Themed collection Mechanistic, computational & physical organic chemistry in OBC

By examining the various contributions to the conformational and stereogenic stability of medium-sized benzo-fused N-heterocyclic atropisomers, this review serves to aid the design, synthesis and study of these pharmaceutically relevant heterocycles.

This review covers the 1,3-dithiol-2-ide structural unit in relation to the dual electronic character of dithiafulvene and in relation to using it as a synthetic building block for constructing for example extended tetrathiafulvalenes.

From isolated molecules to the bulk phase: building models of biocompatible ionic liquids.

This review covers recent computational studies evidencing the presence of glycosyl cations as real intermediates in several glycosylation reactions.

A general view of the medium effects on ionic reactions involves the solvent effect, ion pairing, formation of aggregates and structured environment.

Recent advances in computational investigations of Lewis base amine/imine-catalyzed reactions have been systematically summarized and reviewed for the first time.

Optical purity (op) and enantiomeric excess (ee) become equal when either heterochiral dimerization constant is twice that of homochiral dimerization constant or specific rotations of monomer and dimer are equal.

Sulfonyl migrations, frequently described as ‘unusual’ or ‘unexpected’, from the last 20 years, including 1,2-, 1,3-, 1,4-, 1,5-, 1,6- and 1,7-sulfonyl shifts, through either radical or polar processes, either inter- or intramolecularly are reviewed.

This critical short review focuses on some key features which determine successful enantioselective catalysed multicomponent reactions (MCRs) and are typically underappreciated in the literature.

This review highlights the importance of N-heterocyclic carbene (NHC) basicity for transformations in which NHCs are used as catalysts.

Diazaborines react slowly with H₂O₂ but rapidly with ONOO⁻, offering a new platform for discriminating between these two cellular ROS.

Magnetic evaluations of aromaticity suggest that hydrogen bonding interactions can perturb the Clar sextet characters of acridones, which have implications for their electronic properties.

QM/MM chain-of-states calculations of CTX-M-44 show distinct acylation profiles for ampicillin and cefalexin, the acylation resistance observed for cefalexin attributes to decreased proton affinity induced by the delocalized π-conjugation.

Through a combined crystallographic and computational analysis, we designed and investigated two novel host units for the recognition of neutral and charged guests inspired by a glutamate carboxypeptidase II system and its inhibitors.

In a joint DFT and chemometrics study applied to NMR spectra, we disclose the structure of the main decomposition products of hexamethylenetetramine at thermal conditions. The mechanism involves a protonation of HMTA followed by a ring opening and finally a Sigmatropic rearragnment [1,5-H].

This contribution explores the bifunctional catalytic activity of water clusters ((H₂O)_n with n = 1–5) in organic chemistry similar to that observed in the formation of H₂SO₄ in acid rain.

The mechanism of Pd-catalysed γ-C(sp³)–H arylation of thioethers has been disclosed, wherein all steps proceed through the heterodimeric Pd–Ag pathway.

Investigation on the dynamic processes of 1-(C₅H₅)Si(Me)₃ in its Diels–Alder addition showed that Si(Me)₃ migration is the dominant factor and hydrogen shifts are negligible.

σ-Hole bonding interactions (e.g., tetrel, pnictogen, chalcogen, and halogen bonding) can polarize π-electrons to enhance cyclic [4n] π-electron delocalization (i.e., antiaromaticity gain) or cyclic [4n + 2] π-electron delocalization (i.e., aromaticity gain).

A computational study revealed the mechanistic details and controlling factors of reactivity in intramolecular C–H vinylation through a vinyl cation intermediate.

What computational methods should be used to achieve the most reliable result in computational structure elucidation? A study on the effect of quality and quantity of geometries on computational NMR structure elucidation performance is reported.

Quantum mechanical calculations (DLPNO-CCSD(T) and M06-2X) are employed to gain insights into the mechanism and selectivity in the catalytic synthesis of dihydropyrido[1,2-a]indoles from the cascade reaction between nitrones and allenes.

A simple route to enantiomerically pure (S)-2-aminobutyramide – the chiral component of the anti-epileptic drugs Levetiracetam and Brivaracetam has been developed. This approach is based on the rational design and application of a Viedma ripening process. The practical potential of the process is demonstrated on a large scale.

Aluminum chloride was successfully used instead of liquid superacids to mediate selective reactions of 1-nitronaphthalene with benzene and cyclohexane.

Hammett analysis reveals iodine(III)-mediated oxidative dearomatization reactions proceed through cationic intermediates and not direct nucleophilic attack on an activated phenol.

A mesoionic bicycle, easily synthesized from a proteinogenic amino acid, L-leucine, behaves as both thiazolium-olate and diazolium-olate dipoles, as unveiled by its dipolar cycloadditions.

Peptide “cross-stitching” maintains binding affinity and can enhance helical and proteolytic stability.

Azoarene photoswitches are versatile molecules that interconvert from their E-isomer to their Z-isomer with light.

Aqueous formamide solutions can promote catalytic amidolysis of an activated organophosphate in a regiospecific process.

Vibrational CD and DFT calculations reveal solution-state conformational preferences of orbitides following cyclization.

Aspirin-acetylated COX-2, but not COX-2, triggers the biosynthesis of anti-inflammatory E-series resolvins. The role of aspirin in the molecular mechanism of resolvin formation from EPA is revealed by MD simulations and QM/MM calculations.

A combined computational/experimental approach has revealed key mechanistic aspects in a recently reported dyotropic expansion of hydrindanes into decalins.

Methoxy-d₃ group installed at the C-1 position of a series of epimeric pairs of sugars generated mirror-image VCD patterns in the 2300–1900 cm⁻¹ region depending on the C-1 stereochemistry irrespective of the configurations at other positions.

DFT modelling predicts proximal boron groups can accelerate sulfenate alkylation reactions, depending on boron substituents and boron distance from the reaction site.

The antioxidant capacity of β-carotene has been studied in terms of H-atom abstraction reactions using quantum chemical methods.

A synthetic approach towards the 6H-benzo[c]chromene ring under visible light and transition-metal-free conditions has been developed. A theoretical analysis was performed using DFT methods in order to study the ET mechanism.

The dynamics of the loop controls the promiscuous activity in the HisA enzyme.

Low energy conformations of two carbohydrate-based oxepines were characterized by computational methods and ³J_H,H coupling constant analysis. Oxepine reactivity in Ferrier reactions was correlated with percentage vinylogous anomeric effect (VAE).

Delineation of the mechanism with DFT calculations.

The surprising mechanistic results for the silylation of alcohols revealed multiple intermediates and a higher order of silyl chloride leading up to the rate-determining step.

Activated phenolic esters are promising as lysine-targeted covalent inhibitors of the PI3Kδ enzyme. Quantum chemical calculations on model reactions provide insights into the reaction mechanisms and factors determining inhibitor efficiency.

A computational study of 2,2-azobis(isobutyronitrile) (AIBN)-initiated aerobic oxidative cleavage of alkenes is carried out employing density functional theory (DFT) and high-level coupled-cluster methods.

The intriguing rearrangement of naturally occurring vinyl allene oxides to ketols, cyclopropylcarbinols and Favorskii-type carboxylic acids has been computational justified with model systems.

We present the theoretical verification, revision and enrichment of Beecham's rule for bridged-ring lactones. This provides an alternative way to correlate experimental ECD data with stereochemistry in addition to quantum-chemical calculation.

The mechanism-based mutagenicity and carcinogenicity of diethylnitrosamine (DEN) are believed to act through interactions with cytochrome P450 (P450) enzymes.

The mechanism of the enantioselective intramolecular hydroamination of alkenyl thiourea catalyzed by chiral phosphoramide was revealed using density functional theory calculations.

The most promising types of iodoazolium compounds exhibiting high catalytic activity toward halogen abstraction and carbonyl activation are highlighted.

Mechanistic study and superior performance of electron-rich p-substituted aniline derivatives as catalysts for efficient hydrazone formation and exchange in both protic and aprotic solvents.

D-AllNAc shows in water solution a significant presence of four tautomers arising from pyranoid and furanoid ring forms and anomeric configurations.

Log P values for amino acid derivatives were integrated on one scale allowing comparison between common amino acids and their chemical analogues.

Through DFT calculations, thiourea-like halogen bond (XB)-based catalysts, with XB donor moieties connected via covalent bonds, have been designed and applied to Diels–Alder reaction and sulfa-Michael addition.

The dipeptide isoGln moiety of ManAdDMP significantly contributes to the binding to the NOD2 receptor. Loops 2 and 7 are important for ligand recognition and could be useful for further investigation of NOD2 activation/inhibition.

In this study, the PDB has been inspected for the analysis of HaBs in biological systems, highlighting their importance in four different protein–ligand systems.

Atomistic molecular dynamics simulations shed structural light on the curvature inflicted on DNA upon binding of calicheamicin ε to high-affinity and low-affinity target sites.

The overall molecular dipole moments calculated for some common fluorinated anaesthetics correlate with the respective blood-gas partition. This finding may aid the design of novel last-generation anaesthetics.

Novel homochiral sulfanyl-substituted naphthyltriazoles are synthesized via the triazolization reaction, and their rotational stability is studied in detail.

Transformation of substituted glycals to chiral fused aromatic cores using DFT calculations reveal that the base catalyzed reaction is favorable over sigmatropic [1,5] hydrogen shift and the product formation is governed by aromaticity.

Enzyme-catalyzed synthesis reactions are of crucial importance for a wide range of applications.

Glycosyltransferases (GTs) from the GT1 family are responsible for the glycosylation of various important organic structures such as terpenes, steroids and peptide antibiotics, making it one of the most intensely studied families of GTs.

The importance of the water network in BRD4-BD1 complexes is illustrated using molecular docking and absolute free energy perturbation simulations. 82% of the ligand poses were better predicted when including water molecules as part of the receptor.

Hydrazones and oximes with proximal boronic acids undergo facile exchange, which can be sped up or slowed down with pH control or abolished with oxidation.

The molecules undergo wavelength dependent photochemistry, since photodeamination to QMs takes place only upon excitation to higher excited singlet states, showing unusual anti-Kasha photochemical reactivity.

Ab initio and DFT calculations revealed that β-hydrogen abstraction would be favourable, which supports experimental findings (i.e. β-selective abstraction).

The oxidation mechanism of thiamine (vitamin B1) to thiochrome was investigated by DFT calculations for reaction models, thiamine + oxidant + (H₂O)₈. A key thiazolone intermediate (Int2) was commonly found to intervene during the oxidation.

We present the VRAI-selectivity program which predicts the major product and selectivity not only for transition-state controlled reactions but also for processes controlled by reaction dynamics.

DFT mechanistic investigations uncovered the origins of the reactivity and regioselectivity of Cp*Ir(III)/Cp*Rh(III)-catalyzed allylic C–H amidation reactions.

In the experimental process of preparing 1,4-DHP by a Hantzsch-like reaction, it was found that a by-product named 1,2-DHP was produced.

A series of diamine-tetraamido macrocyclic molecules with different organic linkers are explored as potential CO₂ capturing agents using quantum chemical calculations.

Using Density Functional Theory, the mechanism of the enantioselective phosphoric acid-catalyzed aza-Cope rearrangement was investigated. Stabilization of the preferred reaction pathway was rationalized by studying the non-bonding interactions between substrate and catalyst.

The present paper examines both catalyst-free and KF-mediated hydroboration of carbonyl compounds with the use of quantum-chemical methods.