RSC Advances

Latif, Zartashia; Rehman, Atta Ur; Amin, Nasir; Arshad, Muhammad Imran; Marzouki, Riadh

doi: 10.1039/d3ra02080kpmid: 38024970

The nanocomposites of Co0.5Ni0.5Gd0.03Fe1.97O4/graphene nanoplatelets (CNGF/GNPs) were synthesized by a cost-effective sol–gel auto combustion (SGAC) route. The X-ray diffraction analysis confirmed the cubic structure of the as-prepared nanocomposites, and a crystallite size of 32.28 nm was observed for the 7.5 wt% GNPs. Irregular and unique nanoparticles consisting of short stacks of graphene sheets having a platelet shape were confirmed by the morphological analysis of the as-prepared nanocomposites. Raman analysis revealed a spinel crystal structure along with a new vibrational mode due to the GNPs. The energy bandgap was 3.98 eV for the composite with 7.5 wt% GNP concentration. It was observed that the percentage temperature coefficient of resistance (TCR%) rapidly decreased with an increase in temperature both in low- and high-temperature ranges. Dielectric studies carried out in the frequency range 104–107 Hz confirmed that the graphene-added composites had high values for both the real and imaginary parts of permittivity at low frequencies. A decrease in saturation magnetization with an increase in GNP concentration was observed compared with the pure CNGF samples. Hence, the as-prepared composites are useful for application in high-frequency devices as well as spintronics.

Chen, Lijia; Lowe, Brandon; Fletcher, Steven

doi: 10.1039/d3ra05711apmid: 38024975

Overexpression of the anti-apoptotic protein MCL-1 is associated with a plethora of human cancers, and it reduces the sensitivity of cancer cells to approved chemotherapies. Accordingly, the discovery of MCL-1 inhibitors is an active area of interest. Many inhibitors of the anti-apoptotic MCL-1 protein bear a crucial carboxylic acid that may engage Arg263 in the BH3-binding groove. We previously described the salicylic acid-based dual MCL-1/BCL-xL inhibitor 17cd, which is currently undergoing lead optimization. As part of that process, we wished to investigate bioisosteric replacement of 17cd's key carboxylic acid. Herein we describe the synthesis of a variety of analogues of a simpler analogue of 17cd presenting carboxylic acid surrogates. The acylsulfonamide and tetrazole motifs, which exhibit comparable pKas to the carboxylic acid function, displayed similar, or better, binding affinities to MCL-1 and BCL-xL as the corresponding carboxylic acid-containing lead. Our best compound was acylsulfonamide 7d with a Ki of 800 nM against MCL-1 and 1.82 mM against BCL-xL, and demonstrated an improved effect on the viability of the HL60 acute myeloid leukemia cell line relative to the parent carboxylic acid-containing dual inhibitor from which it was derived.

Liu, Yuankun; Zhang, Xinxia; Liu, Hongrun

doi: 10.1039/d3ra06437apmid: 38024979

Iron–nitrogen co-doped modified corncob (Fe–N-BC) was synthesized using a hydrothermal and calcination method. The material shows excellent oxidation performance and environmental friendliness. When the dosage of Fe–N-BC was 0.6 g L−1, the concentration of H2O2 was 12 mM and pH was 4, ciprofloxacin (CIP) was virtually totally eliminated in 240 min under Fe–N-BC/H2O2 conditions. The TOC removal efficiency was 54.6%, and the effects of various reaction parameters on the catalytic activity of Fe–N-BC were thoroughly assessed. Through electron paramagnetic resonance (EPR) analyses and free radical quenching experiments, it was established that the reactive oxygen species (˙OH, ˙O2−, 1O2) were crucial in the elimination of CIP. Furthermore, the degradation of CIP was accelerated by the synergistic interaction between the transition metal and PFRs. A thorough evaluation was conducted to assess the respective contributions of adsorption and catalytic oxidation in the system. The degradation mechanism of CIP was proposed under Fe–N-BC/H2O2 conditions. Meanwhile, the possible degradation intermediates and pathways were proposed, and the toxicity of the degradation products of CIP was also meticulously investigated in the study. These findings offered the elimination of CIP in water a theoretical foundation and technical support.

Haq, Kautsar Ul; Sa'adah, Nur Lailatus; Siswanto, Imam; Suwito, Hery

doi: 10.1039/d3ra05942apmid: 38024961

Cyclooxygenase-2 (COX-2) is an enzyme involved in inflammation. The overexpression of COX-2 causes chronic inflammation, which can be prevented by COX-2 inhibitors. Generally, COX-2 inhibitors possess a carboxyl group and an aromatic ring in their molecular structure. These moieties are involved in the interaction with the active site of COX-2, thus playing a pivotal role in the inhibitory activity. Regarding the requisite molecular structure of COX-2 inhibitors, derivatives of dihydropyrimidinone (DHPM) are ideal candidates to be explored as COX-2 inhibitors, due to the ease of synthesis and their versatility to be transformed chemically. In this study, we prepared a novel small library consisting of 288 designed DHPM derivatives by varying the constituent components. The selection criteria of potential candidates for the COX-2 inhibitor of the data bank involve in silico studies via molecular docking investigations, prediction of ADMET and druglikeness, as well as molecular dynamics (MD) simulations. Molecular docking served as the initial step of selection, based on the comparison of grid score, docking pose, and interactions with those of lumiracoxib (LUR) as the original ligand of COX-2. The next criteria of selection were scores obtained from the ADMET and druglikeness by comparing the designed candidates with COX-2 inhibitors that were already marketed. Compound RDUE2 and SDT29 were the most potential candidates, which were further analyzed using the MD simulation. The results of the MD simulation indicated that RDUE2 and SDT29 interacted stably with amino acid residues on the active site of COX-2. The estimation of binding free energy indicated that SDT29 exhibited an inhibitory activity comparable to that of LUR, whereas RDUE2 showed a lower inhibitory activity than that of SDT29 and LUR.

Tran, Van Tan; Dao, Van-Duong; Nguyen, Huu-Quang; Tufa, Lemma Teshome; Lee, Jaebeom; Hoang, Van-Tuan; Le, Anh-Tuan

doi: 10.1039/d3ra06754hpmid: 38024966

The rapid and efficient detection of chloride (Cl−) ions is crucial in a variety of fields, making the development of advanced sensing methods such as colorimetric sensors an imperative advancement in analytical chemistry. Herein, a novel, selective, and straightforward paper-based colorimetric sensing platform has been developed utilizing an amorphous photonic array (APA) of magnetoplasmonic Ag@Fe3O4 nanoparticles (MagPlas NPs) for the detection of Cl− in water. Taking advantage of the highly responsive APA, the key principle of this sensing method is based on the chemical reaction between Ag+ and Cl−, which results in the precipitation of high-refractive index (RI) AgCl. This assay, distinct from typical plasmonic sensors that rely heavily on nanoparticle aggregation/anti-aggregation, is premised on the precipitation reaction of Ag+ and Cl−. In the presence of Cl−, a rapid, distinctive color alteration from royal purple to a dark sky blue is visually observable within a short time of a few minutes, eliminating the necessity for any surface modification procedures. Comprehensive assessments substantiated that these sensors display commendable sensitivity, selectivity, and stability, thereby establishing their effective applicability for Cl− analysis in various technological fields.

Kida, Toshiyuki; Teragaki, Ayumi; Ishida, Haruya; Sonoda, Sayaka; Miyasaka, Momoka; Shigemitsu, Hajime

doi: 10.1039/d3ra07537kpmid: 38024982

Significant efforts have been devoted so far to artificially fabricate supramolecular helical nano- and microstructures through the regulated assembly of biological and synthetic building blocks. However, the preparation of supramolecular helical structures with a regulated morphology remains challenging. Here, helical microrods composed of supramolecular α-cyclodextrin (α-CD) assemblies were fabricated by allowing an α-CD/1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)/2-pentanol mixture to stand at 30–60 °C under high humidity conditions. The morphology could be controlled by temperature to produce helical microrods with a regulated pitch and length. These helical rods can be applied as optical devices, chiral separation devices and asymmetric catalysts.

Che, Mingda; Su, Hongjian; Zhao, Xudong; Fu, Daqing; Huang, Renliang; Guo, Xuehui; Su, Rongxin

doi: 10.1039/d3ra06004gpmid: 38024972

Trichloroethylene (TCE) is an Environmental Protection Agency (EPA) priority pollutant that is difficult to be removed by some remediation methods. For instance, TCE removal using persulfate (PS) activated by ferrous iron (Fe(ii)) has been tested but is limited by the unstable Fe(ii) concentration and the initial pH of contaminated water samples. Here we reported a new TCE removal system, in which tannic acid (TA) promoted the activation of PS with Fe(ii) (TA-Fe(ii)-PS system). The effect of initial pH, temperature, and concentrations of PS, Fe(ii), TA, inorganic anions and humic acid on TCE removal was investigated. We found that the TA-Fe(ii)-PS system with 80 mg L−1 of TA, 1.5 mM of Fe(ii) and 15 mM of PS yielded about 96.2–99.1% TCE removal in the pH range of 1.5–11.0. Radical quenching experiments were performed to identify active species. Results showed that SO4˙− and ˙OH were primarily responsible for TCE removal in the TA-Fe(ii)-PS system. In the presence of TA, the Fe-TA chelation and the reduction of TA could regulate Fe(ii) concentration and activate persulfate for continuously releasing reactive species under alkaline conditions. Based on the excellent removal performance for TCE, the TA-Fe(ii)-PS system becomes a promising candidate for controlling TCE in groundwater.

Mansur, Alexandra A. P.; Carvalho, Sandhra C.; Dorneles, Elaine M. S.; Lage, Andrey P.; Lobato, Zelia I. P.; Mansur, Herman S.

doi: 10.1039/d3ra06711dpmid: 38024978

Among almost 200 types of cancers, glioma is considered one of the most common forms of malignant tumors located in the central nervous system (CNS). Glioblastoma (GBM), one of the deadliest types of brain cancer, remains one of the challenges faced by oncologists. Thus, smartly designed nanomaterials biofunctionalized with polypeptides can offer disruptive strategies relying on the earliest possible diagnosis (“seeing is believing”) combined with more efficient therapies for fighting cancer cells. To worsen this scenario, bacteria infections very often pose a serious challenge to cancer-immunodeficient patients under chemotherapy. Thus, in this research, we report for the first time the design and synthesis of novel nanoconjugates composed of photoluminescent ZnS quantum dots (ZnS QDs), which were directly surface biofunctionalized with epsilon-poly-l-lysine (εPL), acting as an amine-rich cell-penetrating peptide (CPP) and antimicrobial peptide agent (AMP). These nanoconjugates (named ZnS@CPP–AMP) were produced through a one-step facile, eco-friendly, and biocompatible colloidal aqueous process to be applied as a proof of concept as nanoprobes for bioimaging GBM cancer cells (U87-MG) associated with synergic antibacterial activity. They were characterized regarding their physicochemical and optical properties associated with the biological activity. The results demonstrated that chemically stable aqueous colloidal nanoconjugates were effectively formed, resembling core–shell (inorganic, ZnS, organic, εPL) nanostructures with positively surface-charged features due to the cationic nature of the amine-rich polypeptide. More importantly, they demonstrated photoluminescent activity, cytocompatibility in vitro, and no significant intracellular reactive oxygen species (ROS) generation. These ZnS@CPP–AMP nanocolloids behaved as fluorescent nanoprobes for bioimaging GBM cancer cells, where the polycationic nature of the εPL biomolecule may have enhanced the cellular uptake. Additionally, they displayed mild antibacterial growth inhibition due to electrostatic interactions with bacterial membranes. Thus, it can be envisioned that these novel photoluminescent colloidal nanoconjugates offer novel nanoplatforms that can be specifically targeted with biomolecules for bioimaging to diagnose highly lethal cancers, such as GBM, and as an adjuvant in antibacterial therapy.

Bedwell, Elizabeth V.; da Silva Emery, Flavio; Clososki, Giuliano C.; Steel, Patrick G.

doi: 10.1039/d3ra07458gpmid: 38024964

Heterocycles are a cornerstone of fragment-based drug discovery (FBDD) due to their prevalence in biologically active compounds. However, novel heterocyclic fragments are only valuable if they can be suitably elaborated to compliment a chosen target protein. Here we describe the synthesis of 5-halo-1H-pyrazolo[3,4-c]pyridine scaffolds and demonstrate how these compounds can be selectively elaborated along multiple growth-vectors. Specifically, N-1 and N-2 are accessed through protection-group and N-alkylation reactions; C-3 through tandem borylation and Suzuki–Miyaura cross-coupling reactions; C-5 through Pd-catalysed Buchwald–Hartwig amination; and C-7 through selective metalation with TMPMgCl.LiCl followed by reaction with electrophiles or transmetalation to ZnCl2 and Negishi cross-coupling. Linking multiple functionalisation strategies emulates a hit-to-lead pathway and demonstrates the utility of pyrazolo[3,4-c]pyridines to FBDD.

Chen, Yulong; Xie, Teng; Chen, Ziqiang; Cui, Zhou; Wen, Cuilian; Sa, Baisheng

doi: 10.1039/d3ra07383apmid: 38024995

Inorganic electrides are considered potential superconductors due to the unique properties of their anionic electrons. However, most electrides require external high-pressure conditions to exhibit considerable superconducting transition temperatures (Tc). Therefore, searching for superconducting electrides under low or moderate external pressures is of significant research interest and importance. In this work, a series of A3Hf2B3-type compounds (A = Mg, Ca, Sr, Ba; B = Si, Ge, Sn, Pb) were constructed and systematically studied based on density functional theory calculations. According to the analysis of the electronic structures and phonon dispersion spectrums, stable one-dimensional electrides Ca3Hf2Ge3, Ca3Hf2Sn3, and Sr3Hf2Pb3, were screened out. Interestingly, the superconductivity of these electrides were predicted from electron phonon coupling calculations. It is highlighted that Sr3Hf2Pb3 showed the highest Tc, reaching 4.02 K, while the Tc values of Ca3Hf2Ge3 and Ca3Hf2Sn3 were 1.16 K and 1.04 K, respectively. Moreover, the Tc value of Ca3Hf2Ge3 can be increased to 1.96 K under 20 GPa due to the effect of phonon softening. This work enriches the types of superconducting electrides and has important guiding significance for the research on constructing electrides and related superconducting materials.