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Fluorine, the tiny robust atom, with its unique features has captured the attention of scientists in recent times, especially in drug discovery with its integration in small molecules, peptides, and proteins. However, studies to understand the 'fluorine effects' on the conformation of molecules that follow 'beyond the rule of 5' are in the infancy yet significant in molecular design and function. For the first time, using short hybrid peptide sequence as an appropriate model, we examined the substitution effect (size, stereoelectronic effect, and hydrogen bonding) using X‐ray diffraction, 2D‐NMR, and CD studies. The comparative study on their folding patterns with hydrogen‐substituted analogs can provide valuable insights into fluorinated substrates' design. [ABSTRACT FROM AUTHOR]

Copyright of University Chemistry is the property of Peking University, College of Chemistry & Molecular Engineering and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The gas-phase electron diffraction (GED) study of tri-tert-butyl methane (TTBM) published in 1972 by Bürgi and Bartell inspired the author to investigate the nature of the intramolecular interactions that are operative in this crowded hydrocarbon. Using the quantum theory of atoms in molecules (QTAIM), a topological analysis of the theoretical charge density of TTBM is carried out. Nine bond paths corresponding to the presence of noncovalent, intramolecular interactions operating at the interfaces that separate the three t-Bu groups do emerge from the QTAIM analysis. This result supports the existence of a network of intramolecular interactions predicted by Bürgi and Bartell in their landmark GED study of TTBM. In addition, the not yet synthesized halogen analogues (t-Bu)3 CX (X=F to I) are also investigated herein. Some information about the remarkable contributions of the pioneers is provided throughout the paper. [ABSTRACT FROM AUTHOR]

Monitoring the structural transitions of individual molecules is of great significance because it helps to in depth explore the properties of molecules and provide diverse possibilities for molecular applications in the fields of chemistry, biology and material science. This review summarizes the strategy of using single‐molecule electrical approaches to study molecular structure transitions at the single‐molecule level in real time. Specifically, through the use of stable single‐molecule devices for real‐time electrical monitoring, the process of molecular structure transitions of a single molecule can be investigated, which helps to explore the nature of molecules in chemical and biological systems. In particular, the detection methods have been extended to the investigation of biological macromolecules for monitoring the conformational changes of nucleotide chains in different systems, such as double helix DNA, aptamer and DNA enzyme. In the end, we discuss the future challenges of probing structural transitions of single molecules, and provide prospects for further breakthroughs in this field. What is the most favorite and original chemistry developed in your research group? Single‐molecule device fabrication and detection. How do you get into this specific field? Could you please share some experiences with our readers? I started to pursue this field during my PhD period. The promise of molecular electronics that might breakthrough the development bottleneck of current microelectronics inspired my great interest. This interest drives me to persist in the pursuit of practical molecular electronic devices as perfect as possible. What is the most important personality for scientific research? Three aspects: interest, persistence and industriousness. The first key to the success should be diligence. How do you keep balance between research and family? It is hard to balance the time. It is very important to have understanding and support from the family. I love them. What's your hobbies? Driving and watching movies. [ABSTRACT FROM AUTHOR]

Cyclometalated complexes are an important class of (pre)catalysts in many reactions including hydride transfer. The ring size of such complexes could therefore be a relevant aspect to consider while modulating their catalytic activity. However, any correlation between the cyclometalating ring size and the catalytic activity should be drawn by careful assessment of the pertinent geometrical parameters, and overall electronic effects thereof. In this study, we investigated the vital role of key stereoelectronic functions of two classes of iridacyclic complexes-five-membered and six-membered cycles-in manupulating the catalytic efficiency in a model hydride-transfer reaction. Our investigation revealed that there exists an interesting multidimensional synergy among all the relevant stereoelectronic factors-yaw angle, bite angle, and the electronic properties of both the ligand and the metal center-that governs the hydride donor ability (hydricity) of the complexes during catalysis. Thus the six-membered chelate complexes with small yaw and large bite angles, strong donor ligand, and electron-rich metal were found to be better catalysts than their five-membered analogues. A frontier molecular orbital analysis supported the significant role of the above stereoelectronic synergistic effect associated with the chelate ring to control the hydride donor ability of the complexes. [ABSTRACT FROM AUTHOR]

The structures and energies of 1,2,7-thiadiazepane 1,1-dioxide and the axial and equatorial conformers of 1,2,7-thiadiazepane 1-oxide were calculated using the hybrid density functional B3LYP with the cc-pVDZ basis set. The results obtained explain the lower stabilities of equatorial conformers compared to the axial analogs and the lower stabilities of sulfones compared to sulfoxides. [ABSTRACT FROM AUTHOR]

Achieving acyclic conformational control over several bonds has been realized by the strategic installation of a vicinal difluoroethane bridge in a generic proline-derived organocatalyst. The torsion angle ϕFCCF is governed by stabilizing hyperconjugative interactions (σ→σ*), thus ensuring a 60° relationship. This effect has been telescoped by positioning a stereogenic fluorine center proximal to the nucleophilic amine. Upon iminium formation, this center is rendered electron deficient, thus triggering a dynamic fluorine iminium ion gauche effect. Consequently, conformational control over five atoms and four bonds can be achieved by reversible formation of an iminium π-bond. [ABSTRACT FROM AUTHOR]

Recently, the experimental and computational chemists have been attracted widely to the click synthesis of 1,2,3 triazoles and their derivatives, mainly due to the fact that they are interesting from structural and mechanistic points of view. Moreover, catalyzed click have been well established as a successful strategy showing high regioselectivity and high yield for the synthesis of 1,2,3-triazoles. In this review, we try to highlight the recently reported computational assessments on the origins and predection of regioselectivity in the catalyzed click synthesis of triazoles from the mechanistic and thermodynamical points of view. In this light, density functional theory (DFT) calculations on the free energy profiles of azide-alkyne cycloaddition reactions have been underscored. The stereoelectronic features for the role of copper, ruthenium, and iridium as catalyst on regioselectivity of click reactions have also be discussed. [ABSTRACT FROM AUTHOR]

The normal and reverse Perlin effect is usually explained by the redistribution of electron density produced by hyperconjugative mechanisms, which increases the electron population within axial or equatorial proton in normal or reverse effect, respectively. Here an alternative explanation for the Perlin effect is presented on the basis of the topology of the induced current density, which directly determines the nuclear magnetic shielding. Current densities around the CAH bond critical point and intra-atomic and interatomic contributions to the magnetic shielding explain the observed Perlin effect. The balance between intra-atomic and interatomic contributions determines the difference in the total atomic shielding. Normal Perlin effect is dominated by intra-atomic part, whereas reverse effect is dominated by interatomic contribution. [ABSTRACT FROM AUTHOR]

Many interests have been focused on prolyl cis- trans isomerization which is related to protein folding and isomer-specific biochemical recognition. Since polyproline can adopt either type I (PPI) helices with all cis amide bonds or type II (PPII) helices with all trans amide bonds, it has been a valuable model to study the prolyl isomerization. Recent studies have shown that stereoelectronic effects govern the stability of PPII structure and the rate of PPII → PPI conversion. To further explore the terminal stereoelectronic effects on polyproline conformation, herein we synthesized a series of host-guest peptides in which (2 S,4 S)-4-fluoroproline (flp) or (2 S,4 R)-4-fluoroproline (Flp) residues are incorporated into the C- or N-terminal end of a peptide and studied the thermodynamic and kinetic consequences on polyproline conformation. Circular dichroism measurements revealed that inserting 4-fluoroproline residues into the C terminus of a polyproline peptide induces a great stereoelectronic effect on PPII stability and PPII → PPI conversion rates. From the C terminus, a (Flp) triplet stabilizes PPII structure and increases the transition barrier of PPII → PPI conversion by 1.53 kJ mol while a (flp) triplet destabilizes PPII conformation and reduce the PPII → PPI transition barrier by 4.61 kJ mol. In contrast, the 4-fluoroproline substitutions at the N terminus do not exhibit distinct stereoelectronic effects on PPII stability and PPII → PPI conversion rates. Our data demonstrate that the C-terminal stereoelectronic effects have a more dramatic impact on PPII stability and PPII → PPI conversion kinetics. [ABSTRACT FROM AUTHOR]

A computational investigation of anomeric effects in piperidine rings bearing fluoro and trifluoromethyl substituents shows for both compounds the most pronounced evidence of the anomeric effect, as expressed as hyperconjugative delocalization of the nitrogen lone pair, in structures with the substituent in the axial position and the N-H bond in the equatorial position. This structure is the lowest-energy structure in the fluoro case but not in the trifluoromethyl case where there is an increased axial penalty associated with the CF group. The anomeric effect is characterized via geometrical evidence, natural bond orbital analysis, electrostatic effects, and energetic criteria. Computational results from a variety of levels of theory are presented including CCSD(T) with complete basis set extrapolation, B2PLYP-D, ωB97XD, B97-D, M06-2X, B3LYP, and MP2 allowing for a comparison of performance. The CCSD(T)/CBS results are very well represented by either B2PLYP-D or ωB97XD with moderate to large basis sets (aug-cc-pVTZ or aug-cc-pVDZ). Hyperconjugation, electrostatic effects, and steric effects play a role in the relative energetic ordering of the isomers considered. [ABSTRACT FROM AUTHOR]

The folding of proteins is directed by a variety of interactions, including hydrogen bonding, electrostatics, van der Waals' interactions, and the hydrophobic effect. We have argued previously that an n→π* interaction between carbonyl groups be added to this list. In an n→π* interaction, the lone pair ( n) of one carbonyl oxygen overlaps with the π* antibonding orbital of another carbonyl group. The tendency of backbone carbonyl groups in proteins to engage in this interaction has consequences for the structures of folded proteins that we unveil herein. First, we employ density functional theory to demonstrate that the n→π* interaction causes the carbonyl carbon to deviate from planarity. Then, we detect this signature of the n→π* interaction in high-resolution structures of proteins. Finally, we demonstrate through natural population analysis that the n→π* interaction causes polarization of the electron density in carbonyl groups and detect that polarization in the electron density map of cholesterol oxidase, further validating the existence of n→π* interactions. We conclude that the n→π* interaction is operative in folded proteins. [ABSTRACT FROM AUTHOR]

Experiments will be presented and reviewed to support the hypothesis that the intrinsic reactivity of formaldehyde may lead to the formation of a rather comprehensive set of defined biomolecules, including D-glucose, thus fostering concepts of evolution considering the existence of a premetabolic system as a primordial step in the generation of life. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Chemistry is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The saturated ring and secondary amine of proline spawn equilibria between pyrrolidine ring puckers as well as peptide bond isomers. These conformational equilibria can be modulated by alterations to the chemical architecture of proline. For example, C in the pyrrolidine ring can be replaced with sulfur, which can be oxidized either stereoselectively to yield diastereomeric S-oxides or completely to yield a sulfone. Here, the thiazolidine ring and peptide bond conformations of 4-thiaproline and its S-oxides were analyzed in an Ac-Xaa-OMe system using NMR spectroscopy, X-ray crystallography, and hybrid density functional theory. The results indicate that the ring pucker of the S-oxides is governed by the gauche effect, and the prolyl peptide bond conformation is determined by the strength of the n → π * interaction between the amide oxygen and the ester carbonyl group. These findings, which are consistent with those of isologous 4-hydroxyprolines and 4-fluoroprolines, substantiate the importance of electron delocalization in amino acid conformation. [ABSTRACT FROM AUTHOR]

There has been growing interest in polyproline type II (PPII) helices since PPII helices have been found in folded and unfolded proteins and involved in a variety of biological activities. Polyproline can also form type I helices (PPI) which are very different from PPII conformation and only exist in certain organic solvents. Recent studies have shown that stereoelectronic effects play a critical role in stabilizing a PPI or PPII helix. Here, we have synthesized a series of host-guest peptides with an electron-withdrawing substituent at the 4 R or 4 S position of proline and used a kinetic approach to further explore stereoelectronic effects on the transition barrier of the interconversion between PPI and PPII conformations. Time-dependent circular dichroism measurements revealed that the rates of PPII → PPI conversion were reduced upon incorporating the hydroxyl-, fluoro-, and methoxy-groups at the 4 R position while the rates would be increased if these substituents were at the 4 S position. We quantified the changes in transition free energy by comparing their rate constants. (4 R,2 S)-4-Fluoroproline and (4 S,2 S)-4-fluoroproline have the largest effect on the transition energy barrier for PPII → PPI conversion. Our results provide important insights into the role of stereoelectronic effects on the PPII → PPI transition state barrier, which has not been reported in past thermodynamic studies. [ABSTRACT FROM AUTHOR]

The polyproline type II (PPII) helix is a prevalent conformation in both folded and unfolded proteins, and is known to play important roles in a wide variety of biological processes. Polyproline itself can also form a type I (PPI) helix, which has a disparate conformation. Here, we use derivatives of polyproline, (Pro)10, (Hyp)10, (Flp)10, and (flp)10, where Hyp is (2 S,4 R)-4-hydroxyproline, Flp is (2 S,4 R)-4-fluoroproline, and flp is (2 S,4 S)-4-fluoroproline, to probe for a stereoelectronic effect on the conformation of polyproline. Circular dichroism spectral analyses show that 4 R electron-with-drawing substituents stabilize a PPII helix relative to a PPI helix, even in a solvent that favors the PPI conformation, such as n-propanol. The stereochemistry at C4 ordains the relative stability of PPI and PPII helices, as (flp)10 forms a mixture of PPI and PPII helices in water and a PPI helix in n-propanol. The conformational preferences of (Pro)10 are intermediate between those of (Hyp)10/(Flp)10 and (flp)10. Interestingly, PPI helices of (flp)10 exhibit cold denaturation in n-propanol with a value of Ts near 70°C. Together, these data show that stereoelectronic effects can have a substantial impact on polyproline conformation and provide a rational means to stabilize a PPI or PPII helix. [ABSTRACT FROM AUTHOR]

The well-known preference of the peptide bond for the trans conformation has been attributed to steric effects. Here, we show that a proline residue with an N-formyl group (H i−1−C′ i−1=O i−1), in which H i−1 presents less steric hindrance than does O i−1, likewise prefers a trans conformation. Thus, the preference of the peptide bond for the trans conformation cannot be explained by steric effects alone. Rather, an n → π* interaction between the oxygen of the peptide bond (O i−1), and the subsequent carbonyl carbon in the polypeptide chain (C′ i) also contributes to this preference. The O i−1 and C′ i distance and O i−1···C′ i=O i angle are especially favorable for such an n → π* interaction in a polyproline II helix. We propose that this electronic effect provides substantial stabilization to this and other elements of protein structure. [ABSTRACT FROM AUTHOR]

Theoretical and analytical thermal and electrical properties are studied through the 2,7-Di([1,1′-biphenyl]-4-yl)-9H-fluorene aromatic system as a prototype of a molecular switch. Variations of the dihedral angles between the two Benzene rings at each end of the molecule have been considered, thus determining the dependence on the structural variation of the molecule when the aromatic system is connected between metal contacts. The molecule is modeled through a Tight-Binding Hamiltonian where—from the analytical process of decimation and using Green's functions—the probability of transmission (T) is calculated by using the Fisher–Lee relationship. Consequently, the thermal and electrical transport properties such as I − V curves, quantum noise (S), Fano factor (F), electrical conductance (G), thermal conductance (κ), Seebeck coefficient (Q), and merit number ( Z T ) are calculated. The available results offer the possibility of designing molecular devices, where the change in conductance or current induced by a stereoelectronic effect on the molecular junctions (within the aromatic system) can produce changes on the insulating–conductive states. [ABSTRACT FROM AUTHOR]

Catalytic hydride delivery from in situ generated metal hydride complexes to substrates represents an important process in a variety of catalysis. Investigations revealed a “multidimensional synergistic control” among the stereoelectronic factors—yaw angle, bite angle, as well as the electronic properties of both the ligand and the metal center within the cyclometalated iridium catalysts—that govern the hydride donor ability (hydricity) of the complexes during catalysis. A frontier molecular orbital analysis provided the rationale of such a correlation. For more details, see the Full Paper by J. Choudhury et al. on page 13051 ff. [ABSTRACT FROM AUTHOR]