Favored Isomer Research Articles

Effect of perturbations on dantrolene - A DFT treatise

Dantrolene and an isomer of dantrolene which is obtained by a pair of centric perturbations (carbon to nitrogen replacement in N-N=CH moiety) are considered within the constraints of density functional theory at the level of B3LYP/6-31++G(d,p). Dantrolene is a skeletal muscle relaxant which interferes with the release of calcium ion from the sarcoplasmic reticulum. Both of the isomeric structures of present interest have exothermic heat of formation values and favorable Gibbs free energy of formation values. They are electronically stable as well. The perturbation results in a more exothermic and more favorable isomer than dantrolene. It is also electronically more stable than the parent structure. Various quantum chemical data have been collected and discussed including IR and UV-VIS spectra.

Trimethylsilyldiazomethane Disassembly at a Three-Fold Symmetric Iron Site.

The reaction of equimolar trimethylsilyldiazomethyllithium (LiTMSD) with high spin (S = 2) PhB(AdIm)3FeCl (PhB(AdIm)3- = tris(3-adamantylimidazol-2-ylidene)phenylborate) affords the corresponding N-nitrilimido complex PhB(AdIm)3Fe-N═N═C(SiMe3). This complex can be converted to the thermodynamically more favorable C-isocyanoamido isomer PhB(AdIm)3Fe-C═N═N(SiMe3) by reaction with an additional equivalent of LiTMSD. While the iron(II) complexes are four-coordinate, the diazomethane is bound side-on in the iron(I) congener PhB(AdIm)3Fe(N,N'-κ2-N2C(H)Si(CH3)3). The latter complex adopts high spin (S = 3/2) ground state and features an unusually weak C-H bond. Photolysis of the iron(II) complexes induces N═N bond cleavage, with the iron(II) cyanide PhB(AdIm)3Fe-C≡N and iron(IV) nitride PhB(AdIm)3Fe≡N complexes being the major products of the reaction. The same products are obtained when the iron(I) complex is photolyzed or treated with a fluoride source. The trimethylsilyldiazomethane-derived ligand disassembly reactions are contrasted with those observed for related tris(carbene)amine complexes.

Photoisomerisation of Exo-Imine Complexes and the Role of MECP in the Reverse Thermal Equilibrium: An Experimental and DFT Computational Investigation.

Complexes [MCl2Cp*]2 (M= Ir, Rh), [RuCl2(p-cymene)]2 and [Ir(C^N)2Cl]2 (HC^N = a, phenylpyridine ; b, phenylpyrazole,) react with imine ligands derived from o-aminophenol to yield complexes with an exocyclic C=N bond which has a cis or trans configuration. The trans isomer is favoured except for sterically crowded complexes Cp*M (M = Ir, Rh) when the imine has a mesityl substituent, for which the cis isomer is favoured. The complexes undergo photoisomerization in visible light but revert back to the original isomer over time or when heated. The rate of the thermal reverse isomerisation depends on the imine substituent and the metal fragment. DFT calculations correctly reproduce the favoured isomer and suggest that the reverse isomerisation occurs by a rehybridisation at the N atom as found in organic imines. In addition, a triplet state, thermally accessible by a Minimum Energy Crossing Point (MECP) provides a low energy pathway for reverse isomerisation in the case of the half-sandwich complexes.

Selective control of donor-acceptor Stenhouse adduct populations with non-selective stimuli

Selective control of donor-acceptor Stenhouse adduct populations with non-selective stimuli

Unexpected polarization properties of sub-nanosized magnesium clusters.

The isotropic electrostatic polarizability (IEP) of sub-nanosized magnesium clusters Mg2-Mg32 was studied in an extensive set comprising 1237 structurally unique isomers. These isomers were found in the course of the global search for the potential energy surface minima of the magnesium clusters at the BP86/6-31G(d) level. The calculation of the polarizability at the same DFT level reveals an unexpected property of the IEP: the linear correlation between the polarizability of the most favorable isomers (and only them) and the cluster nuclearity n. Moreover, for each n, the most stable cluster isomer demonstrates nearly minimal IEP value among all found isomers of a given nuclearity. Surprisingly, these observed features are independent of the cluster structures which are quite different. We hypothesize that the energetic favorability of a cluster structure is related to their low polarizability. Apparently, the atoms forming the cluster tend to arrange themselves in such a way as to provide the most compact distribution of the cluster electron density. A possible explanation of the observed trends, their significance for cluster structure prediction, and the practical applications are discussed.

Effect of Ru particle size on cis/trans ratio of products in the hydrogenation of 2,2,4,4-tetramethyl-1,3-cyclobutanedione to 2,2,4,4-tetramethyl-1,3-cyclobutanediol

Ru/AC catalysts with different particle sizes were prepared by tuning the calcination temperature and atmosphere. The performance in the hydrogenation of 2,2,4,4-tetramethyl-1,3-cyclobutanedione (CBDK) to 2,2,4,4-tetramethyl-1,3-cyclobutanediol (CBDO) was evaluated. Ru/AC catalysts with relatively large Ru particle sizes showed a higher selectivity towards trans-CBDO. The analysis of product distribution at different substrate conversion and DFT calculation revealed that the cis-CBDO is a kinetic favorable product. During the stepwise hydrogenation of both carbonyls, the selectivity of thermodynamic favorable trans isomer increases. The enhanced activity of isomerization reaction over the large Ru particles also accounts for the low cis/trans ratio of products in the CBDK hydrogenation reaction.

Enantioselective Synthesis of α-Alkenylated γ-Lactam Enabled by Ni-Catalyzed 1,4-Arylcarbamoylation of 1,3-Dienes

Enantioselective Synthesis of α-Alkenylated γ-Lactam Enabled by Ni-Catalyzed 1,4-Arylcarbamoylation of 1,3-Dienes

Bulky oxadithiolate-bridged [FeFe]‑hydrogenase mimics [Fe2(μ-R2odt)(CO)4(κ2-diphosphine)] (R = Ph and H) with chelating diphosphines

In order to develop an attractive generation of bulky oxadithiolate-bridged [FeFe]‑hydrogenase mimics with chelating diphosphines, two new series of asymmetrically diphosphine-substituted diiron model complexes [Fe2(μ-R2odt)(CO)4(κ2-diphosphine)] (3–5) with bulky Ph2odt bridge and their reference counterparts (6–8) with common odt bridge were obtained from the Me3NO-assisted substitutions of diiron hexacarbonyl precursors [Fe2(μ-R2odt)(CO)6] (R2odt = (SCHR)2O, R = Ph (1) and H (2)) with different diphosphines such as (Ph2P)2NBn (labelled PNBnP, Bn = benzyl), (Ph2PCH2)2NBn (PCNBnCP), and (Ph2PCH2)2CH2 (DPPP)), respectively. All the as-prepared complexes have been characterized by elemental analysis, IR plus NMR spectroscopies, and particularly by X-ray crystallography for 3–8. It is interesting to note that complexes 3 and 6 chelating by small bite-angle PNBnP diphosphine have the favorable dibasal isomer whereas analogues 4, 5 and 7, 8 chelating by flexible backbone PCNBnCP or DPPP ligands possess the main apical-basal isomer in solution or in the solid state. Further, the electrochemical properties of two pairs of representative complexes 3, 6 and 5, 8 are explored and compared by cyclic voltammetry (CV) in the absence and presence of trifluoroacetic acid (CF3CO2H) as proton source, indicating that the complete protonations of 3, 6 and 5, 8 with higher concentration of CF3CO2H lead to two new catalytic waves for the electrocatalytic proton reduction to hydrogen (H2).

Nitriles with High Gas-Phase Basicity-Part II Transmission of the Push-Pull Effect through Methylenecyclopropene and Cyclopropenimine Scaffolds Intercalated between Different Electron Donor(s) and the Cyano N-Protonation Site.

This work extends our earlier quantum chemical studies on the gas-phase basicity of very strong N-bases to two series of nitriles containing the methylenecyclopropene and cyclopropenimine scaffolds with dissymmetrical substitution by one or two electron-donating substituents such as Me, NR2, N=C (NR2)2, and N=P (NR2)3, the last three being strong donors. For a proper prediction of their gas-phase base properties, all potential isomeric phenomena and reasonable potential protonation sites are considered to avoid possible inconsistencies when evaluating the energetic parameters and associated protonation or deprotonation equilibria B + H+ = BH+. More than 250 new isomeric structures for neutral and protonated forms are analyzed. The stable structures are selected and the favored ones identified. The microscopic (kinetic) gas-phase basicity parameters (PA and GB) corresponding to N sites (cyano and imino in the cyclopropenimine or in the substituents) in each isomer are calculated. The macroscopic (thermodynamic) PAs and GBs, referring to the isomeric mixtures of favored isomers, are also estimated. The total (pushing) substituent effects are analyzed for monosubstituted and disubstituted derivatives containing two identical or two different substituents. Electron delocalization is examined in the two π–π conjugated transmitters, the methylenecyclopropene and cyclopropenimine scaffolds. The aromatic character of the three-membered ring is also discussed.

Phenol in High-mass Star-forming Regions

Phenol, which belongs to the C6H6O isomeric group, is the simplest molecule in the family of alcohol of the aromatic series. Although phenol has yet to be detected in the interstellar medium, a tentative identification was reported toward the Orion KL hot core using the IRAM-30 m line survey. To explore some more species of this isomeric group, we consider ten species to study the fate of their astronomical detection. It is noticed that phenol is the most energetically favorable isomer of this group. In contrast, propargyl ether is the least favorable (having relative energy ∼103 kcal mol−1 compared to phenol) species of this group. So far, the studies associated with the formation of phenol are heavily concentrated on combustion chemistry. Here, we suggest a few key reactions (C6H6 + OH → C6H5 + H2O, C6H6 + O → C6H5OH, C6H6 + H → C6H5 + H2, and C6H5 + OH → C6H5OH + h ν) for the formation of phenol. All these pathways are included in a large gas-grain chemical network to study its formation in high mass star-forming regions and dark cloud environments. It is noticed that the phenyl (−C6H5) formation by the ice-phase hydrogen abstraction reaction of benzene (i.e., C6H6 + OH → C6H5 + H2O if allowed at ∼10 K) could serve as the starting point for the formation of phenol in the gas phase by radiative association reaction C6H5 + OH → C6H5OH + h ν. The gas-phase reaction C6H6 + O → C6H5OH significantly contributes to the formation of phenol, when the ice-phase reaction C6H6 + OH → C6H5 + H2O is not considered at low temperature. Band 4 ALMA archival data of a hot molecular core, G10.47+0.03, are analyzed. It yields an upper limit on phenol abundance of 5.19 × 10−9. Our astrochemical model delivers an upper limit on phenol abundance of ∼2.20 × 10−9 in the hot molecular core, whereas its production in the dark cloud is not satisfactory.

Carbodiphosphorane-Stabilized Parent Dioxophosphorane: A Valuable Synthetic HO2P Source.

Introducing a small phosphorus-based fragment into other molecular entities via, for example, phosphorylation/phosphonylation is an important process in synthetic chemistry. One of the approaches to achieve this is by trapping and subsequently releasing extremely reactive phosphorus-based molecules such as dioxophosphoranes. In this work, electron-rich hexaphenylcarbodiphosphorane (CDP) was used to stabilize the least thermodynamically favorable isomer of HO2P to yield monomeric CDP·PHO2. The title compound was observed to be a quite versatile phosphonylating agent; that is, it showed a great ability to transfer, for the first time, the HPO2 fragment to a number of substrates such as alcohols, amines, carboxylic acids, and water. Several phosphorous-based compounds that were generated using this synthetic approach were also isolated and characterized for the first time. According to the initial computational studies, the addition-elimination pathway was significantly more favorable than the corresponding elimination-addition route for "delivering" the HO2P unit in these reactions.

Selective Isomerization via Transient Thermodynamic Control: Dynamic Epimerization of trans to cis Diols.

Traditional approaches to stereoselective synthesis require high levels of enantio- and diastereocontrol in every step that forms a new stereocenter. Here, we report an alternative approach, in which the stereochemistry of organic substrates is selectively edited without further structural modification, a strategy with the potential to allow new classes of late-stage stereochemical manipulation and provide access to rare or valuable stereochemical configurations. In this work, we describe a selective epimerization of cyclic diols enabled by hydrogen atom transfer photocatalysis and boronic acid mediated transient thermodynamic control, selectively generating less stable cis products from the otherwise favored trans isomers. A range of substitution patterns and ring sizes are amenable to selective isomerization, including stereochemically complex polyols such as estriol, as well as syn to anti epimerization of acyclic vicinal diols. Moreover, this strategy has enabled the divergent epimerization of saccharide anomers, providing access to distinct sugar isomers from α- or β-configured glycosides.

Structure Determination of Europium Complexes in Solution Using Crystal-Field Splitting of the Narrow f-f Emission Lines.

Nine nona-coordinated Eu(III) complexes (1–9) studied here have three unsymmetric β-diketonate ligands and one chiral Ph-Pybox ligand, which can produce eight possible coordination isomers, depending on the position of the three unsymmetric β-diketonate ligands. Substituents on the β-diketonate ligands cause a rational structural rearrangement upon crystallization. Substituents with higher polarity, including −CN, −F, −Cl, −Br, −OMe, and −OEt, employ intercomplex hydrogen bonding to generate an association complex through structural rearrangement upon crystallization. Substituents with lower polarity, including −CF3, −SMe, and −Me, cause the most energetically favorable isomer to crystallize directly from solution. These two crystal structures exhibit well-resolved f–f emission lines with characteristic Stark splitting structures. This work revealed that the configuration of the Eu(III) complexes in solution can be determined by systematic comparison of their Stark splitting structures to those obtained from the solid phase using density functional theory (DFT)-based predictions combined with circular dichroism data.

Crystal structure, MEP/DFT/XRD, thione ⇔ thiol tautomerization, thermal, docking, and optical/TD-DFT studies of (E)-methyl 2-(1-phenylethylidene)-hydrazinecarbodithioate ligand

As small-molecule (E)-methyl 2-(1-phenylethylidene)hydrazinecarbodithioate has been prepared and characterized by X-ray single-crystal analysis. In order to elucidate the nature of the intermolecular interactions in the structural lattice, the Hirshfeld surface analysis (HSA) calculation was correlated to the XRD-packing result. Moreover, the XRD bond lengths and angles were compared to their DFT/B3LYP/6-311G(d,p) relative parameters. Considering the thione isomer as a kineticly favoured isomer, the single proton intra-migration from H-N to form S-H thionethiol tautomerization process was successfully computed via QST2 model. Additionally, Mulliken Atomic Charge (MAC), Natural Population Analysis (NPA), and Molecular Electrostatic Potential (MEP) analyses were carried out to confirm this process. The electron transfer and optical behavior of the ligand in DMSO have been exanimated with TD-DFT and HOMO/LUMO calculations. The thermal behavior of the compound was determined in an open room condition via TG/DTG. The two identified isomers of (E)-methyl 2-(1-phenylethylidene)-hydrazinecarbodithioate (thione and thiol forms) were docked against TcAChE (PDB:1EVE) revealed, conspicuous, different protein–drug structures, however, reflects identical docking scores (−7.2 Kcal/mol each), which is compared to the standard donepezil drug used in this study.

Bimodal substitution behavior in the reaction of N,N’-diisopropylformamidine with [Os3(CO)10(NCMe)2]: Kinetics and molecular structures of the formamidinate-substituted clusters HOs3(CO)9[μ-C(O)NPriC(H)NPri], HOs3(CO)10[μ-NPriC(H)NPri], and HOs3(CO)9[μ3-NPriC(H)NPri

The dinitrogen donor N,N’-diisopropylformamidine [PriN=C(H)NHPri] reacts with the triosmium cluster Os3(CO)10(NCMe)2 at room temperature to yield the isomeric clusters HOs3(CO)9[μ-C(O)NPriC(H)NPri] (1) and HOs3(CO)10[μ-NPriC(H)NPri] (2) in a 1:2.8 ratio. 1 contains an edge-bridging iminocarbamoyl ligand, while 2 contains a bridging formamidinate ligand. Thermolysis of 1 yields 2 plus the face-capped cluster HOs3(CO)9[μ3-NPriC(H)NPri] (3). The decarbonylation of 2 to 3 + CO confirms the molecularity of the observed reaction steps. The three products have been fully characterized in solution by IR and NMR spectroscopies, and the solid-state structures for 1-3 have been determined by X-ray crystallography. The kinetics for the thermolysis reaction were investigated over the temperature range 342–383 K, and the concentration versus time profiles for the conversion of 1 → 2 → 3 + CO have been successfully modeled using two consecutive, irreversible first-order reactions. The bonding in clusters 1-3 have been examined by DFT, and these data support cluster 1 as the kinetic substitution product and cluster 2 as the thermodynamically favored isomer.

Mechanistic study on the reaction of pinB-BMes2 with alkynes based on experimental investigation and DFT calculations: gradual change of mechanism depending on the substituent.

Transition metal-free direct and base-catalyzed 1,2-diborations of arylacetylenes using pinB-BMes2 provided a syn/anti-isomeric mixture of diborylalkenes. The kinetic analysis showed that the reaction rate and isomer ratio were affected by reaction conditions and substituents on the aryl ring. DFT calculations indicated that direct addition proceeded via the interaction of acetylene-π with the BMes2 fragment. In contrast, for the base-catalyzed diboration, the previously isolated sp2–sp3 diborane and borataallene were confirmed as stable intermediates by calculations. The whole reaction pathways can be divided into the Bpin-migration and deprotonation steps, where the borataallene should be considered as a common intermediate. It should be noted that the deprotonation step is reversible and affords the kinetically less favoured isomer under the thermodynamic conditions. As a result, the composition of isomeric products, in the base-catalyzed diboration, is attributed to the small difference of activation barriers between direct and base-catalyzed systems.

Detection of the keto-enol tautomerization in acetaldehyde, acetone, cyclohexanone, and methyl vinyl ketone with a novel VUV light source

The discovery of enols in combustion environments and our atmosphere has garnered increasing attention to the many unanswered questions surrounding enol chemistry. The scarcity of experimental data concerning these enols renders combustion and atmospheric models with a lack of constraining parameters, leading to varying computational predictions. Experimental detection is difficult because mass spectrometry, a powerful tool for probing a wide variety of species, cannot distinguish between enols and their thermodynamically favorable ketone isomers. A solution to this ambiguity is to use tunable vacuum ultraviolet (VUV) light from a synchrotron to identify the presence of the enol by its lower ionization energy compared to the isomer. We present a tabletop-scale VUV light source that implements highly cascaded harmonic generation, a new regime of cascaded nonlinear optics, to provide a set of spectral lines spaced by 1.2 eV. We demonstrate that the variety of photon energies available allows us to detect the keto-enol tautomerization of four aldehydes and ketones. By combining this novel VUV light source with an established microreactor, we first revisit the formation of vinyl alcohol from acetaldehyde and confirm that the observed isomerization is indeed unimolecular. Secondly, we observe the thermal tautomerization of acetone to propen-2-ol for the first time. Finally, we observe the thermal tautomerization of cyclohexanone to 1-cyclohexenol and methyl vinyl ketone to 2-hydroxybutadiene, where the results are in good agreement with those reported at a synchrotron. Our measurements can be used to constrain models, inform future experimental studies of enol reactivity, and potentially enhance current understanding of combustion and environmental chemistry.

The structure of benzonitrile-water complex as unveiled by matrix isolation infrared spectroscopy: Is it linear or cyclic at low temperatures?

The hydrogen bonded interaction of benzonitrile (C6H5CN)-water (H2O) complexes have been studied experimentally using matrix isolation infrared spectroscopy to elucidate the structure(s) of the binary complexes produced at low temperatures. Computations performed at MP2 and B3LYP-D3 level of theory with aug-cc-pVDZ basis set predicted two complexes, of which global minimum complex A has a cyclic structure with the interactions occurring between ortho-hydrogen of C6H5CN and oxygen of H2O and the hydrogen of H2O with π-cloud of CN in C6H5CN. The linear acylic complex B, a local minimum is stabilized through a straight C-H⋯N interaction between nitrogen of C6H5CN and hydrogen of H2O and is present at a relative energy of ∼0.7 kcal/mol with respect to global minimum. While previous gas phase studies using a number of spectroscopic probes identify exclusively the cyclic global complex, our experiments performed under isolated conditions at low temperatures uniquely produced the acyclic linear C6H5CN-H2O complex, a local minimum in the potential energy surface. The CN stretching vibrational mode of C6H5CN was exploited as a unique marker to confirm the generation of local minimum. The effect of matrixes was simulated using Onsager self-consistent reaction field model and as a result, the linear complex (complex B) turned out to be energetically favored isomer under the influence of matrixes. The hydrogen bonding interaction in both the complexes was characterized using Atoms in Molecules, Natural Bond Orbital, Energy Decomposition and Non-Covalent Interaction analyses.

Oxidative Release of Thiol-Conjugated Forms of the Mycotoxin 4-Deoxynivalenol.

Deoxynivalenol (DON) is a trichothecene mycotoxin that is produced by several species of Fusarium, which may infect grain crops. DON, as well as other type-B trichothecenes, contain an α,β-unsaturated carbonyl group that may react with sulfhydryl groups in, for example, amino acids and peptides. Such conjugates have been shown to occur in plants. Nucleophilic addition of thiols to the conjugated double bond in DON afforded several isomeric reaction products, and the thermodynamically favored isomers of DON-10-cysteine and DON-10-glutathione have been prepared and characterized previously. This study reports the preparation and characterization of the kinetically favored DON-10-cysteine isomer. We subsequently studied and compared the rate of the deconjugation reaction of the two DON-10-cysteine isomers and the thermodynamically favored DON-10-glutathione adduct. The deconjugation rate of the thermodynamically favored thiol conjugates was slow with half-lives of weeks even at pH 10.7, while the kinetically favored DON-10-cysteine isomer deconjugated within a few hours, affording free DON. We adapted a simple and rapid oxidation protocol in which the sulfide linkage was oxidized to a sulfoxide or sulfone that, when treated with the base, rapidly eliminated the adducted thiol as its sulfenate or sulfinate to afford free DON. The deconjugation reactions of the sulfoxides and sulfones of thermodynamically favored DON-10-thiols were complete within hours or minutes at pH 10.7, respectively. The increase in deconjugation rates for the kinetically favored DON-10-cysteine were less dramatic. Oxidation of sulfides to sulfoxides is known to occur in vivo, and thus, our data show that thiol-conjugated DON might become bioavailable via sulfide oxidation followed by elimination to regenerate DON. The oxidation-elimination approach could also be useful for the indirect quantification of DON-10-thiol conjugates in plant and animal tissues.

Effect of Chemical Order in the Structural Stability and Physicochemical Properties of B12N12 Fullerenes

The effect of chemical order in the structural and physicochemical properties of B12N12 [4,6]-fullerene (BNF) isomers was evaluated using density functional theory and molecular dynamic calculations. The feasibility to find stable BNF isomers with atomic arrangement other than the well-known octahedral Th-symmetry was explored. In this study, the number of homonuclear bonds in the modeled nanostructures was used as categorical parameter to describe and quantify the degree of structural order. The BNF without homonuclear bonds was identified as the most energetically favorable isomer. However, a variety of BNF arrays departing from Th-symmetry was determined as stable structures also. The calculated vibrational spectra suggest that isomers with chemical disorder can be identified by infrared spectroscopy. In general, formation of homonuclear bonds is possible meanwhile the entropy of the system increases, but at expense of cohesive energy. It is proposed that formation of phase-segregated regions stablishes an apparent limit to the number of homonuclear bonds in stable B12N12 fullerenes. It was found that formation of homonuclear bonds decreases substantially the chemical hardness of BNF isomers and generates zones with large charge density, which might act as reactive sites. Moreover, chemical disorder endows BNF isomers with a permanent electric dipole moment as large as 3.28 D. The obtained results suggest that by manipulating their chemical order, the interaction of BNF’s with other molecular entities can be controlled, making them potential candidates for drug delivery, catalysis and sensing.