Electrocatalytic Palladium Nanoclusters as Versatile Indicators of Bioassays: Rapid Electroanalytical Detection of SARS-CoV-2 by Reverse Transcription Loop-Mediated Isothermal Amplification.

Quantitative polymerase chain reaction (qPCR) is considered the gold standard for pathogen detection. However, improvement is still required, especially regarding the possibilities of decentralization. Apart from other reasons, infectious diseases demand on-site analysis to avoid pathogen spreading and increase treatment efficacy. In this paper, the detection of SARS-CoV-2 is carried out by reverse transcription loop-mediated isothermal amplification, which has the advantage of requiring simple equipment, easily adaptable to decentralized analysis. It is proposed, for the first time, the use of palladium nanoclusters (PdNCs) as indicators of the amplification reaction at end point. The pH of the medium decreases during the reaction and, in turn, a variation in the catalytic activity of PdNCs on the oxygen reduction reaction (ORR) can be electrochemically observed. For the detection, flexible and small-size screen-printed electrodes can be premodified with PdNCs, which together with the use of a simple and small electrochemical equipment would greatly facilitates their integration in field-deployable devices. This would allow a faster detection of SARS-CoV-2 as well as of other future microbial threats after an easy adaptation.

Real-time COVID-19 detection via graphite oxide-based field-effect transistor biosensors decorated with Pt/Pd nanoparticles.

Coronavirus 2019 (COVID-19) spreads an extremely infectious disease where there is no specific treatment. COVID-19 virus had a rapid and unexpected spread rate which resulted in critical difficulties for public health and unprecedented daily life disruption. Thus, accurate, rapid, and early diagnosis of COVID-19 virus is critical to maintain public health safety. A graphite oxide-based field-effect transistor (GO-FET) was fabricated and functionalized with COVID-19 antibody for the purpose of real-time detection of COVID-19 spike protein antigen. Thermal evaporation process was used to deposit the gold electrodes on the surface of the sensor substrate. Graphite oxide channel was placed between the gold electrodes. Bimetallic nanoparticles of platinum and palladium were generated via an ultra-high vacuum (UHV) compatible system by sputtering and inert-gas condensation technique. The biosensor graphite oxide channel was immobilized with specific antibodies against the COVID-19 spike protein to achieve selectivity and specificity. This technique uses the attractive semiconductor characteristics of the graphite oxide-based materials resulting in highly specific and sensitive detection of COVID-19 spike protein. The GO-FET biosensor was decorated with bimetallic nanoparticles of platinum and palladium to investigate the improvement in the sensor sensitivity. The in-house developed biosensor limit of detection (LOD) is 1 fg/mL of COVID-19 spike antigen in phosphate-buffered saline (PBS). Moreover, magnetic labelled SARS-CoV-2 spike antibody were studied to investigate any enhancement in the sensor performance. The results indicate the successful fabrication of a promising field effect transistor biosensor for COVID-19 diagnosis.

One-pot high-yield synthesis of Pd nanocubes for Pd-Ir nanocube-based immunoassay of nucleocapsid protein from SARS-CoV-2.

Pd-Ir nanocubes are promising peroxidase-mimicking nanozymes for immunoassays, enabled by their excellent stability, relatively high catalytic activity, and reproducible performance. A key step involved in the preparation of Pd-Ir nanocubes is the synthesis of Pd nanocubes. However, the traditional method to synthesize Pd nanocubes requires sophisticated and expensive equipment to precisely control the reaction temperature and highly skilled technicians to achieve satisfactory and reproducible product yields. Herein, we report a simple, cost-effective, high-yield (> 99%) and one-pot strategy to synthesize Pd nanocubes with sizes of 7, 18, and 51 nm for the preparation of Pd-Ir nanocubes. The resulting 18 nm Pd-Ir nanocubes display three orders of magnitude higher peroxidase activity compared to horseradish peroxidase, leading to a significantly increased detection sensitivity when applied in the immunoassay of nucleocapsid protein from SARS-CoV-2. Due to the simplicity in both material synthesis and assaying procedures and the excellent detection sensitivity, our method should allow for the generalized application of Pd-Ir nanocube-based immunoassays for the diagnosis of human diseases.

Synthesis of Palladium(II) Complexes via Michael Addition: Antiproliferative Effects through ROS-Mediated Mitochondrial Apoptosis and Docking with SARS-CoV-2.

Metal complexes have numerous applications in the current era, particularly in the field of pharmaceutical chemistry and catalysis. A novel synthetic approach for the same is always a beneficial addition to the literature. Henceforth, for the first time, we report the formation of three new Pd(II) complexes through the Michael addition pathway. Three chromone-based thiosemicarbazone ligands (SVSL1-SVSL3) and Pd(II) complexes (1-3) were synthesized and characterized by analytical and spectroscopic tools. The Michael addition pathway for the formation of complexes was confirmed by spectroscopic studies. Distorted square planar structure of complex 2 was confirmed by single-crystal X-ray diffraction. Complexes 1-3 were subjected to DNA- and BSA-binding studies. The complex with cyclohexyl substituent on the terminal N of thiosemicarbazone (3) showed the highest binding efficacy toward these biomolecules, which was further understood through molecular docking studies. The anticancer potential of these complexes was studied preliminarily by using MTT assay in cancer and normal cell lines along with the benchmark drugs (cisplatin, carboplatin, and gemcitabine). It was found that complex 3 was highly toxic toward MDA-MB-231 and AsPC-1 cancer cells with IC50 values of 0.5 and 0.9 µM, respectively, and was more efficient than the standard drugs. The programmed cell death mechanism of the complexes in MDA-MB-231 cancer cells was confirmed. Furthermore, the complexes induced apoptosis via ROS-mediated mitochondrial signaling pathway. Conveniently, all the complexes showed less toxicity (≥50 µM) against MCF-10a normal cell line. Molecular docking studies were performed with VEGFR2, EGFR, and SARS-CoV-2 main protease to illustrate the binding efficiency of the complexes with these receptors. To our surprise, binding potential of the complexes with SARS-CoV-2 main protease was higher than that with chloroquine and hydroxychloroquine.

Synthesis of novel artesunate-benzothiophene and artemisinin-benzothiophene derivatives.

Natural products are used for the treatment of a variety of diseases for many years. Last decades, design and synthesis of novel biologically active hybrid molecules including natural product is gained big importance due to their unique and new biological properties. In the present study, novel artemisinin-benzothiophene derivatives (12 A-F) are synthesised. Initially, benzothiophene derivatives (4 A-4F) are prepared via the Pd-catalyzed coupling reactions and iodocyclisation reactions. Then, Suzuki-Miyaura coupling reactions were used for the formation of intermediates 6 A-6F (between 64% and 91% yields). Finally, the Steglich esterification reaction between intermediate 6 and artesunate formed the artemisinin-benzothiophene hybrids (9 A-9F) in moderate to excellent yields under very mild reaction conditions. When intermediate 6 was reacted with dihydroartemisinin, product 12 A-12F was also obtained with high yields.[Formula: see text].

PdCl2-catalyzed synthesis of a new class of isocoumarin derivatives containing aminosulfonyl / aminocarboxamide moiety: First identification of a isocoumarin based PDE4 inhibitor.

While anti-inflammatory properties of isocoumarins are known their PDE4 inhibitory potential was not explored previously. In our effort the non-PDE4 inhibitor isocoumarins were transformed into the promising inhibitors via introducing an aminosulfonyl/aminocarboxamide moiety to the C-3 benzene ring attached to the isocoumarin framework. This new class of isocoumarins were synthesized via a PdCl2-catalyzed construction of the 4-allyl substituted 3-aryl isocoumarin ring starting from the appropriate 2-alkynyl benzamide derivative. Several compounds showed good inhibition of PDE4B in vitro and the SAR indicated superiority of aminosulfonamide moiety over aminocarboxamide in terms of PDE4B inhibition. Two compounds 3q and 3u with PDE4B IC50 = 0.43 ± 0.11 and 0.54 ± 0.19 µM and ≥ 2-fold selectivity over PDE4D emerged as initial hits. The participation of aminosulfonamide moiety in PDE4B inhibition and the reason for selectivity though moderate shown by 3q and 3u was revealed by the in silico docking studies. In view of potential usefulness of moderately selective PDE4B inhibitors the compound 3u (that showed PDE4 selectivity over other PDEs) was further evaluated in adjuvant induced arthritic rats. At an intraperitoneal dose of 30 mg/kg the compound showed a significant reduction in paw swelling (in a dose dependent manner), inflammation and pannus formation (in the knee joints) as well as pro-inflammatory gene expression/mRNA levels and increase in body weight. Moreover, besides its TNF-α inhibition and no significant toxicity in an MTT assay the compound did not show any adverse effects in a thorough toxicity studies e.g. teratogenicity, hepatotoxicity, cardiotoxicity and apoptosis in zebrafish. Thus, the isocoumarin 3u emerged as a new, safe and moderately selective PDE4B inhibitor could be useful for inflammatory diseases possibly including COVID-19.

Stable dechlorination of Trichloroacetic Acid (TCAA) to acetic acid catalyzed by palladium nanoparticles deposited on H2-transfer membranes.

Trichloroacetic acid (TCAA) is a common disinfection byproduct (DBP) produced during chlorine disinfection. With the outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic, the use of chlorine disinfection has increased, raising the already substantial risks of DBP exposure. While a number of methods are able to remove TCAA, their application for continuous treatment is limited due to their complexity and expensive or hazardous inputs. We investigated a novel system that employs palladium (Pd0) nanoparticles (PdNPs) for catalytic reductive dechlorination of TCAA. H2 was delivered directly to PdNPs in situ coated on the surface of bubble-free hollow-fiber gas-transfer membranes. The H2-based membrane Pd film reactor (H2-MPfR) achieved a high catalyst-specific TCAA reduction rate, 32 L/g-Pd/min, a value similar to the rate of using homogeneously suspended PdNP, but orders of magnitude higher than with other immobilized PdNP systems. In batch tests, over 99% removal of 1 mM TCAA was achieved in 180 min with strong product selectivity (≥ 93%) to acetic acid. During 50 days of continuous operation, over 99% of 1 mg/L influent TCAA was removed, again with acetic acid as the major product (≥ 94%). We identified the reaction pathways and their kinetics for TCAA reductive dechlorination with PdNPs using direct delivery of H2. Sustained continuous TCAA removal, high selectivity to acetic acid, and minimal loss of PdNPs support that the H2-MPfR is a promising catalytic reactor to remove chlorinated DBPs in practice.