Exploring the Impact of Ring Mobility on the Macroscopic Properties of Doubly Threaded Slide-Ring Gel Networks.

The integration of mechanically interlocked molecules (MIMs) into polymeric materials has led to the development of mechanically interlocked polymers (MIPs). One class of MIPs that have gained attention are slide-ring gels (SRGs), which are generally accessed by crosslinking rings on a main-chain polyrotaxane. The mobility of the interlocked crosslinking moieties along the polymer backbone imparts enhanced properties onto these networks. An alternative synthetic approach to SRGs is to use a doubly threaded ring as the crosslinking moiety, yielding doubly threaded slide-ring gel networks (dt-SRGs). In this study, a photo-curable ligand-containing thread was used to assemble a series of metal-templated pseudo[3]rotaxane crosslinkers that allow access to MIPs that contain doubly threaded interlocked rings. The physicochemical and mechanical properties of these dt-SRGs with varying size of the ring crosslinking moieties were investigated and compared to an entangled gel (EG) prepared by polymerizing the metal complex of the photo-curable ligand-containing thread, and a corresponding covalent gel (CG). Relative to the EG and CG, the dt-SRGs exhibit enhanced swelling behavior, viscoelastic properties, and stress relaxation characteristics. In addition, the macroscopic properties of dt-SRGs could be altered by "locking" ring mobility in the structure through remetalation, highlighting the impact of the mobility of the crosslinks.

Development of Masitinib Derivatives with Enhanced Mpro Ligand Efficiency and Reduced Cytotoxicity.

Recently, a high-throughput screen of 1900 clinically used drugs identified masitinib, an orally bioavailable tyrosine kinase inhibitor, as a potential treatment for COVID-19. Masitinib acts as a broad-spectrum inhibitor for human coronaviruses, including SARS-CoV-2 and several of its variants. In this work, we rely on atomistic molecular dynamics simulations with advanced sampling methods to develop a deeper understanding of masitinib's mechanism of Mpro inhibition. To improve the inhibitory efficiency and to increase the ligand selectivity for the viral target, we determined the minimal portion of the molecule (fragment) that is responsible for most of the interactions that arise within the masitinib-Mpro complex. We found that masitinib forms highly stable and specific H-bond interactions with Mpro through its pyridine and aminothiazole rings. Importantly, the interaction with His163 is a key anchoring point of the inhibitor, and its perturbation leads to ligand unbinding within nanoseconds. Based on these observations, a small library of rationally designed masitinib derivatives (M1-M5) was proposed. Our results show increased inhibitory efficiency and highly reduced cytotoxicity for the M3 and M4 derivatives compared to masitinib.

Balancing ring and stopper group size to control the stability of doubly threaded [3]rotaxanes.

Synthesizing doubly threaded [3]rotaxanes requires the use of larger rings than more traditional singly threaded [2]rotaxanes. A key challenge in accessing stable doubly threaded [3]rotaxanes with large rings is finding the right combination of ring to stopper size. In this study, a series of doubly threaded [3]rotaxanes derived from five different sized macrocycles in the size range of 40-48 atoms and two different stopper groups, which contain 1 or 2 tris(p-t-butylbiphenyl)methyl moieties, were prepared and their kinetic stability examined. These interlocked compounds were synthesized using a metal-templated approach and fully characterized utilizing a combination of mass spectrometry, NMR spectroscopy, and size-exclusion chromatography techniques. The effect of ring size on the stability of the doubly threaded [3]rotaxane was investigated via kinetic stability tests monitored using 1H-NMR spectroscopy. By tightening the macrocycle systematically every 2 atoms from 48 to 40 atoms, a wide range of doubly threaded interlocked molecules could be accessed in which the rate of room temperature slippage of the macrocycle from the dumbbells could be tuned. Using the larger stopper group with a 48-atom ring results in no observable rotaxane, 46-44 atom macrocycles result in metastable rotaxane species with a slippage half-life of ∼5 weeks and ∼9 weeks, respectively, while macrocycles of 42 atoms or smaller yield a stable rotaxane. The smaller sized stopper is not able to fully stabilize any of the [3]rotaxane structures but metastable [3]rotaxanes are obtained with slippage half-lives of 25 ± 2 hours and 13 ± 1 days using macrocycles with 42 or 40 atoms, respectively. These results highlight the dramatic effect that relatively small ring size changes can have on the structure of doubly threaded [3]rotaxanes and lay the synthetic groundwork for a range of higher order doubly threaded interlocked architectures.

The effect of thread-like monomer structure on the synthesis of poly[n]catenanes from metallosupramolecular polymers.

The main-chain poly[n]catenane consists of a series of interlocked rings that resemble a macroscopic chain-link structure. Recently, the synthesis of such intriguing polymers was reported via a metallosupramolecular polymer (MSP) template that consists of alternating units of macrocyclic and linear thread-like monomers. Ring closure of the thread components has been shown to yield a mixture of cyclic, linear, and branched poly[n]catenanes. Reported herein are studies aimed at accessing new poly[n]catenanes via this approach and exploring the effect the thread-like monomer structure has on the poly[n]catenane synthesis. Specifically, the effect of the size of the aromatic linker and alkenyl chains of the thread-like monomer is investigated. Three new poly[n]catenanes (with different ring sizes) were prepared using the MSP approach and the results show that tailoring the structure of the thread-like monomer can allow the selective synthesis of branched poly[n]catenanes.

Correction: Polycatenanes: synthesis, characterization, and physical understanding.

Correction for 'Polycatenanes: synthesis, characterization, and physical understanding' by Guancen Liu et al., Chem. Soc. Rev., 2022, https://doi.org/10.1039/d2cs00256f.

Polycatenanes: synthesis, characterization, and physical understanding.

Chemical composition and architecture are two key factors that control the physical and material properties of polymers. Some of the more unusual and intriguing polymer architectures are the polycatenanes, which are a class of polymers that contain mechanically interlocked rings. Since the development of high yielding synthetic routes to catenanes, there has been an interest in accessing their polymeric counterparts, primarily on account of the unique conformations and degrees of freedom offered by non-bonded interlocked rings. This has lead to the synthesis of a wide variety of polycatenane architectures and to studies aimed at developing structure-property relationships of these interesting materials. In this review, we provide an overview of the field of polycatenanes, exploring synthesis, architecture, properties, simulation, and modelling, with a specific focus on some of the more recent developments.

Tuning Supramolecular Polymer Assembly through Stereoelectronic Interactions.

The supramolecular polymerization of 2,11-dithia[3.3]paracyclophanes through self-complementary intermolecular and transannular amide hydrogen bonding is presented. An n → π* interaction between the amide hydrogen bonding units and the central bridging atom results from the single-point exchange of a carbon atom for a sulfur atom. This orbital donor-acceptor interaction can be strengthened by oxidizing the sulfide to a sulfone which acts to shorten the donor···acceptor distance and increase orbital overlap. Experimental signatures of the increased n → π* interaction include larger isodesmic polymerization elongation constants in solution, changes in characteristic bond stretching frequencies, and geometric/structural changes evaluated by X-ray crystallography. The experimental data are supported by extensive computational investigations of both assembling and nonassembling 2,11-dithia[3.3]paracyclophanes as well as a rationally designed model system to confirm the role of stereoelectronic effects on supramolecular polymer assembly.

Self-Assembling [n.n]Paracyclophanes: A Structure-Property Relationship Study.

Reported here is the synthesis, characterization, and isodesmic supramolecular polymerization of [3.3]paracyclophane-5,8,14,17-tetracarboxamide ([3.3]pCpTA). The self-assembling monomer, a bridge-expanded homolog of [2.2]paracyclophane-4,7,12,15-tetracarboxamide ([2.2]pCpTA), forms homochiral assemblies in nonpolar solution and the solid state through double-helical intermolecular and transannular hydrogen bonding. The additional methylene unit in the [3.3]paracyclophane bridge results in a weakened supramolecular assembly for [3.3]pCpTA compared to [2.2]pCpTA in solution. Likely origins of the change in assembly strength, revealed through X-ray crystallography, computational analysis, and solution-phase spectroscopy, are an increase in (a) the intramolecular and intermolecular deck-to-deck spacing compared to [2.2]paracyclophane resulting from larger amide dihedral angles accompanying transannular hydrogen bonding in the [3.3]paracyclophane and (b) monomer entropy associated with the scissoring motion of the [3.3]paracyclophane bridge.

The association of occupational metals exposure and oxidative damage, telomere shortening in fitness equipments manufacturing workers.

The welding is the major working process in fitness equipment manufacturing industry, and International Agency for Research on Cancer has classified welding fumes as possibly carcinogenic to humans (Group 2B). The present study aimed to evaluate associations between the occupational exposure of metals and oxidative damage and telomere length shortening in workers involved in the manufacture of fitness equipment. The blood metal concentrations were monitored and malondialdehyde (MDA), alkaline Comet assay was determined as oxidative damage in 117 workers from two representative fitness equipment manufacturing plants. MDA levels varied according to workers' roles at the manufacturing plants, and showed a trend as cutting>painting>welding>administration workers. Welders had marginally shorter average telomere lengths than the administrative workers (p=0.058). Cr and Mn levels were significantly greater in welders than they were in administrative workers. There were significantly positive correlations between MDA and Cr and Mn levels, the major components of welding fume. However, the association would be eliminated if co-metals exposure were considered simultaneously. In future, telomere length and MDA might be potential biomarkers for predicting cardiovascular disease in co-metals exposed workers.