Hydrocarbon Oxidations with Hydrogen Peroxide Catalyzed by a Soluble Polymer‐Bound Manganese(IV) Complex with 1,4,7‐Triazacyclononane

Soluble manganese(IV) complexes with polymer‐bound 1,4,7‐triazacyclononanes as ligands (compound 2 ) catalyze the oxidation of alkanes by hydrogen peroxide in acetonitrile at room and lower temperatures. The corresponding alkyl hydroperoxides are the main products. The presence of a relatively small amount of acetic acid is obligatory for this reaction. The oxidation of alkanes and olefins exhibits some features (kinetic isotope effect, bond selectivities) that distinguish this system from an analogous one based on the dinuclear Mn(IV) complex 1 .     

Overcoming Multidrug Resistance (MDR): Design,Biological Evaluation and Molecular Modelling Studies of 2,4-Substituted Quinazoline Derivatives

Some 2,4-disubstituted quinazolines were synthesized and studied as multidrug resistance (MDR) reversers. The new derivatives carried the quinazoline-4-amine scaffold found in modulators of the ABC transporters involved in MDR, as the TKIs gefitinib and erlotinib. Their behaviour on the three ABC transporters, P-gp, MRP1 and BCRP, was investigated. Almost all compounds inhibited the P-gp activity in MDCK-MDR1 cells overexpressing P-gp, showing EC₅₀ values in the nanomolar range ( 1 d , 1 e , 2 a , 2 c , 2 e ). Some compounds were active also towards MRP1 and/or BCRP. Docking results obtained by in silico studies on the P-gp crystal structure highlighted common features for the most potent compounds. The P-gp selective compound 1 e was able to increase the doxorubicin uptake in HT29/DX cells and to restore its antineoplastic activity in resistant cancer cells in the same extent of sensitive cells. Compound 2 a displayed a dual inhibitory effect showing good activities towards both P-gp and BCRP.     

Pushing the Boundaries of Structural Heterogeneity with the Lipid A of Marine Bacteria Cellulophaga

Marine bacteria, which are often described as chemical gold, are considered an exceptional source of new therapeutics. Considerable research interest has been given to lipopolysaccharides (LPSs), the main components of the Gram-negative outer membrane. LPS and its lipid A portion from marine bacteria are known to exhibit a tricky chemistry that has been often associated with intriguing properties such as behaving as immune adjuvants or anti-sepsis molecules. In this scenario, we report the structural determination of the lipid A from three marine bacteria within the Cellulophaga genus, which showed to produce an extremely heterogenous blend of tetra- to hexa-acylated lipid A species, mostly carrying one phosphate and one D-mannose on the glucosamine disaccharide backbone. The ability of the three LPSs in activating TLR4 signaling revealed a weaker immunopotential by C. baltica NNO 15840^T and C. tyrosinoxydans EM41^T, while C. algicola ACAM 630^T behaved as a more potent TLR4 activator.     

A continuous flow reactor for the flexible production of different formulations: CFD-aided design

The increasing need to improve the sustainability of industrial processes requires more flexible and intensified solutions. For this purpose, nowadays lots of efforts are made to switch from batch to continuous processes, the latter being able to ensure the same processing history to all fluid elements, with a consequent better control of the operating conditions and product quality. The present work aims at developing a continuous flow reactor for the production of several fine chemicals, including medical-surgical aids, but also other substances for specific industrial sectors. The plant is basically an inline reactor equipped with various static mixers and side inlets, and it is conceived to ensure on-site production. This is an important feature also in light of the recent COVID-19 pandemic, which asked for flexible and distributed production of chemicals. Numerical simulations based on computational fluid dynamics are employed to study the performance, in terms of pressure drops and degree of mixing, of different static mixers, that is, the Lightnin Inliner Series 50 and Ross low pressure drop (LPD), combining various elements of mixing and injections in different operating conditions in both laminar and turbulent regimes. The results highlighted how numerical simulations may represent a valid tool for supporting the detailed design of such flow reactors by allowing the evaluation of the optimal design solutions.     

One-Pot Synthesis and Antiproliferative Activity of Highly Functionalized Pyrazole Derivatives

A series of highly functionalized pyrazole derivatives has been prepared by a one-pot, versatile and regioselective procedure. Pyrazoles 1 – 29 were tested in cell-based assay to assess their antiproliferative activity against a panel of tumour cells. Additionally, the cytotoxicity of prepared compounds was evaluated against normal human fibroblasts. The antiproliferative activity of the synthesized molecules emerged to be affected by the nature of the substituents of the pyrazole scaffold and derivatives 21 – 23 proved to inhibit the growth of melanoma and cervical cancer cells. Compound 23 was identified as the most active derivative and docking simulations predicted its ability to interact with estrogen receptors.     

Bacterially induced degradation of aqueous solutions of poly(l-lysine)-graft-poly(ethylene glycol) and poly(l-lysine)-graft-dextran: consequences for their lubrication properties

Experimental data are presented comparing the degradation in the lubrication behaviour of aqueous solutions of the brush copolymers poly(l -lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) and poly(l -lysine)-graft-dextran (PLL-g-dex) when aged after exposure to bacterial contamination. While PLL-g-PEG solutions appear to be relatively unaffected by bacteria after a storage period of as much as 8 weeks, PLL-g-dex solutions exposed to bacteria during preparation lead to as much as a twofold increase in friction coefficient, when used as a lubricant in tribological tests, over an 8 week period when compared to reference data from freshly prepared and tested samples. Solutions prepared under sterile conditions and aged for up to 8 weeks do not appear to be degraded. Further experiments implementing the anti-bacterial agent sodium azide effectively prevented bacterial colonization and degradation in lubrication behaviour. Copyright © 2009 John Wiley & Sons, Ltd.     

Cross‐Coupling of Heteroarenes by C?H Functionalization: Recent Progress towards Direct Arylation and Heteroarylation Reactions Involving Heteroarenes Containing One Heteroatom

In recent years, transition metal‐catalyzed direct (hetero)arylation reactions of heteroarenes with (hetero)aryl halides and pseudohalides have received significant attention as eco‐friendly and economic alternatives to classical methods for the construction of heteroaryl‐(hetero)aryl C C bonds by transition metal‐catalyzed cross‐couplings involving the use of stoichiometric amounts of organometallic reagents. This critical review with 430 references covers the results obtained in the period January 2009 to February 2013 in the area of the transition metal‐catalyzed direct inter‐ and intramolecular (hetero)arylation reactions of heteroarenes containing one heteroatom. Particular attention has been given to illustrate chemo‐ and site selectivity aspects of these reactions as well applications of these C C bond forming reactions in the synthesis of pharmaceutically relevant compounds, natural products and their analogues and precursors. The most recent advancements into the mechanism(s) of these reactions have also been briefly reported.

     

Efficient estimation of tuned liquid column damper inerter (TLCDI) parameters for seismic control of base-isolated structures

This paper presents an enhanced base-isolation (BI) system equipped with a novel passive control device composed of a tuned liquid damper and an inerter (TLCDI). With the aim of reducing the seismic response of BI systems, this contribution focuses on the design of the TLCDI providing analytical solutions for the optimal TLCDI parameters, easily implementable in the design phase. The effectiveness of the proposed approach in terms of seismic response reduction and computational gain is validated by comparison with classical numerical optimization techniques. The control performance of two different base-isolated TLCDI-controlled structures is assessed by employing real-ground motion records, and relevant comparisons with both uncontrolled base-isolated structures and equipped with a conventional TLCD are presented.     

The Facets of Diversity: The EFMC Perspective**

Diversity in science refers to cultivating talent, while promoting full inclusion across the community. In medicinal chemistry and chemical biology, it enhances creativity and encourages contributions from multiple perspectives, leading to better decision making and broader scientific impact. The European Federation for Medicinal chemistry and Chemical biology (EFMC) embraces and promotes diversity, to ensure representation of all talents, and enable equality of opportunity through fairness and transparency. EFMC has historically paid continuous attention to diversity in terms of culture, geography and equilibrium between academia and industry, with over the last few years a focus on increasing gender balance, aiming at a fair representation of the scientific community and equal opportunities independently of gender. EFMC promotes cultural diversity as it reinforces openness and mutual respect. All scientific organizations of a scope compatible with its remit are welcome within EFMC, where their members benefit from a welcoming, psychologically safe, and stimulating environment. Herein, we describe the state of diversity within the EFMC, how the situation has evolved over the years and where diversity should be further encouraged.     

Structure–function relationship during the early and long-term hydration of one-part alkali-activated slag

Understanding the mechanisms controlling the early (fresh) and long-term (hardened) hydration of one-part alkali-activated slags (AAS) is key to extend their use as low CO₂ substitutes for ordinary Portland cement (OPC). Their “just add water” use makes them easier and less hazardous to manipulate than the more studied two-part ones. This is due to the absence of liquid alkaline activators, which are environmentally and energy demanding. In this work, numerous experimental techniques have been linked to obtain a comprehensive physico-chemical characterization of a one-part AAS activated with Na₂CO₃ and Ca(OH)₂ powders at several water to solid ratios (w/s). Calorimetry and pH/conductivity measurements describe the functioning of the activators immediately after contact with water. Early reactivity is characterized through in situ X-ray powder diffraction (XRPD) and small amplitude oscillatory shear (SAOS) rheology, which reveal a rapid precipitation of nanometric hydration products (nano-C-A-S-H), which results in a continuous increase in the paste cohesivity until setting. Moreover, SAOS shows that rejuvenating the paste by means of shearing (performed externally to the rheometer in this study) is enough to restore the initial cohesion (i.e., workability) for long time spans until setting occurs. The long-term hydration is characterized by ex situ XRPD on aged AAS pastes, in parallel with mechanical testing on AAS mortar. A correlation can be observed between the amount of nano-C-A-S-H and the increase in compressive strength. Overall, this formulation shows satisfactory fresh and solid properties, demonstrating suitability for low- and normal-strength applications.