limit of MP2 approach and with inclusion of CCSD(T) correction term evaluated with the aug-cc-pVDZ basis set in vacuum, water, dimethylsulfoxide, tetrahydrofurane and ethanol. The infinite basis set limit of MP2 level was determined by two point extrapolation using aug-cc-pVTZ and aug-cc-pVQZ basis sets. Solvent effects, relative energies and binding energies have been considered applying explicit calculations and implicit solvent models. [ABSTRACT FROM AUTHOR]

A molecular structure determines a molecular function(s) and a correct understanding of molecular structure is important for biotechnology. The computational prediction of molecular structure is a frequent requirement for important biomolecular applications such as a homology modeling, a docking simulation, a protein design, etc. where the optimization of molecular structure is fundamental. One of the core problems in the optimization of protein structure is the optimization of side-chains called the side-chain positioning problem. The side-chain positioning problem, assuming the rigidity of backbone and a rotamer library, attempts to optimally assign a rotamer to each residue so that the potential energy of protein is minimized in its entirety. The optimal solution approach using (mixed) integer linear programming, with the dead-end elimination technique, suffers even for moderate-sized proteins because the side-chain positioning problem is NP-hard. On the other hand, popular heuristic approaches focusing on speed produce solutions of low quality. This paper presents an efficient algorithm, called the BetaSCP, for the side-chain positioning problem based on the beta-complex which is a derivative geometric construct of the Voronoi diagram. Placing a higher priority on solution quality, the BetaSCP algorithm produces a solution very close to the optima within a reasonable computation time. The effectiveness and efficiency of the BetaSCP are experimentally shown via a benchmark test against well-known algorithms using twenty test models selected from Protein Data Bank. [ABSTRACT FROM AUTHOR]

Spinning to improve (band) shape: A blend of theoretical and experimental work demonstrates that the rotational conformation of mixed‐valence complexes influences the low‐energy (NIR) transitions in such molecules. Interpretations of the NIR band shapes are presented. [ABSTRACT FROM AUTHOR]

Abstract: A co-culture of Fusarium tricinctum and Fusarium begoniae induced the production of two new linear depsipeptides, subenniatins A and B (1–2), which were not detected when either of the two fungi was cultured alone. The structures of the new compounds were unambiguously determined by analysis of 1D, 2D NMR, and mass spectra, as well as by chemical transformation. Complex NMR spectra were observed for compounds 1 and 2, which were attributed to the presence of rotamers as revealed by 1D NOE and ROESY measurements. Structurally, compounds 1 and 2 are biogenetic building blocks of the cytotoxic enniatins B, B1, A1, and A, which are the major metabolites of F. tricinctum when this fungus is cultured alone. Compounds 1 and 2 were found to be inactive in cytotoxic and antibacterial assays. [Copyright &y& Elsevier]