Molecular modelling of fullerene C60 functionalized by nitric oxide for use in biological environment.

The unique potential of fullerene C60 for various biological applications has ignited significant interest. However, its inherent non-polarity poses a critical challenge for its effective integration within biological systems. This study delves into the intricate physicochemical characteristics of the innovative [C60 + NO] complex using density functional theory and time-dependent density functional theory. The computational analyses encompass molecular charge, surface electrostatic potential, and dipole moment evaluations. Impressively, the dipole moment of the [C60 + NO] complex significantly increases to 12.92 D. Meticulous surface analysis reveals a subtle interplay between molecular structures, indicating weak interactions. The analysis of the absorption spectrum unveils a noteworthy red-shift of 200 nm subsequent to complex formation. To elucidate the electron transfer mechanisms, we explore photo-induced electron transfer through CAM-B3LYP. This exploration elucidates intricate pathways governing electron transfer, with complementary insights gleaned from Marcus theory's outputs, especially the Gibbs free energy of electron transfer. Changes in the physicochemical properties of approaching C60 and NO molecules reveal interesting results compared to separate molecules. These findings resonate profoundly in the context of potential biological and pharmaceutical utilization. With implications for the biomedical area, the outcomes linked to the [C60 + NO] complex kindle optimism for pioneering biomedical applications.

Retraction: Experimental and theoretical studies of the nanostructured {Fe3O4@SiO2@(CH2)3Im}C(CN)3 catalyst for 2-amino-3-cyanopyridine preparation via an anomeric based oxidation.

[This retracts the article DOI: 10.1039/C6RA12299J.].

Azulene-Naphthalene, Naphthalene-Naphthalene, and Azulene-Azulene Rearrangements.

The mechanism(s) of thermal rearrangement of azulenes have been enigmatic for several decades. Herein, we have employed density functional theory (DFT) calculations at the M06-2X/6-311+G(d,p) level together with single-point calculations at the CCSD(T) level to assess possible mechanisms of the experimentally observed azulene and naphthalene automerizations. Of the two mechanisms proposed for naphthalene automerization, it is found that the benzofulvene (BF) route is favored over the naphthvalene mechanism by ∼6 kcal/mol and is energetically lower than the norcaradiene-vinylidene mechanism (NVM) for the azulene-naphthalene rearrangement (Ea ∼ 76.5 (74.6) kcal/mol). Moreover, contrary to older reports, we observe that a pathway involving indenylcarbene intermediates is a viable, alternate mechanism. Therefore, the naphthalene automerization is expected to take place during azulene pyrolysis, especially under conditions of low-pressure FVP, where it will be aided by chemical activation. Furthermore, thermal azulene-azulene isomerization is feasible through vinylidene-acetylene-vinylidene (VAV), dehydrotriquinacene (DTQ), and azulvalene (AV) pathways with activation energies lying below that required for the azulene-naphthalene conversion, i.e., the NVM. These results, together with the previously published NVM, provide reasonable explanations for most of the products of the thermal azulene-naphthalene rearrangement.

Thermal Rearrangement of Azulenes to Naphthalenes: A Deeper Insight into the Mechanisms.

The thermal rearrangement of azulene to naphthalene has been the subject of several experimental and computational studies. Here, we reexamine the proposed mechanisms at the DFT level. The use of different functionals showed that the HF-exchange contribution significantly affects reaction energies and barrier heights. Accordingly, all proposed pathways were investigated with the optimal method, M06-2X/6-311+G(d,p), which confirms the norcaradiene-vinylidene mechanism (A) as the dominant unimolecular route (Ea ≈ 76 kcal/mol) able to account for the major products of pyrolyses using 13C- or substituent-labeled azulenes. Moreover, a facile vinylidene-acetylene interconversion will scramble the terminal carbon atoms in the vinylidene. Several other potential intramolecular reaction mechanisms (B-E) are ruled out because of higher activation energies (>84 kcal/mol) and failure to reproduce the results obtained with substituted and 13C-labeled azulenes and benzazulenes. These experimental results also demonstrate that the proposed free radical or H atom-induced intermolecular methylene walk and spiran mechanisms cannot be major contributors, especially under flash vacuum pyrolysis conditions.

When a "Dimroth Rearrangement" Is Not a Dimroth Rearrangement.

In the Dimroth rearrangement of heterocycles, often pyrimidines, an exocyclic and a ring substituent are interchanged. However, the term Dimroth rearrangement is frequently used even when there is no knowledge of the reaction mechanism and alternatives are likely. Here, we have employed density functional theory (DFT) calculations at the M06-2X/6-311+G(d,p) level to determine the most plausible rearrangement pathways of 3-aminothiocarbonylquinazoline 5, tetrahydrofuranylpyrimidine 21, and 5-allyltriazocine 30. For the rearrangement of quinazoline 5 to 9, the [1,3]-sigmatropic shift of the thioamido group with an activation barrier of 26.7 kcal/mol is much preferred over the Dimroth rearrangement (∼46 kcal/mol). An even lower barrier of 21.6 kcal/mol applies to a stepwise [1,3]-shift. The migration of the tetrahydrofuranyl unit in pyrimidines like 21 → 23 can take place by means of a [1,3]-sigmatropic shift with a low barrier (≤17.5 kcal/mol) rather than a Dimroth rearrangement under acidic conditions and most likely also under neutral conditions (∼30 kcal/mol). In the rearrangement of 5-allyl-6-iminotriazocine 30 to 32, the [3,3]-sigmatropic shift (aza-Cope rearrangement) is preferred over the Dimroth mechanism under neutral conditions, but in the presence of acid, the azonia-Cope rearrangement of an allyl group and the true Dimroth rearrangement have comparable activation energies.

Recovered fluorescence of the Cd-nanocluster-Hg(II) system based on experimental results and computational methods.

Human Serum Albumin, a plasma protein existing in abundance, was selected as a template and reducing agent for the formation of CdNCs due to two factors: its stability and low cost. In the presence of human serum albumin (HSA), a selective and sensitive, low-cost, environmental friendly, and label-free off-on fluorescent sensor was synthesized and characterized for a bioaccumulating and toxic heavy metal, Hg2+ and biothiols. HSA - CdNCs can specifically recognize Hg2+ through aggregating NCs and causing fluorescence quenching. Subsequently, with increase in the concentration of biothiols, Hg2+ was eliminated from the surface of NC, while the fluorescence was restored. The calculated limits of detection (LOD) were 55 pM for Hg(II) and 14 nM for GSH, respectively. The assay was capable of detecting Hg2+ ions and GHS at different concentrations in the range of 0.008 to 8530 nM and 7.5-5157 nM, respectively. Furthermore, the appropriate molecular mechanics (MM) as well as quantum mechanical (QM) methods were performed to optimize and the theoretical investigation of the discussed HSA-profile structures and its interactions with the Cd-NCs (one atom of Cd), Hg2+ and glutathione (G).

Mechanism-Based Inactivation of Cytochrome P450 Enzymes: Computational Insights.

Mechanism-based inactivation (MBI) refers to the metabolic bioactivation of a xenobiotic by cytochrome P450s to a highly reactive intermediate which subsequently binds to the enzyme and leads to the quasi-irreversible or irreversible inhibition. Xenobiotics, mainly drugs with specific functional units, are the major sources of MBI. Two possible consequences of MBI by medicinal compounds are drug-drug interaction and severe toxicity that are observed and highlighted by clinical experiments. Today almost all of these latent functional groups (e.g., thiophene, furan, alkylamines, etc.) are known, and their features and mechanisms of action, owing to the vast experimental and theoretical studies, are determined. In the past decade, molecular modeling techniques, mostly density functional theory, have revealed the most feasible mechanism that a drug undergoes by P450 enzymes to generate a highly reactive intermediate. In this review, we provide a comprehensive and detailed picture of computational advances toward the elucidation of the activation mechanisms of various known groups with MBI activity. To this aim, we briefly describe the computational concepts to carry out and analyze the mechanistic investigations, and then, we summarize the studies on compounds with known inhibition activity including thiophene, furan, alkylamines, terminal acetylene, etc. This study can be reference literature for both theoretical and experimental (bio)chemists in several different fields including rational drug design, the process of toxicity prevention, and the discovery of novel inhibitors and catalysts.

Fabrication of Template-Less Self-Propelled Micromotors Based on A Metal-Sandwiched Polytryptophan Body: An Experimental and DFT Study.

The diverse capabilities of self-propelled micro/nanomotors open up significant opportunities for various environmental and biomedical applications. Here, a synchronized two-lobed bubble exhaust drives micromotor comprising a metal (cobalt and gold) sandwiched polytryptophan body (Au/poly-Trp/Co) in a non-curved direction. The autonomous motion is achieved through the decomposition of chemical fuel to result in a kayak-like system. The ejected oxygen bubbles from the interfacial cobalt/polytryptophan layer, as well as the inert nature of the metal segments (Au-Co), were considered for some computational studies of the electronic properties of the composite and physical phenomena at the kayak/electrolyte interfaces, and confirmed the role of Co-Trp in the fuel decomposition. It is believed that the autonomous motion is the combined result of bubble recoil force, self-electrophoresis, and perturbation in the interfacial hydrogen-bond network of the poly-Trp body and water molecules. The velocity of the micromotor in the range 23±4 to 157±17 µm s-1 at different concentrations of H2 O2 from 1 % to 10 %. Depending on the method of fragmentation, it is possible to have both single and multiple motorized kayaks with lengths of 1.5 and 6 µm, respectively, that can be tailored for environmental applications.

Structural Assessment of Hydrogen Bonds on Methylpentynol-Azide Clusters To Achieve Regiochemical Outcome of 1,3-Dipolar Cycloaddition Reactions Using Density Functional Theory.

This study was focused on the geometries and properties of the structural isomers obtained from a random walk of methylpentynol-HN3 clusters. The theoretical aspects of hydrogen bonding effects on the discussed 1,3-dipolar cycloaddition (1,3-DC) reactions [between methylpentynol (a) as a dipolarophile and azide (b) as a 1,3-dipole] have shown regioselective output concepts. The dipolarophile methylpentynol (a) was applied for the treatment of insomnia. Both methylpentynol (a) and azide (b) can be H-bond acceptor and H-bond donor agents. Because of this trait of them, structures of H-bonding arrays (c-f) and methylpentynol-azide clusters (g-m) can be probable. In this work, regioselectivity of the 1,3-DC reaction [between methylpentynol (a) as a dipolarophile and azide (b) as a 1,3-dipole] was determined based on these structures (c-m) using density functional theory (DFT). The energy levels of the reactants (a and b) and the structures of H-bonding arrays (c-f), methylpentynol-azide clusters (g-m), transition states, and products (1 and 2) were studied, and also, the free energies of the reaction (Δr G and ΔG #, in kcal mol-1) and rate constants were determined using Eyring's equation (k). Structural data were calculated and obtained by the DFT/B3LYP method. Seven different basis sets have been used to obtain the most appropriate results from comparison of data.

Ionically Tagged Magnetic Nanoparticles with Urea Linkers: Application for Preparation of 2-Aryl-quinoline-4-carboxylic Acids via an Anomeric-Based Oxidation Mechanism.

In this exploration, we reported the design and synthesis of a novel ionically tagged magnetic nanoparticles bearing urea linkers, namely, Fe3O4@SiO2@(CH2)3-urea-thiazole sulfonic acid chloride. The structure of the mentioned compound was fully characterized by using several techniques including Fourier transform infrared spectroscopy, energy-dispersive X-ray analysis, elemental mapping analysis, thermogravimetric analysis/differential thermal analysis, scanning electron microscopy, transmission electron microscopy, and vibrating sample magnetometer. In the presence of the novel reusable catalyst, applied starting materials including aryl aldehydes, pyruvic acid, and 1-naphthylamine condensed to afford the desired 2-aryl-quinoline-4-carboxylic acid derivatives via an anomeric-based oxidation pathway under solvent-free conditions.

Catalytic application of sulfamic acid-functionalized magnetic Fe3O4 nanoparticles (SA-MNPs) for protection of aromatic carbonyl compounds and alcohols: experimental and theoretical studies.

Protection techniques of functional groups within the structure of organic compounds are important synthetic methods against unwanted attacks from various reagents during synthetic sequences. Acetal and thioacetal groups are well known as protective functional groups in organic reactions. In this study, acetalization of carbonyl compounds with diols and dithiols and methoxymethylation of alcohols with formaldehyde dimethyl acetal (FDMA) have been carried out using sulfamic acid-functionalized magnetic Fe3O4 nanoparticles (SA-MNPs) as a heterogeneous solid acid catalyst. Products were characterized by FT-IR and NMR spectroscopies. The structural and electronic properties of some products were computed by quantum mechanical (QM) methods. Depending on the stereochemistry and electronic properties that were obtained by computational results, we have suggested that hyperconjugation plays a key role in the structural properties of 2-phenyl-1,3-dioxolane derivatives, and also the electron transfer between π-electrons of the aromatic ring with the 3d orbital of S-atoms influences the 2-phenyl-1,3-dithiane derivatives' structure.

Electrochemical sensing of 2-methyl-4, 6-dinitrophenol by nanomagnetic core shell linked to carbon nanotube modified glassy carbon electrode.

Electrochemical behavior and sensing of 2-methyl-4, 6-dinitrophenol as an herbicide has been investigated by cyclic voltammetry (CV) and square wave voltammetry (SWV). We have synthesized a cefazolin (CEF) immobilized nanomagnetic core-shell (Fe3O4@SiO2-(CH2)3-CEF) and attached it on the modified glassy carbon electrode (GCE/MWCNT) through electrostatic adsorption (GCE/MWCNT/CEF-SiO2@Fe3O4). 2-Methyl-4, 6-dinitrophenol has an oxidation peak that is related to the formation of nitrosamine from hydroxylamine species. This peak was applied for quantifying determination of 2-methyl-4, 6-dinitrophenol. The electrochemical oxidation involves two electron transfers accompanied by two protons. The electrochemical process was controlled by adsorption. The good agreement between the obtained computational studies and the experimental results has demonstrated that outer sphere electron transfer occurred on modified electrode. The new electrochemical sensor was applied to determination of 2-methyl-4, 6-dinitrophenol by SWV in the range of 1.0 × 10-10 to 1.5 × 10-7 M with a detection limit of 0.1 nM. The proposed sensor was applied for determination of 2-methyl-4, 6-dinitrophenol in water samples.

Sub-femtomolar detection of HIV-1 gene using DNA immobilized on composite platform reinforced by a conductive polymer sandwiched between two nanostructured layers: A solid signal-amplification strategy.

This study introduces a signal amplification strategy rely on incorporating a specific polymer film between two typical nanostructured layers, aiming to improve the electrical properties of the platform to be able to transduce small binding event through sub-femtomolar detection of HIV-1 gene at the surface of the constructed biosensing device. The proposed composite was arrayed based on a conductive layer consist of p-aminobenzoic acid (PABA) sandwiched between the electrochemically reduced graphene oxide (ERGO) as the sub-layer, and the gold nanoparticles (AuNPs) as the interfacial layer. We computationally explored that how the use of such design enables the platform to transduce small changes in the interfacial properties of the biosensor, caused by low concentrations of HIV-1 gene, without needing any amplification strategy. Furthermore, it was found that the loin PABA conductive polymer sandwiched between two nanostructure layers play an artwork-ensemble role, which resulted in a good signal repeatability and stability during the relatively long successive incubation and detection procedures. The justification of using such an array of conductive layers was established on the attaining extra low-level of detection limit. The observed performance for probe-DNA immobilized on glassy carbon electrode (GC) modified with ERGO/PABA/AuNPs compared to the GC electrode modified with ERGO/AuNPs inspired us to perform computational calculations, a hybrid of ab-initio and semi-empirical quantum mechanics methods, to discover its probable molecular-scale reasons. A rapid single frequency impedance measurement (SFIM) was also employed to remarkably reduce the measurement time and diminish the probable nonspecific impedance changes. The proposed biosensor was used to evaluate the DNA target over an extremely wide concentration range from 0.1 fM to 10 nM, with a detection limit of 37 aM (S/N = 3).

Determination of Hg2+ and Cu2+ ions by dual-emissive Ag/Au nanocluster/carbon dots nanohybrids: Switching the selectivity by pH adjustment.

An innovative dual-emissive ratiometric nanohybrid probe comprised of red-emitting a (Ag/Au)@insulin nanoclusters (NCs) and blue-emitting carbon dots (CDs) was designed for sensitive and selective ratiometric determination of Hg2+ and Cu2+ ions.The fluorescence intensity of CDs (λex = 340 nm; λem = 420 nm) was unaffected in the presence of the metal ions tested, whereas the red emitting NCs (λex = 340 nm; λem = 640 nm) was strongly quenched by both Cu2+ and Hg2+ ions. Interestingly, the selectivity of the probe toward these two ions was simply switched by controlling the pH of probe solution without using any chelating agent. The probe selectively responded to Hg2+ ions at acidic condition (pH = 4.0), Cu2+ ions at basic condition (pH = 10.0), and Hg2+-Cu2+ mixtures at pHs within this range. The respective detection limitsfor determination of Cu2+ and Hg2+ ions at their specific pH conditions were estimated as 5 nM and 7 nM, over linear ranges of 20-600 nM and 20-2000 nM, respectively. The fabricated ratiometric probe also showed distinguished fluorescence color changes to visual detection of these ions. Finally, the probe was successfully applied to determination of Hg2+ and Cu2+ ions in tap and mineral water samples.

Transduction of interaction between trace tryptophan and surface-confined chromium salen using impedance spectroscopy. A sensing device that works based on highly selective inhibition of mediator's Faradaic process.

It is known that tryptophan (Trp) tends to be electropolymerized over a potential window that is mostly applied for voltammetric determination of Trp. Furthermore, over the applied potential range, most of Trp-sensors suffer from some possible interferences. Knowing these challenges motivated us to establish a novel sensing device able to monitor Trp before approaching the mentioned potential range, decreasing memory-effects and some sources of non-linearity during electrochemical measurements. However, considering its molecular structure, it is unrealistic to expect tryptophan oxidation in negative potentials. This work reports the application of a surface-confined chromium-salen complex that delivered a redox couple attributed to Cr(II)/Cr(III) at a low positive potentials. The recorded cyclic voltammograms (CVs) clarified that Trp has a high inhibitory activity toward the chromium oxidation peak in the alkaline medium at a low potential of -0.18 V vs. Ag/AgCl. The positive shift of the anodic peak potential of redox reaction disclosed that Trp drastically influenced the capability of the interfacial charge transfer of the modified electrode, the features that was exploited in establishing a sensitive Trp detection method using electrochemical impedance spectroscopy. The proposed sensor was successfully employed to determine Trp over a concentration range of 4.0-60.0 nM with the calculated detection limit of 0.78 nM.

Resolving the Multiple Emission Centers in Carbon Dots: From Fluorophore Molecular States to Aromatic Domain States and Carbon-Core States.

Despite many efforts focused on the emission origin of carbon dots (CDs), it is still a topic of debate. This is mainly due to the complex structure of these nanomaterials. Here, we developed an innovative method to evaluate the number and spectral characterizations of various emission centers in CDs. We monitored the photostability of a series of column-separated CDs under UV irradiation to obtain three-dimensional data sets and resolve them using multivariate decomposition methods. The obtained results clearly revealed the presence of three different types of emission centers in CDs, including molecular states, aromatic domain states, and carbon-core states so that their single or coexisting appearance was found to be deeply dependent on the reaction temperature. Furthermore, density functional theory and time-dependent density functional theory were used to investigate the electronic and optical properties of some different aza-polycyclic and corannulene molecules as possible polycyclic aromatic hydrocarbons responsible for the above-mentioned aromatic domain states.

DFT and TD-DFT theoretical studies on photo-induced electron transfer process on [Cefamandole].C60 nano-complex.

The C60 fullerene displays a considerable electronegativity. It has a unique photophysical and electrochemical behavior that can be used as a suitable drug carrier. In the present study, the interaction of C60 fullerene as an electron recipient with the Cefamandole antibiotic was investigated in both ground and excited states using DFT and TD-DFT methods. The study of the interaction of C60 and Cefamandole via electron localization function (ELF) and reduced density gradient (RDG) revealed that the complex formation is of van der Waals type. The data from natural bonding orbitals (NBO) analysis also confirmed the interaction type. The study of absorption and emission spectrum via CAM-B3LYP in the TD-SCF state showed that the emission peak of C60 fullerene in the 591.73nm after the complex formation results in the extinction of this emission spectrum due to charge transfer (CT) from chelator to fluorophore. The photoinduced electron transfer (PET) process was investigated using the electron hole theory.

Experimental and Computational Evidence on the Interaction of Cycloalkyl α-Aminobisphosphonates with Calf Thymus DNA.

Fluorescence spectroscopy, ultraviolet-visible absorption spectroscopy, circular dichroism spectroscopy, viscometry, cyclic voltammetry, and differential pulse voltammetry were applied to investigate the competitive interaction of DNA with the three new cycloalkyl α-aminobisphosphonates (D1-D3) and spectroscopic probe, neutral red dye, and Hoechst (HO), in a Tris-hydrogen chloride buffer (pH 7.4). The spectroscopic and voltammetric studies showed that the groove binding mode of interaction is predominant in the solution containing DNA and α-aminobisphosphonates. Furthermore, the results indicated that α-aminobisphosphonate with the lengthy N alkyl chains and larger heterocyclic ring size had a stronger interaction. The principal component analysis and theoretical quantum mechanical and molecular mechanics (QM-DFT B3LYP/6-31+G* and MM-SYBYL) methods were also applied to determine the number of chemical components presented in complexation equilibrium and identify the structure complexes of DNA with the three new cycloalkyl α-aminobisphosphonates (D1-D3), respectively.

Introduction of a carbon paste electrode based on nickel carbide for investigation of interaction between warfarin and vitamin K1.

In this paper a novel electrochemical sensor based on nickel carbide (Ni3C) nanoparticles as a new modifier was constructed. Ni3C nanoparticle was synthesized and characterized by scanning electron microscopy, X-ray diffraction and first-principles study. Electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) studies confirmed the electrode modification. Afterwards, the new electrode for the first time was used for interaction study between vitamin K1 and warfarin as an anticoagulant drug by differential pulse voltammetry. The adduct formation between the drug and vitamin K1 was improved by decreasing in anodic peak current of warfarin in the presence of different amounts of vitamin K1. The binding constant between warfarin and vitamin K1 was obtained by voltammetric and UV-vis and fluorescence spectroscopic methods. The molecular modeling method was also performed to explore the structural features and binding mechanism of warfarin to vitamin K1. The different aspects of modeling of vitamin K1 and warfarin and their adduct structures confirmed the adduct formation by hydrogen bonding.

Hydrophobic amino acids grafted onto chitosan: a novel amphiphilic chitosan nanocarrier for hydrophobic drugs.

OBJECTIVE: The objective of this study is to develop a novel biocompatible amphiphilic drug delivery for hydrophobic drugs, chitosan (CS) was grafted to a series of hydrophobic amino acids including l-alanine (A), l-proline (P), and l-tryptophan (W) by carbodiimide mediated coupling reaction. MATERIALS AND METHODS: Chemical characteristics of the modified polymers were determined and confirmed by FT-IR, 1H NMR, and UV-vis spectroscopy and the degree of substitution was quantified by elemental analysis. The modified polymers were used to form amphiphilic chitosan nanocarriers (ACNs) by the conventional self-assembly method using ultrasound technique. The morphology and the size of ACNs were analyzed by scanning electron microscope (SEM) and Dynamic light scattering (DLS). RESULTS AND DISCUSSION: The sizes of spherical ACNs analyzed by SEM were obviously smaller than those of determined by DLS. The ACNs effectively surrounded the hydrophobic model drug, letrozole (LTZ), and demonstrated different encapsulation efficiencies (EE), loading capacities (LC), and controlled drug release profiles. The characteristics of ACNs and the mechanism of drug encapsulation were confirmed by molecular modeling method. The modeling of the structures of LTZ, profiles of A, P, and W grafted onto CS and the wrapping process around LTZ was performed by quantum mechanics (QM) methods. There was a good agreement between the experimental and theoretical results. The cell viability was also evaluated in two cell lines compared with free drug by MTT assay. CONCLUSION: The hydrophobic portion effects on ACNs' characteristics and the proper selection of amino acid demonstrate a promising potential for drug delivery vector.