Reactivity of a Hexaaryldiboron(6) Dianion as Boryl Radical Anions.

Our study unveils a novel approach to accessing boryl radicals through the spontaneous homolytic cleavage of B-B bonds. We synthesized a hexaaryl-substituted diboron(6) dianion, 1, via the reductive B-B coupling of 9-borafluorene. Intriguingly, compound 1 exhibits the ability to undergo homolytic B-B bond cleavage, leading to the formation of boryl radical anions, as confirmed by EPR studies, in the presence of the 2.2.2-cryptand at room temperature. Moreover, it directly reacts with diphenylacetylene, producing an unprecedented 1,6-diborylated allene species, where the phenyl ring is dearomatized. Density functional theory computational studies suggest that homolytic B-B bond cleavage is favored in the reaction path, and the formation of the boryl radical anion is crucial for dearomatization. Additionally, it achieves the dearomative diborylation of anthracene and the activation of elemental sulfur/selenium under mild conditions. The borylation products have been successfully characterized by NMR spectra, HRMS, and X-ray single-crystal diffraction.

Advancing Gold Redox Catalysis: Mechanistic Insights, Nucleophilicity-Guided Transmetalation, and Predictive Frameworks for the Oxidation of Aryl Gold(I) Complexes.

Gold redox catalysis, often facilitated by hypervalent iodine(III) reagents, offers unique reactivity but its progress is mainly hindered by an incomplete mechanistic understanding. In this study, we investigated the reaction between the gold(I) complexes [(aryl)Au(PR3 )] and the hypervalent iodine(III) reagent PhICl2 , both experimentally and computationally and provided an explanation for the formation of divergent products as the ligands bonded to the gold(I) center change. We tackled this essential question by uncovering an intriguing transmetalation mechanism that takes place between gold(I) and gold(III) complexes. We found that the ease of transmetalation is governed by the nucleophilicity of the gold(I) complex, [(aryl)Au(PR3 )], with greater nucleophilicity leading to a lower activation energy barrier. Remarkably, transmetalation is mainly controlled by a single orbital - the gold dx 2 -y 2 orbital. This orbital also has a profound influence on the reactivity of the oxidative addition step. In this way, the fundamental mechanistic basis of divergent outcomes in reactions of aryl gold(I) complexes with PhICl2 was established and these observations are reconciled from first principles. The theoretical model developed in this study provides a conceptual framework for anticipating the outcomes of reactions involving [(aryl)Au(PR3 )] with PhICl2 , thereby establishing a solid foundation for further advancements in this field.

Gold(I)-Catalyzed Intramolecular 7-endo-dig Cyclization of Triene-Yne Systems: New Access towards Azulenothiophenes.

We report the direct synthesis of new azulene derivatives through gold-catalyzed cyclization reactions. A five-membered ring as backbone in the applied triene-yne substrates turned out to be crucial to induce the 7-endo-dig cyclization mode necessary to trigger azulene formation. The obtained targets are of high interest due to their potential applications in different fields, like organic materials, medicine or cosmetics. UV/Vis spectra and cyclic voltammetry were measured, based on these the electronic properties were determined. Short two or three step sequences towards the applied starting materials make this approach synthetically highly attractive.

Factors Influencing the Chemoselectivity of Pd(OAc)2 -Catalyzed Cyclization Reactions Involving 1,6-Enynes as a Substrate and PhI(OAc)2 as a Reagent.

It is well documented in the literature that 1,6-enynes are cyclized using PhI(OAc)2 (PIDA) in the presence of Pd(OAc)2 as a catalyst to yield cyclopropyl ketones. In contrast, it has been reported that when 1,6-enynes are substituted by a hydroxy group at the α-position to the alkyne, the chemoselectivity of the cyclization reaction is altered, and polycyclic oxa-heterocycles are formed. This suggests that the hydroxy substituent plays a crucial role in changing the mechanism of the reaction. The aim of this study is to use density functional theory (DFT) calculations at the SMD/M06-D3/def2TZVP//SMD/M06/SDD,6-31G(d) level of theory to shed light on the reason for this change by investigating the detailed mechanistic aspects of these transformations. This study demonstrates that the electronic nature of the Pd catalyst changes from π-philicity to oxophilicity during the catalytic cycle, and this change plays an essential role in controlling the chemoselectivity of the cyclization reactions. In addition, it was found that (1) the hypervalent iodine reagent PIDA serves not only as an oxidant for the oxidation of Pd(II) to Pd(IV), but also as a nucleophile that drives the acetoxypalladation step of the reaction, (2) the oxidation of Pd(II) to Pd(IV) by the iodonium ion [PhIOAc]+ occurs via an interesting mechanism involving coordination of [PhIOAc]+ to the Pd(II) centre, followed by a twist in the hypervalent iodine, and (3) Pd π-complexes are not very susceptible to oxidation. (4) A Pd(II) complex can be six coordinate if the Pd centre is partially oxidized.

Dipole-Transmissive 1,3-Dipolar Cycloadditions for the Rapid Construction of Polycyclic N-Heterocycles: Synthetic and Mechanistic Investigations.

The investigation of distinctive dipole-transmissive dipolar cycloaddition (DTDC) methodology and the formalisation of this concept is reported. A DTDC procedure was able to be developed by taking advantage of the structural complementarity of azide and diazoalkane 1,3-dipoles. Intramolecular azide-alkene 1,3-DCs followed by spontaneous dipole transmission upon work-up furnished intermediate α-diazoisoindole and α-diazoisoquinoline substrates bearing the key secondary diazoalkane 1,3-dipole. N-Derivatisation of the intermediate α-diazoisoindole and α-diazoisoquinolines with a tethered secondary dipolarophile followed by a subsequent 1,3-DC allowed for rapid construction of a range of functionalised polycyclic N-heterocycles. Integrated experimental and theoretical studies established requirements for product formation and revealed the likely mechanistic basis of divergent reactivity observed.

Association between sleep parameters and chronic kidney disease: findings from iranian ravansar cohort study.

INTRODUCTION: The relationship between sleep duration and chronic kidney disease (CKD) has received relatively little attention in the Kurdish community. Considering the ethnic diversity of Iran and the importance of the Kurdish community, the present study investigated the association between sleep parameters and CKD among a large sample of Iranian-Kurds. METHODS: This cross-sectional study was conducted among 9,766 participants (Mage: 47.33, SD = 8.27, 51% female) from the Ravansar Non Communicable Disease (RaNCD) cohort study database. Logistic regression analyses were applied to examine the association between sleep parameters and CKD. RESULTS: Results showed that prevalence of CKD was detected in 1,058 (10.83%) individuals. Time to fall asleep (p = 0.012) and dozing off during the day (p = 0.041) were significantly higher in the non-CKD group compared to the CKD group. Daytime napping and dozing off during the day in females with CKD were significantly more than males with CKD. A long sleep duration (> 8 h/day) was associated with 28% (95% CI: 1.05, 1.57) higher odds of CKD compared to normal sleep duration (7 h/d), after adjusting for confounding factors. Participants who experienced leg restlessness had a 32% higher probability of developing CKD than those who did not experience leg restlessness (95% CI: 1.03, 1.69). CONCLUSION: Results suggest that sleep duration and leg restlessness may be associated with an increased likelihood of CKD. Consequently, regulating sleep parameters may play a role in improving sleep and preventing CKD.

Discovery of Periodinane Oxy-Assisted (POA) Oxidation Mechanism in the IBX-Controlled Oxidative Dearomatization of Pyrroles Mediated by Acetic Acid.

The 2-iodoxybenzoic acid (IBX)-controlled oxidative dearomatization of pyrroles occurs very slowly (or not all) in many organic solvents, including DMSO in which IBX is soluble. Interestingly, although IBX is only partially soluble in acetic acid, this solvent mediates the pyrrole oxidative dearomatization. With the aid of density functional theory (DFT) calculations, we have discovered a new mode of reactivity, termed the periodinane oxy-assisted (POA) oxidation mechanism, which explains this observation.

Application of a fluorescent biosensor based-on magneto-γ-Fe2 O3 -methyldopa nanoparticles for adsorption of human serum albumin.

Understanding and controlling the interaction between the polymer methyldopa (2-amino-3-(3,4-dihydroxyphenyl)-2-methyl-propanoic acid) (PMDP)-γ-Fe2 O3 nanoparticles and biological fluids is important if the potential of nanoparticles (NPs) in biomedicine is to be realized. Physicochemical studies on the interactions between proteins and NPs are influenced by the surface properties of the NPs. To identify the effects of the NP surface, interactions between human serum albumin (HSA) and PMDP-γ-Fe2 O3 NPs were investigated. Here, the adsorption of HSA onto small (10-30 nm diameter) PMDP-γ-Fe2 O3 NPs was quantitatively analyzed using spectroscopic methods. The fluorescence quenching data were checked for the inner-filter effect, the main confounding factor in the observed quenching. The binding constants, Ka , were calculated at different temperatures, using a nonlinear fit to the experimental data, and the thermodynamic parameters ∆H, ∆S and ∆G were given. The obtained thermodynamic signature suggests that hydrophobic interactions at least are present. This result indicates that the structure of the protein turns from a structureless denatured state at pH 3 into an ordered biologically active native state on addition of PMDP-γ-Fe2 O3 NPs. Copyright © 2015 John Wiley & Sons, Ltd.

Cyclization Reactions of 1,5-Diynes: Mechanisms and the Role of the Central Linker.

This study employed computational methods to elucidate the influence of structural features on the cyclization pathways of 1,5-diynes through the 5-endo-dig and 6-endo-dig mechanisms. The results revealed that the nature of the central linker played a significant role in dictating the preferred cyclization pathway. Notably, the capacity of this linker to extend delocalization appears to be the key factor governing the reaction pathway preference.

Mechanistic details for oxidative addition of PhICl2 to gold(I) complexes.

This study demonstrates that the oxidative addition of hypervalent iodine PhICl2 to Au(I) complexes LAuAr follows an unprecedented stepwise mechanism. The energy of the Au(I) dx2-y2 orbital determines the ease of the oxidative addition reaction; the fewer electron-withdrawing substituents present on the Ar ligand, the higher the energy of the dx2-y2 orbital and the easier the oxidative addition.

Interaction studies of water-soluble Zn(II) complex with calf thymus DNA using biophysical and molecular docking methods".

The binding between a fluorescent water-soluble Zn(II) complex of {2-[N-(2-hydroxyethylammonioethyl) imino methyl] phenol} and calf thymus DNA (ct-DNA) was investigated using spectroscopic techniques. The complex was prepared and identified by FT-IR, and 1H NMR spectroscopies. The significant changes in the absorption and the circular dichroism spectra of ct-DNA in the presence of the Zn(II) complex implied the interaction between the Zn(II) complex and ct-DNA. Upon addition of ct-DNA, the fluorescence emission intensity of the Zn(II) complex was increased and indicated the interaction between the Zn(II) complex and ct-DNA was occurred. The binding constant values (Kb) resulted from fluorescence spectra clearly showed the Zn(II) complex affinity to ct-DNA. The fluorescence studies also approved the static enhancement mechanism in the Zn(II) complex-DNA complexation process. The thermodynamic profile exhibited the exothermic and spontaneous formation of ct-DNA-Zn(II) complex system via hydrogen bonds and van der Waals forces. The competitive fluorescence investigation by methylene blue (MB), and Hoechst 33258 demonstrated that the Zn(II) complex could replace the DNA-bound Hoechst and bind to the minor groove binding site in ct-DNA. The viscosity changes were negligible, representing the Zn(II) complex binding to DNA via the groove binding mode. Molecular docking simulation affirmed that the Zn(II) complex is located in the minor groove of ct-DNA near the DG12, DA17, DA18, and DG16 nucleobases.

DNA interaction studies of a cobalt(III) complex containing ß-amino alcohol ligand by spectroscopic and molecular docking methods.

In the present research, the feasibility of a Cobalt(III) complex containing ß-amino alcohol ligands for affinity with the target calf thymus DNA is demonstrated. In the title complex, [Co(C11H15N2O2)2]Cl, the Co(III) atom is six-coordinated with four N atoms and two O atoms from (2-[(E)-({2-[(2-Hydroxyethyl) amino]ethyl}imino)methyl]phenol) ligand (L). To investigate the molecular interaction between the synthesized complex and DNA, some multi-spectroscopic approaches associated with molecular docking were employed in the physiological buffer (pH 7.4). The results indicated that the Co(III) complex proved to be a minor groove binder with a preference for the A-T region, which was substantiated by displacement studies with Hoechst33258 and Methylene blue (MB) as minor groove binder and intercalator. In addition, the results of the molecular docking study revealed that the Co(III) complex approached the gap between the DNA minor grooves near the spot where the Hoechst was. Furthermore, the results of the cytotoxicity and apoptosis tests for the MCF-7 cell line were also indicative of the positive effects of the complex on controlling the growth and viability of breast cancer.Communicated by Ramaswamy H. Sarma.

An unexpected synthesis of azepinone derivatives through a metal-free photochemical cascade reaction.

Azepinone derivatives are privileged in organic synthesis and pharmaceuticals. Synthetic approaches to these frameworks are limited to complex substrates, strong bases, high power UV light or noble metal catalysis. We herein report a mild synthesis of azepinone derivatives by a photochemical generation of 2-aryloxyaryl nitrene, [2 + 1] annulation, ring expansion/water addition cascade reaction without using any metal catalyst. Among the different nitrene precursors tested, 2-aryloxyaryl azides performed best under blue light irradiation and Brønsted acid catalysis. The reaction scope is broad and the obtained products underwent divergent transformations to afford other related compounds. A computational study suggests a pathway involving a step-wise aziridine formation, followed by a ring-expansion to the seven-membered heterocycle. Finally, water is added in a regio-selective manner, this is accelerated by the added TsOH.

Domino Cyclization Reaction of o-Diisocyanoarenes for the Synthesis of Imidazo[1,2-a]pyridinobenzimidazole Backbones.

An efficient procedure to access a variety of connected imidazo[1,2-a]pyridine and benzimidazole skeletons through the C-N bond was described as a new type of Buchwald-Hartwig reaction. Furthermore, the bis(imidazo[1,2-a]pyridin-3-yl)aryl-1,2-diamine scaffolds were obtained by changing the equivalent ratio of the starting materials. Some advantages of the protocol are the formation of four new bonds (C═C, C-N), a transition-metal-free reaction, a broad substrate scope, high yields, and mild reaction conditions. The reaction mechanism was confirmed on the basis of DFT calculations.

Experimental and Molecular Docking Studies on the Interaction of a Water-Soluble Pd(II) Complex Containing ß-Amino Alcohol with Calf Thymus DNA.

The interaction of water-soluble and fluorescent [Pd (HEAC) Cl2] complex, in which HEAC is 2-((2-((2-hydroxyethyl)amino)ethyl)amino) cyclohexanol, with calf thymus DNA (ct-DNA) has been studied. This study was performed using electronic absorption and fluorescence emission spectroscopies, cyclic voltammetry and circular dichroism analyses, dynamic viscosity measurements, and molecular docking theory. From hypochromic effect observed in ct-DNA absorption spectra, it was found that the Pd(II) complex could form a conjugate with ct-DNA strands through the groove binding mode. The Kb values obtained from fluorescence measurements clearly assert the Pd(II) complex affinity to ct-DNA. The fluorescence quenching of the DNA-Hoechst compound following the successive additions of the Pd(II) complex to the solution revealed that the Pd(II) complex is located in the ct-DNA grooves, and Hoechst molecules have been released into solution; moreover, the resulting measurements from relative viscosity authenticate the Pd(II) complex binding to the grooves. Negative quantities of thermodynamic parameters imply that the Pd(II) complex binds to ct-DNA mainly by the hydrogen bonds and van der Waals forces; also, the Gibbs-free energy changes show the exothermic and spontaneous formation of the Pd(II) complex-DNA system. The electrochemical behavior of the Pd(II) complex in the attendance of ct-DNA was investigated using the cyclic voltammetry method (CV). Several quasi-reversible redox waves were observed along with increasing the anodic/cathodic peak currents, as well as a shift in anodic/cathodic peak potentials. Circular dichroism (CD) observations suggested that the Pd(II)-DNA interaction could alter ct-DNA conformation. The results of molecular modeling confirmed that groove mechanism is followed by the Pd(II) complex to interact with ct-DNA.

Structural modification of antineoplastic drug carmofur designed to the inhibition of SARS-CoV-2 main protease: A theoretical investigation.

A coherent account of the reaction mechanistic details, structural modifications, and inhibition potentials of antineoplastic drug carmofur and its modified analogs to inhibition of SARS-CoV-2 main protease (Mpro) is reported. The survey is performed by integrating the density functional based tight binding (DFTB3) with density functional theory (DFT) calculations. The inhibition process commences with nucleophilic attack from the sulfur atom on the carbonyl group, yielding a C-S bond formation, followed by a bond formation of the H-O9 by 2.07 Å, which results in a transition state contains a ring of six atoms. We found that although the direct addition of sulfhydryl group hydrogen to the N3 position is likely to happen, the proper position of the hydrogen to O9 decreases its accessibility. The thermodynamic stability of the complex was calculated to be highly sensitive to the substituent on the N11 position. Compounds with CH2NH2 and CH2F at N11 positions of carmofur revealed high thermodynamic stability to complexation with Mpro but induced no change in substrate-binding pocket comparable to carmofur. Replacing the N11 of carmofur with carbon (C-carmofur) was effective in terms of complexation stability at CH2CH2CH2F and CH2CH2CH2OH substitutions and occupation of S1 subsite by these structures in addition to the S2 subsite. Based on the resulted data, increasing the length of the carbon chain at introduced substitutions in N-carmofur almost decreases the complexation stability while in C-carmofur the trend is reversed. Throughout these information outputs, it was suggested that compounds d, e, i', and k' might be novel and more efficacious drug candidates instead of carmofur. We believe that our characterization of mechanistic details and structural modification on Mpro/carmofur complex will significantly intensify researchers' understanding of this system, and consequently help them to take advantage of results into practice and design various valuable derivatives for inhibition of SARS-CoV-2 main protease.

High selective gas-phase rearrangement reaction of TCDD induced by excess electron attachment: Theoretical insight on the decomposition mechanism of one of the most toxic chemical known to science.

Dioxins are highly toxic chemicals with serious health risks, for which there is no safe level of exposure. Because of the slow decomposition of dioxins, the removal of these persistent environmental pollutants still remains a challenge. Based on theoretical studies, the present work investigates the degradation mechanism of the most toxic type of dioxin-related compounds by low-energy electron irradiation. To explore the rearrangement manner of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced by excess electron attachment, the B3LYP-D3(BJ)/def2-TZVP//B3LYP-D3(BJ)/6-311++G(d,p) level of density functional theory was applied. Electron attachment resulted in a remarkable decrease in the activation barrier of the rearrangement reaction in a thermodynamically preferred reaction. An activation energy as low as 6.6 kcal/mol provides a strong demonstration that this pathway is the most effective in comparison to the neutral or radical rearrangement mechanisms. The attachment of electrons in the above energy range to C-Cl σ∗orbital is more likely than attachment to the LUMO of TCDD with π∗ orbital character. This σ∗ anion then undergoes a C-O σ bond rupture over a small barrier to produce a relatively stable intermediate, n-IM. The formed n-IM is again reactive toward a subsequent C-O bond rupture along with an intramolecular C-C coupling to produce the products, (E)-4,4',5,5'-tetrachloro-[1,1'-bi(cyclohexylidene)]-3,3',5,5'-tetraene-2,2'-dione and (Z)-4,4',5,5'-tetrachloro-[1,1'-bi(cyclohexylidene)]-3,3',5,5'-tetraene-2,2'-dione. The thermodynamic driving force for the anionic mechanism ensures the formation of the products to be irreversible enough to be purified. The purified products, with their active carbonyl groups, can react in many different ways with a wide range of nucleophile compounds.

Direct effects of low-energy electrons on including sulfur bonds in proteins: a second-order Møller-Plesset perturbation (MP2) theory approach.

In an attempt to describe how low-energy electrons (LEEs) damage the polypeptide chain at disulfide bridges, ab initio electronic structure estimates on LEE interactions with cysteine-cysteine (Cys-Cys) disulfide bond model have been performed. Here, the fundamental mechanisms in LEE impression on S-S and C-S bond ruptures in the Cys-Cys model have been discussed. The electronic energy was calculated using the MP2 method with a Hartree-Fock exchange during the SCF and the Møller-Plesset correlation energy correction on the converged HF orbitals with 6-311++G(d,p) atomic orbital basis set. Further, six more sets of diffuse s and p functions with extra basis on the sulfur and relevant carbon atoms were used to describe the added electron to located away as much as possible from the nuclei in anions. The bonds rupture mechanisms involve the primary placement of LEEs to the π* orbital of the model to construct the shape-resonance state following by an adiabatic or nonadiabatic electron migration to either S-S or C-S bond σ* orbital. The formed radical anion undergoes S-S or C-S bonds cleavage by energy barriers of ca. 5.68 and 9.19 kcal/mol, respectively, to produce either (2-amino-2-carboxyethyl) sulfanyl (cysteine radical), aziridine-2-carboxylic acid or mercapto-L-cysteine lesions. In SMD solvent, calculations suggest electronically stable of the formed π* and σ* states by solvation, something that induces either S-S or C-S bond break even when the electron energy is near zero. The required barrier energy of only 0 to < 0.4 eV indicates a high kinetic favorable fragmentation for involved sulfur polypeptides with LEEs.Communicated by Ramaswamy H. Sarma.

New water-soluble Fe3O4@SiO2 magnetic nanoparticles functionalized with levetiracetam drug for adsorption of essential biomolecules by case studies of DNA and HSA.

Communicated by Ramaswamy H. Sarma.

Theoretical mechanistic insight into the gabapentin lactamization by an intramolecular attack: Degradation model and stabilization factors.

PURPOSE: Gabapentin is degraded directly into a high toxicity form known as gabapentin lactam (gaba-L) with a maximizing desire in mild pH and low humidity. This study reports the lactamization process of gabapentin, along with a detailed analysis of the energy landscape, geometry, and thermodynamic and kinetic preference of the process. To investigate the effect of the acidic/basic conditions on the energy landscape, the energy profiles were investigated for both protonation and deprotonation forms of gabapentin. METHODS: All the calculations were performed by using the density functional theory (DFT) and the G4MP2 levels of theory in the conductor-like polarizable continuum model, CPCM, and water as the solvent. RESULTS: The lactamization process is an intramolecular cyclization which results in formation of gabapentin-lactam. The chemically intact gabapentin exists in two forms of a stable, R, and a relatively disordered form, R*. The conversion of stable crystalline form R to the intact unstable isomer R* is considered as the primary step in the gabapentin degradation. The results exhibited that near the unstable geometry, R*, a transition state (TS), is 41.3 kcal/mol higher in energy than the optimized ground state, R* (4.1 kcal/mol). From the intrinsic reaction coordinates (IRC) computations, it can be concluded that this transition state led to the unstable R* in one direction and to gabapentin-lactam in the other. CONCLUSIONS: The thermodynamic stability of the lactam form (-13.63 kcal/mol) clarifies the more thermal stability of gaba-L than its related gabapentin form and the experimental preference for the lactamization. The corresponding energy profile on protonation/deprotonation forms of gabapentin indicates the pH-dependent of the process and the rate reduction in out of the mild pH.