Synthetic prodrug design enables biocatalytic activation in mice to elicit tumor growth suppression

Considering the intrinsic toxicities of transition metals, their incorporation into drug therapies must operate at minimal amounts while ensuring adequate catalytic activity within complex biological systems. As a way to address this issue, this study investigates the design of synthetic prodrugs that are not only tuned to be harmless, but can be robustly transformed in vivo to reach therapeutically relevant levels. To accomplish this, retrosynthetic prodrug design highlights the potential of naphthylcombretastatin-based prodrugs, which form highly active cytostatic agents via sequential ring-closing metathesis and aromatization. Structural adjustments will also be done to improve aspects related to catalytic reactivity, intrinsic bioactivity, and hydrolytic stability. The developed prodrug therapy is found to possess excellent anticancer activities in cell-based assays. Furthermore, in vivo activation by intravenously administered glycosylated artificial metalloenzymes can also induce significant reduction of implanted tumor growth in mice.

Unexpected and frustrating transformations of double-decker silsesquioxanes

This paper outlines an unexpected type of intramolecular transformation of DDSQ during hydrolytic condensation and surprising catalytic reactivity in silylative coupling.

Bimetallic Complexes that merge Metallocene and Pincer-Metal Building Blocks: Synthesis, Stereochemistry and Catalytic Reactivity

This perspective is to illustrate the synthesis and applications of bimetallic complexes by merging a metallocene and a (cyclopentadienyl/aryl) pincer metal complex. Four possible ways to merge metallocene and pincer-metal...

Covalent Organic Frameworks Anchored with Frustrated Lewis Pairs for Hydrogenation of Alkynes with H2

Frustrated Lewis Paris (FLPs) chemistry has been widely explored in the field of catalytic hydrogenation. However, the FLPs, which was usually used as homogeneous catalysts, quickly lost their catalytic reactivity...

Graphene encapsulated low-load nitrogen-doped bimetallic magnetic Pd/Fe@N/C catalyst for the reductive amination of nitroarene under mild conditions

Aniline is a group of important platform molecules and is widely used in the synthesis of other high-value chemicals and pharmaceutical products. How to produce high-value anilines as the high-value chemical intermediates more efficiently and more environmentally has always been a research topic in the industry. Catalytic hydrogenation is an environmentally friendly method for preparing halogenated anilines. Traditional noble metals catalysis face cost and noble metals residue problems. To improve the purity of the product and the activity and recyclability of the catalyst, we prepared a Pd/Fe magnetic bimetallic catalyst supported on N-doped carbon materials to reduce nitrobenzene to aniline under mild conditions. The loading of Pd was very low, which was 1/10 of the content of common commercial precious metal Pd/C and Pt/C catalysts, which was only 0.5%. And the prepared bimetallic Pd/Fe@N/C catalyst showed excellent catalytic reactivity with the conversion rate of nitrobenzene > 99%, and the selectivity of aniline 99% under mild reaction conditions of 0.8 MPa H2 and 40 °C. A variety of halogenated and aliphatic nitro compounds were well tolerated and had been transformed to the corresponding target amine products with excellent selectivity. In addition, the novel N-doped graphene-encapsulated bimetallic magnetic Pd/Fe@N/C catalyst not only had magnetic physical properties, which was easy to separate, recover, and used for the recycling of the catalyst without metal leaching but also catalyzed highly selective reductive amination of aromatics was a green, economical and environmentally friendly reaction with the only H2O as a by-product.

The Influence of Si/Al Ratio on the Physicochemical and Catalytic Properties of MgO/ZSM-5 Catalyst in Transesterification Reaction of Rapeseed Oil

This work presents the comparative physicochemical and catalytic studies of metal oxide MgO catalysts in a transesterification reaction. The influence of the Si/Al ratio in the catalytic material on their catalytic properties in the studied process was extensively evaluated. In addition, the effect of the type of zeolite ZSM-5 form on the catalytic reactivity of MgO based catalysts was investigated. In order to achieve the main goals of this work, a series of MgO/ZSM-5 catalysts were prepared via the impregnation method. Their physicochemical properties were studied using X-ray diffraction (XRD), BET, FTIR and TPD-CO2 methods. The highest activity in the studied process exhibited MgO catalyst supported on ZSM-5 characterized by the highest ratio between silica and alumina. The most active catalyst system in the transesterification reaction was 10% MgO/ZSM-5 (Si/Al = 280), which showed the highest value of higher fatty acid methyl esters (94.6%) and high yield of triglyceride conversion (92.9%). The high activity of this system is explained by the alkalinity, sorption properties in relation to methanol and its high specific surface area compared to the rest of the investigated MgO based catalysts.

Combining Metal-Metal Cooperativity, Metal-Ligand Cooperativity and Chemical Non-Innocence in Diiron Carbonyl Complexes

Several metalloenzymes, including [FeFe]-hydrogenase, employ cofactors wherein multiple metal atoms work together with surrounding ligands that mediate heterolytic and concerted proton-electron transfer (CPET) bond activation steps. Herein, we report a new dinucleating PNNP expanded pincer ligand, which can bind two low-valent iron atoms in close proximity to enable metal-metal cooperativity (MMC). In addition, reversible partial dearomatization of the ligand’s naphthyridine core enables both heterolytic metal-ligand cooperativity (MLC) and chemical non-innocence through CPET steps. Thermochemical and computational studies show how a change in ligand binding mode can lower the bond dissociation free energy of ligand C(sp3)–H bonds by ~25 kcal mol-1. H-atom abstraction enabled trapping of an unstable intermediate, which undergoes facile loss of two carbonyl ligands to form an unusual paramagnetic (S = 1/2) complex containing a mixed-valent iron(0)-iron(I) core bound within a partially dearomatized PNNP ligand. Finally, cyclic voltammetry experiments showed that these diiron complexes show catalytic activity for the electrochemical hydrogen evolution reaction. This work presents the first example of a ligand system that enables MMC, heterolytic MLC and chemical non-innocence, thereby providing important insights and opportunities for the development of bimetallic systems that exploit these features to enable new (catalytic) reactivity.