Rotational Isomers Research Articles

The Gauche Effect in XCH2 CH2 X Revisited.

We have quantum chemically investigated the rotational isomerism of 1,2‐dihaloethanes XCH2CH2X (X = F, Cl, Br, I) at ZORA‐BP86‐D3(BJ)/QZ4P. Our Kohn‐Sham molecular orbital (KS‐MO) analyses reveal that hyperconjugative orbital interactions favor the gauche conformation in all cases (X = F−I), not only for X = F as in the current model of this so‐called gauche effect. We show that, instead, it is the interplay of hyperconjugation with Pauli repulsion between lone‐pair‐type orbitals on the halogen substituents that constitutes the causal mechanism for the gauche effect. Thus, only in the case of the relatively small fluorine atoms, steric Pauli repulsion is too weak to overrule the gauche preference of the hyperconjugative orbital interactions. For the larger halogens, X⋅⋅⋅X steric Pauli repulsion becomes sufficiently destabilizing to shift the energetic preference from gauche to anti, despite the opposite preference of hyperconjugation.

Front Cover: Structure and Properties of Fumaryl Fluoride (Z. Anorg. Allg. Chem. 4/2021)

The cover picture shows a rotating laser wheel of different colors. The three planar rotational isomers of fumaryl fluoride (trans-trans, cis-cis and cis-trans) are placed on a blue circle of light in the picture. The arrows illustrate the intramolecular rotation of fumaryl fluoride, also exemplified by the spinning laser wheel. The molecular structure and the conformational composition of fumaryl fluoride were determined by low-temperature vibrational spectroscopy and single-crystal X-ray structure analysis. More details can be found in the article by Marie C. Bayer, Christoph Jessen, and Andreas J. Kornath on page 258.

Variable-temperature <sup>1</sup>H-NMR Studies on Three C-glycosylflavones Exhibiting Rotational Isomerism

Rotational isomerism has been observed on some C-glycosyl flavonoids with special chemical strutures. It may bring rotamers arising from restricted rotation about one single bond. C-glycosyl flavonoids showed a wide range of biological activities. This emphasizes the significance to understand the conformational stability of C-glycosyl flavonoids in drug development. Three C-glycosyl flavonoids, vaccarin (1), isovitexin-2”-O-arabinoside (2) and spinosin (3), were found to exist as rotamers in the light of their featured behavior in nuclear magnetic resonance spectroscopy (NMR). Some separated signals were observed in their ¹H-NMR and ¹³C NMR spectra. Variable-temperature (VT) ¹H-NMR experiments were then conducted to study the observation and to determine their rotational energy barriers and then evaluate their conformational stability. The temperature varied from 298K to 363K and separated signals merged at high temperature. With the help of Eyring equation, the rotational energy barriers of compounds 1-3 were calculated and found much lower than 24 kcal/mol. When the energy barrier is high enough (> 24 kcal/mol) and the time scale for interconversion (halflife > 1000 s) is long enough for isolation of individual rotamers, the isomers are termed atropisomers, which thus will display axial charity. According to this standard, the compounds 1-3 may not exhibit atropisomerism and isolation of rotamers should be difficult. Their relatively low energy barriers indicate they can be developed as rapidly equilibrating mixture.

Proline Rich Antimicrobial Peptides-----A tool to Counter Antimicrobial Resistance

Bacterial resistant to antibiotics is a global health problem that necessitates the production of new effective therapeutics. Antimicrobial peptides (AMPs) are commonly accepted as viable alternatives to currently used antibiotics. Some AMPs have the ability to work against not only planktonic bacteria but microbial biofilms as well. Proline rich antimicrobial peptides (PR-AMPs) are a distinctive group of AMPs, isolated in various animal sources, exhibiting an exceptionally high proline content. PR-AMPs function through non-lytic mechanisms and are generally regarded as non-toxic to mammalian cells. These peptides block bacterial protein translation by binding on and inactivating the ribosome. Proline, the only cyclic proteinogenic amino acid has the ability to undergo cis-trans isomerisation. When two different pyrrolidine ring conformations (exo and endo pucker) are adopted, these rotational isomers along the peptidyl-proline bond have different stabilities. Protein structure has ability to regulate itself either by preferring unique conformations and by improving hydrophobic interactions. Pseudoprolines (ΨPro) are mimetics of proline and function as molecular hinges. These ΨPro can be used for tailoring cis / trans isomerization around the Xaa- ΨPro amide bond (Xaa can be any amino acid) and hydrophobicity modulation.

Factors of protobiomonomer selection for the emergence the genetic code

The natural selection of specific protobiomonomers during abiogenic development of the prototype genetic code is hindered by the diversity of structural, spatial, and rotational isomers. They have identical elemental composition and molecular mass (M), but can vary significantly in their physicochemical characteristics, such as melting point Tm, the Tm : M ratio, and solubility in water, due to the different arrangement of atoms in the molecule. These parameters differ between cis- and trans-isomers of dicarboxylic acids, spatial monosaccharide isomers, and structural isomers of α-, β-, and γ-amino acids. The stable planar heterocyclic molecules of the major nucleobases comprise four (C, H, N, O) or three (C, H, N) elements and contain a single -C=C bond and two nitrogen atoms in each heterocycle involved in C-N and C=N bonds. They exist as isomeric resonance hybrids of single and double bonds and as a mixture of tautomer forms due to the presence of -C=O and/or -NH2 side groups. They are thermostable, insoluble in water, and exhibit solid-state stability, which is of central importance for DNA molecules as carriers of genetic information. In M Tm diagrams, proteinogenic amino acids and the corresponding codons are distributed in a rather ordered manner relative to the distinct clusters of purine and pyrimidine bases, reflecting the correspondence between codons and amino acids that was established in different periods of genetic code development. The body of data on the evolution of the genetic coding system indicates that the elemental composition and molecular structure of protobiomonomers, and their M, Tm, photostability, and aqueous solubility determined their selection in the emergence of the standard genetic code.

Isomeric effects on the acidity of Al13 Keggin clusters in porous ionic crystals.

We demonstrate a facile synthesis method of a porous ionic crystal (PIC) composed of the little-known δ-Keggin-type cationic polyoxoaluminum cluster ([δ-Al13O4(OH)24(H2O)12]7+, δ-Al13) with an oppositely-charged polyoxometalate, which enabled us to investigate the activity as a solid acid. The δ-Al13 based PIC exhibited much higher activity in pinacol rearrangement, a typical acid-catalyzed reaction, than the PIC based on the well-known and thermodynamically stable rotational isomer (ε-Al13). This work is a rare example of rotational isomers of polyoxoaluminum clusters exhibiting remarkably different catalytic activities.

DFT study of the structure, conformational profile and the vibrational analysis of 2-furancarbothialdehyde and 3-furancarbothialdehyde

The aim of this work is to study theoretically the geometrical structure, conformational prefe­rence, and vibrational properties of rotational isomers of 2- and 3-furancarbothialdehyde. The B3YLP hybrid density functional with the standard 6-311++G basis set is used to carry out all the calculations. The potential energy profile is calculated to determine the more stable conformer. The energy differences between cis and trans conformers show that the trans confor­mers are the preferred conformers with 0.70 kcal/mol and 1.36 kcal/mol for both 2-furan­carbothialdehyde and 3-furancarbothialdehyde respectively. Nine different solvents with the polarity ranging from ε = 1.92 to ε = 78.39 are used to study the effect of solvation on the conformational stability of the two molecules using the integral equation formalism in the polari­zable continuum model (IEF-PCM). The trans conformers are found to be more stable than the cis conformers in the gas phase. For 3-furancarbothialdehyde, the stability of the cis conformer increases as the dielectric constant of the solvent increases. On the other hand, the solvent reverses the conformational stability of 2-furancarbothialdehyde. The cis conformer becomes less stable as the dielectric constant of the solvent increases. The simulated infrared spectra of the molecules, geometrical parameters, and assignments of the vibrational modes are reported. Variations of the relative energy, dipole moment, and solvation energies as a function of the dielectric constant of solvents are investigated.

Isomerization of Na‐Centered Alkyltin Keggin Clusters

AbstractThe Keggin cluster topology, discovered in tungsten polyoxometalates approximately a century ago, is now broadly represented across the periodic table. The alkyltin Keggin clusters are unique in that it is the only Keggin family that appears to favor the rarer β and γ rotational isomers, co‐crystallized as β,γ‐[(BuSn)12(NaO4)(OCH3)12(O)5(OH)7] (β,γ‐NaSn12). Nuclear Magnetic Resonance Spectroscopy (NMR; 1H, 119Sn) studies show lability and ready exchange between hydroxy‐methoxy ligands, accelerated by residual water in polar solvents. Room temperature and heated solutions of β,γ‐NaSn12 show five distinct 23Na NMR peaks, corresponding to all five of the Keggin rotational isomers simultaneously in solution. This is the only example of coexistence of all Keggin isomers simultaneously, providing more in‐depth insight into parameters influencing Keggin isomer stabilization, isolation, and exchange.

Effect of molecular constitution and conformation on positron binding and annihilation in alkanes.

The model-potential approach previously developed by the authors to study positron interactions with molecules is used to calculate the positron binding energy for n-alkanes (CnH2n+2) and the corresponding cycloalkanes (CnH2n). For n-alkanes, the dependence of the binding energy on the conformation of the molecule is investigated, with more compact structures showing greater binding energies. As a result, thermally averaged binding energies for larger alkanes (n ≳ 9) show a strong temperature dependence in the range of 100 K-600 K. This suggests that positron resonant annihilation can be used as a probe of rotational (trans-gauche) isomerization of n-alkanes. In particular, the presence of different conformers leads to shifts and broadening of vibrational Feshbach resonances in the annihilation rate, as observed with a trap-based low-energy positron beam.

TTF-Annulated Silicon Phthalocyanine Oligomers and Their External-Stimuli-Responsive Orientational Ordering.

Orientational control of functional molecules is essential to create complex functionalities as seen in nature; however, such artificial systems have remained challenge. Herein, we have succeeded in controlling rotational isomerism of μ-oxo silicon phthalocyanine (SiPc) oligomers to achieve an external-stimuli-responsive orientational ordering using intermolecular interactions of tetrathiafulvalene (TTF). In this system, three modes of orientations, free rotation, eclipsed conformation, and staggered conformation, were interconverted in response to the oxidation states of TTF, which varied interactions from association due to formation of mixed-valence TTF dimer to dissociation due to electrostatic repulsion between TTF dications. Furthermore, a stable performance of oligomers as a cathode material in a Li-ion battery proved that the one-dimensionally stacked, rotatable structure of SiPc oligomers is useful to control the orientation of functional molecules toward molecular electronics.

TTF‐Annulated Silicon Phthalocyanine Oligomers and Their External‐Stimuli‐Responsive Orientational Ordering

AbstractOrientational control of functional molecules is essential to create complex functionalities as seen in nature; however, such artificial systems have remained challenge. Herein, we have succeeded in controlling rotational isomerism of μ‐oxo silicon phthalocyanine (SiPc) oligomers to achieve an external‐stimuli‐responsive orientational ordering using intermolecular interactions of tetrathiafulvalene (TTF). In this system, three modes of orientations, free rotation, eclipsed conformation, and staggered conformation, were interconverted in response to the oxidation states of TTF, which varied interactions from association due to formation of mixed‐valence TTF dimer to dissociation due to electrostatic repulsion between TTF dications. Furthermore, a stable performance of oligomers as a cathode material in a Li‐ion battery proved that the one‐dimensionally stacked, rotatable structure of SiPc oligomers is useful to control the orientation of functional molecules toward molecular electronics.

Structure and Properties of Fumaryl Fluoride

The molecular structure and the conformational composition of fumaryl fluoride were determined by low‐temperature vibrational spectroscopy and single‐crystal X‐ray structure analysis. Three planar rotational isomers, trans‐trans‐, cis‐cis‐ and cis‐trans‐fumaryl fluoride were identified. C4H2F2O2 crystallizes in the monoclinic space group P21/c with four formula units per unit cell. Besides, Lewis acid‐base adducts between fumaryl fluoride and arsenic pentafluoride were synthesized. These adducts, which contain O–As bonding interactions, were found to crystallize as the monoadducts trans‐cis‐C4H2F2O2·AsF5 and cis‐trans‐C4H2F2O2·AsF5. Moreover, the diadduct trans‐trans‐C4H2F2O2·2 AsF5 was determined by X‐ray crystallography. The experimental data are discussed together with quantum chemical calculations of trans‐trans‐, cis‐cis‐, and cis‐trans‐fumaryl fluoride.

Investigation of the rotamers of 3-furfural by microwave spectroscopy

The rotational spectrum of 3-furfural (3-FF) was investigated using Fourier transform microwave spectroscopy from 6 to 19 GHz in order to examine the rotational isomerism properties of the formyl group relative to the furan ring backbone. Two planar rotamers with the formyl group anti or syn to the ring oxygen atom were observed with the latter being identified in the gas phase for the first time. The observed relative intensity of ~8:1 (anti:syn) of transitions is consistent with quantum chemical calculations at the B3LYP-D3(BJ)/aug-cc-pVTZ level which predict that the anti rotamer is more stable than the syn by 4.86 kJ/mol. Transitions due to singly-substituted 13C isotopologues for both rotamers and the 18O isotopologues for the anti form were assigned. The resulting sets of rotational constants allowed derivation of accurate ground state effective (r0) and mass dependent (rm(1)) geometries for the furan ring of each rotamer for comparison with their equilibrium (re) geometries. The syn/anti arrangement of the formyl group appears to have little effect on the geometry of the furan ring itself but the exocyclic group is rotated slightly closer to the oxygen atom of the heterocycle when in the anti arrangement.

Capturing Lacunary Iron-Oxo Keggin Clusters and Insight Into the Keggin-Fe13 Cluster Rotational Isomerization.

The formation mechanism of ferrihydrite is the key to understand its treatment of pollutants in waste water and purification of surface water and groundwater. Although emerging evidence suggests that formation of the ferrihydrite occurs through the aggregation of prenucleation clusters, rather than classical atom-by-atom growth, its formation mechanism remains unclear. Herein, an iron-oxo anionic cluster of [Fe22 (μ4 -O)8 (μ3 -OH)20 (μ2 -OH)18 (CH3 COO)16 (H2 O)2 ]4- viewed as a dimer of bivacant β-Keggin-Fe13 clusters was for the first time obtained by using lanthanide ions as stabilizers. Upon dissolution in a mixed solution of isopropanol and water, the lacunary β-Keggin-Fe13 cluster can transform into an α-Keggin-Fe13 cluster, distinctly demonstrating that the Keggin-Fe13 cluster rotational isomerization can be realized through the vacant Keggin-Fe13 cluster.

Synthesis, spectral characterization, solution and solid-state conformations of N-nitroso-2,7-diaryl-1,4-diazepan-5-ones by NMR and XRD studies

Nitroso derivative of 2,7-diaryl-1,4-diazepan-5-ones 9–12 are synthesized and characterized using spectroscopic techniques such as IR, EI-MS and NMR spectra. The stereochemical investigation of nitroso compounds has been carried out with 1D (1H, 13C & DEPT-135) and 2D (COSY & HSQC) NMR spectral data. Rotational isomers (syn and anti rotamers) of 9–12 are identified and categorized by room temperature NMR spectral studies. Furthermore, the conformation of the ring and the orientation of NN=O function have been arrived on the basis of chemical shifts, coupling constants and dihedral angles. In solution state, syn and anti rotamers of the compounds 9–11 exist in equilibrium between flattened boat conformation with quasi-axial orientations of the aryl groups at C-2 and C-7. Nevertheless, compound 12 and its syn and anti rotamers prefer to adopt equilibrium between chair conformations with axial orientation of aryl substituents. In order to validate the solution state conformation, the compound 12 is crystallized and the crystal structure is solved by single crystal XRD study. The compound 12 exists in an alternate chair conformation and aryl groups at C-2 & C-7 occupy axial orientations in solid state also.

Ion Charge Influence on the Molecular Structure of Polyethylene Terephthalate Films after Irradiation with Swift Heavy Ions

We report here experimental results investigating the influence of the initial swift heavy ion charge on the structure of polyethylene terephthalate (PET) film after irradiation, using a structurally sensitive X-ray diffraction method. Kr ions with an energy of 100 MeV and charges of 13+, 14+, and 15+ were each used at irradiation fluences of 5 × 1010, 7.5 × 1010, 1 × 1011, 2.5 × 1011 and 5 × 1011 ions/cm2. At constant energy and irradiation fluence, the post-irradiation structural changes in PET film show a clear dependence on the initial ion charge. As either the fluence or ion charge increase, the latent tracks begin to overlap, leading to cross-linking of PET chain molecules to form rotational isomers (rotamers). We use the fluence corresponding to the onset of overlapping to estimate the size of latent tracks for different ion charges. At the highest fluences, the latent tracks become entirely overlapped, and the interchain cross-linking extends throughout the whole film. Since this cross-linking is due to the dipole–dipole interaction of subunits of repeat units of PET chain molecules, it is reversible, in contrast to the well-known chemical cross-linking of polymer chain molecules under irradiation.

Not only AIE: Light-sensitivity of 4-dimethylamino-2′-hydroxychalcones beneficial to highly efficient photochemical synthesis of 4′-dimethylaminoflavanones

4-dimethylamino-2′-hydroxychalcone in crystals is well known for its aggregation induced emission (AIE) in the red region of spectrum. We however observe that in liquid solutions this dye and its analogues undergo reversible wavelength-dependent light-induced cyclization to the flavanone derivatives. Special care thus should be taken when this compound is used for optoelectronic applications requiring high purity, especially via solution-processed methods. The discussed intramolecular cyclization proceeds faster in nonpolar medium and is quenched completely in the presence of protic solvents or via formation of aggregates in crystal phase. In spite of that quantum yield of a single photoinduced transformation does not exceed 1%, continuous irradiation affords 92% of product which makes it the most efficient preparation route for 4′-dimethylminoflavanone and its derivatives among the ones reported before. According to the DFT and TDDFT calculations supported by the experimentally investigated spectral features, the mechanism of photoinduced formation of a 4′-dimethylaminoflavanone involves several transformations: excited state intramolecular proton transfer (ESIPT), excited and ground state rotational isomerization from s-trans to s-cis isomer, cyclization and enol-keto tautomerization via proton transfer in the ground state.

Azetidine-based selective glycine transporter-1 (GlyT1) inhibitors with memory enhancing properties

A strategy to conformationally restrain a series of GlyT1 inhibitors identified potent analogs that exhibited slowly interconverting rotational isomers. Further studies to address this concern led to a series of azetidine-based inhibitors. Compound 26 was able to elevate CSF glycine levels in vivo and demonstrated potency comparable to Bitopertin in an in vivo rat receptor occupancy study. Compound 26 was subsequently shown to enhance memory in a Novel Object Recognition (NOR) behavioral study after a single dose of 0.03 mg/kg, and in a contextual fear conditioning (cFC) study after four QD doses of 0.01–0.03 mg/kg.

Flexible Luminescent MOF: Trapping of Less Stable Conformation of Rotational Isomers, In Situ Guest-Responsive Turn-Off and Turn-On Luminescence and Mechanistic Study.

Flexible and dynamic CuI metal-organic framework [Cu(I)-MOF (1)] with well-defined nanoporous channel built with flexible terpyridine ligand offers a scaffold for the inclusion of different classes of guest molecules through a single-crystal-to-single-crystal (SCSC) transformation in the vapor phase at ambient conditions with visual color change. Thus, Cu(I)-MOF (1) offers a potential platform for molecular recognition and undergoes guest-responsive structural dynamism that can be triggered by interfacial interactions. Despite having the stable conformation of the rotational isomers, it selectively encapsulates the less stable conformation (eclipsed and gauche) into its cavity from their vapor phases in the SCSC process. All of the guest-exchanged processes are reversible. It shows selectivity toward less polar guest in a class. The intermediate of all of the guest-exchanged processes appeared as a black material (H2O@Cu(I)-MOF) (1z) prior to the encapsulation of each guest that happens through the SCSC manner followed by encapsulation of the guests replacing H2O in situ at ambient conditions through SCSC transformation. This confirms that the process is a two-step process leading to a common intermediate. The MOF loses its luminescence behavior with H2O removing lattice solvents in situ and appears as a black material, and it regains its luminescence property with the guests replacing H2O. Thus, the MOF displays both luminescence "turn-off" and "turn-on" before and after incorporation of the guests, respectively, leading to a common turn-off mechanism. A fluorescence titration experiment shows selectivity toward aniline among benzene and its derivatives.

Computational insights of two‐dimensional infrared spectroscopy under electric fields in phosphorylcholine

AbstractInfluence of static electric field in biological cells causes electroporation, which results in the increase of permeability of the cells and phospholipid bilayer. However, the precise mode of action of electric fields on phospholipid bilayer and their quantum mechanics are still unclear. Therefore, to understand the quantum‐based biological effect, we aimed to study two‐dimensional infrared (2D‐IR) spectra‐adopted quantum mechanics/molecular mechanics (QM/MM) simulations under the influence of static electric fields on Phosphorylcholine, an important component in phospholipid membrane. Initially, QM/MM studies were performed under the influence of electric field, ranging from −1.543 to 1.028 V/nm. A multilayer ONIOM model (in combination with DFT/B3LYP/6‐31G [d, p] and DREIDING force fields) was used to obtain 2D‐IR simulated spectra to calculate electrostatic interaction in the biological system. The results demonstrated that the phosphate group played an important role on α‐rotation in LUMO and the chlorine atom had a major contribution in HOMO. In addition, decreased number of hydrogen bonds demonstrated that uncoupling reaction of the P‐O stretching vibrations while the electric field was −1.542 V/nm. Moreover, we observed that the electric field is −1.028 V/nm, there is no rotational isomerization in phosphorylcholine. We concluded that the static electric fields significantly affect the anharmonic frequencies, vibration coupling and the structure of the phosphorylcholine.