Electrochemical sensor for detection of imipramine antidepressant at low potential based on oxidized carbon nanotubes,ferrocenecarboxylic acid,and cyclodextrin: application in psychotropic drugs and urine samples

Imipramine (IMP), a tricyclic antidepressant drug, is commonly prescribed for treatment of psychiatric patients suffering from different forms of depression. The appropriate amount of drug intake is crucial to ensure the optimum therapeutic effects minimizing severe collateral effects and toxicity. Therefore, the monitoring of imipramine is essential for its clinical applications. Herein, we report an electrochemical sensor based on a composite of ferrocenecarboxylic acid (FCA), β-cyclodextrin (CD), and oxidized multi-walled carbon nanotubes (f-CNT) modified glassy carbon electrode for detection of IMP at low potential. The electrochemical behavior of the proposed sensor was characterized by scanning electron microscopy, Raman spectroscopy, and cyclic voltammetry. The results show that imipramine determination using the proposed sensor occurs around 0 V vs Ag/AgCl in phosphate buffer pH 7.0. The calibration curves were obtained by cyclic voltammetry and differential pulse voltammetry, with linear ranges of 10 to 350 μmol L^?1 and 0.1 to 10 μmol L^?1, respectively. A detection limit of 0.03 μmol L^?1 was obtained for the detection of IMP. The sensor was applied for IMP determination in psychotropic drugs and urine samples and the results show a recovery percentage between 99 and 101% for the analyte.     

Insights into the free-energy dependence of intramolecular dissociative electron transfers

To study the relationship between rate and driving force of intramolecular dissociative electron transfers, a series of donor-spacer-acceptor (D-Sp-A) systems has been devised and synthesized. cis-1,4-Cyclohexanedyil and a perester functional group were kept constant as the spacer and acceptor, respectively. By changing the aryl substituents of the phthalimide moiety, which served as the donor, the driving force could be varied by 0.74 eV. X-ray diffraction crystallography and ab initio conformational calculations pointed to D-Sp-A molecules having the cis-(cyclohexane) equatorial(phthalimido)-axial(perester) conformation and the same D/A orientation. The intramolecular dissociative electron-transfer process was studied by electrochemical means in N,N-dimethylformamide, in comparison with thermodynamic and kinetic information obtained with models of the acceptor and the donor. The intramolecular process consists of the electron transfer from the electrochemically generated phthalimide-moiety radical anion to the peroxide functional group. The electrochemical analysis provided clear evidence of a concerted dissociative electron-transfer mechanism, leading to the cleavage of the O-O bond. Support for this mechanism was obtained by ab initio MO calculations, which provided information about the LUMO of the acceptor and the SOMO of the donor. The intramolecular rate constants were determined and compared with the corresponding intermolecular values, the latter data being obtained by using the model molecules. As long as the effective location of the centroid of the donor SOMO does not vary significantly by changing the aryl substituent(s), the intramolecular dissociative electron transfer obeys the same main rules already highlighted for the corresponding intermolecular process. On the other hand, introduction of a nitro group drags the SOMO away from the acceptor, and consequently, the intramolecular rate drops by as much as 1.6 orders of magnitude from the expected value. Therefore, a larger solvent reorganization than for intermolecular electron transfers and the effective D/A distance and thus electronic coupling must be taken into account for quantitative predictions of intramolecular rates.     

Nitroxyl peptides as catalysts of enantioselective oxidations

The achiral, nitroxyl-containing alpha-amino acid TOAC (TOAC = 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid), in combination with the chiral alpha-amino acid C(alpha)-methyl valine [(alphaMe)Val], was used to prepare short peptides (from di- to hexa-) that induced the enantioselective oxidation of racemic 1-phenylethanol to acetophenone. The best catalyst was an N(alpha)-acylated dipeptide alkylamide with the -TOAC-(alphaMe)Val- sequence folded in a stable, intramolecularly hydrogen-bonded beta-turn conformation with large, lipophilic (hydrophobic) N- and C-terminal blocking groups. We rationalized our findings by proposing models for the diastereomeric intermediates between (R)-[and (S)]-1-phenylethanol and the catalyst Fmoc-TOAC-L-(alphaMe)Val-NHiPr, based on the X-ray diffraction structure of the latter.     

Anomalous distance dependence of electron transfer across peptide bridges

The first investigation on the distance dependence of a dissociative electron transfer process across peptide bridges is reported. This study was carried out by using a series of donor-peptide-acceptor systems in which the donor is a phthalimido moiety, the peptide bridges are provided by alpha-aminoisobutyric acid (Aib) homooligomers, and the acceptor is a peroxide functional group. The intramolecular electron transfer from the electrogenerated phthalimido radical anion to the peroxide was studied in comparison with the thermodynamic and kinetic information obtained with models of the acceptor and the donor. The intramolecular rate constants were determined in N,N-dimethylformamide by taking into account the corresponding intermolecular values. The experimental results point to an unusual non-exponential dependence of the intramolecular electron transfer rate on the number of bridge units. The same trend could be verified also by taking into account the actual donor-acceptor edge-to-edge distance. The peculiar distance dependence that was observed for the intramolecular electron transfer rate is attributed to the mediating effect of the intramolecular C=O...H-N hydrogen bonds.     

Reversible Control of Nanoparticle Functionalization and Physicochemical Properties by Dynamic Covalent Exchange

Existing methods for the covalent functionalization of nanoparticles rely on kinetically controlled reactions, and largely lack the sophistication of the preeminent oligonucleotide‐based noncovalent strategies. Here we report the application of dynamic covalent chemistry for the reversible modification of nanoparticle (NP) surface functionality, combining the benefits of non‐biomolecular covalent chemistry with the favorable features of equilibrium processes. A homogeneous monolayer of nanoparticle‐bound hydrazones can undergo quantitative dynamic covalent exchange. The pseudomolecular nature of the NP system allows for the in situ characterization of surface‐bound species, and real‐time tracking of the exchange reactions. Furthermore, dynamic covalent exchange offers a simple approach for reversibly switching—and subtly tuning—NP properties such as solvophilicity.     

Chemical Composition,Antioxidant, Antimicrobial and Cytotoxic/Cytoprotective Activity of Non-Polar Extracts of Grape (Vitis labrusca cv. Bordeaux) and Blackberry (Rubus fruticosus) Seeds

The aim of this study was to compare the influence of the extraction method, chemical composition, antimicrobial effects, antioxidant activity, and cytotoxicity on human cells of the non-polar extracts of grape (Vitis labrusca) and blackberry (Rubus fruticosus) seeds. The Soxhlet (Sox), Bligh–Dyer (BD), and ultrasound (US) methods were used for extractions. For blackberry non-polar seed extract, extraction via the BD method showed the highest mean values of total phenolic content (TPC), expressed in milligrams of gallic acid equivalent per 100 mL of non-polar seed extracts (102.37 mg GAE/100 mL), and higher antioxidant activity in relation to the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, expressed in milligrams of gallic acid equivalent per 100 mL of non-polar seed extracts (11.50 mg AAE/100 mL), if compared with the Sox and US extractions. Similar results were obtained for the non-polar grape seed extracts, where BD extraction obtained the highest values for TPC (28.61 mg GAE/100 mL) and DPPH (35.36 mg AAE/100 mL). The type of extraction method had an impact on the composition of fatty acids. Only the non-polar blackberry and grape seed extracts obtained via the Sox method showed some in vitro inhibitory effect against Escherichia coli (IAL 2064) and Staphylococcus aureus (ATCC 13565). Regardless of the extraction method used, the non-polar blackberry and grape seed extracts did not decrease the cell viability (IC₅₀ >1000 µg/mL) of cancer and normal cell lines, thus indicating the relative safety of the extracts. All the seed extracts decreased the generation of reactive oxygen species in the cell lines. Blackberry and grape seed lipid fractions can be utilized as antioxidants, and the extraction methods used cause significant changes in relation to their bioactivity and chemical composition.     

A One-Pot Approach to Novel Pyridazine C-Nucleosides

The synthesis of glycosides and modified nucleosides represents a wide research field in organic chemistry. The classical methodology is based on coupling reactions between a glycosyl donor and an acceptor. An alternative strategy for new C-nucleosides is used in this approach, which consists of modifying a pre-existent furyl aglycone. This approach is applied to obtain novel pyridazine C-nucleosides starting with 2- and 3-(ribofuranosyl)furans. It is based on singlet oxygen [4+2] cycloaddition followed by reduction and hydrazine cyclization under neutral conditions. The mild three-step one-pot procedure leads stereoselectively to novel pyridazine C-nucleosides of pharmacological interest. The use of acetyls as protecting groups provides an elegant direct route to a deprotected new pyridazine C-nucleoside.     

Crystallization of tetrahedral patchy particles in silico

We investigate the competition between glass formation and crystallization of open tetrahedral structures for particles with tetrahedral patchy interactions. We analyze the outcome of such competition as a function of the potential parameters. Specifically, we focus on the separate roles played by the interaction range and the angular width of the patches, and show that open crystal structures (cubic and hexagonal diamond and their stacking hybrids) spontaneously form when the angular width is smaller than about 30°. Evaluating the temperature and density dependence of the chemical potential of the fluid and of the crystal phases, we find that adjusting the patch width affects the fluid and crystal in different ways. As a result of the different scaling, the driving force for spontaneous self-assembly rapidly grows as the fluid is undercooled for small-width patches, while it only grows slowly for large-width patches, in which case crystallization is pre-empted by dynamic arrest into a network glass.     

Benzyl N‐[(Benzyloxy)methyl]carbamate: An Improved Aminomethylation Electrophile for the Synthesis of (Benzyloxy)carbonyl (Cbz)‐Protected Chiral β2‐Amino Acids

α‐Aminomethylation of (R)‐DIOZ‐alkylated (DIOZ=4‐isopropyl‐5,5‐diphenyloxazolidin‐2‐one) substrates is a key step in the asymmetric synthesis of β²‐amino acids, but it is unfortunately often accompanied by formation of transcarbamation by‐products. Aminomethylation was tested using a range of electrophiles, and the amount of by‐product formation was assessed in each case. Benzyl N‐[(benzyloxy)methyl]carbamate electrophile 3d is unable to form this by‐product due to its inherent benzyl substitution. Use of electrophile 3d showed an improved impurity profile in aminomethylation, thus leading to easier intermediate purification.     

Independent sets of words and the synchronization problem

The synchronization problem is investigated for the class of locally strongly transitive automata introduced in Carpi and D?Alessandro (2009) [9]. Some extensions of this problem related to the notions of stable set and word of minimal rank of an automaton are studied. An application to synchronizing colorings of aperiodic graphs with a Hamiltonian path is also considered.