Rotational Barriers Research Articles

Strategies to increase the quantum yield: Luminescent methoxylated imidazo[1,5-a]pyridines

A series of methoxylated imidazo[1,5-a]pyridines is presented and their optical and electrochemical properties investigated and interpreted on the basis of density functional theory calculations. The photophysical properties are discussed in relation to the chemical structure. The key role of the 1,3 substitutions on the imidazo[1,5-a]pyridine nucleus on rotational barriers and on frontier molecular orbitals is discussed in relation to the experimental hyperchromic effect, photoemission quantum yield and electrochemical properties. Depending on the position of the introduced methoxy substituents on the imidazo[1,5-a]pyridine nucleus, we are able to tune the Stokes shift and to increase the emission quantum yield from 22% to 50%.

Low rotational barriers for the most dynamically active methyl groups in the proposed antiviral drugs for treatment of SARS-CoV-2, apilimod and tetrandrine

A recent screening study highlighted a molecular compound, apilimod, for its efficacy against the SARS-CoV-2 virus, while another compound, tetrandrine, demonstrated a remarkable synergy with the benchmark antiviral drug, remdesivir. Here, we find that because of significantly reduced potential energy barriers, which also give rise to pronounced quantum effects, the rotational dynamics of the most dynamically active methyl groups in apilimod and tetrandrine are much faster than those in remdesivir. Because dynamics of methyl groups are essential for biochemical activity, screening studies based on the computed potential energy profiles may help identify promising candidates within a given class of drugs.

Atomically Precise Engineering of Single‐Molecule Stereoelectronic Effect

AbstractCharge transport in a single‐molecule junction is extraordinarily sensitive to both the internal electronic structure of a molecule and its microscopic environment. Two distinct conductance states of a prototype terphenyl molecule are observed, which correspond to the bistability of outer phenyl rings at each end. An azobenzene unit is intentionally introduced through atomically precise side‐functionalization at the central ring of the terphenyl, which is reversibly isomerized between trans and cis forms by either electric or optical stimuli. Both experiment and theory demonstrate that the azobenzene side‐group delicately modulates charge transport in the backbone via a single‐molecule stereoelectronic effect. We reveal that the dihedral angle between the central and outer phenyl ring, as well as the corresponding rotation barrier, is subtly controlled by isomerization, while the behaviors of the phenyl ring away from the azobenzene are hardly affected. This tunability offers a new route to precisely engineer multiconfigurational single‐molecule memories, switches, and sensors.

Atomically Precise Engineering of Single-Molecule Stereoelectronic Effect.

Charge transport in a single-molecule junction is extraordinarily sensitive to both the internal electronic structure of a molecule and its microscopic environment. Two distinct conductance states of a prototype terphenyl molecule are observed, which correspond to the bistability of outer phenyl rings at each end. An azobenzene unit is intentionally introduced through atomically precise side-functionalization at the central ring of the terphenyl, which is reversibly isomerized between trans and cis forms by either electric or optical stimuli. Both experiment and theory demonstrate that the azobenzene side-group delicately modulates charge transport in the backbone via a single-molecule stereoelectronic effect. We reveal that the dihedral angle between the central and outer phenyl ring, as well as the corresponding rotation barrier, is subtly controlled by isomerization, while the behaviors of the phenyl ring away from the azobenzene are hardly affected. This tunability offers a new route to precisely engineer multiconfigurational single-molecule memories, switches, and sensors.

Quantifications and Applications of Relative Fisher Information in Density Functional Theory.

Though density functional theory is widely accepted as one of the most successful developments in theoretical chemistry in the past few decades, the knowledge of how to apply this new electronic structure theory, to help us better understand chemical processes and transformations, is still an unaccomplished task. The information-theoretic approach is emerging as a viable option for that purpose in the recent literature, providing new insights about steric effect, cooperativity, electrophilicity, nucleophilicity, stereoselectivity, homochirality, etc. In this work, based on the result from a recent paper by one of us [ J. Chem. Phys, 2019, 151, 141103], we present two quantifications of the relative Fisher information and discuss their physiochemical properties and possible applications. To that end, their analytical properties have been elucidated. They have also been applied to six categories of systems to illustrate their applicability. A better descriptor to quantify the single bond rotation barrier has been obtained. The relative Fisher information can also simultaneously determine electrophilicity and nucleophilicity, and effectively describe helical structures with different homochiral and heterochiral propensities. As integral parts of the information-theoretic approach, these newly introduced quantities will provide us with more analytical tools toward the long-term goal of crafting a chemical reactivity theory in the density-based language.

NHC-Catalyzed Desymmetrization of N-Aryl Maleimides Leading to the Atroposelective Synthesis of N-Aryl Succinimides.

Although the construction of axially chiral C-C bonds leading to the atroposelective synthesis of biaryls and allied compounds are well-known, the related synthesis of compounds bearing axially chiral C-N bonds are relatively rare. Described herein is the N-heterocyclic carbene-catalyzed atroposelective synthesis of N-aryl succinimides having an axially chiral C-N bond via the desymmetrization of N-aryl maleimides. The NHC involved intermolecular Stetter-aldol cascade of dialdehydes with prochiral N-aryl maleimides followed by oxidation afforded N-aryl succinimides in good yields and ee values. Preliminary studies on rotation barrier for the C-N bond, the temperature dependence, and detailed DFT studies on mechanism are also provided.

NHC‐Catalyzed Desymmetrization of N‐Aryl Maleimides Leading to the Atroposelective Synthesis of N‐Aryl Succinimides

AbstractAlthough the construction of axially chiral C−C bonds leading to the atroposelective synthesis of biaryls and allied compounds are well‐known, the related synthesis of compounds bearing axially chiral C−N bonds are relatively rare. Described herein is the N‐heterocyclic carbene‐catalyzed atroposelective synthesis of N‐aryl succinimides having an axially chiral C−N bond via the desymmetrization of N‐aryl maleimides. The NHC involved intermolecular Stetter‐aldol cascade of dialdehydes with prochiral N‐aryl maleimides followed by oxidation afforded N‐aryl succinimides in good yields and ee values. Preliminary studies on rotation barrier for the C−N bond, the temperature dependence, and detailed DFT studies on mechanism are also provided.

Free H‐Bonding Interaction Sites in Rigid‐Chain Polymers and Their Filling Approach: A Molecular Dynamics Simulation Study

AbstractHydrogen bond (H‐bond) plays an important role in structure evolution and properties of various polymers. Due to directivity and saturation of H‐bond, its formation is influenced by macromolecular chain conformation but the relationship is still not well understood up to now. In this paper, amorphous models of polyamide 66 (PA66), polyamide 6T (PA6T), and poly(p‐phenylene‐terephthamide) (PPTA) are built to study influence of chain rigidity on H‐bonding formation by utilizing Molecular Dynamics simulation. Compared with PA66 and PA6T, it is found that chain rigidity of PPTA is more remarkable and corresponding conformation adjustment is hindered more significantly, which leads to considerable weak H‐bonds and free H‐bonding sites. After introducing benzimidazole moiety into PPTA, more H‐bonds form due to more potential H‐bonding sites in benzimidazole units. However, the newly added H‐bonding donor and acceptor are in the co‐ring, and there is a high rotational energy barrier for benzimidazole ring, both of which hinder the formation of strong H‐bonds. Therefore, a strategy is proposed to fill free H‐bonding sites in rigid‐chain polymers through adding oligomers with high movement ability. Thus, the H‐bonds in rigid‐chain polymers are effectively enhanced due to bridging effect of oligomers and tensile modulus of the aramid is improved significantly.

The Control of Intramolecular Through-Bond and Through-Space Coupling in Single-Molecule Junctions

The Control of Intramolecular Through-Bond and Through-Space Coupling in Single-Molecule Junctions

Structure, Z' = 2 Crystal Packing Features of 3-(2-Chlorobenzylidene)-5-(p-tolyl)furan-2(3H)-one.

3-(2-Chlorobenzylidene)-5-(p-tolyl)furan-2(3H)-one (1), C18H13ClO2, crystallizes with Z = 8 and Z′ = 2, and the structure at 100 K has orthorhombic (Pna21) symmetry. Each kind of molecule takes part in π–π stacking interactions to form infinite chains parallel to the c axis. We believe that the existence of two forms can be explained by the probable rotation around a single C–C bond. The quantum chemical modeling reveals that these molecules are almost equivalent energetically, and they can be described as the two most stable conformers (rotamers) with a minor rotational barrier of about 0.67 kcal/mol.

Carbonyl-to-Alkyne Electron Donation Effects in up to 10-nm-Long, Unimolecular Oligo(p-phenylene ethynylenes).

We synthesized some of the longest unimolecular oligo(p-phenylene ethynylenes) (OPEs), which are fully substituted with electron-withdrawing ester groups. An iterative convergent/divergent (a.k.a. iterative exponential growth – IEG) strategy based on Sonogashira couplings was utilized to access these sequence-defined macromolecules with up to 16 repeating units and 32 ester substituents. The carbonyl groups of the ester substituents interact with the triple bonds of the OPEs, leading to (i) unusual, angled triple bonds with increased rotational barrier, (ii) enhanced conformational disorder, and (iii) associated broadening of the UV/Vis absorption spectrum. Our results demonstrate that fully air-stable, unimolecular OPEs with ester groups can readily be accessed with IEG chemistry, providing new macromolecular backbones with unique geometrical, conformational, and photophysical properties.

Atroposelective Synthesis, Structure and Properties of a Novel Class of Axially Chiral N‐Aryl Quinolinium Salt

AbstractInspired by naturally occurring molecules containing atropisomeric N+‐C axes, we have developed a novel synthetic approach to generate a library of axially chiral N‐aryl quinolinium salts. Enantiopurities up to 93 % ee were obtained via a four‐step route from commercially available precursors. Axial stereochemistry was controlled through an enantioselective ring‐closing Buchwald–Hartwig coupling reaction. The structure and properties of the salts were examined by X‐ray crystallography, DFT, UV‐Vis, and fluorescence spectroscopy, revealing high rotational barriers and solvatochromic behaviour.

Target Designing Phase Transition Materials through Halogen Substitution.

Crystalline materials have received extensive attention due to their extraordinary physical and chemical properties. Among them, phase transition materials have attracted great attention in the fields of photovoltaic, switchable dielectric devices, and ferroelectric memories, etc. However, many of them suffer from low phase transition temperatures, which limits their practical application. In this work, we systematically designed crystalline materials, (TMXM)2 PtCl6 (X=F, Cl, Br, I) through halogen substitution on the cations, aiming to improving phase transition temperature. The resulting phase transition of (TMXM)2 PtCl6 (X=F, Cl, Br, I) get a significant enhancement, compared to the parent compound [(CH3 )4 N]2 PtCl6 ((TM)2 PtCl6 ). Such phase transition temperature enhancement can be attributed to the introduction of halogen atoms that increase the potential energy barrier of the cation rotation. In addition, (TMBM)2 PtCl6 and (TMIM)2 PtCl6 have a low symmetry and crystallize in the space group C2 /c and P21 21 21 , respectively. This work highlights the halogen substitution in designing crystal materials with high phase transition temperature.

Computational studies of fluorinated propenes: The fluorine "cis effect," barrier heights of the internal rotation of CX3 (X = H or F) group, and π-bond strengths

The (E)- and (Z)-geometrical isomers of fluorinated propenes (CWZ = CY−CX3, W, X, Y, and Z = H or F) are computationally investigated. Our calculations show that geometrical isomers with two fluorine atoms located at the cis positions of the CC bond tend to undergo additional energy lowering compared to the trans isomers. Natural bond orbital analysis suggests that the origin of this lowering of energy is the same as that of the typical fluorine cis effects observed for 1,2-dihaloethenes. The barrier height magnitude of the internal rotation of the methyl or trifluoromethyl group is shown to be sensitive to the substitution patterns in the fluorinated propenes. The change in the rotational barrier heights is closely related to the differences in the magnitude of intramolecular repulsive non-bonded steric interactions. Furthermore, the π-bonds in fluorinated propenes are shown to be weaker for the derivatives possessing two fluorine atoms at both ends of the CC bond. The OH radical reactions of the fluorinated propenes are initiated by the attack of the OH radicals on the π-bond. Nevertheless, no obvious correlation is found between the rate constants for the OH radical reactions and the π-bond strengths of the fluorinated propenes.

Gyroscopes and the Chemical Literature, 2002-2020: Approaches to a Nascent Family of Molecular Devices.

Research directed toward the goal of molecular gyroscopes since the coverage of a previous review (2002) is described. Such species are a subclass of molecular rotors, which are comprised of rotators and stators. Major categories include (1) systems in which a rotator is embedded in a cage-like stator reminiscent of mechanical toy gyroscopes and (2) molecules that have been engineered to crystallize with parallel rotators and voids or other features that enable the rotator to rotate in the solid state (amphidynamic crystals). Particular attention is given to structural data and strategies for the minimization of rotational barriers. Synthetic routes are also described. Some allied types of molecules and supramolecular assemblies are also treated.

Conformational analysis of 2,5‐diaryl‐4‐methyl‐2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐ones: Multinuclear NMR and DFT calculations

AbstractConformational exploration of five 2,5‐diaryl‐4‐methyl‐2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐ones has been carried out based on a combination of their NMR chemical shifts determined in CDCl3 and the scrutiny of their computed relative energies and absolute shieldings calculated at the DFT/GIAO/B3LYP/6–311++G(d,p) level. The very flat potential energy curves corresponding to the three relevant single bond rotations were explored by calculating the energy of the rotational barriers and comparing the experimental chemical shifts with those theoretically calculated in each rotamer by statistical analysis.

Illuminating the dark conformational space of macrocycles using dominant rotors.

Three-dimensional conformation is the primary determinant of molecular properties. The thermal energy available at room temperature typically equilibrates the accessible conformational states. Here, we introduce a method for isolating unique and previously understudied conformations of macrocycles. The observation of unusual conformations of 16- to 22-membered rings has been made possible by controlling their interconversion using dominant rotors, which represent tunable atropisomeric constituents with relatively high rotational barriers. Density functional theory and in situ NMR measurements suggest that dominant rotor candidates for the amino-acid-based structures considered here should possess a rotational energy barrier of at least 25 kcal mol-1. Notable differences in the geometries of the macrocycle conformations were identified by NMR spectroscopy and X-ray crystallography. There is evidence that amino acid residues can be forced into rare turn motifs not observed in the corresponding linear counterparts and homodetic rings. These findings should unlock new avenues for studying the conformation-activity relationships of bioactive molecules.

Handed Mirror Symmetry Breaking at the Photo-Excited State of π-Conjugated Rotamers in Solutions

The quest to decode the evolution of homochirality of life on earth has stimulated research at the molecular level. In this study, handed mirror symmetry breaking, and molecular parity violation hypotheses of systematically designed π-conjugated rotamers possessing anthracene and bianthracene core were evinced via circularly polarized luminescence (CPL) and circular dichroism (CD). The CPL signals were found to exhibit a (−)-sign, and a handed dissymmetry ratio, which increased with viscosity of achiral solvents depending on the rotation barrier of rotamers. The time-resolved photoluminescence spectroscopy and quantum efficiency measurement of these luminophores in selected solvents reinforced the hypothesis of a viscosity-induced consistent increase of the (−)-sign handed CPL signals.

Molecular dynamics investigation of the structural flexibility of H2O2 and H2S2 in response to medium polarity

Hydrogen peroxide (H2O2) and hydrogen persulfide (H2S2) are the simplest members of the peroxide and persulfide families, and both are signaling molecules that regulate several biological functions. Rotation about the O–O and S–S bonds impacts the strength of these molecules as H-bond donors or acceptors and tunes their polarity and stability by converting the polar equilibrium skewed structure (ϕHOOH ~ 112°, ϕHSSH ~ 91°) to the nonpolar less stable trans (ϕ = 180°) or the most polar and least stable cis (ϕ = 0°) conformers. The change in geometry in response to the structure and polarity of the microenvironment is an important feature that would influence how these molecules interact with or permeate through biological systems. Consistent with larger energy barriers for rotation about the S–S bond, quantum chemical calculations with MP2(full)/6–311++G(3df,3pd) reveal that when interacting with a single water, ethanol, or n-pentane molecule in the gas phase, the geometry of H2S2 is more rigid (ϕHSSH = 91 ± 3°) than that of H2O2 (ϕHOOH = 112 ± 8°). Molecular dynamics simulations of a single H2O2 or H2S2 in liquid water (ε = 80), ethanol (ε = 25), or n-pentane (ε = 2) reveal that, compared to the gaseous monomer, H2O2 maintains a more polar geometry in ethanol and water. Interestingly, the distribution of ϕHOOH significantly shifts towards the nonpolar conformation as solvent polarity decreases; the fraction of structures with ϕHOOH ≥ 160° is 0.10, 0.14, and 4.30% in water, ethanol, and n-pentane, respectively. The high-energy cis conformation of H2O2 was negligible in all solvents, especially in n-pentane. The equilibrium geometry of H2S2 is hardly influenced by solvent polarity and both cis and trans conformations are essentially absent in the three solvents. In contrast to rigid H2S2, H2O2 is thus a flexible molecule whose geometry depends on the environment polarity, a property that enables stabilizing H2O2 in different microenvironments and possibly plays a role in how biological systems discriminate between H2O2 and the rigid and polar close analog, H2O.

Molecular polarizabilities of some energetic compounds.

The dependence of sensitivity of an explosive on its molecular structure may be mainly attributed to the molecular deformability, which can be expressed by some characteristic parameters, resonance energy for aromatic an explosive, strain energy for a strained-ring or strained-cage explosive, large π-π separation energy for a large π-π linked-explosive, bond rotational energy barriers of C-NO2, N-NO2, O-NO2 for C-NO2, N-NO2, O-NO2 bond-based explosives, and so on. Molecular polarizability of an explosive is also an important molecular deformability index, which can be effectively used to compare impact sensitivities of explosive's isomers, isoelectronic species, and similar structures. Interestingly, comparing the molecular polarizabilities under external electric fields with different energy levels of isomeric N20(Ih) and N20(D3d) clusters and the Mo2N20 and Re2N20 complex compounds, it is found that there are different energy thresholds of significant molecular expansion.