Utilization of α‐halocarbonyl compounds in the synthesis of thiazole,thiadiazole, and thiophene derivatives

The behavior of ethyl 2‐phenylthiocarb‐ amoyl acetate 1 toward a variety of several α‐halo‐ carbonyl compounds was investigated. Thus, reaction of 1 with α‐bromoketones, hydrazonoyl bromides, and 2‐chloro‐N‐arylacetamides afforded the corresponding dihydrothiazole, 1,3,4‐thiadiazole, and thiophene derivatives, respectively. The synthesis of thiazolidin‐4‐one 11 , thiazolidin‐5‐one 12 , and some azo derivatives of thiazolidin‐5‐one were described. 5‐Arylazothiazoles 17 and 19 were synthesized by condensation of hydrazonoyl bromides 3 with different thiourea derivatives. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:299–305, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20206     

A New Radical Allylation Reaction of Dithiocarbonates

A radical allylation reaction without tin: The xanthate group in aliphatic xanthates can be replaced by an allyl unit [Eq. (a)]. This radical chain reaction is propagated by ethyl radicals generated by extrusion of sulfur dioxide from ethanesulfonyl radicals, which are themselves derived from allyl ethyl sulfone.     

A generic approach to decipher the mechanistic pathway of heterogeneous protein aggregation kinetics

Amyloid formation is a generic property of many protein/polypeptide chains. A broad spectrum of proteins, despite having diversity in the inherent precursor sequence and heterogeneity present in the mechanism of aggregation produces a common cross β-spine structure that is often associated with several human diseases. However, a general modeling framework to interpret amyloid formation remains elusive. Herein, we propose a data-driven mathematical modeling approach that elucidates the most probable interaction network for the aggregation of a group of proteins (α-synuclein, Aβ42, Myb, and TTR proteins) by considering an ensemble set of network models, which include most of the mechanistic complexities and heterogeneities related to amyloidogenesis. The best-fitting model efficiently quantifies various timescales involved in the process of amyloidogenesis and explains the mechanistic basis of the monomer concentration dependency of amyloid-forming kinetics. Moreover, the present model reconciles several mutant studies and inhibitor experiments for the respective proteins, making experimentally feasible non-intuitive predictions, and provides further insights about how to fine-tune the various microscopic events related to amyloid formation kinetics. This might have an application to formulate better therapeutic measures in the future to counter unwanted amyloidogenesis. Importantly, the theoretical method used here is quite general and can be extended for any amyloid-forming protein.

Amyloid formation is a generic property of many protein/polypeptide chains.     

Xanthates as Chain‐Transfer Agents in Controlled Radical Polymerization (MADIX): Structural Effect of the O‐Alkyl Group

The capability of three chain‐transfer agents, O‐alkyl‐S‐(1‐ethoxycarbonyl)ethyl xanthates (CH₃CHCO₂C₂H₅)S(CS)OZ′, to control the free‐radical polymerization of styrene and ethyl acrylate by the MADIX process was examined. The reactivity of the xanthates varied according to the following trend: Z′  CH₂CH₃ < CH₂CF₃ < CH[P(O)(OEt)₂]CF₃. This change in reactivity allowed a lowering of the polydispersity index from 2.0 for Z′  CH₂CH₃ to 1.15 for Z′  CH[P(O)(OEt)₂]CF₃ in the case of the polymerization of styrene.

Evolution of M _w/M _n with conversion during the polymerization of ethyl acrylate in the presence of xanthates X₁ , X₂ and X₃ . Reaction conditions: [EA]₀ = 4.6 M , [X]₀ = 5.75 × 10⁻² M , [AIBN]₀ = 1.72 × 10⁻³ M ; T = 80 °C ; solvent: toluene.     

Treating Tumors at Low Drug Doses Using an Aptamer–Peptide Synergistic Drug Conjugate

Combination chemotherapy must strike a difficult balance between safety and efficacy. Current regimens suffer from poor therapeutic impact because drugs are given at their maximum tolerated dose (MTD), which compounds the toxicity risk and exposes tumors to non‐optimal drug ratios. A modular framework has been developed that selectively delivers drug combinations at synergistic ratios via tumor‐targeting aptamers for effective low‐dose treatment. A nucleolin‐recognizing aptamer was coupled to peptide scaffolds laden with precise ratios of doxorubicin (DOX) and camptothecin (CPT). This construct had an extremely low IC₅₀ (31.9 nm ) against MDA‐MB‐231 breast cancer cells in vitro, and exhibited in vivo efficacy at micro‐dose injections (500 and 350 μg kg^?1 dose^?1 of DOX and CPT, respectively) that are 20–30‐fold lower than their previously‐reported MTDs. This approach represents a generalizable strategy for the safe and consistent delivery of combination drugs in oncology.     

Convenient Synthesis of Some Novel Pyridazinone‐Bearing Triazole Moieties

The chemoselective reactions of 2‐(5‐mercapto‐4‐phenyl‐4H‐[1,2,4]triazol‐3‐ylmethyl)‐6‐p‐tolyl‐4,5‐dihydro‐2H‐pyridazin‐3‐one ( 3 ) with different electrophiles were evaluated. Triazole 3 reacted with alkyl halides in the presence of triethylamine in alcohol to give the corresponding S‐substituted derivatives. On the basis of S‐chemoselective reactions of triazole 3 , a series of amino acid 10a – d and dipeptide derivatives 12a – d were prepared via azide coupling of the corresponding hydrazides 9 and 15 with amino acid ester hydrochlorides, respectively. N‐Substituted triazoles 6a – c or 7a – d attached to pyridazin‐3‐one moiety were successfully formed by the reaction of 3 with activated acrylic acid derivatives or with amines. Antibacterial activities of the synthesized derivatives were investigated through correlation with Escherichia coli FabH inhibitory activities using molecular modeling docking software. The antimicrobial activity of synthesized compounds was evaluated, showing best inhibition zone for N‐substituted carboxylic acid 5a and N‐substituted nitrile 5c parallel to the molecular modeling studies.     

Alternating Radical Stabilities: A Convergent Route to Terminal and Internal Boronates

Pinacolato boronates (Bpin) with an empty p‐orbital on boron stabilize an adjacent carbon radical, in contrast to diethanolamino boronates [B(DEA)] where the boron is sp³‐hybridized. By alternately placing a pinacol or diethanolamine moiety on the boron atom, thus stabilizing or not stabilizing the corresponding adjacent radical, it is possible to control the behavior of α‐boronyl xanthates and construct a large variety of terminal or internal boronates in a modular fashion. The remarkable tolerance of polar groups and the ability to introduce quaternary centers are particularly noteworthy features of this process.     

HfN Nanoparticles: An Unexplored Catalyst for the Electrocatalytic Oxygen Evolution Reaction

Water electrolysis is one of the most promising methods to produce H₂ and O₂ as high potential fuels. Comparing the two half‐reactions, the oxygen evolution reaction (OER) is the more difficult to be optimized and still relies on expensive noble metal‐based catalysts such as Ru or Ir. In this paper, we prepared nanoparticles of HfN and Hf₂ON₂ and tested them for the OER for the first time. The HfN sample, in particular, showed the highest activity, requiring an overpotential of only 358 mV at 10 mA cm^?2 in Fe‐free electrolyte and, above all, exhibiting long‐term stability. This result places this system amongst one of the most promising catalysts for OER tested to date, in terms of sustainability, activity and stability. The prepared nanoparticles are small (less than 15 nm in diameter), well‐defined in shape and crystalline, and were characterised before and after electrochemical testing also via electron microscopy (EM), powder X‐ray diffraction (PXRD) and X‐ray photoelectron spectroscopy (XPS).     

Heliotropium bacciferum Forssk. (Boraginaceae) extracts: chemical constituents,antioxidant activity and cytotoxic effect in human cancer cell lines

Heliotropium bacciferum (Boraginaceae) is a perennial herb, growing in the Bechar region of Algeria, where it is traditionally used for skin diseases and tonsillitis. Herein, we report the isolation and characterization of sixteen secondary metabolites from the aerial part extracts. They include a sterol (1), megastigman type nor-isoprenoids (2, 3, 4, 6, 8, 10), C-11 terpene lactones (5 and 9), and a monoterpene (7) from the chloroform extract (HB-C); monoterpene glucoside (14), and phenolic compounds (11–13, 15, 16) from the methanol one (HB-M). Their structures were elucidated by spectroscopic methods including 1D and 2D NMR experiments, and ESIMS analysis. HB-M showed a significant and concentration dependent scavenging activity in vitro against the radicals DPPH and ABTS, related to the phenol derivatives (11–13, and 15–16), and HB-C inhibited the growth of colon cancer cell lines, mainly for the presence of the antiproliferative C-11 terpene lactones (5 and 9).