The Effect of Hyperconjugation and Hydrogen Bonding on the Conformers of Methylated Monosaccharides.

The conformational landscapes of four 1-O-methylated monosaccharides-methyl a-glucose, methyl b-glucose, methyl a-galactose, and methyl b-galactose-were characterized using jet-cooled broadband rotational spectroscopy, supported by density functional theory calculations. A newly designed, simple pulsed nozzle assembly was used to introduced the sugar samples into a jet expansion without thermal degradation, eliminating the need for a complex and expensive laser ablation system. Ten conformers were experimentally identified by assigning their rotational spectra, and the intricate methyl internal rotation splittings were analysed. Notably, methylation alters the directionality of intramolecular hydrogen bonding of a-galactose highlighting its impact on structural preference. Natural bond orbital, intrinsic bond strength, and non-covalent interaction analyses were conducted to explore the interplay between hydrogen bonding and hyperconjugation. A set of σ to σ* neutral hyperconjugative interactions were found to override a strong hydrogen bond, driving a preference for the gauche conformers.

Hybrid Local and Charge Transfer Emitters Utilizing Hyperconjugation Effect Towards Solution-Processed Ultra-Deep-Blue OLEDs with External Quantum Efficiency Approaching 12.

Hybrid local and charge transfer (HLCT) excited state materials, which possess weak donor-acceptor (D-A) pure organic structures, deserve one of the most promising efficient and stable blue emitters. Through high-lying reverse intersystem crossing (hRISC) process, 75% triplet excitons generated by electrical excitation could be harvested and utilized in organic light-emitting diodes (OLEDs). However, there are still significant challenges to achieve high-efficiency ultra-deep-blue HLCT emitters with low Commission Internationale de l'Eclairage (CIE) 1931 chromaticity coordinate y values. Here, a series of novel blue HLCT emitters based on spiro[1,8-diazafluorene-9,2'-imidazole] structure were designed and synthesized by fine-tuning the spiro[fluorene-9,2'-imidazole] core structure in our previous work through heteroatom substitution and hyperconjugation effect. The target emitters were endowed with excellent photophysical and electrochemical merits, thermal stability and solution processibility. The solution-processed OLED device based on 4',5'-bis(4-(9H-carbazol-9-yl)phenyl)spiro[1,8-diazafluorene-9,2'-imidazole] (NFIP-CZ) achieved efficient ultra-deep-blue emission (CIEx,y = 0.1581, 0.0422) with the maximum external quantum efficiency (EQEmax), maximum current efficiency (CEmax) and maximum power efficiency (PEmax) of 11.94%, 4.07 cd·A-1 and 2.56 lm·W-1. The record EQE is a breakthrough in both solution-processed and vacuum vapor deposition ultra-deep-blue HLCT-OLEDs currently.

Hyperconjugation-Driven Isodesmic Reaction of Indoles and Anilines: Reaction Discovery, Mechanism Study, and Antitumor Application.

Isodesmic reactions, in which chemical bonds are redistributed between substrates and products, provide a general and powerful strategy for both biological and chemical synthesis. However, most isodesmic reactions involve either metathesis or functional-group transfer. Here, we serendipitously discovered a novel isodesmic reaction of indoles and anilines that proceeds intramolecularly under weakly acidic conditions. In this process, the five-membered ring of the indole motif is broken and a new indole motif is constructed on the aniline side, accompanied by the formation of a new aniline motif. Mechanistic studies revealed the pivotal role of σ→π* hyperconjugation on the nitrogen atom of the indole motif in driving this unusual isodesmic reaction. Furthermore, we successfully synthesized a diverse series of polycyclic indole derivatives; among quinolines, potential antitumor agents were identified using cellular and in vivo experiments, thereby demonstrating the synthetic utility of the developed methodology.

What Determines the Lewis Acidity of a Bismuthane? Towards Bi-Based FLPs.

Aiming at intramolecular frustrated Lewis pairs (FLPs) based on soft Lewis acidic bismuth centers, a phosphine function was combined with a dichloridobismuthane unit on a phenylene backbone utilizing a scrambling approach. The reaction between two equivalents of BiCl3 and (o-(Ph2P)C6H4)3Bi yielded (o-(Ph2P)C6H4)BiCl2(THF), the structure of which indicated Bi…P interactions and thus a pronounced Lewis acidity at the bismuth center that was confirmed by the Gutmann-Beckett method. However, the system turned out to be insufficient to be utilized for FLP reactivity. Hence, the chloride ligands were exchanged by iodide and C2F5 substituents, respectively. Despite a lower electronegativity the iodide compound exhibits a shorter Bi…P contact, while the C2F5 substituents led to a further decrease of the Lewis acidity, despite their high group electronegativity. DFT calculations rationalized this by a quenching of the Lewis acidity inherent to the σ*(Bi-C) orbital by negative hyperconjugation from occupied p-orbitals at the F atoms. Furthermore, it turned out that the strength of the covalent Bi-X σ-bond is a more important factor than the charge at Bi in determining the energetic accessibility and thus Lewis acidity of the antibonding σ*(Bi-C) orbital.

Hydroxyl Group as the 'Bridge' to Enhance the Single-Molecule Conductance by Hyperconjugation.

For designing single-molecule devices that have both conjugation systems and structural flexibility, a hyperconjugated molecule with a σ-π bond interaction is considered an ideal candidate. In the investigation of conductance at the single-molecule level, since few hyperconjugation systems have been involved, the strategy of building hyperconjugation systems and the mechanism of electron transport within this system remain unexplored. Based on the skipped-conjugated structure, we present a rational approach to construct a hyperconjugation molecule using a hydroxyl group, which serves as a bridge to interact with the conjugated fragments. The measurement of single-molecule conductance reveals a two-fold conductance enhancement of the hyperconjugation system having the 'bridging' hydroxyl group compared to hydroxyl-free derivatives. Theoretical studies demonstrate that the hydroxyl group in the hyperconjugation system connects the LUMO of the two conjugated fragments and opens a through-space channel for electron transport to enhance the conductance.

Theoretical and computational study of benzenium and toluenium isomers.

Four methods of computational quantum chemistry are used in a study of hyperconjugation in protonated aromatic molecules. Benzene, benzenium, toluene, and four isomeric forms of toluenium are examined using the self-consistent field level of theory followed by configuration interaction and coupled cluster calculations, as well as density functional theory. Results for proton affinities, geometric parameters, atomic populations, dipole moments, and polarizabilities are reported. The calculated results are in good agreement with previous computational studies and with experimental data. The presence of hyperconjugation is evident from the shortened carbon-carbon bond lengths in the aromatic ring and concomitant changes in dipole moments and polarizabilities. The proton affinities of benzene and toluene compare well with experimental values. The examination of all of the toluenium isomers reveals that the position of the methyl group has a minor impact on the strength of hyperconjugation, although the most stable isomer is found to be the para form. Mulliken population analyses indicate that the addition of a proton contributes to aromatic hyperconjugation and increases the strength of π-bonds at the expense of σ-bonds.

A Study of the Correlation between the Bulkiness of peri-Substituents and the Distortion of a Naphthalene Ring.

A systematic study on the distortion of a naphthalene ring was performed using steric repulsion between peri-substituents at the 1- and 8-positions. The introduction of bromo groups into the methyl groups of the 1,8-dimethylnaphthalene enhanced the steric repulsion to distort the naphthalene ring. X-ray crystallography revealed that 1,8-bis(bromomethyl)naphthalene had a vertical distortion with a 11.0° dihedral angle (α) between peri-substituents which disturbed the coplanarity of the naphthalene ring. On the other hand, the dihedral angle of 1,8-bis(dibromomethyl)naphthalene was smaller (α = 8.3°) despite the bulkier substituents. In this case, horizontal distortion of the naphthalene ring increased. These distortions should non-electronically activate the naphthalene framework. In order to evaluate their reactivity, nitration and hydrogenation were carried out; however, the 1,8-bis(dibromomethyl)naphthalene was intact under the employed conditions. A DFT calculation suggested that the inertness of the 1,8-bis(dibromomethyl)naphthalene is presumably due to the negative hyperconjugation of the (dibromo)methyl group.

3-Chloro-N,N-di-methyl-propan-1-aminium chloride.

The organic cation in the title mol-ecular salt, C5H13NCl+·Cl-, exhibits the gauche effect with a C-H bond of the C atom ß to the chloro group donating electrons to the anti-bonding orbital of the C-Cl bond to stabilize the gauche conformation [Cl-C-C-C = -68.6 (6)°], as confirmed by DFT geometry optimizations that show a lengthening of the C-Cl bond relative to that of the anti conformation. Of further inter-est is the higher point group symmetry of the crystal (), compared that of the that of the mol-ecular cation, which arises from a supra-molecular head-to-tail square arrangement of four mol-ecular cations that circulate in a counterclockwise direction when viewed down the tetra-gonal c axis.

Theoretical Study on the Origin of Abnormal Regioselectivity in Ring-Opening Reaction of Hexafluoropropylene Oxide.

That nucleophiles preferentially attack at the less sterically hindered carbon of epoxides under neutral and basic conditions has been generally accepted as a fundamental rule for predicting the regioselectivity of this type of reaction. However, this rule does not hold for perfluorinated epoxides, such as hexafluoropropylene oxide (HFPO), in which nucleophiles were found to attack at the more hindered CF3 substituted ß-C rather than the fluorine substituted α-C. In this contribution, we aim to shed light on the nature of this intriguing regioselectivity by density functional theory methods. Our calculations well reproduced the observed abnormal regioselectivities and revealed that the unusual regiochemical preference for the sterically hindered ß-C of HFPO mainly arises from the lower destabilizing distortion energy needed to reach the corresponding ring-opening transition state. The higher distortion energy required for the attack of the less sterically hindered α-C results from a significant strengthening of the C(α)-O bond by the negative hyperconjugation between the lone pair of epoxide O atom and the antibonding C-F orbital.

Rotation-Inversion Isomerization of Tertiary Carbamates: Potential Energy Surface Analysis of Multi-Paths Isomerization Using Boltzmann Statistics.

Potential energy surface (PES) analyses at the SMD[MP2/6-311++G(d,p)] level and higher-level energies up to MP4(fc,SDTQ) are reported for the fluorinated tertiary carbamate N-ethyl-N-(2,2,2-trifluoroethyl) methyl carbamate (VII) and its parent system N,N-dimethyl methyl carbamate (VI). Emphasis is placed on the analysis of the rotational barrier about the CN carbamate bond and its interplay with the hybridization of the N-lone pair (NLP). All rotational transition state (TS) structures were found by computation of 1D relaxed rotational profiles but only 2D PES scans revealed the rotation-inversion paths in a compelling fashion. We found four unique chiral minima of VII, one pair each of E- and Z-rotamers, and we determined the eight unique rotational TS structures associated with every possible E/Z-isomerization path. It is a significant finding that all TS structures feature N-pyramidalization whereas the minima essentially contain sp2 -hybridized nitrogen. We will show that the TS stabilities are affected by the synergetic interplay between NLP/CO2 repulsion minimization, NLP→σ* (CO) negative hyperconjugation, and two modes of intramolecular through-space electrostatic stabilization. We demonstrate how Boltzmann statistics must be applied to determine the predicted experimental rotational barrier based on the energetics of all eight rotamerization pathways. The computed barrier for VII is in complete agreement with the experimentally measured barrier of the very similar fluorinated carbamate N-Boc-N-(2,2,2-trifluoroethyl)-4-aminobutan-1-ol II. NMR properties of VII were calculated with a variety of density functional/basis set combinations and Boltzmann averaging over the E- and Z-rotamers at our best theoretical level results in good agreement with experimental chemical shifts δ(13 C) and J(13 C,19 F) coupling constants of II (within 6 %).

Interheteromolecular Hyperconjugation Boosts (De)hydrogenation for Reversible H2 Storage.

Interheteromolecular hyperconjugation is ubiquitous in organic systems, affecting bond length, dipole moments, conformations and so on, while its effect on (de)hydrogenation reactivity in a heterogeneous thermo-catalytic system has rarely been explored. Herein, the N-heterocycles containing a benzene ring and aliphatic chain [N-ethylcarbazole (NEC) and N-propylcarbazole (NPC)] were utilized to study the correlation between interheteromolecular hyperconjugation and catalytic (de)hydrogenation. Density functional theory calculations, variable-temperature 1 H nuclear magnetic resonance spectroscopy, and catalytic experiments showed that the presented hyperconjugation between NEC and NPC weakened the electron cloud density of aromatic rings and thus facilitated the reactivity with hydrogen featuring unpaired electrons. Therefore, an extremely low temperature of 80 °C was enough for the hydrogenation. Moreover, this interheteromolecular hyperconjugation was general in other N-heterocycles (e. g., N-methyindole and NPC) and was also effective to (de)deuterate as revealed by isotope experiments. This work expands the application of interheteromolecular hyperconjugation to heterogeneous thermocatalysis for reversible H2 storage.

Computational study on the prototropic tautomerism between simple oxo-, thio-, carbon-, aza-hydrazones, and their respective azines.

Most hydrazone compounds prefer the azine tautomeric states. However, oxygen-/sulfur-substituted compounds prefer hydrazone tautomers. In this study, density functional theory at M062X level with the basis set of 6-311 + + g(2d, 2p), with MP2/cc-pVTZ for reference, was used to investigate the different tautomeric mechanisms between hydrazone and azine forms with oxygen, sulfur, carbon, and nitrogen as negative centers. The energetic stabilities are in the order as oxygen- < sulfur- < imine- < amidino- < carbene-substituted hydrazones with respect to their azine tautomeric structures. Resonance of the molecular structures might be the geometrical basis for their energy stabilities and were estimated based on HOMED indices. Further, the increased proton affinities in the trend as hydroxyl < sulfhydryl < imine terminal groups account for their increasing azine preferences. Proton release was examined for the reversible equilibrium from azine to hydrazone by calculating the transition energy barrier of H transfer. It is favorable to form hydrazone tautomers for oxygen and sulfur containing groups, while it is less favorable for amino-substituted ones. Azine form is the most stable tautomer for methyl substituted.

Halogen Atom Participation in Guiding the Stereochemical Outcomes of Acetal Substitution Reactions.

Acetal substitution reactions of α-halogenated five- and six-membered rings can be highly stereoselective. Erosion of stereoselectivity occurs as nucleophilicity increases, which is consistent with additions to a halogen-stabilized oxocarbenium ion, not a three-membered-ring halonium ion. Computational investigations confirmed that the open-form oxocarbenium ions are the reactive intermediates involved. Kinetic studies suggest that hyperconjugative effects and through-space electrostatic interactions can both contribute to the stabilization of halogen-substituted oxocarbenium ions.

Unveiling the effect of 2D silagraphene structural diversity on electronic properties: DFT, DOS, and ELF studies.

Recently, fully π-functional two-dimensional (2D) materials have been reported for electronic device applications. Graphene is one of these 2D materials that is attributed to 2D electron confinement effects and exhibits an aromatic character; however, it is characterized by vanishing the bandgap energy. Hence, research was focused on the discovery of graphene-based 2D materials to reduce the bandgap energy. Herein, we investigate the silagraphene structures (SixCy) using DFT calculations to undertake and improve structural, physico-chemical, and electronic properties. Various types of 2D networks have been investigated by considering C-C and C-Si bonds in relative positions. Both conjugation and hyperconjugation phenomenon have been deeply examined and it seemed that they take advantage of each other depending on the C-C and C-Si bond positions. Localized orbital locator (LOL) and electron localization function (ELF) were also performed to examine the electronic densities in the investigated 2D networks and unveil the electronic properties of the studied materials.

Analysis of Conformational Preferences in Caffeine.

High level DLPNO−CCSD(T) electronic structure calculations with extended basis sets over B3LYP−D3 optimized geometries indicate that the three methyl groups in caffeine overcome steric hindrance to adopt uncommon conformations, each one placing a C−H bond on the same plane of the aromatic system, leading to the C−H bonds eclipsing one carbonyl group, one heavily delocalized C−N bond constituent of the fused double ring aromatic system, and one C−H bond from the imidazole ring. Deletion of indiscriminate and selective non-Lewis orbitals unequivocally show that hyperconjugation in the form of a bidirectional −CH3 ⇆ aromatic system charge transfer is responsible for these puzzling conformations. The structural preferences in caffeine are exclusively determined by orbital interactions, ruling out electrostatics, induction, bond critical points, and density redistribution because the steric effect, the allylic effect, the Quantum Theory of Atoms in Molecules (QTAIM), and the non-covalent interactions (NCI), all predict wrong energetic orderings. Tiny rotational barriers, not exceeding 1.3 kcal/mol suggest that at room conditions, each methyl group either acts as a free rotor or adopts fluxional behavior, thus preventing accurate determination of their conformations. In this context, our results supersede current experimental ambiguity in the assignation of methyl conformation in caffeine and, more generally, in methylated xanthines and their derivatives.

Epigenetic Modifications and Neurodegenerative Disorders: A Biochemical Perspective.

Methylations in living cells are methyl groups attached to amino acids, DNA, RNA, and so on. However, their biochemical roles have not been fully defined. A theory has been postulated that methylation leads to hyperconjugation, and the electron-donating feature weakens a nearby chemical bond, which increases the bond length of C4-N4 of 5-methylcytosine, therefore weakening the C4-N4 bond and resulting in stronger protonation or hydrogen bonding of the N4 nitrogen atom. Protonation can give rise to the generation of mutagenic and carcinogenic strong acids such as HCl, which are also capable of solubilizing stressful, insoluble, and stiff salts. Insoluble and rigid salts such as calcium oxalate and/or calcium phosphate were recently proposed as a primary cause of some neurodegenerative disorders. Protonation of nitrogen atoms in 5-methylcytosine enhances the interaction with negatively charged phosphate groups and contributes to the formation of compact heterochromatin. The electronegativity of the oxygen atoms in the modifications of 5-hydroxymethylcytosine or 5-formylcytosine can shorten the lengths of adjacent bonds with no increase of cation affinity in N4. The carboxyl group in 5-carboxylcytosine is a weak acid capable of antagonizing mutagenic HCl and modestly helping solubilize insoluble salts. Electron delocalization of the methyl group in N4-methylcytosine results in a lower affinity of N4 to cations. The positive charge at N3 in the resonance structure of 3-methylcytosine is lessened by the electron-donating attribute of the methyl group attached to the N3 atom, consequently reducing acid formation. The electron delocalization of three methyl groups decreases the positive charge in the amino nitrogen in the side group of lysine 4 in histone H3, weakening interactions with phosphate groups and consequently activating gene expression. The carbonyl oxygen in 8-oxo-7,8-dihydroguanine draws protons and accumulates HCl, accounting for its moderate mutation propensity and potential capacity to solubilize stiff salts. The biochemical insight will further our understanding on the crosstalk of genetics and epigenetics in the etiology of neurodegenerative diseases.

Molecular structure, NBO analysis of the hydrogen-bonded interactions, spectroscopic (FT-IR, FT-Raman), drug likeness and molecular docking of the novel anti COVID-2 molecule (2E)-N-methyl-2-[(4-oxo-4H-chromen-3-yl)methylidene]-hydrazinecarbothioamide (Dimer) - quantum chemical approach.

Prospective antiviral molecule (2E)-N-methyl-2-[(4-oxo-4H-chromen-3-yl)methylidene]-hydrazinecarbothioamide has been probed using Fourier transform infrared (FTIR), FT-Raman and quantum chemical computations. The geometry equilibrium and natural bond orbital analysis have been carried out with density functional theory employing Becke, 3-parameter, Lee-Yang-Parr method with the 6-311G++(d,p) basis set. The vibrational assignments pertaining to different modes of vibrations have been augmented by normal coordinate analysis, force constant and potential energy distributions. Drug likeness and oral activity have been carried out based on Lipinski's rule of five. The inhibiting potency of 2(2E)-methyl-2-[(4-oxo-4H-chromen-3-yl)methylidene]-hydrazinecarbothioamide has been investigated by docking simulation against SARS-CoV-2 protein. The optimized geometry shows a planar structure between the chromone and the side chain. Differences in the geometries due to the substitution of the electronegative atom and intermolecular contacts due to the chromone and hydrazinecarbothioamide were analyzed. NBO analysis confirms the presence of two strong stable hydrogen bonded NH⋯O intermolecular interactions and two weak hydrogen bonded CH⋯O interactions. The red shift in NH stretching frequency exposed from IR substantiates the formation of NH⋯O intermolecular hydrogen bond and the blue shift in CH stretching frequency substantiates the formation of CH⋯O intermolecular hydrogen bond. Drug likeness, absorption, distribution, metabolism, excretion and toxicity property gives an idea about the pharmacokinetic properties of the title molecule. The binding energy of the nonbonding interaction with Histidine 41 and Cysteine 145, present a clear view that 2(2E)-methyl-2-[(4-oxo-4H-chromen-3-yl)methylidene]-hydrazinecarbothioamide can irreversibly interact with SARS-CoV-2 protease.

Targeting the Rich Conformational Landscape of N-Allylmethylamine Using Rotational Spectroscopy and Quantum Mechanical Calculations.

The highly variable conformational landscape of N-allylmethylamine (AMA) was investigated using Fourier transform microwave spectroscopy aided by high-level theoretical calculations to understand the energy relationship governing the interconversion between nine stable conformers. Spectroscopically, transitions belonging to four low energy conformers were identified and their hyperfine patterns owing to the 14 N quadrupolar nucleus were unambiguously resolved. The rotational spectrum of the global minimum geometry, conformer I, shows an additional splitting associated with a tunneling motion through an energy barrier interconnecting its enantiomeric forms. A two-step tunneling trajectory is proposed by finding transition state structures corresponding to the allyl torsion and NH inversion. Natural bond orbital and non-covalent interaction analyses reveal that an interplay between steric and hyperconjugative effects rules the conformational preferences of AMA.

Planar Cyclopenten-4-yl Cations: Highly Delocalized π Aromatics Stabilized by Hyperconjugation.

Theoretical studies predicted the planar cyclopenten-4-yl cation to be a classical carbocation, and the highest-energy isomer of C5 H7 + . Hence, its existence has not been verified experimentally so far. We were now able to isolate two stable derivatives of the cyclopenten-4-yl cation by reaction of bulky alanes CpR AlBr2 with AlBr3 . Elucidation of their (electronic) structures by X-ray diffraction and quantum chemistry studies revealed planar geometries and strong hyperconjugation interactions primarily from the C-Al σ bonds to the empty p orbital of the cationic sp2 carbon center. A close inspection of the molecular orbitals (MOs) and of the anisotropy of current (induced) density (ACID), as well as the evaluation of various aromaticity descriptors indicated distinct aromaticity for these cyclopenten-4-yl derivatives, which strongly contrasts the classical description of this system. Here, strong delocalization of π electrons spanning the whole carbocycle has been verified, thus providing rare examples of π aromaticity involving saturated sp3 carbon atoms.

The Combination of Cross-Hyperconjugation and σ-Conjugation in 2,5-Oligosilanyl Substituted Siloles.

Reaction of a 2,5-dilithiated silole with excess dichlorodimethylsilane gives the respective 2,5-bis(chlorodimethylsilyl) substituted silole. This compound can be converted to 2,5-bis(oligosilanyl) substituted siloles by addition of a suitable oligosilanide. In the UV spectra of the thus obtained compounds the lowest energy absorptions are bathochromically shifted compared to the absorptions of the two constituents, namely the 2,5-disilyl substituted silole and a trisilane. The bathochromic shift is interpreted as being caused by a mixed σ-conjugation/cross-hyperconjugation. This assumption is supported by TD-DFT calculations, which show a significant contribution from Si-Si bonds to the HOMO of the molecule.