Steric Nature Research Articles

Unraveling the Isotropic Hyperfine Coupling Constants of Nitroxide Radicals via Molecular Electrostatic Potential Analysis.

Nitroxide radicals have wide and promising applications as organic magnetic materials. Modulating the isotropic hyperfine coupling constants (HFCCs) of these radicals through proper structural design is an effective strategy for their application as spin probes and spin labels. In the present work, density functional theory calculations were carried out to develop a robust descriptor based on the molecular electrostatic potential for nitrogen HFCCs of nitroxide radicals. Forty nitroxide radicals from five distinct classes, namely, derivatives of cyclic, acyclic, imino, nitronyl, and benzimidazole nitronyl nitroxides, were selected, and the molecular electrostatic potential (MESP) at the nitrogen atom (VN) of the NO moiety was calculated. The VN values efficiently capture the electronic changes associated with the steric and electronic nature of these systems. A significant correlation between VN values and the experimental HFCCs of nitrogen nuclei demonstrates the applicability of VN as a simple and efficient descriptor for monitoring HFCCs. Furthermore, a good correlation between VN and experimental nitrogen HFCCs for each class of nitroxide radicals indicates the use of VN in the evaluation of the magnetic nature of the nitroxide radicals. The findings in this work are expected to facilitate the design of novel nitroxide radicals with desirable magnetic properties based on MESP topology analysis.

Alkylphosphine makes difference: Highly robust Palladium(II) phosphine sulfonate catalysts for nonalternating copolymerization of ethylene with carbon monoxide

Production of polyketone realizes the direct conversion of cost effective and abundant olefin and carbon monoxide (CO) monomers. However, copolymerization of ethylene with CO shows a high tendency for the formation of strictly alternating structures, and they feature a high melting temperature (Tm) of 260 °C that impedes the processing by using the conventional injection molding and extrusion. Nonalternating preference in such copolymerization is a very promising method to circumvent the processability issues. In this study, we present a series of phosphine-sulfonate Pd catalysts for nonalternating copolymerization of ethylene and CO, since rare study has investigated the electronic and steric nature systematically in such ligand platform in this field. The usage of dicyclohexyl substituents on phosphorus moiety exhibits unexpected nonalternating preference with up to 29.2 mol% extra ethylene incorporation, thus lowing the Tm values to 162 °C. Notably, such alkyl substituted phosphine sulfonate Pd catalyst exhibits high thermally robust nature in this nonalternating copolymerization.

3,4-selective polymerization of isoprene by iron-based system: The key role of borate salts for enhancing catalytic activities and broadening 1,10-phenanthroline ligand scope

The catalytic system of iron(III) compound/alkylaluminum/1,10-phenothroline(Phen) has been long disclosed for efficient 3,4-selective polymerization of isoprene to achieve semi-crystalline 3,4-polyisoprene product, that finds important application in the current tire industry. Nevertheless, such a system is highly sensitive to the steric nature of Phen ligands, even a subtle variation (e.g. introducing methyl group to its 2,9-position) will result in significantly decreased catalytic activities. In this research, we disclose a facile method, i.e. in-situ addition of borate salts, that can well address such a long unsolved issue. By doing such, the pristine catalytic activities were able to be greatly enhanced (ca. 4-fold higher) without damaging the selectivity of the active species. Such a method was also applicable for various substituted Phen ligands, such as Phen2,9-(nBu)2, Phen2,9-(sBu)2, Phen2,9-(tBu)2, Phen2,9-(nHex)2, etc., which greatly broadens the ligand scope of such iron(III) based catalytic system. Mechanistic studies revealed that the attraction of alkyl group by borate salts to form the cationic active species might play a governing role in enhancing the activities.

Potassium phenoxides bearing bulky yet flexible substituents as highly active catalysts for ring opening polymerization of biobased macrolactone of ethylene brassylate

Well-controlled and efficient ring opening polymerization of biobased ethylene brassylate is of great challenge due to its stainless ring structure that often results in inferior reactivities as well as the presence of two ester groups in the monomer that often lead to extensive intra-/inter- molecular transesterification side reactions. This report discloses a family of potassium phenoxide complexes that bear bulky yet flexible substituents. The bulky nature of the ligand could suppress undesired transesterification reactions, allowing the polymerization proceed in a well controlled manner, as revealed from the detailed kinetic studies that linear relationships between −ln(1-x) (x denotes the polymer yield) and the polymerization time and between molecular weights of the obtained polymers and polymer yields. The flexible substituents on the ligand allowed more monomer accessing to the active species, which eventually gave rise to TOFs in a range of 3604–3780 h−1, that were much higher than analogues in previous reports. Moreover, systematic evaluation of the polymerization behaviors demonstrated that the catalytic efficiency of the complexes was closely related to the steric nature of the metal center, increased the steric congestion would give rise to much lower monomer conversions. A plausible mechanism was proposed based on the polymerization results, and such a mechanism was further confirmed by NMR monitoring studies.

Synthesis, spectroscopic, chemical reactivity, topology analysis and molecular docking study of ethyl 5-hydroxy-2-thioxo-4-(p-tolyl)-6-(trifluoromethyl)hexahydropyrimidine-5-carboxylate

The organofluorine hexahydropyrimidine derivatives are used in the drug discovery due to its steric nature to hydrogen and its extreme electronegativity. The Ethyl 5-hydroxy-2-thioxo-4-(p-tolyl)-6-(trifluoromethyl)hexahydropyrimidine-5-carboxylate (ETP5C) compound was synthesized and characterized by NMR (13C and 1H), FT-IR and UV–Vis spectroscopic techniques for experimentally and theoretically and elemental analyses, mass spectra also investigated. The most stable structure of synthesized molecule was studied by PES analysis in gas and liquid medium. The structural parameters such as bond length and bond angle of the title molecule have been obtained by DFT/B3LYP/6–311++G (d,p) set and compared with the structurally related experimental data of the compounds. The π-to-π* transition of the ETP5C molecule is identified using UV–Vis absorption spectral analysis. In addition, the chemical stability and reactivity are investigated using HOMO-LUMO analysis. The minimal HOMO-LUMO energy gap (4.6255 eV) clearly explains that the ETP5C molecule is more reactive for receptors. The nucleophilic and electrophilic regions such as active sites have been shown by MEP, ELF, LOL and Fukui functions. The second order optical effect has been explained by NLO analysis. The docking was performed with antineoplastic proteins that exhibit against the development of tumor cells.

A Pd-catalyzed route to carborane-fused boron heterocycles.

Due to the expanding applications of icosahedral carboranes in medicinal and materials chemistry research, their functionalizations have become one of the central themes in boron-rich cluster chemistry. Although several strategies for incorporating nitrogen-containing nucleophiles on a single boron vertex of the icosahedral carboranes (C2B10H12) have been developed, methods for preparing clusters with vicinal B-N moieties are still lacking. The steric bulk of icosahedral carboranes and disparate electronic and steric nature of the N-containing groups have rendered the vicinal diamination challenging. In this article, we show how a developed Pd-catalyzed process is used to incorporate an array of NH-heterocycles, anilines, and heteroanilines with various electronic and steric profiles onto the vicinal boron vertices of a meta-carborane cluster via sequential or one-pot fashion. Importantly, oxidative cyclizations of the cross-coupling products with indoles and pyrroles appended to boron vertices generate a previously unknown class of all-boron-vertex bound carborane-fused six- and seven-membered ring heterocycles. Photophysical studies of the meta-carborane-fused heterocycles show that these structures can exhibit luminescence with high quantum yields and are amenable to further manipulations.

Coordination-Induced Conformational Control Enables Highly Luminescent Metallo-Cages.

In recent years, luminescent materials have received a great deal of attention due to their wide range of applications. However, exploring a simple solution to overcome the fluorescence quenching resulting from the aggregation of conventional organic fluorophores remains a valuable area of investigation. In this study, we successfully constructed two metallo-cages, namely, SA and SB, through coordination-driven self-assemblies of the triphenylamine (TPA)-based donor L with different diplatinum(II) acceptors LA and LB, respectively. These metallo-cages take advantage of their steric nature and curved conformation to more effectively limit the free rotation of the benzene ring and hinder π-π stacking in the solid state, which successfully inhibited fluorescence quenching and realizing highly efficient luminescent properties. Therefore, this work offers a new design strategy for preparing materials with excellent luminescent properties.

Extending the π‐System in MnI Diimine Tricarbonyl Complexes: Impacts on Photochemistry, Electrochemistry, and CO2 Catalytic Reduction Activity

AbstractThe complex [Mn(bpy)(CO)3Br], has been previously studied as both an electrocatalyst and a photocatalyst, in conjugation with a photosensitizer, for CO2 reduction to CO. This study considers the relationship between this catalytic activity and the steric and electronic nature of the aromatic diimine ligand. To this end, the π‐system in the bidentate ligand is increased step‐wise from 2,2′‐bipyridine (bpy) to 2‐(2‐pyridyl)quinoline (pq) to 2,2′‐biquinoline (bqn) in a series of three fac‐[Mn(α‐diimine)(CO)3Br] complexes. It is found that the propensity of these complexes to photochemically dimerize trends with the energy of the α‐diimine π* energy. Electrochemically, it is observed that the second reduction event in these systems becomes increasingly thermodynamically favorable and approaches the potential of the first reduction event as the π‐system expands. In fac‐[Mn(bqn)(CO)3Br], the second reduction is more favorable than the first reduction, precluding the formation of a dimer intermediate; even though, chemical reduction of fac‐[Mn(bqn)(CO)3Br] confirms that the dimer, [Mn(bqn)(CO)3Br]2 is able to form and not prevented by steric considerations. Though the second reduction potential is more positive for bqn and pq than for bpy, the CO2 reduction mechanism changes such that the overpotential for carbon dioxide reduction occurs at more negative potentials, leading to a decrease in overall catalytic activity.

Regioselective Rhodium‐Catalyzed 1,2‐Hydroboration of Pyridines and Quinolines Enabled by the Tris(8‐quinolinyl)phosphite Ligand**

AbstractA Rh(I) complex [κ2(P,N)‐{P(Oquin)3}RhCl(PPh3)] (1) bearing the P,N ligand tris(8‐quinolinyl)phosphite, P(Oquin)3, has been synthesized and structurally characterized. The molecular structure of complex 1 shows that P(Oquin)3 acts as a bidentate P,N chelate ligand. Reactivity studies of 1 reveal that the triphenylphosphine ligand can be replaced by Pcy3 or removed upon oxidation with concomitant coordination of a second 8‐quinolyl unit of P(Oquin)3. In addition, the Rh(III) complex [RhCl2{OP(Oquin)2}] (3), resulting from treating 1 with either wet CDCl3 or, sequentially, with HCl and water, was identified by X‐ray diffraction analysis. Complex 1 catalyzes the 1,2‐regioselective hydroboration of pyridines and quinolines, affording N‐boryl‐1,2‐dihydropyridines (1,2‐BDHP) and N‐boryl‐1,2‐hydroquinolines (1,2‐BDHQ) in high yield (up to >95 %) with turnover numbers (TONs) of up to 130. The system tolerates a variety of substrates of different electronic and steric nature. In comparison with other transition‐metal‐based hydroboration catalysts, this system is efficient at a low catalyst loading without the requirement of base or other additives.

One‐Pot Access to Tetrasubstituted 2‐Aminothiophenes via Regio‐ and Chemoselective Domino Reactions of Dithioesters with Fumaronitrile at Room Temperature

AbstractHerein, we report a one‐pot viable protocol to synthesize tetrasubstituted 2‐aminothiophenes engaging readily accessible α‐enolic dithioesters and abundant fumaronitrile under transition metal‐free conditions at room temperature in open air. The reaction proceeds via successive Michael‐type addition/intramolecular cyclization/isomerization cascades. The added features are benign conditions, exclusive regio‐ and chemoselectivity, excellent atom‐/step‐economy, easy purification, and tolerance of wide range of functional groups of a diverse electronic and steric nature. This protocol not only provided a robust and modular approach to various 2‐aminothiophenes in moderate to excellent yields, but also demonstrated the potential of dithioesters and fumaronitrile in the challenging intermolecular cross‐coupling reactions widening the arsenal of synthetic methods.

Catalyst-Controlled Divergent Cycloisomerizations of N-Propargyl Indoles.

Herein, a new series of catalyst-controlled divergent cycloisomerizations of indole-tethered alkynes was developed utilizing readily available, versatile, and flexible N-propargyl indoles as substrates and BrettPhosAuNTf2 and PtCl4 as catalysts, where the chemodivergency was attributed to both the steric and electronic nature of the catalysts. A broad spectrum of N-propargyl indoles could be employed in this protocol, enabling the divergent synthesis of a library of 9H-pyrrolo[1,2-a]indoles and 4H-pyrrolo[3,2,1-ij]quinolines. Moreover, the reactions could be performed at mmol scales.

Theoretical insight into the unexpected initial (3 + 2) cycloaddition reaction of mesitonitrile oxide with 1, 4-diazepine derivatives: A computational study

1,4-Diazepine as an active drug component underlies the potency of most psychotic, anticancer, anticonvulsant, and antibacterial drugs in the market and is, therefore crucial in chemotherapeutic treatment in biomedicine. Proper functionalization of this moiety can afford even more potent drugs. As a result of their therapeutic significance, this study aims at precisely giving a comprehensive computational insight into the unexpected initial reactivity of 1,4-diazepine derivatives and mesitonitrile oxide. The initial reaction between mesitonitrile oxide and 1,4-diazepine derivatives proceeds via a (3 + 2) cycloaddition reaction which leads to the formation of a cycloadduct where the mesitonitrile oxide unexpectedly adds across the imine functionality at the expense of the potential olefinic carbon-carbon double bond. Calculations at the density functional theory (DFT) M06/6-311G (d, p) level of theory indicate that the initial (3 + 2) cycloaddition reaction of mesitonitrile oxide (1,3-dipole) and 1,4-diazepine derivatives (dipolarophile) in all cases proceeds to form the cycloadduct where the 1,3-dipole adds preferentially to the imine functionality at the expense of the potential olefinic carbon-carbon double bond. In light of the parent reaction, the most kinetically favored cycloadductP3A had a rate constant of 5.1 × 106 M−1s−1, which is about 12 manifolds faster than the next competing stereoisomer P1A with a rate constant of 4.1 × 105 M−1s−1 and about 1024 faster than the most favored cycloadduct P3B with a rate constant of 7.2 × 10−19 M−1s−1 in the unfavored pathway (Path B). Irrespective of the electronic and steric nature of the electron-donating (EDG) and electron-withdrawing (EWG) substituents placed on the dipolarophile, the selectivities of the reaction were maintained. Rationalization of the potential energy surface depicts that the 1,3-dipole adds across the dipolarophile via an asynchronous concerted mechanism. Rationalization of the HOMO-LUMO energies of the mesitonitrile oxide (1,3-dipole) and the 1,4-diazepine derivatives (dipolarophile) depict that the EDG-substituted dipolarophile react as nucleophiles, whereas the dipole reacts as an electrophile. Conversely, the HOMO-LUMO interaction between the EWG-substituted dipolarophile indicates that the EWG-substituted dipolarophile react as electrophiles, whereas the dipole reacts as a nucleophile. The electrophilic parr function at various reactive sites of the dipolarophile shows that the 1,3-dipole preferentially adds across the local centers with the largest electrophilic NBO or Mulliken spin densities which is consistent with the energetic trend observed. The reactivity of the 1,4-diazepine derivatives and the mesitonitrile oxide showed poor stereoselectivity.

The complement protein C1q modulates the activities of anti-influenza HA-stem and anti-SARS-Cov2-nonRBD antibodies and alters viral evolution

Abstract The broadly neutralizing hemagglutinin (BN-HA) stem antibodies represent an universal vaccine prospect. However, our understanding of how these antibodies interact with the influenza virus is limited by excluding other immune elements, such as complement, in our experimental systems. Here, we show that the Fc binding protein of the complement system, C1q, grants BN-HA stem Abs a novel attachment inhibition (AI) and boosts virus neutralization (VN) activity. C1q promotes AI even if added to preformed BN-HA Ab-virion-RBC complexes, pointing at the steric nature of the phenomenon. Most probably by the same mechanism of steric hindrance, C1q also contributes to fusion inhibition. By employing a panel of engineered avidity-reverted anti-BNHA Abs we show that the C1q-mediated VN enhancement is independent of Ab avidity. We also show that C1q’s presence expands the escape viral repertoire beyond the HA stem domain. Among selected viral variants, near-RBS mutations (E156K-Sb, R224I-Ca, S145N-Ca) modulate HA avidity while causing antigenic drift. Expanding our discoveries to SARS-CoV-2, we identified non-RBD anti-SARS-CoV-2 spike Abs which exhibit C1q-VN enhancement. With an increased SARS-CoV-2 spike per viral particle amount, C1q-VN increased concomitantly. Altogether, our results emphasize the general role of C1q in Ab-mediated antiviral activity and viral evolution. NIH/NIAID intramural funding

Radical-Cascade Avenue to Access 1,2-Dithioles Employing Dithioesters and Edman’s Reagent

An operationally simple and efficient domino etiquette has been developed for the facile construction of 1,2-dithioles employing easily accessible dithioesters as a three-atom CCS synthon and aryl isothiocyanates as a two-atom CS unit in the absence of any catalyst and additive at room temperature under open air. The reaction proceeded efficiently affording the desired 1,2-dithioles in good yields having various functional groups of a diverse electronic and steric nature. This approach avoids possible toxicity and tiresome workup conditions and features easy to handle, cheap, and readily accessible reagents, O2 as a green oxidant, and gram-scale ability. Notably, the final S-S bond formation and cascade ring construction follow a radical pathway, which has been recognized via a radical trapping experiment with BHT during the course of the reaction. Notably, the exocyclic C═N bond at position 3 of 1,2-dithiole possesses Z stereochemistry.

Carbonyl functionalized polyethylene materials via Ni- and Pd-diphosphazane monoxide catalyzed nonalternating copolymerization

Polyethylenes are currently the most prevalent synthetic polymers in the world, and the introduction of functional groups into polyethylene backbone can reduce problematic environmental persistence and enhance compatibility with other materials. This target can be addressed by transition-metal-catalyzed nonalternating copolymerization of ethylene with carbon monoxide, but it is generally impeded by the facile formation of alternating polyketones in kinetics. The reduction of carbonyl density in polyketones could weaken their inter-chain dipolar interaction, thus gradually approaching to polyethylene materials in term of crystalline and tensile properties. In this contribution, we communicate our continued efforts to investigate on the electronic and steric nature of Ni- and Pd-coordinated cationic [P,O] type catalysts, and they were used for nonalternating carbonylative copolymerization of ethylene, which resulted carbonyl functionalized polyethylenes with comparable molecular weight and desirable mechanistic property similar to those of commercial high-density polyethylene, and the incorporated carbonyls in polyethylene chains impart photodegradability. Notably, Pd complex 5 with an electron donating substituent on phosphine moiety yielded polyethylene products with a uniform dispersion of isolated carbonyls and a high molecular weight of ∼100 kg/mol.

Regio- and Chemoselective Access to Dihydrothiophenes and Thiophenes via Halogenation/Intramolecular C(sp2)-H Thienation of α-Allyl Dithioesters at Room Temperature.

An operationally simple, practical, and efficient cascade approach employing α-allyl dithioesters and NBS/NIS has been achieved to access a series of dihydrothiophenes and thiophenes containing diverse functional groups of different electronic and steric natures in good to excellent yields at room temperature in open air. The reaction proceeds via the electrophilic addition of a halogen source (NBS/NIS) to an allylic double bond, followed by intramolecular regio- and chemoselective S-cyclization. This protocol avoids potential toxicity and tedious work-up conditions, and features easy synthesis from readily available starting materials under catalyst-free conditions. Furthermore, 4,5-dihydrothiophenes were aromatized to thiophenes by treatment with KOH in DMF at room temperature. A probable mechanism for the formation of dihydrothiophenes and thiophenes from α-allyl dithioesters has been suggested. Notably, a large-scale experiment and the transformations of products indicated the potential utility of this reaction compared to competing processes for the synthesis of 4,5-dihydrothiophenes and thiophenes.

Direct Measurement of Surfactant-Mediated Picoforces among Nanoparticles in a Quasi-Two-Dimensional Environment.

The lack of methodologies which enable us to measure forces acting between nanomaterials is one of the factors limiting the full comprehension of their behavior and their more effective exploitation in new devices. Here we exploit the irreversible adsorption of surfactant-decorated nanoparticles at the air/water interface to investigate interparticle forces and the effect of the surfactant structure on them. We measured the interparticle repulsive forces as a function of the modulation of the interparticle distance by simultaneously performing compression isotherms and the grazing incidence small-angle X-ray scattering (GISAXS) structural characterization of the monolayers at water–vapor interfaces. Our results demonstrate that the short-range interparticle forces are strongly affected by the presence of the organic ligands, which are shown to be able to influence the interparticle repulsions even when added in micromolar amounts. In particular, we demonstrate the predominant steric nature of short-range forces, which are accounted for in terms of the compression-induced stretched-to-coiled conformational transition of the ligand hydrophobic tail.

Cooperative triple catalysis enables regioirregular formal Mizoroki–Heck reactions

The Mizoroki–Heck reaction between alkenes and aryl halides represents one of the most important methods for C−C bond formation in synthetic chemistry. Governed by their electronic and steric nature, alkenes are generally arylated with high regioselectivity, which conversely hampers diversity, in particular, if the regioirregular isomer is targeted. Usually, electron-poor alkenes selectively afford the corresponding β-coupled products, and achieving the opposite regioselectivity to obtain their α-arylated congeners is highly challenging. It would be desirable to access the irregular α-regioisomer by simple variation of the reaction conditions, keeping the standard substrates, thereby significantly enlarging the product space. Herein, we describe an intermolecular α-arylation of electron-poor alkenes through cooperative nickel, photoredox and sulfinate catalysis. This triple catalysis system operates under mild conditions and features excellent functional group tolerance. The orchestration of radical, transition metal and ionic bond-forming and -cleaving reactions in a single process is highly challenging, but certainly opens valuable doors in terms of reactivity. Moreover, the intermolecular α-arylation, α-alkenylation and α-alkynylation of styrenes could also be achieved through a one-pot process.

Catalytic Asymmetric Construction of CF3-Substituted Chiral sp3 Carbon Centers

AbstractDue to the unique steric and electronic nature of the fluorine atom, organofluorine compounds have received significant attention in the fields of pharmaceuticals and agrochemicals. In particular, the CF3 group is frequently found in biologically active compounds. However, compared to aryl- and alkenyl-CF3-containing molecules, the construction of sp3 carbon-based alkyl-CF3-containing molecules, particularly via catalytic enantioselective synthesis, remains a considerable challenge in spite of their high potential in medicinal applications. This short review focuses on recent advances in this research area, and the reported strategies are categorized according to reaction types and starting substrates. In addition, chiral catalysts, substrate scope, and reaction mechanisms are briefly summarized. 1 Introduction2 Stereoselective Introduction of a CF3 Group2.1 Nucleophilic Addition to Carbonyls and Imines2.2 Electrophilic Substitution at the α Position of Carbonyls2.3 Allylic Nucleophilic Substitution3 Stereoselective Functionalization of CF3-Substituted Molecules3.1 Electrophilic Substitution of α-CF3 Carbonyls3.2 Substitution of α-Halo CF3 Compounds3.3 Addition-Type Reactions with CF3-Substituted Alkenes4 Conclusion and Outlook

Low‐coordinate cobalt(0) N‐heterocyclic carbene complexes as catalysts for hydrosilylation of alkynes

AbstractAmong the great efforts of developing cobalt‐based catalysts for hydrosilylation reactions, cobalt (II) and cobalt(I) complexes are the extensively studied ones. In contrast, explorations on cobalt(0) complexes are relatively rare. Presented herein is the investigation on the catalytic performance of low‐coordinate cobalt(0) N‐heterocyclic carbene (NHC) complexes in the hydrosilylation reaction of alkynes, which disclosed the fine performance of [(CyIDep)Co(η2‐CH2CHSiMe3)2] (CyIDep denotes for a 1,3‐bis(2′,6′‐diethylphenyl)imidazole‐2‐ylidene that bears fused cyclohexyl group on the imidazole backbone) in catalyzing the syn‐addition of a series of symmetric and unsymmetric internal alkynes with H2SiPh2, producing vinylsilanes with high regio‐selectivity. Mechanistic study indicates that the catalytic reaction likely proceeds on a cobalt(0)/cobalt(II) cycle and that the high selectivity is governed by the steric nature of the NHC ligand.