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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]

The anomeric effect, one of the classic stereoelectronic effects in organic chemistry, describes the preference of an electronegative substituent at the anomeric carbon of glycosides to adopt the axial configuration. Herein, we briefly survey the history and broad applications of the anomeric effect in organic synthesis. Particularly, we highlight the recent investigations on the related metallo-anomeric effect in carbohydrate chemistry and the possible strategies for its easy regulation via the alteration of the metal, oxidation state, ligand, and structure of the substrate. A positive interplay between scientific research and organic chemistry teaching would profoundly help students to understand the basic concepts and advanced applications of the metallo-anomeric effect. [ABSTRACT FROM AUTHOR]

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]

[Display omitted] • The STM-BJ method is used to monitor single-molecule conductance states. • Single-molecule conductance tests reveal conjugation regulation mechanisms. • An external electric field regulates the stereoelectronic effect and lateral effect. Conjugated molecules have diverse applications across electronics, optoelectronics, and sensors. Their conjugated characteristics determine the molecular electronic and photonic properties, which are crucial for the design of functional materials. This study investigates the conjugation-regulated molecular transport properties by a combination of scanning tunneling microscopy break junction technologies and theoretical simulations. Two conductance states, which originate from π-contact and σ-contact, respectively, are found and can be further regulated by conjugation. With increasing conjugation, the high conductance state of π-contact can be enhanced through the lateral effect between the molecular conjugated backbones and gold substrates, while the low conductance state of σ-contact, which varies with the molecular torsion angle, is mainly affected through the stereoelectronic effect. Moreover, the high electric field increases the lateral interaction of the π-contacts while decreasing the conductance of the σ-contacts. These conjugation-regulated lateral and stereoelectronic effects provide valuable insights into functionalization and optimization of molecular materials and devices. [ABSTRACT FROM AUTHOR]

A general method for chemo- and diastereoselective modification of anticancer natural product arglabin with nitrogen- and carbon-centered pronucleophiles under the influence of nucleophilic phosphine catalysts was developed. The locked s-cis-geometry of α-methylene-γ-butyrolactone moiety of arglabin favors for the additional stabilization of the zwitterionic intermediate by electrostatic interaction between phosphonium and enolate oxygen centers, leading to the unprecedentedly high efficiency of the phosphine-catalyzed Michael additions to this sesquiterpene lactone. Using n-Bu 3 P as the catalyst, pyrazole, phthalimide, 2-oxazolidinone, 4-quinazolinone, uracil, thymine, cytosine, and adenine adducts of arglabin were obtained. The n-Bu 3 P-catalyzed reaction of arglabin with active methylene compounds resulted in the predominant formation of bisadducts bearing a new quaternary carbon center. All synthesized Michael adducts and previously obtained phosphorylated arglabin derivatives were evaluated in vitro against eleven cancer and two normal cell lines, and the results were compared to those of natural arglabin and its dimethylamino hydrochloride salt currently used as anticancer drugs. 2-Oxazolidinone, uracil, diethyl malonate, dibenzyl phosphonate, and diethyl cyanomethylphosphonate derivatives of arglabin exhibited more potent antiproliferative activity towards several cancer cell lines and lower cytotoxicity towards normal cell lines in comparison to the reference compounds, indicating the feasibility of the developed methodology for the design of novel anticancer drugs with better therapeutic potential., (© 2024 Wiley-VCH GmbH.)