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Finding low-energy structures of ligand-protected clusters is challenging due to the enormous conformational space and the high computational cost of accurate quantum chemical methods for determining the structures and energies of conformers. Here, we adopted and utilized a kernel rigid regression based machine learning method to accelerate the search for low-energy structures of ligand-protected clusters. We chose the Au25(Cys)18 (Cys: cysteine) cluster as a model system to test and demonstrate our method. We found that the low-energy structures of the cluster are characterized by a specific hydrogen bond type in the cysteine. The different configurations of the ligand layer influence the structural and electronic properties of clusters. [ABSTRACT FROM AUTHOR]

Methyl nitrite has two stable conformational isomers resulting from rotation about the primary C–O–N–O dihedral angle: cis-CH3ONO and trans-CH3ONO, with cis being more stable by ∼5 kJ/mol. The barrier to rotational interconversion (∼45 kJ/mol) is too large for isomerization to occur under ambient conditions. This paper presents evidence of a change in conformer abundance when dilute CH3ONO is deposited onto a cold substrate; the relative population of the freshly deposited cis conformer is seen to increase compared to its gas-phase abundance, measured by in situ infrared spectroscopy. We observe abundance changes depending on the identity of the bath gas (N2, Ar, and Xe) and deposition angle. The observations indicate that the surface properties of the growing matrix influence conformer abundance—contrary to the widely held assumption that conformer abundance in matrices reflects gas-phase abundance. We posit that differences in the angle-dependent host-gas deposition dynamics affect the growing surfaces, causing changes in conformer abundances. Quantum chemistry calculations of the binding energies between CH3ONO and a single bath-gas component reveal that significant energetic stabilization is not observed in 1:1 complexes of N2:CH3ONO, Ar:CH3ONO, or Xe:CH3ONO. From our results, we conclude that the growing surface plays a significant role in trapping cis-CH3ONO more effectively than trans-CH3ONO, likely because cis-CH3ONO is more compact. Taken together, the observations highlight the necessity for careful characterization of conformers in matrix-isolated systems, emphasizing a need for further study into the deposition dynamics and surface structure of chemically inert matrices. [ABSTRACT FROM AUTHOR]

N-Alkylated oligo- and poly(p-benzamide)s exist as dynamic helical structures with all-cis amide conformation. Imidazole N-alkylated amides also show cis conformational preference, but their major conformer is changed from cis to trans by addition of acid. Here, based on those findings, we designed and synthesized aromatic triamides 3 and hexaamides 4 containing an imidazole ring as candidate foldamers anticipated to exhibit acidinduced conformational change. X-ray structure analysis of oligomer 3c showed that it takes all-cis conformation in the crystal. In solution, all the oligoamides examined existed as an equilibrium mixture of 4 conformers, among which the major conformer was the folded all-cis structure as judged from the low-temperature ¹H NMR spectra. When trifluoroacetic acid-d was added to a solution of the oligoamides in methylene chlorided2, only 2 conformers were observed in the low-temperature ¹H NMR spectra, and the major conformer was the (trans, cis) form with respect to the amide bonds of the imidazole at the 4 and 2 positions. Experimental and theoretical analysis of the CD spectra indicated that the conformation of hexaamides 4 changes upon the addition of acid. Our results suggest that N-alkylated imidazole amide can serve as a key structural motif for the construction of foldamers with acid-switchable conformation. [ABSTRACT FROM AUTHOR]

The conformational energy landscapes of allyl ethyl ether (AEE) and allyl ethyl sulfide (AES) were investigated using Fourier transform microwave spectroscopy in the frequency range of 5–23 GHz aided by density functional theory B3LYP-D3(BJ)/aug-cc-pVTZ calculations. The latter predicted highly competitive equilibria for both species, including 14 unique conformers of AEE and 12 for the sulfur analog AES within 14 kJ mol−1. The experimental rotational spectrum of AEE was dominated by transitions arising from its three lowest energy conformers, which differ in the arrangement of the allyl side chain, while in AES, transitions due to the two most stable forms, distinct in the orientation of the ethyl group, were observed. Splitting patterns attributed to methyl internal rotation were analyzed for AEE conformers I and II, and the corresponding V3 barriers were determined to be 12.172(55) and 12.373(32) kJ mol−1, respectively. The experimental ground state geometries of both AEE and AES were derived using the observed rotational spectra of the 13C and 34S isotopic species and are highly dependent on the electronic properties of the linking chalcogen (oxygen vs sulfur). The observed structures are consistent with a decrease in hybridization in the bridging atom from oxygen to sulfur. The molecular-level phenomena that drive the conformational preferences are rationalized through natural bond orbital and non-covalent interaction analyses. These show that interactions involving the lone pairs on the chalcogen atom with the organic side chains favor distinct geometries and energy orderings for the conformers of AEE and AES. [ABSTRACT FROM AUTHOR]

In this study, we present a comprehensive first-principles computational investigation focused on the structural characteristics, electronic properties, and coupling integrations of three cationic Gemini surfactants: 12-4-12, 12-3-12, and 12-2-12 ((CH3(CH2)11)(CH3)2-N+-(CH2)n-N+(CH3(CH2)11)(CH3)2, where n = 2, 3, or 4). By employing Density Functional Theory (DFT) computations, we aimed to gain insights into the fundamental aspects of these surfactant molecules, and the intermolecular interactions among these surfactant molecules. We examined different conformers of each surfactant, including parallel, wing, and bent conformers, and compared their relative stability and properties. We elucidated that the complex structural characteristics, electronic properties, and molecular arrangements of the surfactants vary according to the number of carbon atoms in the central spacer. We also conducted experimental Raman spectroscopy on the three surfactants to compare the results with our computational findings. Furthermore, we computed the coupling behaviors of different conformers of 12-4-12 surfactants in order to gain insights into their coupling mechanism. [ABSTRACT FROM AUTHOR]

N-Hydroxyurea (HU) is an important chemotherapeutic agent used as a first-line treatment in conditions such as sickle cell disease and β -thalassemia, among others. To date, its properties as a hydrated molecule in the blood plasma or cytoplasm are dramatically understudied, although they may be crucial to the binding of HU to the radical catalytic site of ribonucleotide reductase, its molecular target. The purpose of this work is the comprehensive exploration of HU hydration. The topic is studied using ab initio molecular dynamic (AIMD) simulations that apply a first principles representation of the electron density of the system. This allows for the calculation of infrared spectra, which may be decomposed spatially to better capture the spectral signatures of solute–solvent interactions. The studied molecule is found to be strongly hydrated and tightly bound to the first shell water molecules. The analysis of the distance-dependent spectra of HU shows that the E and Z conformers spectrally affect, on average, 3.4 and 2.5 of the closest H2O molecules, respectively, in spheres of radii of 3.7 Å and 3.5 Å, respectively. The distance-dependent spectra corresponding to these cutoff radii show increased absorbance in the red-shifted part of the water OH stretching vibration band, indicating local enhancement of the solvent's hydrogen bond network. The radially resolved IR spectra also demonstrate that HU effortlessly incorporates into the hydrogen bond network of water and has an enhancing effect on this network. Metadynamics simulations based on AIMD methodology provide a picture of the conformational equilibria of HU in solution. Contrary to previous investigations of an isolated HU molecule in the gas phase, the Z conformer of HU is found here to be more stable by 17.4 kJ·mol−1 than the E conformer, pointing at the crucial role that hydration plays in determining the conformational stability of solutes. The potential energy surface for the OH group rotation in HU indicates that there is no intramolecular hydrogen bond in Z-HU in water, in stark contrast to the isolated solute in the gas phase. Instead, the preferred orientation of the hydroxyl group is perpendicular to the molecular plane of the solute. In view of the known chaotropic effect of urea and its N-alkyl-substituted derivatives, N-hydroxyurea emerges as a unique urea derivative that exhibits a kosmotropic ordering of nearby water. This property may be of crucial importance for its binding to the catalytic site of ribonucleotide reductase with a concomitant displacement of a water molecule. [ABSTRACT FROM AUTHOR]

From coupled-cluster singles and doubles model including connected triples corrections [CCSD(T)] calculations on the water dimer and B97D/CC on the water-circumcoronene complex at a large number of randomly generated conformations, interaction potentials for the physisorption of water on graphene are built, accomplishing almost sub-chemical accuracy. The force fields were constructed by decomposing the interaction into electrostatic and van der Waals contributions, the latter represented through improved Lennard-Jones potentials. Besides, a Chemistry at Harvard Macromolecular Mechanics (CHARMM)-like term was included in the water–water potential to improve the description of hydrogen bonds, and an induction term was added to model the polarization effects in the interaction between water and polyaromatic hydrocarbons (PAHs) or graphene. Two schemes with three and six point charges were considered for the interactions water–water and water-PAH, as Coulomb contributions are zero in the water-graphene system. The proposed fitted potentials reproduce the ab initio data used to build them in the whole range of distances and conformations and provide results for selected points very close to CCSD(T) benchmarks. When applied to the water-graphene system, the obtained results are in excellent agreement with p-CCSD(T), revised symmetry-adapted perturbation theory based on density functional theory monomer properties (DFT-SAPT), and diffusion Monte Carlo reference values. Furthermore, the stability of the various conformers water-PAH and water-graphene, as well as the different trends observed between these systems are rationalized in terms of the modifications of the electrostatic contribution. [ABSTRACT FROM AUTHOR]

The design and synthesis of analogs of natural products can be a valuable source of medicinal preparations for the pharmaceutical industry. In the present study, the structural elucidation of eleven derivatives of 2,4-dihalogeno substituted synthetic analogues of the natural compound carvacrol was carried out by means of NMR experiments, and of another thirteen by DFT calculations. By selective NOE experiments and the irradiation of CH signals of the isopropyl group, individual conformers were assigned as syn and anti. By comparing GIAO/B3LYP/6-311++G(d,p)-calculated and experimentally measured vicinal 3JCH spin-spin constants, this assignment was confirmed. An unusual relationship is reported for proton-carbon vicinal couplings: 3JCH (180°) < 3JCH (0°). The conformational mobility of carvacrols was studied by 2D EXSY spectra. The application of homonuclear decoupling technique (HOBS) to these spectra simplifies the spectra, improves resolution without reducing the sensitivity, and allows a systematic examination of the rotational barrier of all compounds via their CH signals of the isopropyl group in a wider temperature interval. The rate constants of the isopropyl rotation between syn and anti conformers were determined and the corresponding energy barriers (14–17 kcal/mol) were calculated. DFT calculations of the energy barriers in carvacrol derivatives allowed the determination of the steric origin of the restricted isopropyl rotation. The barrier height depends on the size of the 2- and 4-position substituents, and is independent of the derivatization of the OH group. [ABSTRACT FROM AUTHOR]

Many conformers of 3-aminopropionitrile are known. Due to the biomedical importance of 3-aminopropionitrile a full investigation of structural, vibrational, and other associated properties of all possible conformers was performed. The geometrical structures, relative stability, and vibrational frequencies of the gauche and trans 3-aminopropionitrile conformers have been studied using ab initio (CCSD/6-311+G(d,p)) and DFT (B3LYP and M06 functionals at 6-311+G(d,p) and aug-cc-pVDZ basis set) calculations. The conformational and vibrational studies of 3-aminopropionitrile molecule were presented here are in very good interpretation of the calculated data compared with very poor interpretation in previous studies. The results showed that the gauche 2 conformer is more stable by 0.19 kcal/mol than gauche 1, outlined as enthalpy change ΔH between the conformers, at CCSD/6-311+G(d,p). Additionally, the population analysis shows that the gauche conformers are more prevalent than the trans conformers in the gas phase, present at 72.8%, with gauche 2 being the dominating gauche conformer at 40.1%. These results are in good agreement with earlier experimental and theoretical conclusions. All minima conformers' thermodynamic characteristics have also been studied. The relevant bond lengths, bond angles, and dihedral angles were calculated at a different level of theory for all possible conformers. The geometrical outcomes of the conformers agree very well with the previous experimental results. Electrostatic potential surface (ESP) has been used to interpret the structure-activity relationship. The atomic charges are examined, together with the energy difference between HOMO (Highest Occupied Molecular Orbital) and LUMO (Lowest Unoccupied Molecular Orbital). Additionally, the HOMO-LUMO energy gap and other relevant molecular properties are computed. The most stable conformers' stabilization energy has been determined by the Natural Bond Orbital (NBO) analysis. [ABSTRACT FROM AUTHOR]

Motivation Popular shape-based alignment methods handle molecular flexibility by utilizing conformational ensembles to select the most fitted conformer. However, the initial conformer library generation step is computationally intensive and limiting to the overall alignment process. In this work, we describe a method to perform flexible alignment of two molecular shapes by optimizing the 3D conformation. SENSAAS-Flex, an add-on to the SENSAAS tool, is able to proceed from a limited set of initial conformers through an iterative process where additional conformational optimizations are made at the substructure level and constrained by the target shape. Results In self- and cross-alignment experiments, SENSAAS-Flex is able to reproduce the crystal structure geometry of ligands of the AstraZeneca Molecule Overlay Test set and PDBbind refined dataset. Our study shows that the point-based representation of molecular surfaces is appropriate in terms of shape constraint to sample the conformational space and perform flexible molecular alignments. Availability and implementation The documentation and source code are available at https://chemoinfo.ipmc.cnrs.fr/Sensaas-flex/sensaas-flex-main.tar.gz [ABSTRACT FROM AUTHOR]

High-resolution direct absorption infrared spectra of metastable cis-formic acid (HCOOH) trapped in a cis-well resonance behind a 15 kcal/mol barrier are reported for the first time, with the energetically unstable conformer produced in a supersonic slit plasma expansion of trans-formic acid/H2 mixtures. We present a detailed high-resolution rovibrational analysis for cis-formic acid species in the OH stretch (ν1) fundamental, providing first precision vibrational band origin, rotational constants, and term values, which in conjunction with ab initio calculations at the couple-cluster with single, double, and perturbative triple [CCSD(T)]/ANOn (n = 0, 1, 2) level support the experimental assignments and establish critical points on the potential energy surface for internal rotor trans-to-cis isomerization. Relative intensities for a- and b-type transitions observed in the spectra permit the transition dipole moment components to be determined in the body fixed frame and prove to be in good agreement with ab initio CCSD(T) theoretical estimates but in poor agreement with simple bond-dipole predictions. The observed signal dependence on H2 in the discharge suggests the presence of a novel H atom radical chemical mechanism for strongly endothermic "up-hill" internal rotor isomerization between trans- and cis-formic acid conformers. [ABSTRACT FROM AUTHOR]

Crystal nucleation rates have been measured in the supercooled melts of two richly polymorphic glass-forming liquids: ROY and nifedipine (NIF). ROY or 5-methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile is known for its crystals of red, orange, and yellow colors and many polymorphs of solved structures (12). Of the many polymorphs, ON (orange needles) nucleates the fastest with the runner up (Y04) trailing by a factor of 103 when compared under the same mobility-limited condition, while the other unobserved polymorphs are slower yet by at least 5 orders of magnitude. Similarly, of the six polymorphs of NIF, γ ′ nucleates the fastest, β ′ is slower by a factor of 10, and the rest are slower yet by at least 5 decades. In both systems, the faster-nucleating polymorphs are not built from the lowest-energy conformers, while they tend to have higher energies and lower densities and thus greater similarity to the liquid phase by these measures. The temperature ranges of this study covered the glass transition temperature Tg of each system, and we find no evidence that the nucleation rate is sensitive to the passage of Tg. At the lowest temperatures investigated, the rates of nucleation and growth are proportional to each other, indicating that a similar kinetic barrier controls both processes. The classical nucleation theory provides an accurate description of the observed nucleation rates if the crystal growth rate is used to describe the kinetic barrier for nucleation. The quantitative rates of both nucleation and growth for the competing polymorphs enable prediction of the overall rate of crystallization and its polymorphic outcome. [ABSTRACT FROM AUTHOR]

The conformational landscape of myrtenol (2-pinen-10-ol) and its robustness upon hydration were investigated theoretically and experimentally by employing a synergic combination of quantum chemical calculations and Fourier transform microwave spectroscopy coupled to a supersonic jet expansion. Relaxed potential energy surfaces have been carried out, and the lowest energy conformers of the monomer were found to be associated with different geometries of the hydroxymethyl group from those previously reported [Sedo et al., J. Mol. Spectrosc. 356, 32 (2019)]. Geometry optimizations and harmonic vibrational frequency calculations allowed characterization of the equilibrium structure of the possible conformers of myrtenol. Among the nine predicted structures, four have been observed, analyzed, and identified. The controversy on the geometry was solved with the deuteration of the hydroxyl group, which led to the determination of substitution (rs) geometry, in agreement with the present theoretical results. Interestingly, the four observed conformers exhibit the same orientation of OH as in the allyl alcohol molecule. Furthermore, hydrogen bonding linking myrtenol to water was studied. One monohydrate has been observed and identified. Non-covalent interactions and natural bond orbital analysis were performed to depict the interactions responsible for the stabilization of the observed structure. We conclude that the structure of the hydroxymethyl group is robust and does not change upon hydration. [ABSTRACT FROM AUTHOR]

Conformational analysis of N,N-dialkylamides of diphenylphosphorylacetic acid has been carried out using the methods of dipole moments, IR spectroscopy, and quantum chemistry DFT B3PW91/6-311++G(df,p), including the CPCM model. In solution, N,N-diethyl-, N,N-dibutyl- and N,N-dioctylamides exist as equilibrium mixture of conformers, in which forms with cis-orientation of phenyl rings and synclinal orientation of the Csp3‒Csp2(C=O) bond relative to the phosphoryl group predominate, the carbonyl group and P‒Csp3 bond being anticlinal. The stabilization of the preferred conformers is facilitated by intramolecular hydrogen contacts and the possible presence of the p,π-conjugation between the phosphoryl group and the phenyl ring in their molecules. [ABSTRACT FROM AUTHOR]

The structure, stability, and bonding characteristics of 1,1‐ and 1,2‐ethenediol, their radical cations, and their protonated and deprotonated species were investigated using high‐level ab initio G4 calculations. The electron density of all the neutral and charged systems investigated was analyzed using the QTAIM, ELF, and NBO approaches. The vertical ionization potential (IP) of the five stable tautomers of 1,2‐ethenediol and the two stable tautomers of 1,1‐ethenediol go from 11.81 to 12.27 eV, whereas the adiabatic ones go from 11.00 to 11.72 eV. The adiabatic ionization leads to a significant charge delocalization along the O‐C‐C‐O skeleton. The most stable protonated form of (Z)‐1,2‐ethenediol can be reached by the protonation of both the anti‐anti and the syn‐anti conformers, whereas the most stable deprotonated form arises only from the syn‐anti one. Both charged species are extra‐stabilized by the formation of an O‐H···O intramolecular hydrogen bond (IHB) which is not found in the neutral system. (Z)‐1,2‐ethenediol is predicted to be less stable, less basic, and more acidic than its cis‐glycolaldehyde isomer. The most stable protonated species of (E)‐1,2‐ethenediol comes from its syn‐syn conformer, although the anti‐anti conformer is the most basic one. Contrarily, the three conformers yield a common deprotonated species, so their acidity follows exactly their relative stability. Again, the (E)‐1,2‐ethenediol is predicted to be less stable, less basic, and more acidic than its trans‐glycolaldehyde isomer. Neither the neutral nor the protonated or the deprotonated forms of 1,1‐ethenediol show the formation of any O‐H···O IHB. The most stable protonated species is formed by the protonation of any of the two tautomers, but the most stable deprotonated form arises exclusively from the syn‐anti neutral conformer. The conformers of 1,1‐ethenediol are much less stable and significantly less basic than their isomer, acetic acid, and only slightly more acidic. [ABSTRACT FROM AUTHOR]

An empirical model was developed to predict organic solvophobic effects using N‐phenylimide molecular balances functionalized with non‐polar alkyl groups. Solution studies and X‐ray crystallography confirmed intramolecular alkyl‐alkyl interactions in their folded conformers. The structural modularity of the balances allowed systematic variation of alkyl group lengths. Control balances were instrumental in isolating weak organic solvophobic effects by eliminating framework solvent‐solute effects. A 19F NMR label enabled analysis across 46 deuterated and non‐deuterated solvent systems. Linear correlations were observed between organic solvophobic effects and solvent cohesive energy density (ced) as well as changes in solvent‐accessible surface areas (SASA). Using these empirical relationships, a model was constructed to predict organic solvophobic interaction energy per unit area for any organic solvent with known ced values. The predicted interaction energies aligned with recent organic solvophobic measurements and literature values for the hydrophobic effect on non‐polar surfaces confirmed the model's accuracy and utility. [ABSTRACT FROM AUTHOR]

Acid-base properties are the simplest expression of compounds' coordinating ability. In the present work, we studied in silico how the gas-phase Brønsted acidity (GA) of several polycyano-substituted compounds change when cyano (CN) groups are replaced by 1,2,2-tricyanovinyl (TCNV) groups in (iso)cyanic acid, dicyanoamine, cyanoform, and hydrogen tetracyanoborate. Different tautomers and conformers/isomers are included in this study. Gas-phase acidity values are compared with the acidities of various acids, including percyanated protonated monocarba-closo-dodecaborate (carborane acid) and dodecaborate, as well as hydrogen cyanide and 1,2,2-tricyanoethene. An estimation of acetonitrile (MeCN), dimethylsufoxide (DMSO), and 1,2-dichloroethane (DCE) acidities is presented using the COSMO-RS method and correlation analysis. The strongest acid with four TCNV groups shows remarkable acidic properties. [ABSTRACT FROM AUTHOR]

Mirabegron, commonly known as "Myrbetriq", has been widely prescribed as a medicine for overactive bladder syndrome for over a decade. However, the structure of the drug and what conformational changes it may undergo upon binding its receptor remain unknown. In this study, the authors employed microcrystal electron diffraction (MicroED) to reveal its elusive three‐dimensional (3D) structure. They find that the drug adopts two distinct conformational states (conformers) within the asymmetric unit. Analysis of hydrogen bonding and packing demonstrated that the hydrophilic groups are embedded within the crystal lattice, resulting in a hydrophobic surface and low water solubility. Structural comparison revealed the presence of trans‐ and cis‐ forms in conformers 1 and 2, respectively. Comparison of the structures of Mirabegron alone with that of the drug bound to its receptor, the beta 3 adrenergic receptor (β3AR) suggests that the drug undergoes major conformational change to fit in the receptor agonist binding site. This research highlights the efficacy of MicroED in determining the unknown and polymorphic structures of active pharmaceutical ingredients (APIs) directly from powders. [ABSTRACT FROM AUTHOR]

4-Azidopyridine (1) and SiCl4 react with the formation of the hexacoordinate silicon complex SiCl4(4-azidopyridine)2 (2). Upon dissolving in warm chloroform, the complex dissociates into the constituents 1 and SiCl4 and forms back upon cooling. Depending on the cooling, two different crystalline modifications of 2 were obtained, which feature two different trans-conformers. Slow cooling to room temperature afforded conformer 2′, which features coplanar pyridine rings. Rapid cooling to −39 °C afforded crystals of conformer 2″, in which the planes of the pyridine ligands are nearly orthogonal to one another. Whereas 2′ resembles the molecular arrangement of various other known SiX4(pyridine)2 (X = halide) complexes, 2″ represents the first crystallographically confirmed example of a SiX4(pyridine)2 complex in this conformation. Conformers 2′ and 2″ were studied with 13C and 29Si solid state NMR spectroscopy. Their differences in 29Si chemical shift anisotropy, as well as energetic differences, were further investigated with computational analyses. In spite of the similar stabilities of the two conformers as isolated molecules, the crystal packing of 2″ is less stable, and its crystallization is interpreted as a kinetically controlled effect of seed formation. (3+2)-cycloaddition of 1 and phenylacetylene in toluene at 110 °C yields a mixture of 1-(4-pyridyl)-4-phenyl-1,2,3-triazole (1,4-3) and 1-(4-pyridyl)-5-phenyl-1,2,3-triazole (1,5-3) in approximate 1:2 molar ratio. The crystal structures of the two isomers were determined via X-ray diffraction. In chloroform (at 60 °C), this reaction is slow (less than 2% conversion within 4 h), but the presence of SiCl4 enhanced the rate of the reaction slightly, and it shifted the triazole isomer ratio to ca. 1:6 in favor of 1,5-3. [ABSTRACT FROM AUTHOR]

Nyulászi and Schleyer demonstrated that the aromaticity of 5,5-electropositive substituents cyclopentadiene is comparable to that of furan, calling it "hyperconjugative aromaticity." Considering the valuableness of the cyclopentadiene (Cp) group in organic chemistry, in this study, for the first time, the anomeric effect has been used to increase its hyperconjugative aromaticity. The anomeric effect in the tetrahydropyrans containing Cp ring in the anomeric position has been explored using B3LYP/6–311 ++ G(d,p) computational method. Hyperconjugative aromaticity of Cp in axial and equatorial conformers of tetrahydropyran has been obtained by nucleus-independent chemical shift, aromatic stabilization energy, isomerization stabilization energy, and NBO analysis. The results show that placing Cp in the axial position increases its aromaticity through anomeric effect. On the other hand, electron withdrawing groups on Cp greatly improve the anomeric effect and consequently its aromaticity. [ABSTRACT FROM AUTHOR]

The uptake of hydrogen atoms (H-atoms) at reducible metal oxide nanocrystal surfaces has implications in catalysis and energy storage. However, it is often difficult to gain insight into the physicochemical factors that dictate the thermodynamics and kinetics of H-atom transfer to the surface of these assemblies. Recently, our research group has demonstrated the formation of oxygen-atom (O-atom) defects in polyoxovanadate-alkoxide (POV-alkoxide) clusters via conversion of surface oxido moieties to aquo ligands, which can be accomplished via addition of two H-atom equivalents. Here, we present the dependence of O-atom defect formation via H-atom transfer at the surface of vanadium oxide clusters on the length of surface alkoxide ligands. Analysis of H-atom transfer reactions to low-valent POV-alkoxide clusters [V6O7(OR)12]1− (R = Me, Et, nPr, nBu) reveals that the length of primary alkoxide surface ligands does not significantly influence the thermodynamics of these processes. However, surface ligand length has a significant impact on the kinetics of these PCET reactions. Indeed, the methoxide-bridged cluster, [V6O7(OMe)12]1− reacts ∼20 times faster than the other derivatives evaluated. Interestingly, as the aliphatic linkages are increased in size from –C2H5 to –C4H9, reaction rates remain consistent, suggesting restricted access to available ligand conformers as a result of the incompatibility of the aliphatic ligands and acetonitrile may buffer further changes to the rate of reaction. [ABSTRACT FROM AUTHOR]

Five stable tautomer and rotamers of the 2-(2-Mercaptophenyl)-1-azaazulene (thiol, thione, R1, R2, and R3) molecules were studied using density functional theory (DFT). The geometries of the studied tautomer and rotamers were fully optimized at the B3LYP/6-31G(d,p) level. Thermodynamic calculations were performed at M06-2X/6-311G++(2d,2p) and ωB97XD/6-311G++(2d,2p) in the gas phase and ethanol solution conditions modeled by the solvation model based on density (SMD). The kinetic constant of tautomer and rotamers conversion was calculated in the temperature range 270–320 K using variational transition state theory (VTST) accompanied by one-dimensional wigner tunneling correction. Energy refinement at CCSD(T)/6–311++G(2d,2p) in the gas phase has been calculated. All the studied DFT methods qualitatively give similar tautomer stability orders in the gas phase. The ethanol solvent causes some reordering of the relative stability of 2-(2-Mercaptophenyl)-1-azaazulene conformers. The transition states for the 2-(2-Mercaptophenyl)-1-azaazulene tautomerization and rotamerization processes were also determined. The reactivity, electric dipole moment, and spectroscopic properties of the studied tautomer and rotamers were computed. The hyper-Rayleigh scattering (βHRS), and depolarization ratio (DR) exhibited promising optical properties when nonlinear optical properties were calculated. [ABSTRACT FROM AUTHOR]

The crystal structure determination of metal complexes of curcuminoids is a relevant topic to assess their unequivocal molecular structure. We report herein the first two X-ray crystal structures of homoleptic metal complexes of a curcuminoid, namely Dimethoxycurcumin (DiMeOC), with gallium and indium. Such successful achievement can be attributed to the suppression of interactions from the phenolic groups, which favor an appropriate molecular setup, rendering Dimethoxycurcumin gallium ((DiMeOC)2-Ga) and Dimethoxycurcumin indium ((DiMeOC)3-In) crystals. Surprisingly, the conformation of ligands in the crystal structures shows differences in each metal complex. Thus, the ligands in the (DiMeOC)2-Ga complex show two different conformers in the two molecules of the asymmetric unit. However, the ligands in the (DiMeOC)3-In complex exhibit three different conformations within the same molecule of the asymmetric unit, constituting the first such case described for an ML3 complex. The cytotoxic activity of the (DiMeOC)2-Ga complex is 4-fold higher than cisplatin against the K562 cell line and has comparable activity towards U251 and PC-3 cell lines. Interestingly, this complex exhibit three times lesser toxicity than cisplatin and even slightly lesser cytotoxicity than curcumin itself. [ABSTRACT FROM AUTHOR]

Context: Bilirubin is an important molecule, used as a marker of some liver diseases, and it can also be toxic and cause jaundice, especially in newborns. The main treatment for neonatal jaundice is phototherapy with blue light, which is still widely studied because the photophysical processes involved are not fully understood. Methods: Calculations based on the density functional theory (DFT) at M062X/6-31G(d,p) level were performed in order to evaluate the structural, electronic, and topological properties of bilirubin isomers. It was found that the ZZ conformation can form a greater number of hydrogen bonds, which gives the isomer greater energy stabilization compared to the other ZE, EZ, and EE isomers, and that the EE isomer is the conformer with the lowest energy of stabilization. The hydrogen bonds were characterized by the quantum theory of atoms in molecules (QTAIM) and for the ZZ isomer four hydrogen bonds (HBs) were found classified as intermediate, ∇2ρ(r) > 0, H(r) > 0. The ZE, EZ, and EE isomers show weak HBs, ∇2ρ(r) > 0, H(r) > 0. [ABSTRACT FROM AUTHOR]

Boronic acids and their conjugate esters have been employed in a variety of biomedical applications. This work reports structural, bonding, and thermochemical calculations for the boronic acids, RB(OH)2 (R = H, methyl, phenyl, and ortho-methyl-phenyl) and the corresponding ethylene glycol diesters, RB(−OCH2CH2O−), in the presence of explicit NH3 and/or H2O molecules. Calculations were performed in vacuo and in polarizable continuum model (PCM) aqueous media using density functional theory (DFT) and second-order Moller-Plesset perturbation theory (MP2) with the Dunning-Woon aug-cc-pVTZ basis set. These results quantify the relative stability of N→B dative-bonded, water-inserted Owater→B (Ow→B) dative-bonded, Zwitterionic, and hydrogen-bonded conformers on the model RB(OH)2⋅NH3⋅H2O and RB(−OCH2CH2O−)⋅NH3⋅H2O potential energy surfaces (PESs). In the PCM aqueous media model, conformers containing an H3N→B dative bond and a water molecule bridging the NH3 and acid/ester moieties were found consistently to be lower in energy than arrangements with either a H3N⋯H(H)Ow→B linkage or Zwitterionic forms, [H4N]+[HOw−BR(OH)2]− or [H4N]+[HOw−BR(−OCH2CH2O−)]−. For the acids, however, conformers with a H3N⋯HOwH moiety hydrogen bonded to the boronate hydroxyl group(s) proved to be lowest in energy. [ABSTRACT FROM AUTHOR]

Chirality transfer from the chiral molecule (R)‐1,2‐propylene oxide to the achiral anion of the 1‐ethyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquid is observed. The chiral probe selectively affects one part of the binary ionic liquid, i. e., it has previously been shown experimentally and theoretically that this particular imidazolium cation can be affected by chirality transfer, but in the present system chirality is almost exclusively transferred to the anion and not to both parts of the solvent (anion and cation). This observation is of high relevance because of its selectivity and because anion effects are usually much more important in ionic liquid research than cation effects. From ab initio molecular dynamics simulations, a conformational analysis and dissected vibrational circular dichroism spectra are obtained to study the chirality transfer. While in the neat ionic liquid two mirror imaged trans conformers of the anion occur almost equally, we observe an excess of one of these conformers in the presence of the chiral solute, causing optical activity of the anion. Although the cis conformers are not tremendously affected by the chirality transfer, they gain in total population when (R)‐1,2‐propylene oxide is dissolved in the ionic liquid. [ABSTRACT FROM AUTHOR]

Small peptides in solution adopt a specific morphology as they function. It is of fundamental interest to examine the structural properties of these small biomolecules in solution and observe how they transition from one conformation to another and form functional structures. In this study, we have examined the structural properties of a simple dipeptide and a five-residue peptide with the application of far-UV circular dichroism (CD) spectroscopy as a function of temperature, fluorescence anisotropy, and all-atom molecular dynamics simulation. Analysis of the temperature dependent CD spectra shows that the simplest dipeptide N-acetyl-tryptophan-amide (NATA) adopts helical, beta sheet, and random coil conformations. At room temperature, NATA is found to have 5% alpha-helical, 37% beta sheet, and 58% random coil conformations. To our knowledge, this type of structural content in a simplest dipeptide has not been observed earlier. The pentapeptide (WK5) is found to have four major secondary structural elements with 8% 310 helix, 14% poly-L-proline II, 8% beta sheet, and 14% turns. A 56% unordered structural population is also present for WK5. The presence of a significant population of 310 helix in a simple pentapeptide is rarely observed. Fluorescence anisotropy decay (FAD) measurements yielded reorientation times of 45 ps for NATA and 120 ps for WK5. The fluorescence anisotropy decay measurements reveal the size differences between the two peptides, NATA and WK5, with possible contributions from differences in shape, interactions with the environment, and conformational dynamics. All-atom molecular dynamics simulations were used to model the structures and motions of these two systems in solution. The predicted structures sampled by both peptides qualitatively agree with the experimental findings. Kinetic modeling with optimal dimensionality reduction suggests that the slowest dynamic processes in the dipeptide involve sidechain transitions occurring on a 1 ns timescale. The kinetics in the pentapeptide monitors the formation of a distorted helical structure from an extended conformation on a timescale of 10 ns. Modeling of the fluorescence anisotropy decay is found to be in good agreement with the measured data and correlates with the main contributions of the measured reorientation times to individual conformers, which we define as dynamic elements. In NATA, the FAD can be well represented as a sum of contributions from representative conformers. This is not the case in WK5, where our analysis suggests the existence of coupling between conformational dynamics and global tumbling. The current study involving detailed experimental measurements and atomically detailed modeling reveals the existence of specific secondary structural elements and novel dynamical features even in the simplest peptide systems. [ABSTRACT FROM AUTHOR]

We present a comprehensive host‐guest study of four substituted and unsubstituted [10]cycloparaphenylenes with the fullerenes C60 and C70. Within this study, the influence on the complexation behavior was investigated experimentally and computationally. Due to the increased steric demand the substitution on the nanohoop results in an energetic penalty, which could be partially compensated by additional substituent‐fullerene interactions. These attractive interactions are intensified in the C70 complexes and with an increased degree of substitution. For the computational investigation conformer ensembles were taken into account, providing reliable structures with Boltzmann weighted energies. An analysis of the noncovalent interactions elucidated the origin of the enhanced substituent‐C70 interaction. The ellipsoid fullerene C70 can be considered as a π‐extended version of C60, which is able to increase the attractive van der Waals interactions within these supramolecular complexes. [ABSTRACT FROM AUTHOR]

Non-membrane-bound biomolecular condensates have been proposed to represent an important mode of subcellular organization in diverse biological settings. However, the fundamental principles governing the spatial organization and dynamics of condensates at the atomistic level remain unclear. The Saccharomyces cerevisiae Lge1 protein is required for histone H2B ubiquitination and its N-terminal intrinsically disordered fragment (Lge11-80) undergoes robust phase separation. This study connects single- and multi-chain all-atom molecular dynamics simulations of Lge11-80 with the in vitro behavior of Lge11-80 condensates. Analysis of modeled protein-protein interactions elucidates the key determinants of Lge11-80 condensate formation and links configurational entropy, valency, and compactness of proteins inside the condensates. A newly derived analytical formalism, related to colloid fractal cluster formation, describes condensate architecture across length scales as a function of protein valency and compactness. In particular, the formalism provides an atomistically resolved model of Lge11-80 condensates on the scale of hundreds of nanometers starting from individual protein conformers captured in simulations. The simulation-derived fractal dimensions of condensates of Lge11-80 and its mutants agree with their in vitro morphologies. The presented framework enables a multiscale description of biomolecular condensates and embeds their study in a wider context of colloid self-organization. [ABSTRACT FROM AUTHOR]

Oxalyl diisothiocyanate, ((CO)NCS)2, has been studied in solid argon matrices at 4.2 K with the aid of infrared (IR) spectroscopy. The spectra show mainly signals attributed to the most stable anti‐anti conformer, which is corroborated by comparison to computed anharmonic fundamental IR transitions. Upon irradiation with 254 nm UV light, oxalyl diisothiocyanate eliminates carbon monoxide under formation of carbonyl diisothiocyanate, CO(NCS)2. This reaction is only slightly exothermic by 0.4 kcal mol−1 at the DLPNO‐CCSD(T)/def2‐QZVPP//B3LYP‐D3/def2‐TZVPP level of theory. Remarkably, photolysis produces mostly the less stable syn‐anti conformer of carbonyl diisothiocyanate. Subsequent annealing at 30 K for two minutes results in a structural relaxation to the 0.7 kcal mol−1 more stable syn‐syn conformer confirming a low torsional barrier height between the isomers. [ABSTRACT FROM AUTHOR]

Azapeptides have gained much attention due to their ability to enhance the stability and bioavailability of peptide drugs. Their structural preferences, essential to understanding their function and potential application in the peptide drug design, remain largely unknown. In this work, we systematically investigated the conformational preferences of three azaamino acid residues in tripeptide models, Ac-azaXaa-Pro-NHMe [Xaa = Asn (4), Asp (5), Ala (6)], using the popular DFT functionals, B3LYP and B3LYP-D3. A solvation model density (SMD) was used to mimic the solvation effect on the conformational behaviors of azapeptides in water. During the calculation, we considered the impact of the amide bond in the azapeptide models on the conformational preferences of models 4–6. We analyzed the effect of the HB between the side-chain main chain and main-chain main-chain on the conformational behaviors of azapeptides 4–6. We found that the predicted lowest energy conformation for the three models differs depending on the calculation methods. In the gas phase, B3LYP functional indicates that the conformers tttANP-1 and tttADP-1 of azapeptides 4 and 5 correspond to the type I of β-turn, the lowest energy conformation with all-trans amide bonds. Considering the dispersion correction, B3LYP-D3 functional predicts the conformers tctANP-2 and tctADP-3 of azapeptide 4 and 5, which contain the cis amide bond preceding the Pro residue, as the lowest energy conformation in the gas phase. The results imply that azaAsx and Pro residues may involve cis-trans isomerization in the gas phase. In water, the predicted lowest energy conformer of azapeptides 4 and 5 differs from the gas phase results and depends on the calculational method. For azapeptide 6, regardless of calculation methods and phases, tttAAP-1 (β-I turn) is predicted as the lowest energy conformer. The results imply that the effect of the side chain that can form HBs on the conformational preferences of azapeptides 4 and 5 may not be negligible. We compared the theoretical results of azaXaa-Pro models with those of Pro-azaXaa models, showing that incorporating azaamino acid residue in peptides at different positions can significantly impact the folding patterns and stability of azapeptides. [ABSTRACT FROM AUTHOR]

Isoprene is the most abundant nonmethane volatile organic compound emitted into the troposphere by terrestrial vegetation. Reaction with ozone represents an important isoprene removal process from the troposphere and is a well‐known source of Criegee intermediates (CIs), which are reactive carbonyl oxides. Three CIs, formaldehyde oxide (CH2OO), methyl vinyl ketone oxide (MVK‐oxide) and methacrolein oxide (MACR‐oxide) are formed during isoprene ozonolysis. All three CIs contain strongly absorbing ππ* states, electronic excitation, which leads to dissociation to form aldehyde/ketone + oxygen products. Here, we compare the excited state chemistry of CH2OO, MVK‐oxide and MACR‐oxide in order to ascertain how increasing molecular complexity affects their photodynamics. In CH2OO, vertical excitation to the S2 state leads to prompt O‐O bond fission with a unity quantum yield. Branching into both the O (1D) + H2CO (S0) and O (3P) + H2CO (T1) product channels is predicted, with 80% of trajectories dissociating to form the former product pair. Analogous vertical excitation of the lowest energy conformers of MVK‐oxide and MACR‐oxide also undergoes O‐O bond fission to form O + MVK/MACR products—albeit with a nonunity quantum yield. In the latter case, ca. 10% and 25% of trajectories remain as the parent MVK‐oxide and MACR‐oxide molecules, respectively. Additionally, at most only 5% of the dissociating trajectories form O (3P) + MVK/MACR (T1) products, with a greater fraction forming O (1D) + MVK/MACR (S0) products (cf. CH2OO). This latter observation coupled with the greater fraction of undissociated trajectories aligns with the bathochromic shift in the electronic absorption of the MACR‐oxide and MVK‐oxide (cf. CH2OO). We discuss the implications of the results in a broader context, including those that are relevant to the atmosphere. [ABSTRACT FROM AUTHOR]

The diagonal components and the trace of two tensors which account for chiroptical response of the leucoindigo molecule C16H12N2O2 that is, static anapole magnetizability, and dynamic electric dipole‐magnetic dipole polarisability depending on the frequency of impinging light, are a function of the ϕ dihedral angle of torsion about the central CC bond, assumed to lie in the y direction of the coordinate system. They vanish for symmetry reasons at ϕ=0∘ and ϕ=180∘, corresponding respectively to C2v and C2h point group symmetries, that is, cis and trans conformers characterized by the presence of molecular symmetry planes. Nonetheless, diagonal components and average value of static anapole polarizability and optical rotation tensors vanish at ϕ=90∘, where leucondigo is unquestionably chiral from the geometrical viewpoint. Vanishing values of the average chiroptical properties have been observed also in the proximity of other ϕ angles. Attempts have been made to explain the occurrence of accidental zeros of chiroptical properties in terms of transition frequencies and scalar products appearing in the numerator of their quantum mechanical definitions. Within the electric dipole approximation, the presence of anomalous vanishing values of tensor components of anapole magnetizability and electric‐magnetic dipole polarizability is ascribed to physical achirality, arising from the lack of either toroidal or spiral electron flow along the x, y and z directions. [ABSTRACT FROM AUTHOR]

The effect of halogen bonding interactions on polymorphism in Cu(2I5YP)2X2 has been investigated, where 2I5YP = 2-iodo-5-halopyridine, Y = Br or Cl and X = Cl or Br; these complexes are abbreviated as 2I5Y-X. Two conformers are possible for 2I5Y-X complexes: the syn-conformer where the two iodine atoms are located on the same side of the coordination sphere and the anti-conformer where the iodine atoms are located on the opposite side of the coordination sphere. The anti-conformers are more stable than the corresponding syn-conformer by 4.0 kJ mol−1 in 2I5Y-Br, whereas, in 2I5Y-Cl the syn- and anti- have almost the same stability (energy difference = 0.45 kJ mol−1). In 2I5Br-Cl, crystals of the syn- and anti-conformers were characterized using single crystal X-ray diffraction. However, only the anti-conformer of 2I5Br-Br was produced. The syn-conformer crystallizes in the monoclinic space group C2/c. Two packing polymorphs of anti-2I5Cl-Cl were characterized; they crystallized in the P1¯ and P21/n space groups. On the molecular level, the syn-conformer is stabilized by C6–H⋯X hydrogen bonding interactions and the anti-conformer is stabilized by I2⋯Cu interactions. On the supramolecular level, the C–I⋯Cl and C–Y⋯Cl interactions are stronger in the C2/c phase than the corresponding interactions in the P21/n phase as indicated by Y⋯Cl and I⋯Cl distances. The possibility of crystallizing the syn-conformer depends on the nature of the halogens atoms in the complex; the lighter the halogen on position two of the pyridine ring and the heavier the halogen on position five of the pyridine ring, the higher the possibility of crystallizing the syn-conformer. syn-Conformers are not observed in 2I5Y-Br complexes. These conclusions were supported by density functional theory calculations and analyzing the electron density using quantum theory of atoms in molecules (QTAIM). Both conformers of 2I5Br-Cl and 2I5I-Cl complexes show antiferromagnetic interactions; the data were fit to a 1D-uniform AFM chain model. The interactions are stronger in the syn-conformer than the corresponding anti-conformer as indicated by J/kB values, which are −3.77(8) K, −1.88(6) K, −1.75(6) K and −1.5(4) K for syn-2I5Br-Cl, anti-2I5Br-Cl, syn-2I5I-Cl and anti-2I5I-Cl, respectively. [ABSTRACT FROM AUTHOR]

Context: Hydrogen bonds (HB) influence the conformational preferences of biomolecules and their optical and electronic properties. The directional interaction of molecules of water can be a prototype to understand the effects of HBs on biomolecules. Among the neurotransmitters (NT), L-aspartic acid (ASP) stands out due to its importance in health and as a precursor of several biomolecules. As it presents different functional groups and readily forms inter- and intramolecular HBs, ASP can be considered a prototype for understanding the behavior of NTs when interacting by HB with other substances. Although several theoretical studies have been performed in the past on isolated ASP and its formed complexes with water, both in gas and liquid phases, using DFT and TD-DFT formalisms, these works did not perform large basis set calculations or study electronic transitions of ASP-water complexes. We investigated the HB interactions in complexes of ASP and water molecules. The results show that the interactions between the carboxylic groups of ASP with water molecules, forming cyclic structures with two HBs, lead to more stable and less polar complexes than other conformers formed between water and the NH2 group. It was observed that there is a relationship between the deviation in the UV–Vis absorption band of the ASP and the interactions of water with the HOMO and LUMO orbitals with the stabilization/destabilization of the S1 state to the S0 of the complexes. However, in some cases, such as 1:1 complex ASP-W2, this analysis may be inaccurate due to small changes in ΔE. Methods: We studied the landscapes of the ground state surface of different conformers of isolated L-ASP and the L-ASP-(H2O)n complexes (n = 1 and 2) using the DFT formalism, with the B3LYP functional, and six different basis sets: 6–31 + + G(d,p), 6–311 + + G(d,p), D95 + + (d,p), D95V + + (d,p), cc-pVDZ, and, cc-pVTZ basis sets. The cc-pVTZ basis set provides the minimum energy of all conformers, and therefore, we performed the analysis with this basis set. We evaluated the stabilization of the ASP and complexes using the minimum ground state energy, corrected by the zero point energy and the interaction energy between the ASP and the water molecules. We also calculated the vertical electronic transitions S1 ← S0, and their properties using the TD-DFT formalism at B3LYP/cc-pVTZ level with the optimized geometries for S0 state with the same basis set. For the analysis of the vertical transitions of isolated ASP and the ASP-(H2O)n complexes, we calculated the electrostatic energy in the S0 and S1 states. We performed the calculations with the Gaussian 09 software package. We used the VMD software package to visualize the geometries and shapes of the molecule and complexes. [ABSTRACT FROM AUTHOR]

Context: Viscosity and viscosity index are the crucial properties of lubricant base stocks. Molecular dynamics simulation and quantum calculation were used to simulate the five isomers of C26H54 to study the intrinsic relationship between viscosity, viscosity index, and the molecular structure of isoalkanes. The results showed that the intermolecular interaction energy and the volume of rigid-like groups were the intrinsic factors that affected the viscosity and which could describe the viscosity quantitatively. The molecule conformation was studied by calculating the rotational energy barrier of the dihedral angle in the isoalkane molecule, and combined with molecular dynamics, the effect of temperature on the molecular conformation at 313 K and 373 K was further investigated. The α, β, and γ carbon atoms adjacent to the tertiary carbon in the isoalkane molecule were difficult to rotate due to steric hindrance and could be regarded as rigid-like groups at 313 K. The tertiary carbon and the three adjacent carbon atoms formed a regular tetrahedral rigid-like group at 373 K. The changes in the intermolecular interaction energy and the volume of the rigid-like group with temperatures could better describe the viscosity index and reveal the fundamental reasons that affect the viscosity and the viscosity index. The molecular-level understanding of the relationship between the molecular structure and properties of isoalkanes provided theoretical support and scientific guidance for designing isoalkane molecules with specific properties. Methods: Molecular dynamics simulation and quantum calculation were performed using Material Studio 8.0 software. The Amorphous Cell module was used to create an amorphous cell. The Foricite module was used for molecular dynamics simulation; the forcefield was assigned as COMPASS II. Nose–Hoover thermostat and Berendsen barostat were applied to maintain the temperature and pressure, respectively. To describe the non-bond interactions, the Ewald method was applied to calculate the van der Waals and electrostatic interactions. The Conformers module was used to study the conformation and the Dmol3 module was used to calculate the conformational energy with fine quality; the functional of GGA-PW91 and the basis set of DNP were used to calculate the energy. [ABSTRACT FROM AUTHOR]

The structure and interactions of oxygenated aromatic molecules are of atmospheric interest due to their toxicity and as precursors of aerosols. Here, we present the analysis of 4-methyl-2-nitrophenol (4MNP) using chirped pulse and Fabry–Pérot Fourier transform microwave spectroscopy in combination with quantum chemical calculations. The rotational, centrifugal distortion, and 14N nuclear quadrupole coupling constants of the lowest-energy conformer of 4MNP were determined as well as the barrier to methyl internal rotation. The latter has a value of 106.4456(8) cm−1, significantly larger than those from related molecules with only one hydroxyl or nitro substituent in the same para or meta positions, respectively, as 4MNP. Our results serve as a basis to understand the interactions of 4MNP with atmospheric molecules and the influence of the electronic environment on methyl internal rotation barrier heights. [ABSTRACT FROM AUTHOR]

Free energy profiles along the reaction coordinate were analyzed for several model systems by modeling elementary processes of the catalytic cycle of enzymes. A substantial contribution of fast non-limiting steps, which are conformational changes/adjustments, and proton transfer steps to the implementation of the catalytic cycle and high rates of enzymatic reactions is shown. The rate constants of conformational changes and proton transfer steps were determined from an analysis of the free energy profiles. In most cases, the lifetimes of the conformers lie in a range of 10−10 s. A distinctive feature of enzymatic catalysis is the multistep character of the reactions, while the catalytic cycle is accomplished in the conformationally flexible polymer matrix with the conformational adjustment of the active site of the enzyme. [ABSTRACT FROM AUTHOR]

The rotational spectrum of 2-thiophenecarboxaldehyde was investigated by using supersonic jet Fourier transform microwave spectroscopy. The measurements were extended to the 34S, 33S, 13C, and 18O isotopologs for the cis conformer, as well as to the 34S and 13C isotopologs for the trans conformer, leading to an accurately structural determination of the two observed conformers. The unchanged experimental Pcc values upon isotopic substitution indicate effective planar geometries of the two conformers. The ring structures of thiophene are slightly different between the cis and trans conformers. Two isomers of the monohydrated complex of 2-thiophenecarboxaldehyde, formed between a cis or trans monomer with water stabilized by an O—H⋯O hydrogen bond (HB) and an additional (C=O)CH⋯O(H2O) or (Cring)CH⋯O(H2O) HB, respectively, were observed in jet expansion. The noncovalent interactions attributed to the stabilization of the monomer and the monohydrated complex are revealed by quantum chemical methods. The interaction energy for trans-w-1 is 4 kJ mol−1 larger than that of cis-w-1, attributed to the relative stronger CH⋯O HB. The relative abundance of the two conformers of the 2-thiophenecarboxaldehyde monomer and the two isomers of the complex was estimated in the jet. [ABSTRACT FROM AUTHOR]

The interest in investigating the structure and reactivity of halogen- and methoxy-substituted benzaldehydes has been motivated by the practical relevance of these substances in various fields, from the fragrance industry to agrochemicals and drug manufacturing. In this study, 3-chloro-4-methoxybenzaldehyde (3CMBA) was investigated by matrix isolation infrared spectroscopy and quantum chemistry calculations. Molecules of the compound were isolated in cryogenic argon and xenon matrices and the conformational composition of the as-deposited materials characterized by infrared spectroscopy. Two nearly degenerated conformers, differing by the orientation of the aldehyde group relatively to the chlorine ring substituent, were successfully trapped into the matrices from the room temperature vapor of the compound, the cis conformer being slightly higher in energy than the trans form. Both conformers belong to the Cs point group and have the methoxy group pointing to the opposite direction of the chlorine atom. The as-deposited matrices of 3CMBA were then irradiated by tunable monochromatic UV-light. Irradiation within the 302–299 nm range induced conversion of the cis into the trans conformer, while irradiation in the 298–296 nm range induced the inverse photoisomerization. Irradiation at higher energy (250 nm) was found to lead to decarbonylation of both conformers. Very interestingly, the observed UV-induced processes were found to take place in an essentially selective way as a function of the irradiation wavelength. In particular, the conformational isomerization reactions of 3CMBA occur with only a residual number of molecules undergoing simultaneous decarbonylation. [ABSTRACT FROM AUTHOR]

We present detailed ab initio scattering calculations using the R-matrix method for electron collisions with the most stable conformer of α-alanine. The shape resonances that we identify are in good agreement with earlier calculations and experiments. Core-excited and mixed-character resonances are identified and characterized computationally for the first time. Dissociative electron attachment results are discussed in relation to the resonances identified. [ABSTRACT FROM AUTHOR]

We have studied the potential energy surface of [ M 2 D A B C O ] 4 + cations (M = Zn, Cd, and Hg), which are considered as a model for the DABCO linker in metal-organic frameworks, a new prospective class of materials. Relativistic four-component and two-component calculations of parity violating energy difference (PVED) for twisted isomers of [ M 2 D A B C O ] 4 + cations have been performed. The right-twisted conformers of [ M 2 D A B C O ] 4 + are more stable than the left-twisted ones. The increase in PVED with the nuclear charge of the transition metal atom M (ZM) is discussed. [ABSTRACT FROM AUTHOR]

6-Bromopyridine-2-carbaldehyde (abbreviated as BPCA) is used both as a building block in supramolecular chemistry and as a ligand for transition metal catalysts and luminescent complexes. In this study, the structure and vibrational spectra of BPCA were investigated in both the room temperature neat crystalline phase and for the compound isolated in cryogenic Ar, Kr and Xe matrices. The experimental studies were complemented by quantum chemical DFT(B3LYP)/6-311++G(d,p) calculations. For the crystalline compound, infrared and Raman spectra were obtained and interpreted. Comparison of the obtained infrared spectrum of the crystal with those obtained for the isolated molecules of BPCA in the studied cryomatrices helped to conclude that the intermolecular interactions in the crystal do not significantly perturb the intramolecular vibrational potential. Structural analysis further supports the existence of weak coupling between the intermolecular interactions and the structure of the constituting molecular units in crystalline state. The intermolecular interactions in the BPCA crystal were also evaluated by means of Hirshfeld analysis, which revealed that the most important interactions are weak and of the H...N, H...O, H...H, H...Br and Br...Br types. The conformer of BPCA present in the crystal was found to correspond to the most stable form of the isolated molecule (trans), which bears stabilizing C–H...O=C and C(=O)H...N interactions. This conformer was shown to be the single conformer present in the as-deposited cryogenic matrices prepared from the room temperature gaseous compound. Broadband UV irradiation of matrix-isolated BPCA (λ ≥ 235 nm) resulted in the conversion of the trans conformer into the higher-energy cis conformer, where repulsive C–H...H–C(=O) and C=OLP...LPN (where LP designates a lone electron pair) interactions are present, and decarbonylation of the compound with formation of 2-bromopyridine (plus CO). The decarbonylation reaction was found to be more efficient in the more polarizable Xe matrix, indicating stabilization of the radicals initially formed upon breaking of the C–C(HO) and C–H (aldehyde) bonds in this medium, and testifying the occurrence of the decarbonylation reaction with involvement of radical species. TD-DFT calculations were used to access the nature of the excited states associated with the observed UV-induced reactions. As a whole, this study provides fundamental data to understand the physicochemical behavior of the compound, bridging the properties of the isolated molecule to those of the neat crystalline com-pound. Such information is of fundamental importance for the understanding of the role of BPCA in supramolecular chemistry and to potentiate its applications in synthesis and as a ligand for transition metal catalysts and luminescent complexes. [ABSTRACT FROM AUTHOR]

Glycerol is a symmetrical, small biomolecule with high flexibility in molecular conformations. Using a 1H-NMR spectroscopic Karplus analysis in our way, we analyzed a rotational isomerism in the glycero backbone which generates three kinds of staggered conformers, namely gt (gauche-trans), gg (gauche-gauche), and tg (trans-gauche), at each of sn-1,2 and sn-2,3 positions. The Karplus analysis has disclosed that the three rotamers are consistently equilibrated in water keeping the relation of 'gt:gg:tg = 50:30:20 (%)' at a wide range of concentrations (5 mM~540 mM). The observed relation means that glycerol in water favors those symmetric conformers placing 1,2,3-triol groups in a gauche/gauche geometry. We have found also that the rotational isomerism is remarkably changed when the solvent is replaced with DMSO-d6 or dimethylformamide (DMF-d7). In these solvents, glycerol gives a relation of 'gt:gg:tg = 40:30:30 (%)', which means that a remarkable shift occurs in the equilibrium between gt and tg conformers. By this shift, glycerol turns to also take non-symmetric conformers orienting one of the two vicinal diols in an antiperiplanar geometry. [ABSTRACT FROM AUTHOR]

Staggered decamethyl-ferrocene (*Fc) becomes the lower energy conformer at low temperature, whereas the eclipsed conformer of ferrocene (Fc) is more stable. The powerful infrared (IR) spectroscopy which has remarkably provided signatures of ferrocene (Fc) in eclipsed and staggered conformers recently is employed to investigate methylation of Fc. The most significant consequences of the full methylation of Fc in the IR spectra are the blue shift of the band at ~ 800 cm−1 in Fc to ~ 1500 cm−1 in *Fc, and the enhancement of the C–H stretch band at ~ 3200 cm−1 region in *Fc. Further analysis reveals large impact of Fc methylation on core electron energies of the centre Fe atom (1s22s22p63s23p6). The Fe core electron energy changes can be as large as ~ 10 kcal mol−1 and are directional—the Fe 2pz and 3pz orbitals along the *Cp–Fe–*Cp axis (Cp centroids, vertical) change more strongly than other Fe core electrons in px and py orbitals. The directional inner shell energy changes are evidenced by larger inner shell reorganization energy. Energy decomposition analysis (EDA) indicates that methyl groups in *Fc apparently change the physical energy components with respect to Fc. The large steric energy of *Fc evidences that the closest hydrogens on adjacent methyl groups of the same *Cp ring in crystal structure are 0.2–0.4 Å closer than the hydrogens on nearest-neighbour methyl groups on opposing rings in *Fc. A significant increase in Pauli repulsive energy contributes to the large repulsive steric energy in *Fc. [ABSTRACT FROM AUTHOR]

Different molecular balances were designed previously to compare noncovalent interactions. However, some balances are difficult to synthesise and there is a need for developing a computational approach. In this work, we probe noncovalent interactions of π systems using DFT methods to assess their reliability in reproducing experimentally measured conformer populations. Based on our results, the PW6B95D3 functional performed best, followed by M11L and ωB97XD. Additionally, the simulation of the rotation of the hydroxyl group revealed stabilising OH⋯Alkyne and OH⋯Nitrile interactions that are difficult to identify experimentally. These methods were then applied to compare the strengths of sulfur⋯π interactions in molecules which have not been explored experimentally. Compared to the hydroxyl counterpart, the simulation of the thiol group rotation showed that the geometry of the conformer with the two sulfur lone pairs oriented towards the aromatic ring or the double bond is stabilised, suggesting that S(LP)⋯π interactions can be attractive in nature. The ability of sulfur to rearrange its electronic surrounding to form an attractive interaction with π systems, including those with either electron‐donating or withdrawing groups, was also confirmed. Overall, the results show a promising future for both qualitative and quantitative assessments of the strengths of noncovalent interactions using selected DFT techniques. [ABSTRACT FROM AUTHOR]

Evaluation of DFT calculated vibrational parameters for the IR and VCD spectra similarity of perezone (1) and dihydroperezone (2) was undertaken. Conformational sets were obtained using different search engines, and the parameters needed for spectra prediction were obtained using several combinations of commonly employed functionals and basis sets, and then weighted spectra were generated and compared with observed traces to provide infrared similarity (SIR) and enantiomeric similarity index (ESI) values. These values evidenced a poor performance of the evaluated levels of theory that were overcome when using the individual scaling factors approach, providing 16% to 139% increases of the ESI values. The best performing level of theory was the B3LYP/DGDZVP2 with ESI values of 0.722 and 0.792 for 1 and 2. Moreover, a correlation analysis showed that the irregular DFT performance arises from rotational strength deviations, which suggests to discard conformational abundance accuracy as the main source of differences. Furthermore, a similarity guided conformational analysis showed that conformations with high ESI values prefer particular orientations of the CC bonds directly attached to the stereogenic carbon atom, with more distant dihedral angles having less influence. Additionally, folded and extended conformers appear to be equally capable to yield high individual ESI values, although abundances of folded conformers just account for 16% of the total population. Nevertheless, abundance optimization showed that a high ESI similarity value of 0.834, is possible when the population of these conformers is increased to 26%, suggesting that a larger abundance of these conformers might be present in solution. [ABSTRACT FROM AUTHOR]

This research refers to the study and understanding of the conformational space of the positive-charged anthocyanidin structures in relation with the known chemical reactivities and bioactivities of these compounds. Therefore, the planar (P) and nonplanar (Z) conformers of the three hydroxylated anthocyanidins pelargonidin, cyanidin, and delphinidin were analyzed throughout the conformational space at the B3LYP/6–311 ++ G** level of theory. The outcome displayed eleven new conformers for pelargonidin, fifty-four for cyanidin, and thirty-one for delphinidin. Positive-charged quinoidal structures showed a significant statistical weight in the conformational space, thus coexisting simultaneously with other resonance structures, such that under certain reaction conditions, the anthocyanidins behave as positive-charged quinoidal structures instead of oxonium salts. The calculations of the permanent dipole moment and the polarizability showed relationships with the quantity and arrangement of hydroxyls in the structure. In addition, theoretical calculations were used to analyze the frontier molecular orbitals (HOMO–LUMO) of the three anthocyanidins. The novel conception of this work lies in the fact that dipole moment, polarizability, and HOMO–LUMO values were related to the reactivity/bioactivity of these three anthocyanidins. HOMO–LUMO energy gaps were useful to explain the antioxidant activity, while the percent atom contributions to HOMO were appropriate to demonstrate the antimutagenic activity as enzyme inhibitors, as well as the steric and electrostatic requirements to form the pharmacophore. Delphinidin was the strongest antioxidant anthocyanidin, and pelargonidin the best anthocyanidin with antimutagenic activity. [ABSTRACT FROM AUTHOR]

The biomolecules conformations model's selection is a problem of continuing interest in computational drug development. This work presents an overview detail of the used method to select the conformational models of both N-E-caffeoyl and N-E-feruloyl tyramine (Ct and Ft) and their sulfured analogs, using the density functional theory calculation in the gas phase and solutions. The contribution of the antioxidant properties of the possible conformers was studied, and the diversity contributions of each model in the different controlled mechanisms were investigated. Our study includes hydrogen atom transfer (HAT), single-electron transfer–proton transfer (SET-PT), and sequential proton loss electron transfer (SPLET) mechanisms. The results revealed that the antioxidant activity of Ct models was higher than that found in Ft conformers. It must be stressed that all models selected revealed contributions in the global antioxidant activity in gas phase and solutions. Note that the importance of the semi-quinone structure stability and its contribution in the antioxidant activity of all Ct models was studied and evaluated. These results were in agreement with those obtained with the iron reduction method and not consent with DPPH method. However, the diversity contributions of each model in the different mechanisms studied controlled the antioxidant activity. In contrast, the hydrogen atom transfer mechanism is dominant in vacuum and the sequential proton loss electron transfer mechanism represents the most thermodynamically preferred reaction pathway in both methanol and water medium. On the basis of the parameters calculated, it can be concluded that all sulfured Ct and Ft investigated have an antioxidant activity higher than that of their hydroxyl analogs. These results can be used for both food and pharmaceutical industries. [ABSTRACT FROM AUTHOR]

The reaction of Criegee intermediates with water is one of the dominant removal mechanisms for these species in the atmosphere. The reactivity of alkyl substituted Criegee intermediates has been shown to be affected by the nature and location of the substituents. CCHOO, acetaldehyde oxide, can be considered as a prototypical Criegee intermediate with a single alkyl substituent to examine the conformer specific reactivity for Criegee intermediates. Pulsed Fourier-transform microwave spectroscopy has been used to probe the products resulting from the reaction between CCHOO and water. The hydrogen-bonded complex between CCHOO and water together with the reaction product, hydroxyethyl hydroperoxide, were observed in the discharged plasma of a CCHI2/O2/water gas mixture. The experimentally determined rotational parameters support the identification of the complex between water and the syn-CCHOO conformer and two conformers of hydroxyethyl hydroperoxide, produced from the anti-CCHOO conformer and water. Published by AIP Publishing. [ABSTRACT FROM AUTHOR]